Misbah EE Review 2018

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com Evaluating Exam Review Book 2018
Pharmacy Prep
Evaluating Exam
Review Book
Misbah Biabani, Ph.D

Toronto Institute of Pharmaceutical Sciences (TIPS) Inc.
Toronto, ON M2N 6K7
2018
Pharmacy Prep
Professional Exams Preparation Center
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Toronto Institute of Pharmaceutical Sciences Inc.
© 2000 to 2018 TIPS Inc. All Rights Reserved.
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is 1
illegal to reproduce without permission. This manual is being used during review sessions conducted by
PharmacyPrep.
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Disclaimer
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The information contained in the notes intended as an educational aid only. It is not intended
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©2000-2018 TIPS Inc. All rights reserved.
Foreword by
Misbah Biabani, Ph.D
Coordinator, Pharmacy Prep
Toronto Institute of Pharmaceutical Sciences (TIPS) Inc
4789 Yonge St. Unit 415-417
Toronto ON M2N 6K7, Canada
PharmacyPrep.
Content
Abbreviations
Part 1. Biomedical Sciences 15%

1. Human Anatomy
2. Gastrointestinal System
3. Nervous System
4. Cardiovascular System
5. Endocrine System
6. Renal System
7. Liver Function and Pathophysiology
8. Respiratory System
9. Urinary System
10. The Eye and Ear
11. Blood and Anemia
12. Biochemistry
13. Nutrition
14. Microbiology
15. Cell and Molecular Biology
16. Pharmacogenetics
17. Immunology and Immunizations
18. Biotechnology
19. Toxicology
Part 2. Pharmaceutical Sciences 25%

20. Pharmacokinetics
21. Rates and Orders of Reactions
22. Pharmacodynamics
23. Basics of Medicinal Chemistry
24. Medicinal Chemistry and Pharmacology of Autonomic Nervous System Drugs.
25. Medicinal Chemistry and Pharmacology of Histamines, Serotonin, Prostaglandin and
Non-Steroidal Anti-inflammatory Drugs
PharmacyPrep.
26. Medicinal Chemistry and Pharmacology of Cardiovascular Drugs

27. Medicinal Chemistry and Pharmacology of Psychiatric & Neurological Drugs
28. Medicinal Chemistry and Pharmacology Endocrine Drugs
29. Medicinal Chemistry and Pharmacology of Respiratory Drugs
30. Medicinal Chemistry and Pharmacology of Musculoskeletal Drugs
31. Medicinal Chemistry and Pharmacology of Antimicrobial Drugs
32. Drug Metabolism
33. Biopharmaceutics
34. Physical Pharmacy
35. Pharmaceutical Excipient
36. Rheology
37. Pharmaceutical Dosage Forms
38. Drug Delivery Systems
39. Pharmaceutical Analysis
Part 3. Social/Behavioural/Administrative Sciences 10%
40. Canadian Healthcare System
41. Canadian Pharmacy Law and Jurisprudence
42. Pharmacist Scope of Practice in Canada
43. Pharmacy Management
44. Pharmacoeconomics
45. The New Drug Approval Process
46. Evidence Based Medicine and Epidemiology
47. Biostatistics
48. Hospital Pharmacy
Part 4a. Pharmacy Practice (50%)
Professional Practice Skills (15%)-workflow
49. Pharmacy Calculations. Basics
50. Pharmacy Calculations. Dose Calculations
51. Pharmacy Calculations. Dilutions and Allegations
52. Brand and Generic Name Indexes
PharmacyPrep.
53. Prescription Processing and Medication Dispensing

54. Safety of Medications in Special Populations
55. Promoting Medication Adherence
56. Professional Pharmacy Communication Skills
57. Bioethics and Professional Ethics
58. Drug Information Resources and Literature Evaluation
59. Medication Errors and Patient Safety Practices
60. Health Promotion and Disease Prevention
61. Collaboration and Teamwork
62. Sterile Preparations
63. Compounding and Storage Conditions
Part 4b. Pharmacy Practice-Clinical Pharmacy (35%)
64. Pharmaceutical Care and Drug Related Problems
65. Adverse Drug Reactions and Management
66. Drug Interactions
67. Clinical Biochemistry and Therapeutic Drug Monitoring
68. Quality Assurance in Pharmacy Practice
69. OTC and Prescription Drugs for Dermatological and Foot Conditions
70. OTC and Prescription Drugs for Ophthalmic, Ear and Mouth Disorders
71. OTC Drugs Antihistamine, Decongestants, Antitussives, Expectorants
72. OTC Drugs for Nausea, Vomiting, Constipation, Diarrhea, Hemorrhoids
73. Analgesics, and Topical Pain Relievers
74. Asthma and Chronic Obstructive Pulmonary Disease (COPD)
75. Smoking Cessation
76. Insomnia
77. Eating Disorders
78. GERD, Ulcers, Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS)
79. Diabetes Mellitus Type I and Type 2
80. Thyroid Disorders
81. Contraception
82. Gynaecologic and Genitourinary Disorders
PharmacyPrep.
83. Rheumatoid Arthritis, Osteoarthritis and Gout arthritis

84. Osteoporosis
85. Hypertension
86. Coronary Artery Diseases
87. Stroke
88. Congestive Heart Failure
89. Cardiac Arrhythmias
90. Peripheral Vascular diseases
91. Neurological Disorders and Pain Management
92. Anxiety Disorder
93. Depression
94. Psychosis and Schizophrenia
95. Dementia
96. Seizures and Epilepsy
97. Parkinson’s Disease
98. Antimicrobial Agents
99. Anticancer Drugs and Chemotherapy
100. Pharmacognosy and Natural Products
PharmacyPrep.
Pharmacyprep.com Human Anatomy
1
Human Anatomy
Questions Alerts!
Common questions in pharmacy exam is to ask!
· Anatomy of body movements like abduction, adductions, supine and prone.
· Anatomical planes such as sagittal and midsagittal plane.
· Skeletal bones and joints. Patella (kneecap), hip joints or bowl and socket (ilium, ischium, pubis), skull
bones, knee joints have popliteal spaces.
· Muscles. Flexor and Extensor muscles, Actin and myosin muscle fibers for muscle contraction, masseter
muscles are attached to mandibles.
This chapter reviews essentials and definitions of systemic human anatomy terminology and provide a basic
understanding of how the human body is structured with emphasis on clinical applications. This chapter also
reviews cellular mechanism in human physiology. A special emphasis is on drug-induced diseases and effects of
adverse drug reactions on various organs.
Body Movements (Fig 1.1)
· Abduction: Movement away from the midline of the body.

· Adduction: Movement toward the midline of the body.
· Extension: Lengthening or straightening of a flexed limb.
· Flexion: Bending of a part of the body.
· Dorsiflexion: Backward (upward) bending of the foot.
· Plantar flexion: Bending of the sole of the foot downward toward the ground.
· Pronation: Act of turning the hand so that the palm faces downward.
· Supination: Act of turning the hand so that the palm is uppermost.
· Eversion: Outward turning.
· Fascia: Fibrous membrane separating and enveloping muscles.
· Anterior (ventral): Front side of the body (example: Abdomen is anterior to the spinal cord).
· Posterior (dorsal): Back of the body (example. Spinal cord is posterior to the stomach).
· Lateral view = from the side of the body
· Medial view = from the middle of body (between two legs)
· Deep: Away from the surface.
· Superficial: On the surface (example. Superficial veins can be viewed through skin).
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to 1-1
reproduce without permission. This manual is being used during review sessions conducted by PharmacyPrep.
· Proximal: Near the point of attachment to the trunk or near the beginning of a structure (Example.
The proximal end of the stomach is at the esophagus or the proximal end of the upper bone joins
with shoulder bone).
Fig 1.1
Distal: Far from the point of attachment to the trunk or from the beginning of a structure (Example. The distal
end of the stomach is at the small intestine).
Inferior. Below another structure. Caudal (pertaining to the head) means inferior in human. (Example. The
urinary bladder lies inferior to the kidney)
opposite opposite
Abduction Adduction
Extension Flexion
Lateral Medial
Dorsal Ventral
Proximal Distal
Anatomical planes (Fig 1.1)

· Sagittal plane: Plane created by an imaginary line that is parallel to the median plane. Separates the body
into right and left portions.
· Midsagittal plane (median plane): Plane created by an imaginary line that divides the body into right and left
halves. Separates the body/body part into equal right/left portions.
· Parasagittal plane: Divides the body into unequal right and left portions.
· Coronal plane/frontal. Divides the body/body part into anterior and posterior portions.
· Transverse plane/horizontal. Divides the body/body part into superior and inferior portions.
· Oblique plane: Passes through the body/body part at an angle.
Anatomical positions
Postural: Positions such as standing, sitting, lying down, turning right or left.
Orthostatic: Standing upright and lying down supine.
Fowler’s position: Seated position with back support (Head elevated)
Trendelenburg position: Sleeping position with Feet elevated and head lowered.
Skeletal Joints (Fig 1.2)

Weight bearing joints
Shoulder joint: consists of humerus, scapula, synovial membrane, articular cartilage, articular capsule, articular
liquid, and ligament.
Knee joint: consists of femur (longest bone), tibia, patella, meniscus, articular cavity, serous bag, and articular
capsule & cartilage. Patella (knee cap) bone is present in knee joint. Popliteal spaces or nerves are present in
knee joint.
Hip joint (socket and ball): consists of Ilium, ischium, and pubis.
Shoulder joint Ball & socket (Rotary cuff: is a group of Cranial bones
muscles that stabilize the shoulder) “ PEST OF”
Knee joint Hinge joint
Hip joint Ball &Socket
The major skull bones include Cranial bones (8), Facial bones (14), Ossicles (ear bones) (3)
Cranial bones (protect brain): Frontal bones, parietal, occipital, temporal, sphenoid and ethmoid bone.
Parietal (2), Ethmoid, Sphenoid, Temporal (2), Occipital, Frontal
Tennis elbow (lateral epicondylosis): inflammation and pain of outer side of elbow involving humerus
and usu. This results from excessive use of forearm or twisting.
Tendons: Connect muscle to bone

Ligaments: Connect bone to bone
Anterior cruciate ligament is connecting between three bones of knee such as thighbone (femur), shinbone
(tibia) and kneecap (patella).
Muscles:
· Trapeziusà neck
· Triceps brachià shoulder (anterior). Triceps are in only in arms.
· Biceps brachià upper arm (biceps) and thighs.

· Femorus is present in back of thigh and leg.
· Quadriceps --> thighs
· Gluteus medium is in hip.
· Psoas muscleà hip
· Largest muscleàgluteus maximus (which forms part of the buttock).
· Fastest muscle isà eyelid elevator.
· Longest single muscleà Sartorius muscle (which stretches from the pelvis to below the knee (more than 15
inches or 40 cm long).
· Smallest muscle is stapedius (found inside the middle ear and less than 0.04 inch (1 mm) long).
· Strongest muscle: Masseter muscle (which elevates during mastication. It can exert a force equivalent in 100
kg (220 lbs).
· Muscles account for 40% of total body weight.
· Muscle fibers actin and myosin helps in muscle contraction.
Three types of muscle tissues

Skeletal muscle (muscle attached to skeleton tendons, bones); Voluntary
Smooth muscle (organs, stomach, blood vessels muscle): involuntary
Cardiac muscle (Heart muscle): involuntary
Types of tissues and functions. Four basic types of tissues, epithelial (covering), connective (support), muscle
(movement), and nervous (control/integration).
· Epithelium: its functions include covering, secretion, absorption, and sensitivity.
· Connective tissue: Support, cartilage, bone, blood, fibrous tissue of ligament (chondrocytes).
· Muscle tissue, skeletal muscle tissue, cardiac muscle tissue, smooth muscle tissues.
· Nervous: Control and integration.
Tissue functions: Protection, absorption, filtration, excretion, secretion, and sensory reception.
Epithelium tissue present at sites of rapid diffusion, such as the lining of lung alveoli.
Endothelium tissue present in the lining of blood vessels (arteries, veins, capillaries).
Mesothelium present at sites where very little activity is occurring, such as Bowman's capsule in the kidney and
the lining of major body cavities.
Epithelial tissue: Covering/lining or glandular, are 2 basic types endocrine "ductless" produce hormones.
Exocrine have ducts, sweat, oil, saliva, bile enzymes, mucin (mucus).
· Connective Tissue: support protection, insulation, transportation. Characteristics, large extra cellular matrix.
Four basic classes of connective tissue:
· Connective tissue proper. Loose, adipose, areolar storage, support organs or vessels, Dense. Regular,
elastic (tendons and ligaments).
· Cartilage. Cushion, structure, support, and laid down before bone.
· Osseous (bone): Bring in beef bone, compact, rigid, and spongy marrow.
· Blood: RBCs, WBCs, and platelets, and plasma matrix.
Tips
1 Supination 2. flexion 3. Abduction
4 Extension 5. adduction 6. Parasagittal plane
7 Sagittal plane 8. Midsagittal plane 9. Kneecap
10 Biceps bronchi 11 Triceps bronchi 12 dysphagia
13 Joints 14 Hormone glands 15 Blood vessels
16 Extensor muscles 17 Flexor muscles 18 Pubis
19 Ilium 20 Ischium 21 transverse plane
22 Endocrine glands 23 Arteries 24 Skull bones
25 Moving away from 26 Moving closer to body 27 slicing vertically
body
28 slicing vertically from 29 Slicing vertically from side 30 Slicing horizontal
middle line lines
31 dysuria 32 Dyspnea
· Adduction à ( )
· Abduction à ( )
· Sagital planes à ( )
· Para sagital plane à( )
· Mid sagital plane à( )
· Transverse plane à ( )
· Hip joints have à ( )
· Flexor muscles are present inà ( )
· Extensor muscles are present inà ( )
· Epithelial tissue is present in à ( )
· Endothelial tissues is present in à ( )
· Skull bones are à???
· Movement away from the midline of the body ( )
· Act of turning the hand so that the palm is uppermost ( )
· bending part of the body ( )
· movement toward the midline of the body ( )
· lengthening or straightening of the flexed limb ( )
· found in arms and thighs ( )
· Found in arms only ( )
· Separates the body into unequal right and left portions ( )
· Separates the body into equal right and left portions ( )
· Separates the body into right and left portions ( )
· It protects the front of the joint ( )
· Difficulty in breathing ( )
· Difficulty in swallowing ( )
· Difficulty in urination ( )
· Found in limbs, foot, arms ( )
· Hip joints have ( )
· Which one is a part of the shoulder? ( )
· Popliteal space is present knee ( )
PharmacyPrep.com Gastrointestinal System
2
Gastrointestinal System
Questions Alerts!
· Stomach secretions (intrinsic factor, HCL, gastrin). Pepsin is digestive enzyme present in GIT break
downs proteins.
· Role of small intestine in absorption of nutrients, drugs and supplements
· Large intestine (colon) bacteria and excessive absorption of water that cause constipation.
· Disease of GI system like GERD, peptic ulcers, Crohn's disease, ulcerative colitis and irritable bowel
syndrome (IBS) symptoms.
This chapter review anatomy, physiology and pathophysiology of the gastrointestinal system, common disease
that occurs in gastrointestinal tract.
Mouth
· Tongue has bony attachments (styloid
process, hyoid bone) attached to the floor of
the mouth by frenulum.
· Posterior exit from mouth guarded by a ring
of palatine/lingual tonsils.
· Ducted salivary glands open at various points
into the mouth. This process involves teeth
(muscles of mastication move jaws) and
tongue (extrinsic and intrinsic muscles).
· Mechanical breakdown, plus some chemical
(ptyalin, enzyme in saliva) secretion.
· Saliva amylase does hydrolysis of starch and
glycogen into maltose.
Esophagus
· The esophagus is about 10" long.
· Food moves through esophagus by peristalsis.
Stomach
Question Alerts!
1) Intrinsic factor secreted from parietal cells
deficiency cause?
2) Pernicious anemia should be treated by parenteral
(SC/IM) vitamin B12.
3) Elderly persons have deficiency of vitamin B12
4) Gastrin is secreted from pyloric gland of stomach.
5) What are stomach secretions occur in response to
protein diet? Gastrin and pepsin.
Fig 2.2
· Cardioesophageal sphincter guarding entrance from esophagus.

· Pyloric sphincter guarding the outlet is much better defined.
· Fundus, body and pylorus recognised as distinct regions.
· Stomach secretes both acid and mucus (for self protection).
· Surface area increased by rugae, which serves as temporary store for food.
Stomach Secretions Purpose Source

Mucus Lubricant, protects surface from acid. Mucus Cell
Intrinsic factor Vitamin B 12 absorption (in small intestine ilium). Parietal cell
Acid (H+) Kills bacteria, breaks down food, converts pepsinogen. Parietal cell
Pepsinogen Broken down to pepsin (a protease) Chief Cell
Gastrin Stimulates acid secretion (in response protein) G Cell
*Deficiency of intrinsic factors causes a type megaloblastic anemia i.e. pernicious anemia.
Gastric acid secretion mechanism. In the parietal cells CO2 and H2O are converted H+ and HCO3- catalyzed by
carbonic anhydrase. The parietal cells secrete HCl into the lumen of the stomach and concurrently absorb HCO3-
into the blood stream.
Gastric acid stimulations. Gastric acid production is stimulated by three mechanisms.
Vagal stimulation. Vagal nerve innervates parietal cells and stimulates H+ secretion directly.
Histamine release. Histamine is released from mast cells in the gastric mucosa and diffuses to nearby parietal
cells.
Gastrin: It is released in response to eating a meal (protein), thus stimulates parietal cells to secrete H+.
Pathophysiology of gastric acid secretions causes gastric ulcer, duodenal ulcers and Zollinger-Ellison
syndrome.
Question Alerts!
1) What enzymes are released into small intestines? Pancreatic and bile secretions.
2) A patient with ileostomy, what oral dosage is NOT suitable? Oral drugs especially Sustain release (SR,
CR MR CD) d f
Gastric emptying Time: The caudad region of stomach contract to propel food into the duodenum. The rate of
gastric emptying time is fastest if gastric content is isotonic. Fat inhibits gastric emptying time (i.e. increase
gastric emptying time).
Stomach ---à (Pyloric sphincter)-à Duodenum à Jejunum àileum
Prokinetic drugs (metoclopramide, domperidone) decrease gastric emptying time
Small intestine: Consist of duodenum, jejunum, and ileum.

Duodenum: First part of the small intestine, C-shaped 10" (inch) long and curves around the head of
pancreas and the entry of common bile duct.
· Highest drug absorption in the body takes place here.
· Pancreases is a large glandular organ attached near the stomach.
· Pancreas secretes intestinal enzymes (pancreatic lipase, amylase, protease), and these helps in
the digestion of carbohydrates.
· Bile secretions are bile salts, bilirubin, phospholipids, and cholesterol.
Jejunum: It is 8 to10 feet long: The majority of food absorption takes place in the jejunum.
Secretion
· Secretin stimulates pancreas to produce watery fluid, high in bicarbonates concentration.
· Pancreozymin stimulates pancreas to produce a viscous fluid low in bicarbonate concentration.
Ileum: It is 12 feet long. Towards the end of the small intestine, accumulations of lymphoid tissue
(Peyer’s patches) are more common here.
Large Intestines: It is also known as colon.

· Jejunum terminates at caecum.
· Highest basic or pH.
· Animals digest cellulose in colon.
· The large intestine reabsorbs water then eliminates drier residues as feces.
· Its primary purpose is to extract (absorbed) water from feces.
· Colon consists of higher flora and fauna in GI tract 90 to 99% anaerobic bacteria. Example B. fragilis and C.
difficle anaerobic and aerobic E. coli.
· Colon bacterial produce vitamin K 2 (menaquinone).
Diseases of the gastrointestinal system

Diseases of the Mouth and Jaw
· Oral thrush is caused by Candida albicans, and moniliasis.
· Gingivitis (gum inflammation) is caused by Fusobacterium sp.
· Stomatitis is Inflammation of mouth cavity. Herpes stomatitis caused by herpes infection, and aphthous
stomatitis caused by oral hygiene or damage to mucus membrane.
Disease of the Salivary Glands: Sjogren syndrome (dry mouth, dry eyes) is autoimmune disease, it is associated
with rheumatoid arthritis.
Sialorrhea is an excessive secretion of saliva in infants, children, Parkinson’s disease. Can cause by mucosal
irritation.
Dyspepsia: Defined as pain or discomfort in the upper abdomen. Symptoms are nausea, fullness, early satiety,
bloating or regurgitation. The dyspepsia could be due to esophagitis, GERD, peptic ulcer (GU or DU) 15-25%,
Reflux esophagitis, 5-15%, gastric or esophageal cancer (<2%).
Diseases of the Esophagus: Gastro esophageal reflux disease (GERD) is reflux of gastric acid contents into
esophagus. Also referred as heartburn, or regurgitation. Extra esophageal symptoms include cough, laryngitis
and asthmatic syndrome. But the common symptoms are heartburn, regurgitation of acid or bile and hyper
salivation.
Diseases of the stomach.

· Gastritis (inflammation of gastric or stomach lining). Caused by NSAIDS, cigarette smoking, and heavy
alcohol.
· Gastroenteritis: Inflammation of entire GI tract.
· Peptic ulcer: There are two main causes of Helicobacter pylori infections or drug induced (NSAIDS).
Diseases of the small intestine.

· Duodenal ulcers are mainly caused by Helicobacter pylori and the second most common reason is
medications like NSAIDs.
· Zollinger Ellison syndrome is excessive secretion of HCl
· Celiac disease is caused by sensitivity to gluten in cereals. This is due to inability of absorption of gluten (it
mainly effects on upper part of small intestine).
Diseases of the Colon

· Inflammatory bowel disease (IBD): Consist of two conditions, Crohn’s disease and ulcerative colitis.
· IBD symptom are diarrhea, abdominal pain, and rectal bleeding and weight loss.
· Ulcerative colitis occurs mainly in colon and Crohn's disease occurs from esophageal to rectum.
· Crohn's disease (small intestine and colon), chronic inflammatory of ileum, and colon, this can lead to fistula.
ULCERATIVE COLITIS CROHN'S DISEASE

Localized to colon. Site of origin is Occurs from esophageal to rectum. Skip Patches are found entire GI
rectum. system. Site of origin is terminal ileum.
Fistula (ulcers in GI tissue) are present Crohn's.
Drug of choice 5ASA 5ASA or Oral prednisone
Fistula are treated by infliximab, adalimumab or metronidazole
10-20 liquid stools per day containing Less common liquid stools per day containing blood and mucus.
blood and mucus.
Pain, diarrhea, blood in stools Crampy abdominal Pain, diarrhea, blood in stools, weight loss.
(bloody diarrhea), weight loss (Toxic megacolon).
Marked increase risk of colon cancer Slight increase risk of colon cancer.
Irritable bowel syndrome (IBS): This can cause severe chronic diarrhea, constipation, bloating and
cramps, nausea and vomiting (No bleeding).
Bristol-stool chart is used to determine severity.
Pseudo membranous colitis. Clostridium difficile over growth (produce exotoxin) cause diarrhea. C.
difficile is communicable disease. The drug of choice is metronidazole po, vancomycin po.
· Amebic colitis is caused by Entamoeba histolytica
· Cholera is caused by Vibrio cholera.
Hernia: a perturbation of GI tract at the junction of esophagus and stomach.
Fig 2.3
TYPES OF HERNIA
Inguinal Near the opening of the inguinal canal More common in elderly
Femoral Occurs in the femoral canal
Umbilical Occurs at Navel
Incisional Occurs at site of previous surgical incision
Diaphragmatic Upper abdomen at midline
(epigastric)
Hiatal hernia Occurs when part of the stomach pushes up
through the diaphragm into chest.
Digestion and Absorption

Digestive enzymes are classified based on their target substrates
· Proteases and peptidases split proteins into small peptides and amino acids.
· Lipases split fat into three fatty acids and a glycerol molecule.
· Carbohydrases split carbohydrates such as starch and sugars into simple sugars such as glucose.
· Nucleases split nucleic acids into nucleotides.
GI secretions include saliva, gastric secretions, pancreatic secretions and bile.
Carbohydrates digestion: The most common site of carbohydrate absorption is small intestine. Only
monosaccharides such as glucose, fructose, and galactose are absorbed.
Amylase: Hydrolyse starch and glycogen into maltose. There is amylase in saliva and stomach.
· Maltase: Converts maltose into glucose + glucose
· Sucrase: Converts sucrose into glucose + fructose.
· Trehalase: degrades carbohydrate to glucose.
· Glucosidase: breakdown sucrose and starch to glucose (Acarbose inhibits alpha glucosidase).
· Lipase is released mainly from the pancreases into the GI track to help breakdown fat. (Orlistat, Xenical
inhibit lipase)
· Lactase: Converts lactose (milk) into glucose + galactose.
Pancreatic Secretions (High HCO 3 isotonic, pancreatic lipase, amylase, proteases).
Disorder of carbohydrate absorption. Lactose

intolerance results from absence of brush ENZYME ENZYME PRODUCT
border lactase. Thus, non-absorbed lactose Amylase Starch and glycogen Maltose
cause osmotic diarrhea. Maltase Maltose Glucose + glucose
Milk intolerance can result from 2 reasons. 1) Sucrase Sucrose Glucose + Fructose
Lactose intolerance 2) milk protein allergies Lactase Lactose Glucose + galactose
Lipid Absorption. Bile acids emulsify lipids in the small intestine, increase surface for digestion. Pancreatic
lipases, hydrolyse, lipids to fatty acids, monoglycerides, cholesterol and lysolecithin.
Lipid absorption disorders. Malabsorption of lipids thus causing fatty stools, this also referred as stethorrhea.
Stethorrhea can cause by
· Pancreatic diseases such as pancreatitis, and cystic fibrosis.
· Hyper secretion of gastrin
· Ileal resection
· Bacterial overgrowth
Absorption of Proteins (small intestine): Trypsin and chymotrypsin are secreted by pancreas, which helps in
digestion of proteins.
· Trypsin is secreted in the inactive form as trypsinogen and is converted to trypsin by enzyme enterokinase.
· Chymotrypsin is secreted in the inactive form as chymotrypsinogen and converted to chymotrypsin by
trypsin.
Pepsin Trypsin and chymotrypsin

Proteins ………..> Proteins and oligopeptides ………………….> oligopeptide à amino acids
(stomach) (small intestine)
Absorption of nucleic acid:

· Nucleaseà Nucleic acid into nucleotide.
· Ribonuclease à Hydrolyses RNA
· Deoxyribonuclease à Hydrolyses DNA
Absorption of water (H 2 O): It is isosmotic in the small intestine and gallbladder.
Absorption of Vitamins and Nutrients: Fat soluble vitamins (ADEK) are absorbed in small intestine along
with other lipids. Vitamin B12 is absorbed in the ileum and that requires intrinsic factor.
Absorption of calcium: Mainly occurs in small intestine, which assisted by active form of vitamin D3, 1,
25-dihydroxycholecalciferol, which is produced in kidney. Chronic renal failure or vitamin D deficiency
results in inadequate intestinal Ca2+ absorption, causing rickets in children and osteomalacia in adults.
The mechanism of calcium absorption is passive absorption.
Absorption of Iron: It is absorbed as heme iron (iron bound to hemoglobin or myoglobin) or as free
Fe2+. In intestinal cells, heme iron is degraded to Fe2+ and released. The free Fe2+ binds to apoferritin
and is transported into the blood.
The iron absorbed from small intestine in the form of ferrous Fe2+
Transferrin: Free Fe2+ circulates binds transferring and transports it from small intestine to its storage
sites in the liver and from the liver to the bone marrow for the synthesis of hemoglobin.
Innervations of GI tract. Autonomic innervations.

Cholinergic: It is usually excitatory on functions of GI tract. It is carried via the vagus and pelvic nerves.
· Vagus nerve innervates the esophagus, stomach, pancreases and upper large intestine
· Pelvic nerve innervates the lower large intestine and rectum, and anus.
Adrenergic
· It usually inhibitory on the functions of GI tract
· Direct post ganglion adrenergic innervations of blood vessels and some smooth muscles.
Tips
Practice answering tips from table:
1. diarrhea 2. constipation 3. Bloating
4. cramps 5. Proteases 6. nuclease
7. 2 glucoses 8. Colon 9. gluten present in cereal
10 Alpha glucosidase 11 95-100% anaerobic 12 Fructose + glucose
bacteria
13 Peptidase 14 Enterokinase 15 Chymotrypsin
16 Trypsin 17 Vitamin D 3 18 Deficiency of intrinsic factors
19 Parenteral vitamin 20 Alcohol dehydrogenase 21 wheat
B 12
22 rye 23 oats
· The most basic part of the GI tract ( )

· Irritable bowel disease symptoms ( )
· The proteins are digested by ( )
· What converts nucleic acid into nucleotides ( )
· The pernicious anemia is caused by ( )
· What digest peptides into amino acids ( )
· pernicious anemia is treated by ( )
· What converts inactive trypsinogen into trypsin ( )
· What enzyme oxidizes alcohol to aldehyde and acids ( )
· What are the major bacteria present in colon ( )
· Breakdown sucrose & starch to glucose ( )
· Gluten is present in ( )
· Allergic component in milk ( )
· Celiac is caused by ( )
· Soya milk allergies due to ( )
· A patient with chronic renal failure have deficiency of vitamin? ( )
· Pernicious anemia is caused by à ( )
· Pernicious anemia is treated by à ( )
· Maltase breakdowns maltose to à ( )
· Sucrase breakdowns sucrose to à ( )
· Alcohol dehydrogenase: ethanol à acetaldehyde à acetic acid
· Irritable bowel symptoms (IBS) include à ( )
· Active Vitamin D is à ( )
· Bacteria in colon makes --> ( )
PharmacyPrep.com Nervous System
3
Nervous System
Questions Alerts!
· What section of brain controls voluntary and involuntary movements?
· Blood brain barrier definition and functions
· Peripheral nerves, radial nerves, ulnar nerves. Sciatica. Cranial nerves.
· Types of Neurological disorders: Multiple sclerosis, Chronic spasticity, Bell's Palsy, Neuralgia, Seizures
or epilepsy, Fibromyalgia, and Parkinson's disease.
· Sciatica pain site is buttocks and back of thighs.
· Causes of multiple sclerosis
Fig 3.2
Fig 3.1
Question Alerts!
1) Voluntary and involuntary movements are controlled by?
2) What section of brain coordination and control balance?
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to
3-1
reproduce without permission. This manual is being used during review sessions conducted by
PharmacyPrep.
Nervous system divided into central nervous system and peripheral nervous system. The central nervous system
consists of brain and spine.
Brain
· Cerebrum: largest section of brain and controls voluntary (Think and
decide what to say) and involuntary movements (autonomic
functions).
· Brain stem: Is the posterior part of the brain consist of pons and
medulla oblongata and mid brain.
· Cerebellum: Controls balance (GAIT) and modifies body movements
(Motor). Maintain body coordination and balance.
· Spinal cord. Vertebral column, epidural space, meninges, spinal cord,
dorsal vertebra, and spinal nerve.
· Thalamus: affects sensory levels, awareness and alertness.
Corpus Collasum connects and communicates between right and left hemisphere of brain.
Mesolimbic pathways are Frontal lobe

present in? Frontal lobes Motor Cognitive Behavior Arousal
Medulla oblongata is present Voluntary movements Memory Personality Attention
in? Temporal lobe Planning, Initiation Problem solving Social and sexual
Spontaneity Judgment Impulse control
Frontal lobe: Motor, cognitive, Language Abstract Mood and affect
behavioral and arousal. Language expression Abstract thinking
Temporal lobe (auditory, Eye movement Executing
speech, memory information functions
retrieval)
Brain stem ( breathing, digestion, heart control, blood vessel control, alertness)
Occipital lobe (visual reception, interpretation)
Parietal lobe (processing sensory input, sensory discrimination, body orientation, somatic area).
Wernicke’s area: In temporal lobe language comprehension.
Vestibular system: Reflex adjustment of head, eyes and postural muscles provide a stable visual image and
steady posture.
Vestibular ocular reflexes. Nystagmus

The direction of the nystagmus is defined as the direction of the fast (rapid eye) movement. Therefore, the
nystagmus occurs in the same direction
as the head rotation. Normally initial
Question Alerts!
rotation of the head causes the eyes to
1) Blood brain barrier is present at?
move slowly in the opposite direction to
2) Drugs that cross BBB. Rifampin, Cefuroxime sodium, Cefotaxime,
maintain visual fixation.
Carabapenam, Atropine, physostigmine, Diphenhydramine, and
ethanol.
Meninges
· The meninges are three concentric
membranes that surround and protect brain and spinal cord.
· The dura mater: outer most membrane.
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PharmacyPrep.
· The arachnoid: middle layer, transparent, flexible

· The pia mater: inner layer, is fine, and delicate.
Cerebro Spinal Fluid (CSF): The CSF is outside of the brain and circulates through the cavities inside the brain
called ventricles.
Blood brain barrier: The blood brain barrier (BBB) is the barrier between cerebral capillary blood and
cerebrospinal fluid (CSF). BBB is formed by capillary endothelial cells that line cerebral micro vessels form tight
junctions and lacks large intracellular spaces. Further neural tissue covers capillaries. Together constitutes forms
BBB.
The CSF fills the ventricles and the subarachnoid space. Three functions of BBB
· Protects brain from endogenous or exogenous toxins. It prevents escape of neurotransmitters from CNS into
blood circulations.
· Lipids soluble drugs cross faster than water-soluble (polar) drugs.
In capillary lining of BBB have, enzymes such as monoamine oxidase (MAO), cholinesterase and some other
enzymes. These enzymes prevent catecholamines, serotonin, and acetylcholine, to enter into brain.
Peripheral Nervous System: All nerves of the body residing outside of the brain and
spinal cord comprise the peripheral nervous system.
Periphery can be divided into sensory (somatic) and autonomic.

· Ulnar nerve: Passes through the shoulder, elbow to wrist.
· Sciatic nerve runs through buttock, thighs down to foot. It divides into tibia and
common fibular nerve. Which supplies the muscles of posterior thigh and all of the
leg and foot.
· Intercostal nerve is that anterior divisions of the thoracic spinal nerves.
· Radial nerve runs through forearm, wrist to finger tips. It supplies to muscles of
forearm.
· Popliteal nerve. Passes in knee joint.
· Axillary nerve (circumflex): It supplies the deltoid and teres minor muscles, shoulder joint, and skin on back
of arm.
· Phrenic nerve: connect from neck down to lungs. Phrenic nerve injuries can result in to brachial palsy.
(phrenic nerve palsy)
· Vagus nerve: A parasympathetic nerve innervate four organs liver, GI, Heart, and lungs.
PERIPHERAL NERVE COMMENTS

Radial nerve damage cause Wrist drop
Ulnar nerve damage cause Claw hand (small fingers hand contract)
CRANIAL NERVES
CRANIAL NERVE: origin from brain and spread to facial function.
Olfactory smell
Optic vision
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PharmacyPrep.
Oculomotor: Eye upward, medial, downward movement

Trochlear: Eye down and in movement
Trigeminal: Touch forehead and cheek, clench teeth
Abducens Look side to side
Facial Taste for the anterior 2/3 of tongue
Acoustic Hearing
Glossopharyngeal: Posterior 1/3 of the tongue
Vagus Defecation, slowed heart rate

Spiral accessory: shoulder shrug
Hypoglossal: tongue movement
Nerve Cell: Nerve cell consists of dendrite, cell body, axon, myelin sheath, and synapse.
Question Alerts!
Myelin sheath damage is associated with?
MS
Fig 3.3
Pathology of neurological disorders

Fig 3.2
Degenerative diseases: Alzheimer’s, Parkinsonism, Multiple sclerosis, and ALS (Amyotrophic lateral sclerosis).
Alzheimer’s: deficiency of acetylcholine
Parkinson’s: deficiency of dopamine
Multiple sclerosis: autoimmune or degeneration of myelin sheet
ALS: unknown
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PharmacyPrep.
Seizures or epilepsy: Excessive excitation of neurons due to disorderly inhibition of cortical neurons.
Parkinson's disease: Decrease in dopamine or imbalance of dopamine negrostratial pathway.
Suppressing (antipsychotic drugs) the dopamine cause extra pyramidal symptoms (EPS)
Extra pyramidal symptoms (EPS is side effect of antipsychotic drugs) "Akathisia, Dystonia, Parkinsonism, Tardive
Dyskinesia". These symptoms are the side effect of antipsychotic drugs like haloperidol.
Akathisia = restlessness or cannot sit still.

Parkinsonism: (“TRAP”) Tremors (hand shaking), rigidity, ataxis, postural instability, Dyskinesia = involuntary
movement or shaking
Dystonia = involuntary muscle spasm
Tardive dyskinesia = involuntary movement of lips, tongue, and chewing motion.
Ataxia = lack of muscle coordination in voluntary movements.
Migraine Headache: Vasodilatation of intracranial extra cerebral blood vessels.
Vertigo: False sensation of moving or spinning or object moving usually accompanied by nausea and loss of
balance.
Meniere's disease produces sudden episode attack of vertigo along with ringing in ears (tinnitus) and
progressive deafness. Episodes can last from minutes to hours. Associated with nausea and vomiting. Beta-
histine is used for treatment.
Chronic spasticity: Spasticity is an involuntary velocity dependant increase in muscle tone resulting in injury to
motor pathway in brain or spinal cord. It is common in MS, stroke, spinal cord injury and cerebral palsy. It can
impair feeding, dressing, bowel function, hygiene and gait.
Bell's Palsy: Paralysis of lower motor neuron of facial nerve (effects on eye). It is often due to herpes simplex
virus (HSV 1 ) infection causing inflammation and edema.
Multiple Sclerosis: The multiple sclerosis (MS) is characterized by destruction of myelin sheet (demylenation)
and axonal degeneration & loss in CNS. The MS is chronic and can be caused by autoimmune mediated action.
Treatment: Interferons beta (first line therapy), glatiramer acetate (Immunomodulators similar to interferon
beta), Mitoxantrone, natalizumab, Fingolimod (spingosine-1-phosphate receptor agonist), Teriflunomide, and
laqinimod.
Temperature regulation: The homeostatic mechanisms regulate body temperature (37.5 °C) or 98.6 °F
Sympathetic nervous system innervate heat loss by vasodilatation and sweat production. Sympathetic nervous
system innervate adrenal gland than increase metabolic rate.
Thalamus à pituitary gland à thyroid à Increase metabolic rate.
Hyperthermia = >38.2 °C or 100 °F
High fever is defined >40.5 °C
Hyperpyrexia (fever) = a fever >41.5 °C are rare
Hypothermia = <35 °C, if <32 °C it can cause ventricular arrhythmias.
(CTMA p85)
Drug induced reaction characterized by genetic susceptibility to generalized and sustain skeletal muscle
contraction after exposure to depolarizing muscle relaxants such as succinylcholine, halothane or isoflurane.
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PharmacyPrep.
Malignant hyperthermia is the side effects of drugs that cause fever symptoms. Example. Halothane, and
succinylcholine.
Treatment: Dantrolene 2.5 mg/kg for Q5min
Neuroleptic malignant syndrome (NMS) induced by antipsychotic drugs. Characterized by hyperthermia or
hyperpyrexia (>41.5 °C) and muscle rigidity, autonomic instability e.g. cardiac arrhythmias.
Treatment: Bromocriptine 2.5-20 mg TID.
Heat stroke: Core body temp. >40.6 °C
Antipyretics (NSAIDs) reduce fever by inhibiting cyclooxygenase, this inhibits prostaglandin synthesis. Therefore,
analgesics decrease set-point temperature. In response that cause heat loss in the form of sweating,
vasodilatation.
Diagnostic techniques.
Electroencephalograph (EEG): The EEG consist of alternating excitatory and inhibitory synaptic potential in the
pyramidal cells of the cerebral cortex.
CT scan (computed tomography) of brain. Demonstrates generalized waves of spike and wave discharge.
Cerebrospinal fluid (CSF) sample is taken by Lumbar puncture.
FMRI. The functional MRI is used brain scanning.
Tips
1. Sciatic nerve 2 Blood brain barrier 3 Adrenal medulla
4 Tardive dyskinesia Protects brain from endogenous 6 Bradykinesia
5 &exogenous toxins
7 Nissl substance 8 Multiple sclerosis 9 Cerebrum
1 it prevents escape of 1 lipid soluble drugs cross faster
0 neurotransmitter from CNS 1 than H 2 O soluble drugs
into blood circulations
· What is the barrier between cerebral capillary blood and cerebrospinal fluid (CSF) the CSF fills the ventricles
& the subarachnoid space ( )
· A CNS disease where the myelin sheath of motor neurons is degenerating or being destroyed, which
interferes with neuronal impulses ( )
· The nerve that pass through buttocks, thighs down to foot ( )
· What part of brain controls voluntary and involuntary movements ( )
· Inappropriate posture of neck, face and limbs is referred as ( )
· Functions of blood brain barrier ( )
· Slow movement ( )
· The dark granular inside neuronal cell bodies ( )
· Sciatica is à ( )
· The longest and largest nerve is --> ( )
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PharmacyPrep.
PharmacyPrep.Com Cardiovascular System
4
Cardiovascular System
Question Alerts!
Carotid artery supply
blood to? Brain
What arteries supply
blood to eyes?
external carotid
artery
Questions Alerts!
· Definitions and disease associated with thrombus, embolus, ischemia, aneurism, atherosclerosis,
plaques, and edema.
· Concept of depolarization and repolarization
· Electrode potential curve (P wave is atrial depolarization, QRS is ventricular depolarisation, QT wave
is mechanical contractions of ventricles).
· Diagnostics. ECG. Electrocardiography, and Echocardiography and biological markers.
Conduction System of the Heart (fig 4.4)
Fig 4.4
Fig 4.5
Blood flow sequence: Vena cava à right atrium à right ventricle à left pulmonary arteryà LUNGS à left
pulmonary vein à left atrium à left ventricle à aorta à systemic circulation
Septal defect: Ventricular septal defect is a hole in the wall separating the two lower chambers of the heart.
Types of pacemakers
Natural (main) pacemaker of heart is SA node. Latent pacemaker of heart is AV node, bundles of His and
purkinje fibres.
· Pulse direction’s SA node à AV node à Bundles His à Purkinje Important concept!
fibres Depolarisation and repolarisation?
Depolarization (inward current): Carrying +ve charge into cell
Increase Na+ influx into cell
Decrease K+ efflux out to cell
Repolarization (outward current or hyper polarization). Take +ve charge out of cell
Increase K+ efflux out to cell
Increase Cl- influx into cell
Myocardial action potential curve: Myocardial action potential

curve reflects action potential, which describes electrical activity
of five phases. This occurs in atrial and ventricular myocytes and
purkinje fibers.
· Phase 0: Rapid depolarization: Na+ enters the cell
· Phase 1: Early rapid repolarisation: K+ leaves the cell
· Phase 2: Plateau: Ca2+ enters the cell
· Phase 3: Final rapid repolarisation: K+ pumped out of
the cell
· Phase 4: Slow depolarization: K+ inside the cell and
Na+, Ca2+ outside the cell.
Phase 1 to starting phase 3 is absolute refractor period or
effective refractory period. The cell cannot respond to any stimuli. (NO action potential can be initiated).
During Phase 3 is relative refractory period. The cell ability to respond stimuli increases or cell can respond to
strong stimuli.
Electrocardiograph Wave Forms: The electrical activity occurred during depolarization and repolarization
transmitted through electrodes attached to the body and
transformed by an electrocardiograph (ECG) in to series of
waveforms.
· P wave indicates atrial depolarization.
· PR interval indicates the spread of the impulse from
the atria through Purkinje fibres. (Beginning of initial
depolarisation of ventricle).
· QRS complex indicates ventricular depolarization.
· ST segment indicates phase 2 of the action potential
the absolute refractory period.
· T wave shows phase 3 of the action potential
ventricular repolarization.
· Q-T interval. Mechanical contraction of the ventricles (Torse de pointes).

· U wave caused by hypokalemia.
Torsade de pointes: This is also called the Q-T interval. A problem in one of the ion channels can prolong the Q-T
interval. A prolonged Q-T interval can increase risk for a type of arrhythmia called torsade de pointes.
· Thrombus is blood clot.

Question Alerts!
· Embolus is moving blood clot.
1) Definition of Atherosclerosis.
· Aneurysm is abnormal dilatation of arteries. Can cause stroke.
2) Diseases that cause by plaques?
· Stenosis is constriction or narrowing of opening.
Angina, MI, ischemic stroke.
Atherosclerosis is increased in LDL, progressively hardens the
arteries and veins. Cause CAD (angina, MI), stroke, ischemia,
and PVD.
Plaques are progressive accumulation of lipids and inflammatory cells. Site of injuries in arteries results
formation of plaques. Sheer stress may result in plaque rupture, collagen exposure, platelet aggregation,
and clot formation. Examples of diseases that comes from plaques are angina, myocardial infarction, atrial
fibrillation, cerebral stroke, embolism and peripheral vascular diseases (DVT and PE).
Cardiac oxygen consumption: When increased size of the heart.
Laplace's Law: Laplace's law describes how tension in the vessel

wall increases with Trans mural pressure. According to Laplace’s law, tension is proportional to the radius of a
sphere.
Autonomic effects on heart rate and conduction velocity.
Inotropic: Force of contraction (The ability of the cardiac muscle to develop force at given muscle length).
Positive (+ve) inotropics: Digoxin, ACEI, DHP-CCB
Negative (-ve) inotropics: BBs, verapamil, diltiazem
Chronotropic: Heart rate (the number of action potential that occur per unit time).
Positive (+ve) chronotropic. DHP-CCB
Negative (-ve) chronotropic: Amiodarone, BBs, NDHP-CCBs, digoxin, "(ABCD)"
Dromotropic: Conduction
Positive (+ve) dromotropic: amitriptyline
Negative (-ve) dromotropic: Na+& K+ channel blockers.
Stroke volume: The volume of blood ejected from the ventricle on each beat. (Pulse).
Ejection fraction: The fraction of end-diastolic volume ejected in each stroke volume. Ejection fraction in
congestive heart failure is <40%.
Ejection fraction: Stroke volume/end diastolic volume
Cardiac output: stroke volume x heart rate
Pre-load = Volume of blood fills in ventricles in diastolic state

After load= Force to overcome peripheral resistance.
Example: Vasodilators (hydralazine, nitrates, CCBs) decrease preload and after load.
Diagnostics
Blood pressure. Sphygmomanometer.
Normal 120/80
BP is diagnosed in 2 office visits if BP average >140/90 mm Hg, in presence of DM, renal, atherosclerosis, and
cerebrovascular.
If the average SBP/DBP is 140-159/90-99 mmHg, treatment is recommended in the presence of risk factors
smoking, FH, truncal obesity, sedentary lifestyle, male >55 yo, female >60yo.
Coronary artery disease: ECG and biological marker (Troponin and Creatine kinase CK-MB)
Electrocardiogram (ECG), and measures cardiac rhythms.
ECG - used for excluding atrial fibrillation.
Echocardiogram: Shows the presence of regional valve motion abnormalities, size of heart chambers.
Echocardiogram allows for identification of valvular abnormalities and other MI problems.
MRI, MR angiography (MRA), or CT angiography used for confirmation of degree of arterial occlusion or
neurologic conditions like cerebral ischemia.
Tips
Find answers from the table.
1. Absolute refractory period 2. Repolarization 3 arrhythmia
4. Phase 0 5. Phase 1 to starting phase 3 6 Relative refractory period
7. Phase 3 8. + ve inotropic 9 –ve inotropic
10 Digoxin 11 ACEI 12 Dihydropyridine CCBs
13 Beta blockers 14 stroke 15 brain attack
16 cerebral embolism
· Absence of rhythm ( )
· Drugs that cause +ve inotropic effect ( )
· Rapid depolarization ( )
· Increase in force of contraction ( )
· The cell cannot respond to any stimuli ( )
· The cell ability to respond stimuli increases or cell can respond to strong stimuli ( )
· Decrease in force of contraction ( )
· Excessive negative charge in cell occurs ( )
Select True/False Statements

· A brain attack that occurs when a wandering clot (embolus) or some other particle forms in a blood vessel
usually in the heart and flow into in the brain cerebral vessel is cardiogenic cerebral embolism. True/False
· Drugs that cause –ve chronotropic effect (digoxin, beta blockers) True/False
· Stroke or brain attack happens when brain cells die because of inadequate blood flow to the brain
(True/False)
PharmacyPrep.Com Endocrine System
5
Endocrine System
Questions Alerts!
· Hormone of anterior and posterior pituitary gland, thyroid hormone, Insulin, corticosteroid hormones.
· Hypothyroid and hyperthyroidism symptoms. Lab investigations of serum TSH
· Hypoglycemia and hyperglycemia symptoms.
· Insulin function, Pathophysiology of diabetes and diabetic ketoacidosis
· Hypo corticosteroids (Addison diseases) and hyper corticosteroids (Cushing's disease).
Definitions
· Amniocentesis: surgical puncture of the amniotic sac
· Cystoscopy: process of viewing the urinary bladder
· Dysmenorrhea: Painful periods
· Embryology: study of the growth and development of the human organism
· Gynecologist: specialist in the diseases of the female reproductive system
· Hydrocele: accumulation of water in the scrotum;
· Menorrhagia: Excessive bleeding during menstruation
· Nephritis: Inflammation of the kidney
· Primigravida: first pregnancy
· Spermatogenesis: creation of new sperm
· Urology: study of urinary tract
Endocrine system
Consists of a group of organs that have NO DUCTS and therefore are also known as DUCTLESS GLANDS
that secrete hormones directly into the blood stream..
Major endocrine glands: Pituitary Gland (present under hypothalamus), the master endocrine gland.
Testes, Ovaries, Thyroid Gland (neck), Adrenal Gland (on kidney), Pancreas Gland (endocrine and
exocrine)
Other glands
· Parathyroid Gland (neck)
· Thymus Gland (chest)
· Pineal Gland (brain)
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Pituitary Gland
· Located at the base of the brain.
· Consists of two parts: anterior lobe and posterior lobe.
· It is sometimes known as the master gland.
· It controls the functions of other endocrine glands and is in turn controlled by the hypothalamus.
Endocrine Types of hormone Target tissue Physiologic actions

Gland
Hypothalamus Houses releasing and Anterior Controls release of anterior pituitary hormone
inhibiting hormones pituitary
Anterior Thyroid-stimulating Thyroid Production of thyroid hormone (T 4 and T 3 , and
Pituitary gland hormone (TSH) calcitonin).
Adrenocorticotropic (ACTH) Adrenal Secretion of cortisol
cortex
Growth hormone (GH) Bones; soft Stimulates growth of bones and soft tissues
tissues
Follicle-stimulating hormone Females; Promotes growth of ovarian follicle;
(FSH) ovary Stimulates estrogen secretion
Stimulates sperm production
Males:
Testes
Luteinizing hormone (LH) Females: Stimulates ovulation
Ovary Stimulates progesterone secretion
Males. Stimulates testosterone secretion
Testes
Prolactin Females: Promotes breast development; stimulates milk
breast secretion
Posterior Vasopressin (antidiuretic Kidney Causes water retention

Pituitary gland hormone)
Oxytocin (formed in Uterus Causes contraction
hypothalamus and stored in Breasts Causes ejection of milk
posterior pituitary gland).
Pineal Melatonin Brain; anterior Sets the body’s “time clock”.
pituitary; Causes sleep in response to darkness
reproductive
organs;
possibly other
sites.
Thyroid Thyroid hormone (Triiodo T 3 Most cells Increases the metabolic rate; necessary for
and levothyroxine T 4 ), and normal growth and development.
calcitonin. Calcitonin takes Ca from Blood à Bones
Parathyroid Parathyroid hormone (PTH) Bone; kidney; Increase amount of calcium in the bloodstream.
intestine ¯ amount of phosphate in the bloodstream
- PTH = - Ca (by bone resorption)
- PTH = ¯ phosphate
Thymus Thymosin T lymphocytes Enhances the production of T lymphocytes
Pancreas Insulin Most cells Promotes use and storage of nutrients

Secreted from beta cells particularly glucose, after eating
Glucagon Most cells Maintains glucose levels in the bloodstream
Secreted from alpha cells during periods of no food
Somatostatin and gastrin Digestive Inhibits digestion and absorption of nutrients.
Secreted from delta cells system Inhibit secretion of insulin, glucagon and gastrin.
F cells? pancreatic Somatostatin are growth hormone inhibiting
polypeptides hormone (GHIH).
Adrenal Epinephrine Kidney Increases Na+ retention and K+ excretion
Medulla
Adrenal cortex Zona Aldosterone Kidney Increases Na+ retention and K+ secretion
glomerulosa
(out)
Z. fasciculata Cortisol Most cells Increases glucose in the bloodstream
Z. reticularis Androgens Females: bone Puberty growth spurt and sex drive in females.
and brain
Testes (male) Testosterone Male sex Stimulates production of sperm; responsible for
organs; body as development of sex characteristics. Promotes
a whole. sex drive.
Ovaries Estrogen Female sex Stimulate uterine and breast growth;
(female) organs; body as responsible for sex characteristics.
a whole
Progesterone Uterus Prepares for pregnancy
Question Alerts!
1) Insulin & glucagons released from? Beta cell & alpha cells
2) Epinephrine released?
3) Aldosterone hormones released from?
4) Aldosterone antagonist spironolactone act on collecting duct and prevent K+ secretion causes
hyperkalemia.
Physiological effects of some pituitary hormones

· Somatostatin: opposes the effects of Growth Hormone-Releasing Hormone (GHRH)
· Prolactin: It is synthesized and secreted by lactotrope cells in the anterior pituitary gland, breast and the
deciduas.
Effects
· Stimulates the mammary glands to produce milk (lactation).
· Provides the body with sexual gratification after sexual acts
· immune tolerance of the fetus by the maternal organism during pregnancy.
· Stimulate proliferation of oligodendrocyte precursor cells which differentiate into oligodendrocytes, the
cells responsible for the formation of myelin coatings on axons in the central nervous system.
Thyroid Gland (Fig 5.3): Secretes thyroid hormones (LEVOTHYROXINE, TRIIDOTHYRONIN AND CALCITONIN),
which in turn control the body’s metabolic rate.
Thyroxin or Levothyroxine (T 4 ): Naturally occurs in levo (L) isomer form produced in the thyroid gland.
T 4 Converts in the liver and other organs to T 3 by deiodination (deiodinase).

· Controls the rate of metabolism in the body.
Triiodothyronine (T 3 ): Metabolically active form.
Calcitonin (a peptide): Hypocalcemic hormone.

· Secreted by parafollicular cells (C-cells).
· Reduces blood calcium ion concentration by moving Ca from
blood to bones.
· Used in treatment of osteoporosis associated vertebral
fracture.
· Hypercalcemia stimulates calcitonin production.
Functions of thyroid hormones:

Question Alerts!
· Growth and development
1) Conversion of T4 to T3 by deiodination.
· Proper function of all body system
2) Calcitonin production is stimulated by?
· Maintenance of all body tissues.
Carbohydrate, fat, protein, and
vitamin metabolism (Basal Metabolic Rate).
· Affects the secretion of other hormones (insulin, NE, Epi, cortisol, estrogen and
testosterones.
Mechanism of action
· At the target cell, proteases split protein carrier off from the thyroid hormone and most of T 4 is
deiodinated to T 3.
· T 3 (and probably some T 4 ) enter the cell through membrane transport proteins and bind to a
specific nuclear receptor.
Hypothyroidism Hyperthyroidism
Thyroid gland is under active and Overactive thyroid gland causing an
produces insufficient thyroid hormone. abundance of thyroid hormone.
Thyrotoxicosis is the general term for over
activity of the thyroid gland.
Symptoms Fatigue Heat intolerance
Sensitivity to cold Profuse sweating
Dry flaky skin and Coarse hair Diffusely enlarged nontender goiter.
Slowed speech (deep voice) Nervousness, irritability, anxiety and
Puffy face, hands, feet insomnia
Hearing loss Weigh loss in spite of increased appetite
Decreased libido Tremor and muscle weakness
Weight gain Tachycardia
Constipation Diarrhea
Impaired memory
Hypertension, bradycardia
Slow return of deep tendon reflexes
Diseases Hashimoto (autoimmune, the most Graves disease (diffuse toxic goiter) the
common type of hypothyroidism. most common form of hyperthyroidism,
Common on in elderly). autoimmune disorder. Antibodies (long-
Myxedema (If untreated Myxedema acting thyroid stimulators) bind to and
and coma may develop. activate TSH receptors.
Dwarfism
Mental retardation Plummer’s disease (toxic nodular goiter)
Serum TSH assay The most sensitive test for detecting ¯ serum TSH
the hypothyroid state. - serum TSH
Sensitive TSH Commonly used in patient receiving Sensitive TSH assay
assay replacement therapy (levothyroxine) to
control treatment.
Free thyroxin This is not separate test but estimation
index (FTI) of free T 4 level mathematical
interpretation of relationship of RT 3 U
and serum T 4 levels.
(Free T 4 ) Serum free thyroxine ¯ FT4 Elevated T 4 indicates hyperthyroidism
(TT 3 ) Serum total triiodothyronine ¯ TT3 Disproportionate rise indicated

hyperthyroidism.
Useful in early detection and rule out of
hyperthyroidism
Pregnancy Levothyroxine is used to treat. Propylthiouracil the treatment of choice.
Adequate dose thyroxin, necessary for
development of the fetal brain.
Serum TSH >6 mU/L <0.3 mU/L
Thyroid function tests (normal serum TSH is 0.3 to 6 mU/L)
Parathyroid Glands: Four tiny glands in the posterior surface of the thyroid gland, which is positioned on
the esophagus, produce parathyroid hormone (PTH), which regulates the calcium metabolism in the
body.
Parathyroid hormone: Reabsorbs calcium in kidney.
Hypoparathyroidism Hyperparathyroidism
Decrease production of PTH Increase production of PTH
Decrease blood calcium Increase blood calcium levels
Increase blood phosphate levels Decrease blood phosphate levels
Causes convulsions Causes muscle weakness
Causes hypokalemia Causes muscle atrophy
Causes neuromuscular irritability Causes fatigue
Parathyroid hormone analog: Teriparatide.
Pancreas: In the pancreas the acini which produces digestive enzymes. Islets produce 3 types of hormones.
o Insulin produced by beta cells
o Glucagon produced by alpha cells
o Somatostatin produced delta cells (extra pancreatic cells)
Insulin
· Increase glucose uptake into cell.
· Glycogenesis: Increased glycogen storage in liver, and muscle.
· Decrease gluconeogenesis: Decrease synthesis of glucose from non-carbohydrate source.
· Lipogenesis: Fat/triglyceride storage (adipose tissue).
- glucose uptake
¯ glycogenesis
¯ gluconeogenesis
Insulin
· Insulin acts on liver, adipose tissue and muscles.
· Produced by beta cells of islets of langerhans.
· Insulin is peptide
· Stored in vesicles in combination with zinc
· 51 amino acid chain
· Half life insulin is 3 to 5 min Controls blood glucose concentration
· Decrease insulin secretion
Insulin function in carbohydrate, protein and fat metabolism

Carbohydrate metabolism Protein metabolism: Fat metabolism:
Increase glucose uptake Increase RNA and DNA synthesis Increase storage of fatty acid in
Decrease glycogenolysis Increased protein synthesis adipose tissue
Decrease ketogenesis Increased cell growth Increase lipogenesis
Decrease glucogenesis Increased amino acid transport Decrease lipolysis
Increase lipogenesis
Glucagon
· Stimulated breakdown of glycogen to glucose (glycogenolysis) in the liver
· Increase blood glucose levels.
DIABETES MELLITUS
This is a primary disorder of carbohydrate metabolism that exhibits the following characteristics. A defective
or deficient insulin secretory response. Glucose underutilization and hyperglycemia.
Types of diabetes:
§ Insulin-Dependent/Type 1 (IDDM)
§ Non-Insulin Dependent/Type 2 (NIDDM)
§ Secondary Diabetes (e.g. pancreatic disease)
§ Impaired Glucose tolerance
§ Gestational diabetes (i.e. glucose intolerance w/onset during pregnancy)
Diabetic Patient
Insulin or resistance
Influx of glucose inside the cell
Cell starvation * Polyphagia (increased appetite)
Glucose in blood (hyperglycemia)
Osmotic diuresis
Glucose in urine (glycosuria)
* Polyuria (profound loss of water and electrolytes)
* Polydipsia (intense thirst)
HYPOGLYCEMIA HYPERGLYCEMIA
Autonomic Sweating, palpitation, fatigue, hungry, tremors Polyphagia, polyuria, hyperglycemia,
FPG <4 mmol/L (shaking). glycosuria, polydipsia
<70 mg/dL
CNS Confusion, nervousness, disorientation. Dizzy,
FPG <2-3 mmol/L anxious, headache, irritable, blurred vision.
<50 mg/dL
Treatment GLUCOSE TAB, DEXTROSE TAB
FPG: Fasting blood glucose level (8 hours without calories intake); Normal glucose FPG: 5 to 6 mmol/L or 80 to
120 mg/dL.
Diabetic microangiopathy, atherosclerosis, myocardial infarction, cerebral stroke, gangrene of the lower
extremities.
· Diabetic nephropathy, Progressive proteinuria and chronic renal failure (CRF)

· Diabetic retinopathy, cataract formation or glaucoma
· Diabetic Neuropathy pain (numbness, tingling,
pin feeling and burning).Symmetric peripheral Question Alerts!
neuropathy affects motor and sensory nerves of What is NOT complication of
the lower extremities. Schwann cell injury, myelin hyperglycemia?
degeneration, axonal damage.
· Autonomic neuropathy, sexual impotence, bowel and bladder dysfunction.
· Effects of insulin deficiencies. Cataract, retinopathy (blindness), neuropathy, nephropathy premature
atheroma (increase blood fatty acids) and cardiovascular.
Insulin requirement increase Insulin requirement decrease

Heavy meals Physical activity
Emotional Stress Exercise Question Alerts!
Infections What decreases insulin
Pregnancy requirement?
Diabetes Insipidus (DI): Anti diuretic hormone (vasopressin) deficiency causes diabetes insipidus
Insufficient ADH due to dysfunction of hypothalamic nuclei (e.g. tumors, hydrocephalus, histocytosis, trauma).
Passage of large volumes of dilute urine. Decrease in ADH causes large volume of dilute urine, Polyurea,
Polydipsea, and Polyphagea.
Treatment: Anti diuretic hormone

Diabetes insipidus central Diabetes insipidus nephrogenic
There is NO ADH production ADH present but kidney does not respond.
Autoimmune Acquired or drugs (lithium)
THYMUS GLAND
· Regulates the development of T-lymphocytes in immune system
PINEAL GLAND
· Small cone shaped gland
· Smallest of all glands located in mid brain
· Large in children and begins to shrink at puberty
· Only brain structure that does not come in a pair
· Produces melatonin and dimethyl tryptamine in the dark
Functions
· Influences circadian rhythms e.g. sleep and temperature
· Sexual development
· metabolism
· Regulates the mating behavior
· Regulates day and night cycle.
Adrenal Gland (Fig 5.4): Two adrenal glands one on top of each kidney.
Adrenal gland Control by Hormones HYPER HYPO
Adrenal medulla Sympathetic Epinephrine Hypertension hypotension
(chromaffin cells) Pheochromocytoma
Cortex: outer Renin-angiotensin Aldosterone Ascites Hyperkalemia
Middle layer ACTH Corticosteroids Cushing Syndrome Addison Disease
Inner layer ACTH Androgens Gynecomastia hypogonadism
Inner part (medulla): Secretes epinephrine (adrenalin)

Epinephrine increases BP, HR, vasoconstriction and blood supply to skeletal muscle. Norepinephrine increases
effects of epinephrine.
Adrenal Cortex:
Outer layer: secrete aldosterone
Middle layer: Corticosteroids
Inner layer: Androgen
§ ACTH regulates the secretion of mineral corticoids. e.g. aldosterone helps regulate salt and water
balance by retaining salt and water and excreting potassium.
Glucocorticoids
§ Control glucose metabolism and protein synthesis.
§ The principle glucocorticoids are cortisol and cortisone.
● Androgens are male sex hormones mainly testosterone.
Functions of ACTH: The ACTH stimulates the cortex of the adrenal gland and boosts the synthesis of
corticosteroids, mainly glucocorticoids but also mineral corticoids and sex steroids (androgens).
· ACTH is also related to the circadian rhythm in many organisms.

· The half-life of ACTH in human blood is about 10 minutes.
Hypo corticosteroids: Addison's disease (chronic adrenal insufficiency, or hypocortisolism).
Causes auto immune reaction, HIV and tuberculosis.

Signs and symptoms: Chronic fatigue that gradually worsens, Muscle weakness, weight loss and loss of appetite,
nausea, diarrhea, or vomiting.
Treatment: Replacement of missing cortisol and fludrocortisones.
Hypercorticosteroids: Cushing's syndrome or hypercortisolism or hyperadrenocorticism is caused by high levels

of cortisol in the blood.
Signs and symptoms: Rapid weight gain, Moon face, Buffalo hump, reduced libido and Easy bruising.
Treatment. Removal of adrenals. Post operative steroid replacement (hydrocortisone or prednisolone).
Ovaries: Produces two hormones estrogen and progesterone.

Estrogen: Controls the development of female sex characteristics and reproductive system.
Progesterone: Prepares the lining of the uterus for implantation of a fertilized egg.
HYPER HYPO
Estrogen Weight gain Hot flushes, night sweat, dry skin, mood swings,
Increase risk of blood clot, mood vaginal atrophy, dryness, bone loss, yeast
changes, breast cancer, headache, infection. Urinary incontinence
edema
Progestins Most of symptoms of estrogen Infertility, vaginal bleeding or spotting.

deficiency. +
Breast tenderness, acne
OCP side effects Menopause symptoms
Dysmenorrhea
· Menstrual pains are referred as dysmenorrhea.
· It is most common from age 20 to 25.
· Primary when no underlying cause is found.
· Secondary when a cause is identified as a gynecological disorder.
Endometriosis: associated with dysmenorrhea, menstrual pain, infertility.

Common cause of secondary dysmenorrhea. Endometriosis gives pelvic pain, spotting before normal periods
and may cause infertility.
Ovulation cycle and menstruation

Question Alerts!
· During the menstrual cycle estrogen is Ovulation Tests detects? LH
produced by the ovarian follicles.
· After ovulation estrogen is produced by
the corpus luteum.
· During pregnancy ovulation does not occur. It is suppressed by high levels of estrogen and
progesterone's.
Pregnancy test: Human chorionic gonadotropin (hCG) hormone levels are elevated in first 3 months of
pregnancy (first trimester). Progestin's in pregnancy is produced by ovaries, corpus luteum and placenta.
Question Alerts!
Hormone that detected in pregnancy tests? hCG
Menstrual cycle
Menopause: Cessation of menstrual periods for at least 6 mo, is referred as menopause. Occurs when the
ovaries stop producing estrogen. Ovarian follicles are depleted at approximately 51 year of age.
Most common vasomotor symptoms: Hot flushes, night sweat, mood swings, sleeplessness, lethargy, and
depression. Urogenital atrophy (this leads to dryness of the vagina, dyspareunia (painful intercourse).
Hormones Deficiencies Excessive (over production)

Thyroids Myxedema Graves
Hoshimoto Serum TSH ↓
Serum TSH ↑
Adrenal corticoids Addison disease Cushing syndrome
Insulin DM Hypoglycemia
Glucagon Hyperglycemia
Anterior pituitary Acromegaly
ADH Diabetes insipidus SIDH
Tips
1. adrenal medulla 2. pituitary gland 3. posterior pituitary gland
4. diabetes insipidus 5. glucose 6. H 2 O + CO 2
7. excessive urination 8. outer adrenal cortex 9. sensitivity to cold
10. bradycardia 11 Weight gain 12. Glycogen
13. constipation 14 dry skin 15. weight loss
16. tachycardia 17. diarrhea 18. sensitivity to heat
19. sweating 20. palpitation 21. fatigue
22. polyhagia 23. polyurea 24. Blurred vision
25. polydipsea
· Glycolysis; Glucose→( )
· Glycogenesis; Glucose→( )
· Glycogenolysis; Glycogen→( )
· Gluconeogenesis: fats & proteins→( )
· Epinephrine is released from? ( )
· Aldosterone is released from? ( )
· ACTH is secreted by? ( )
· Oxytocin is secreted from? ( )
· ADH is secreted from? ( )
· Deficiency of ADH gives… ( )
· Symptom of diabetes insipidus ( )
· Symptoms of diabetes mellitus ( )
· Symptoms of hypoglycemia ( )
· What hormones are released from posterior pituitary gland? ( )
· Hypothyroidism laboratory investigation include ( )
· Epinephrine is released from? ( )
· Aldosterone is released from? ( )
· Testosterone to 5-hydroxy testosterone is catalyzed by? ( )
· Diabetes mellitus symptoms? ( )
· Hypoglycemia symptoms? ( )
· Symptoms of hyperthyroidism? ( )
· Symptoms of hypothyroidism? ( )
· Symptoms of Cushing syndrome? ( )
· Addison disease is à ( )
PharmacyPrep.Com Renal System
6
Renal System
Questions Alerts!
· Filtration, Secretion and Reabsorption process.
· Types and causes of acute renal failure. Symptoms of chronic renal disease and acute renal
failure (pre-renal acute renal failure is due to lack of blood perfusion).
· Creatinine clearance in renal diseases
· Metabolic acidosis (increase in CO2) and alkalosis (Increase in HCO3).
Fig 6.2
Fig 6.1
Nephron. A nephron is the basic unit of renal function.

There are millions of nephron present in each kidney. Question Alerts!
Nephron has three major functions. What factors does NOT effect on
· Filtration reabsorption?
· The filtration occurs at glomerular or
bowman capsules.
· Creatinine clearance is the measure of glomerular filtration rate (eGFR). Normal creatinine
clearance is 80 to 120 mL/min.
· Reabsorption
· Transportation of ions or drugs back into blood from nephron is referred as reabsorption.
· Secretion
· Secretion of ions or small molecular drugs into nephron from nephron walls.
Acute Renal Failure (ARF): The acute renal failure (ARF) is rapid decline in the renal ability to clear the blood of
toxic substances, causing accumulation of metabolic waste products, like blood urea nitrogen.
Three types of ARF

Question Alerts!
· Prerenal ARF (occurs due to problems in organs liver, heart and blood
What causes of pre-renal acute
circulations).
renal failure?
· Intrinsic ARF (occurs due to problems in kidney). Drugs such as
aminoglycoside, NSAIDs. Sepsis.
· Post-renal ARF (occurs due to problems in organs after kidney like ureter or bladder).
Prerenal ARF is characterized by inadequate blood circulation (perfusion) to the kidneys, which leaves them
unable to filter the blood properly. Many patients with prerenal ARF are critically ill and experience shock (very
low blood pressure). There is often poor perfusion within many organs, which may lead to multiple organ
failure.
Causes. Some of the most important causes of prerenal ARF are dehydration, heart failure, sepsis (severe
infection), and severe blood loss.
Prerenal ARF is associated with a number of pre-existing medical conditions, such as atherosclerosis
("hardening" of the arteries with fatty deposits), which reduces blood flow. Dehydration caused by drastically
reduced fluid intake or excessive use of diuretics (water pills) is a major cause of prerenal ARF. Many people
with severe heart conditions are kept slightly dehydrated by the diuretics they take to prevent fluid build up in
their lungs, and they often have reduced blood flow (under perfusion) to the kidneys.
Symptoms of prerenal ARF include the following: Dizziness, dry mouth, Low blood pressure (hypotension), rapid
heart rate, slack skin, thirst, weight loss. Urine output is usually low in people with prerenal ARF. The patient
also may have symptoms of heart or liver disease.
PRE-RENAL ARF INTRINSIC ARF POST ARF

In adequate blood perfusion, CHF, Aminoglycosides, NSAIDS Cancers in ureter or bladder.
hemorrhagic, hypovolemia, severe blood loss, Infections, sepsis
dehydration, sepsis.
Chronic kidney diseases (CKD): Slow progressive decline in kidney function can cause accumulation of metabolic
waste like BUN. (CrCl >30 and <60 ml/min)
Albumin creatinine ratio (ACR) >200 mg/mmol (non-diabetic nephropathy), ACR >3 mg/mmol (diabetic
nephropathy).
Risk Factors
· High blood pressure (uncontrolled)
· Atherosclerosis
· Blood loss
· Chronic liver disease

· Heart disease
· Blood sugar (diabetes)
· Autoimmune disease like systemic lupus erythromatus
Chronic kidney disease affects blood.

· ↑ urea (azotemia or uremia) and creatinine concentration
· Anemia (↓ erythropoietin’s)
· ↑ blood acidity (acid-balance)
· ↓ absorption Ca and vitamin D 3 concentration
· ↑ Parathyroid hormone (PTH)
· Normal or slightly ↑ K concentration
CKD can cause azotemia, anemia, vitamin D 3 deficiency, decrease Ca concentration, and increased blood activity
(acidosis).
CKD can cause decrease drug (metabolite) clearance and drug half-life (T 1/2 ) increase.
The drug of choice to treat chronic kidney disease are ACEi or ARBs.
Nephrotic syndrome: Severe prolonged loss of protein into urine decrease blood proteins like albumin.
Chronic nephritis syndrome: Glomeruli are damaged and kidney function degenerates over a period of time.
Symptoms are vomiting, nausea, edema, high blood pressure, difficulty in breathing, itchy and fatigue.
Electrolytes and Disorders

Electrolytes present in blood Na+, K+, Ca2+, Mg2+, Cl-, and CO 3 -.
Electrolytes
Extracellular (interstitial and plasma) Intracellular

Na+, Cl -, Ca2+ K+, Mg2+, Phosphate
Calcium (Ca2+): In normal adults, there are approximately 1400 g of calcium in the body, of which 99% in bones.
The total of 0.1% calcium is present in blood (plasma). The most common source of calcium is dairy products.
Calcium plays an important role in propagation of neuromuscular activity and regulation of endocrine functions.
Parathyroid hormone (PTH) helps to dissolve calcium ion from bones and moves calcium to blood, thereby hyper
PTH can cause hypercalcemia. Helps in calcium reabsorption in kidney.
Calcitonin is secreted from thyroid gland. It helps in movement of Question Alerts!

calcium ion from the blood to bone formation. Thereby Drug that case hypercalcemia?
hypercalcemia stimulates secretion of calcitonin from thyroid Hydrochlorothiazide
gland. Chlorothiazide
Metolazone
Vitamin D: The active form of vitamin D is 1, 25-dihydroxy vitamin
D 3 (chole-calciferol). It enhances absorption of calcium when calcium is low in the blood. Calcium is primarily
absorbed by carrier-mediated diffusion at small intestine (jejunum, and duodenum).
* Blood coagulation
* Bone and tooth structural integrity
* Normal values. 8.8 to 10.3 mg/dL or 2.20 to 2.56 mmol/L.
Hypercalcemia
Causes. Malignancy or metastatic bone disease.
· Hyperparathyroidism. Excessive parathyroid hormone secretion. Drugs that cause hypercalcemia are
Thiazide diuretics (Increase Ca reabsorption therefore decrease Ca secretion). Vitamin D intoxication can
cause excessive absorption of Ca.
· Treatment: Hypercalcemia can be treated with drugs such as calcitonin, bisphosphonates, zoledronic acid,
corticosteroids, and prednisone.
· PTH Increase Ca2+ reabsorption by activating adenylate cyclase in the distal tubule.
Hypocalcemia
Causes. Due to deficiency of vitamin D.
· Hypoparathyroidism (due to decrease in PTH secretion).
· Drugs that can cause hypocalcemia are corticosteroids. The corticosteroids counteract the effects of vitamin
D. Loop diuretics increase Ca2+ excretion therefore cause hypocalcemia (furosemide, ethacrynic acid).
Excess of phosphate in total parenteral nutrition.
Phosphorus
· Phosphorus is an intracellular ion. Phosphorus is found primarily in bone (85%) and soft tissues (14%).
Hypophosphatemia
· Hyperparathyroidism (excessive PTH) causes hypophosphatemia.
· Hypophosphatemia (seen mostly in primary hyperparathyroidism and malignancy-associated
hypercalcemia). Exacerbates hypercalcemia by increasing renal synthesis of 1, 25-dihydroxycholecalciferol,
reducing bone formation and increasing bone resorption.
Hyperphosphatemia
· Occurs due to hypoparathyroidism (low PTH).
· Drugs that prevent bone resorption (death) are referred as antiresorptive agents.
· Antiresorptive agents are bisphosphonates, clodronate disodium, pamidronate disodium and zoledronic
acid.
Potassium (K+): Potassium distributed primarily in intracellular (98%) and extracellular (2%) in muscle tissues.
· Major cation in intracellular space.
· Maintenance of proper electrical conduction in cardiac and skeletal muscles (muscle and nerve excitability).
· Plays a role in acid base equilibrium acidosis.
· Range of normal value 3.5 to 5 mEq/L.
Potassium regulated by.

· Kidneys (renal function)
· Aldosterone
· Arterial pH
· Insulin (insulin decrease K+ in blood by shifting K+ into cell.)
· K+ supplement intake
· Sodium delivery to distal tubule
Aldosterone increase K+ secretion. Drugs that inhibits or blocks aldosterone hormone can cause hyperkalemia
such potassium sparing diuretics, ACEi, and ARBs.
Hyperkalemia
Causes. Renal insufficiency and drugs. The drugs that cause hyperkalemia includes K+ sparing diuretics
(Spironolactone, Triamterene, and Amiloride), ACEi, and ARBs etc.
· Adrenal insufficiency (aldosterone hormones)
· During vigorous exercise
· Cellular breakdown (tissue damage, hemolysis, burns, infections)
· Metabolic acidosis, and cardiac arrest.
Hypokalemia
Symptoms: Malaise (feeling NOT well), confusion, dizziness, ECG changes, muscle weakness and pain.
Causes: Excessive mineral corticoid activity, vomiting, and diarrhea
Drugs that cause hypokalemia. Diuretic Thiazide, loop diuretics, and acetazolamide increase secretion of K+.
Corticosteroids, penicillin (piparicillin, ticaracillin), beta 2 agonist, and amphotericin.
· Glucosuria
· Alkalemia
· Administration of insulin and glucose
Chloride (Cl-)
· The most abundant extracellular anion is Cl- (Na+ is the most abundant extracellular cation).
· Maintenance of acid base balance relationship between Na, and Cl.
Hyperchloremia (Cl- excess) and hypernatremia (Na+ excess in the blood)

Caused by:
· Renal insufficiency when chloride intake exceeds excretion
· Dehydration
· Excessive salt intake
Hypochloremia
Caused by:
· Excess loss of GI fluids
· Diuretic therapy: Thiazide, and loop diuretics. Hypochloremic alkalosis is caused by: thiazides.
· Fasting
· Adrenal insufficiency
Sodium (Na+)
· Sodium is the predominant cation of the extra cellular fluid (ECF).
· Norma sodium levels (135 to 147 mEq/L or mmol/L).
· Sodium is essential in establishing osmotic pressure relation between intracellular and extra cellular fluid.
Hyponatremia
· Caused by cirrhosis, CHF, nephrosis or the administration of osmotic active solutes such as albumin or
mannitol (osmotic diuretic).
Hypernatremia
Caused by:
· Loss of free water (not body fluid)
· Loss of hypotonic fluid
· Excessive sodium intake
· Drugs that contain (beta lactam, ticaracillin, antacids such as sodium carbonate).
HYPO HYPER
CALCIUM LOW PTH, FUROSEMIDE, HIGH PTH, THIAZIDES,
CORTICOSTEROIDS,
POTASSIUM THIAZIDES, LOOP, K+ SPARINGS, ACEI, ARB,
PHOSPHATE HIGH PTH
SODIUM DEHYDRATION CKD
Acid Base Disorders

Body produces two types of acids; volatile (CO 2 ) and non-volatile or fixed acids (HCl. phosphoric acid, sulfuric
acid).
Normal blood pH 7.35 – 7.45

Metabolic acidosis: ↓ Bicarbonates (HCO 3 -) in blood and↑ CO 2 in blood
pH of blood is reduced (↓) in metabolic acidosis (acidic) pH of urine is increased (alkaline).
Carbonic anhydrase, is present in most cells, catalyzes the reversible reaction between CO 2 and H 2 O ---
>HCO 3 -
Drugs that ↓ Bicarbonates (HCO 3 -) cause metabolic acidosis are acetazolamide, amiloride, triamterene,
spironolactone (potassium sparing), and ↑ CO 2 overdose of ASA, lactic acidosis, and ketoacidosis.
Treatment: Sodium bicarbonate (NaHCO 3 ).
Metabolic alkalosis (pH >7.45): ↑ Bicarbonates (HCO3-) in blood and ↓ CO2 in blood.
Drugs and disease that cause metabolic alkalosis. Thiazide and loop diuretics, hypercalcemia, high concentration
of alkali administration, and vomiting.
Treatment: Ammonium chloride (NH 4 Cl) or ascorbic acid (vitamin C).
Respiratory Acidosis:
This occurs due to inadequate ventilation of CO 2 by lungs. Predisposing factor for respiratory acidosis such as
asthma, beta-blockers, sleep apnea, CNS depressants, pulmonary edema or embolism, and cardiac arrest.
Respiratory Alkalosis
Due to increase secretion of CO 2 . HYPERVENTILATION.
Not very common
Example: Over dose of ASA
CO 2 HCO 3 pH ventilation
Metabolic acidosis ↑ ↓ ↓ normal
Metabolic alkalosis ↓ ↑ ↑ Normal
Respiratory acidosis ↑ normal ↓ Hypoventilation
Respiratory alkalosis ↓ normal ↑ Hyperventilation
Tips
1. Hypokalemia 2. in kidneys 3. Creatinine clearance
4. ↓HCO 3 ↑CO 2 5. ↑HCO 3 ↓ CO 2 6. Azotemia
7. Renal perfusion 8. Ureter 9. Bladder or prostate
10 Flow rate 11 pH 12 Tonicity
13 Metabolism 14 Hypocalcemia 15 Hypercalcemia
· Excessive blood urea nitrogen in blood ( )

· The most common cause of pre-renal acute renal failure is due to ( )
· What happens in metabolic acidosis? ( )
· What happens in metabolic alkalosis? ( )
· Intrinsic acute renal failure occurs in? ( )
· Post renal acute renal failure can occur in? ( )
· Factors that affect reabsorption ( )
· Glomerular filtration (GFR) measures…( )
· Chronic renal disease may cause…( )
· Adrenal gland cancer (pheochromocytoma) may cause…( )
· Due to deficiency of Vit D ( )
· Stimulates secretion of calcitonin from thyroid gland ( )
· albuminuria is --> ( )
· Albuminuria is indicator of --> ( )
· The most common extra cellular cation is--> ( )
· The most common extra cellular anion is--> ( )
· What happens in metabolic acidosis? ( )
· What happens in metabolic alkalosis? ( )
· Write the examples of drugs that cause metabolic acidosis? ( )
· Write the examples of drugs that cause metabolic alkalosis? ( )
· What is the abundant metal in body? ( )
· Pre-renal ARF is due to à ( )
Select True or False statements

· Normal serum potassium levels à ( )
· If it is defect in renal filtration, CrCl à ( )
· Normal CrCl is à ( )
· In renal disease CrCl is à ( )
· Azotemia or uremia is à ( )
· Potassium sparing diuretics gives à ( )
· Pyuria and dysuria is symptoms of à ( )

· Lactic acidosis is SE of à ( )
· Summary of electrolytes action in kidney (True/ False)

· Proximal convoluted tubule = Reabsorbs Na+, Cl-, Ca2+(True/ False)
· Distal convoluted tubule = Reabsorbs Na+, Cl-, Ca2+(True/ False)
· Thin descending loop of Henle = Reabsorbs H 2 O (True/ False)
· Thick ascending loop of Henle = Reabsorbs: Na+, K+, Cl-, Mg2+, Ca2+ (True/ False)
· Collecting tubule = Reabsorbs Na+ in exchange of K+ or H+ (regulated by aldosterone). Reabsorption of H 2 O is
regulated by ADH (vasopressin). (True/ False)
www.pharmacyprep.com Liver function and Pathophysiology
7
Liver and Chronic Liver Diseases
Questions Alerts!
· Causes of chronic liver diseases like ascites (peritonitis).
· Hepatitis A, B, C infections causes of infections
· Hepatitis A and B vaccines and treatment.
Definitions
· Necrosis cellular breakdown example: Acetaminophen
· Steatosis: Hepatocytes filled with small droplet of
lipid. Example: Tetracycline’s
Drugs transportation into the bile from the liver

· There are transporters for anions, bile salts, cations,
and neutral organic compounds.
· Release small intestine.
Question Alerts!
1) Enterohepatic recirculation is recirculation bile from small intestine to liver.
2) Drugs that involve in enterohepatic recirculation? Increase action of oral drugs with phase II metabolism.
3) Erythromycin estolate cause cholestatic jaundice.
4) Sulfa drugs in last trimester of pregnancy can cause KERNECTERUS.
5) Cholestyramine binds with bile and prevents reabsorption of bile into liver.
6) Decrease in blood flow to liver alters extent of drug metabolism.
Oral drugs passage to liver: Mesenteric veins à portal veins à liver à hepatic vein à heart à systemic
circulationà Renal or hepatic elimination.
Enterohepatic recirculation
· This term refers to drugs emptied via bile into the small intestine and then reabsorbed from the intestinal
lumen into PORTAL VEIN to the systemic circulation.
· It can allow the body to conserve endogenous substances such as bile acids, vitamins D and B 12 , estrogen
etc. It may be responsible for some of the long half-lives of drugs.
· Antibiotic therapy interferes with the process of enterohepatic recirculation by drugs, which have been
conjugated can be hydrolyzed by gut enzymes such as glucuronidase and then reabsorbed as the active drug
or as a metabolite. A decrease in bacterial flora as a consequence of antibiotic therapy can decrease the
amount of sulfatase and glucuronidase containing bacteria. This could then lead to an increased rate of
elimination of the drug.
Chronic liver disease: Ascites, hepatic encephalopathy, cholestatic disease, Wilson’s disease, alcoholic liver
disease and viral hepatitis.
CHRONIC LIVER DISEASES

Spontaneous Bacterial Chronic cholestasis Ascites Hepatic encephalopathy
Peritonitis (Jaundice or obstructive)
history of fever, Yellow skin, eye, itchy skin. Aldosterone retain Confusion, psychosis.
abdominal pain. Abdominal pain, dark urine. water.
Excessive fluid retention
in peritoneal cavities.
hyperbilirubinemia Abdominal cancers, Ammonia released in

abdominal infections, TB blood.
and GI problems,
Treatment: antibiotics Treatment. Antihistamine or Drug of choice is Lactulose can trap
cholestyramine spironolactone. ammonia gas.
Peritoneal dialysis
associated infection:
Associated risk with S.
aureus in peritoneal
catheter in dialysis.
Chronic Cholestasis (cholestasis jaundice, obstructive jaundice, or jaundice).

· Cholestasis is a condition in which obstruction of bile from liver to intestine, it is also referred to as
obstructive jaundice. Symptoms are pruritus (itching) and are due to hyperbilirubinemia associated with
liver diseases. Cholestyramine removes excess of bilirubin from the body. Antihistamines can be used for
non-specific pruritus.
· Jaundice: The jaundice is a yellowish discoloration of skin and whites of eye caused by high levels of pigment
bilirubin in the blood stream. The urine is dark because excessive bilirubin in blood excreted through kidney.
The other characteristic symptoms are pale stools and generalized itchiness.
Ascites or Hydroperitoneum
· The accumulation of fluid in peritoneal cavity and cause abdominal distention is referred to as ascites, this is
due to high plasma aldosterone levels. Symptoms include abdominal distention. Ascites is caused due to
infections such as tuberculosis, heart failure, cirrhosis, and portal hypertension, and various cancers.
· Drug of choice is spironolactone is inhibitor of aldosterone, because aldosterone hormone increases Na/H 2 O
retention. Alternate furosemide can be added to enhance diuresis.
Hepatic Encephalopathy: (Porto Systemic Encephalopathy).

· Condition in which brain function is impaired by presence of toxic
substances, absorbed from colon, which is normally detoxify and
removed by liver. This condition occurs in severe liver damage such as
liver cirrhosis.
· Symptoms include: Drowsiness, confusion, difficulty in performing task
(e.g. writing) and coma.
· Drug of choice is lactulose to achieve 2 to 3 bowel movement a day. If
no improvement in 1 to 2 days add metronidazole.
Fig 7.2
Wilsons Disease
· Excessive copper can cause Wilsons disease. The drug of choice is the penicillamine and treatment is
lifelong. Pyridoxine (vitamin B 6 ) 25 mg daily should be given with penicillamine to counteract its anti-
pyridoxine effect.
· Avoid food that has high copper content such as peanuts, chocolate, shellfish, mushrooms, and liver.
The liver cirrhosis is the destruction of normal liver tissue. Cirrhosis results from permanent damage
(IRREVERSIBLE) or scarring of the liver. It is end stage of chronic liver diseases, hepatitis B & C, ascites, chronic
hepatitis and hepatic encephalopathies.
The most common cause is due to alcohol abuse or continued excessive intake of alcohol over long period of
time.
Cholestatitis: Retention of bile acids because of the obstruction of bile ducts. Cholestatitis can lead to
hyperbilirubinemia.
Viral Hepatitis: There are 5 types of hepatitis viral infection, hepatitis A, B, C, D, and E. However, the common
infections are hepatitis A, B and C.
Most common symptoms of hepatitis are flu like symptoms, loss of appetite, fatigue, mild fever, muscle or joint
aches, nausea and vomiting. Less common symptoms are light colored stools, jaundice (yellowing of skin, and
whites of the eye), generalized itching, internal bleeding, and altered mental state.
Hepatitis A
· Hepatitis A is acute infection
· Transmits through food contaminations such as water, food or orofecal
· Vaccine available
· Hepatitis A vaccine is recommended to travelers.
Hepatitis B and C
· Hepatitis B and C are chronic. Hepatitis B is 90% chronic in children and 5% in adults.
· The most common is hepatitis B.
· Hepatitis B is DNA type of virus, where as other hepatitis are RNA type.
· Transmission through body fluids, such as blood transfusion, sexual contact and sharing needles (drug
abuse and spa).
· Hepatitis C is often chronic in adults (acute hepatitis C, is 80% becomes chronic likely within first year of
infection).
· Hepatitis C has NO vaccine.
· Hepatitis B vaccine also protects hepatitis D infections.
· Interferon alfa (IFN alfa) is the drug of choice to treat acute viral hepatitis and chronic hepatitis.
ALT (liver ALP AST Bilirubin

specific)
Hep A ↑ ↑ ↑
Hep B&C ↑ ↑ ↑
Liver cirrhosis ↑ ↑ ↑ ↑Serum unconjugated bilirubin
Jaundice ↑ ↑(specific)
(cholestasis)
Alpha 1- antitrypsin deficiency occurs in liver cirrhosis. (deposition of excessive abnormal (A1AT) occurs in
cirrhosis).
Drugs associated with liver cirrhosis are amiodarone, methotrexate and methyldopa.
ALP (alkaline phosphatase); have 5 minor sources (liver, bile duct, kidney, bone, placenta)
ALT>AST by 1000 x in acute viral hepatitis
AST can also come from muscle
DRUGS THAT CAN CAUSE HEPATOTOXICITY

Drugs Maximum dose/TIPS
Acetaminophen > 4g daily
Tetracycline >2g daily
Methotrexate >25mg/wk
Vitamin A chronic use over 40,000 U daily
Salicylates chronic use >2g daily
Iron single dose >1g
Cyclophosphamide
6-Mercaptopurines
Tips
1. Penicillamine 2. Ascites 3. Wilsons disease
4. Cholestatitis 5. hepatic 6. Hepatitis B
encephalopathy
7. Hepatitis C 8. Infections 9. Tuberculosis
10 Cancer 11 GI surgeries 12 Chronic liver disease
13 Sexual contact 14 water 15 Orofecal
16 Interferon alfa 17 Portal hypertension 18 Spironolactone
· What type of hepatitis is chronic? ( )

· What is the treatment of hepatitis? ( )
· Hepatitis A transmits by? ( )
· Hepatitis B and C transmits by? ( )
· Ascites is caused by? ( )
· What is a DNA type of virus ( )
· Accumulation of fluid in peritoneal cavity ( )
· It is caused by excessive copper ( )

· Drug of choice to treat Wilsons disease ( )
· Retention of bile acids because of obstruction of bile ducts ( )
· A type of hepatitis that has no vaccine ( )
· The drug of choice to treat ascites ( )
· Lactulose is used in what type of chronic liver disorder? ( )
· What type of hepatitis is chronic à ( )
· What is treatment of hepatitis à ( )
· Hepatitis A transmits by à ( )
· Hepatitis B and C transmits by à ( )
· Ascitis is caused by à( )
· If takes Hep B vaccine, this also protects à( )
Select True or False statements:

· Cholestatitis: Retention of bile acids because of the obstruction of bile ducts. Example: Penicillins (isoxazole
type) (True/False)
· Cholestatitis can lead to hyperbilirubinemia example: Rifampin (True/False)
· Bacterial peritonitis: Chronic liver disease, history of fever, abdominal pain. (True/False)
· Causes of ascites include à infections, TB, cancer, GI surgeries, chronic liver disease (True/False)
· Lactulose is used in what type of chronic liver disorder à hepatic encephalopathy (decrease NH 3 )
(True/False)
www.pharmacyprep.com Respiratory System
8
Respiratory System
Questions Alerts!
· Tidal volume. The volume inspired or expired with each normal breathing.
· Asthma symptoms and triggers.
· Definition of emphysema is COPD.
· Differences between COPD (terminal bronchioles or alveoli) and asthma (bronchus).
Fig 8.1
Question Alerts!
Which of the following does NOT open into respiratory tract?
A) Nasopharynx
B) Laryngeal pharynx
C) Frontal sinus
D) Bronchus
E) Alveoli
Lung volume
Tidal volume: Can be measured by Spirometer (FEV 1 ). (In asthma, expiratory flow rate decreased). The volume
inspired or expired with each normal breath.
Residual volume: The volume that remains in the lung after a maximal expiration.
The residual volume cannot be measured by spirometer.
Lung capacities:
Total lung capacity: The sum of all four lung volumes (tidal volume, inspiratory lung volume, expiratory lung
volume, residual volume). The volume in the lungs after maximal inspiration.
Forced expiratory volume (FEV 1 ): The volume of air that can be expired in 1 second after maximal inspiration.
This is measured by spirometer.
Spirometer: Measure volume that has been exhaled at the end of the first second (FEV 1 ). The spirometer is used
for diagnosis of obstructive lung diseases such as asthma and COPD.
Peak flow meter: is test to determine asthma severity for patient at home. This test measures the highest
forced expiratory flow.
LOWER RESPIRATORY TRACT

Physiology Ventilation. Air moves from Atmosphereà URTàLRTàalveoli
Respiration. Gaseous exchange occurs at alveoli capillary membrane.
Factors that decrease the · Increased in resistance to air flow

respiration · Decrease ventilation
· Decrease diffusion
· Mucosal edema.
· Increased bronchial secretion
· Bronchospasm
Arrangement of Bronchiole · Tracheobronchial tubes have smooth muscle fibers arranged on a spiral
smooth muscles around the tube.
Disease Asthma, COPD is Emphysema and Bronchitis
UPPER RESPIRATORY TRACT
Anatomy Sinus (prenasal cavity in & around the nasal cavity)
Nasal cavity
Pharynx
Larynx
Trachea (past outside thoracic cavity)
Disorders Acute rhinitis
Acute pharyngitis
Acute tonsillitis
Acute laryngitis
Common cold (most prevalent of URI, and NOT life threatening but causes severe
discomfort).
Treatment Antihistamineà Runny nose
Decongestants (Sympathomimetics)ànasal congestion
AntitussiveàCough
Antibioticsà Infections
ExpectorantsàBring up mucus
RESIRATORY PATHOLOGY
ASTHMA COPD (Emphysema + Chronic bronchitis)
Obstructive Obstructive
Site Bronchus or bronchial tubes Alveoli (enlarged, over-stretched, loss of long elasticity).
Air trapped in lung.
Cause Inflammation in bronchus Permanent (irreversible) enlargement alveoli
(emphysema) and /or Chronic bronchitis.
Symptoms Wheezing, cough, sputum, and SOB. Shortness of breath (SOB) (dyspnea), fatigue, cough,
sputum
Treatment Bronchodilators Bronchodilators (SABD, LABD, LAMA)
Steroids (ICS, PO, IV) acute COPD bronchodilators, anticholinergic, for
exacerbations oral steroids (not used? inhaled
corticosteroids) Antibiotics (pneumonia)
Eosinophilic Neutrophil due to bacterial infections.
Obstruction of airflow is reversible Obstruction of airflow is irreversible
Immunization Flu vaccine annually Flu vaccine annually and Pneumococcal vaccine Q5-10y in
Pneumococcal vaccine high risk.
Prevention Avoid triggers (allergens, exercise, Causes of COPD, smoking, Alpha1-antitripsine deficiency,
emotional stress, cold air, (NO air pollution, secondary smoke.
trigger is warm air)
Cystic fibrosis:
Autosomal recessive disorder that is caused by a mutation on chromosome 7. This mutation results in a
defective membrane CT channel (CFTR).
Signs: The mutation leads to secretion of thick mucus, which lodges in lungs, liver and pancreas.
Tips
1 asthma 2 emphysema 3 dyspnea
4 COPD 5 Emboli formation in lungs 6 Autosomal recessive disorder
7 Wheezing 8 Vital capacity
· Difficulty in breathing (dyspnea)

· Permanent enlargement of the alveoli (emphysema)
· Emphysema is…(COPD)
· What respiratory condition occurs in bronchus or bronchial tube (Asthma)
· What respiratory condition can occur in bronchioles & alveoli (COPD)
· Pulmonary embolism is floating clot in blood circulation in the lung tissues.
· Cystic fibrosis is a --> multi organ disease but mainly effect on lungs due to the long thick lung secretions
blocks small airway and thus inflammation (a restrictive respiratory disease)
· Cough in asthma sounds like--> Wheezing
· Alpha1-antitripsine deficiency? COPD
· When maximum amount of air a person can expel from the lung after a maximum inhalation, is referred as.
Vital capacity. This depends on age, gender, height, mass and ethnicity. ?
www.pharmacyprep.com Urinary System
9
Urinary System
Questions Alerts!
Urinary tract infection symptoms Bladder (cystitis), Urethra (urethritis), Ureter (ureteritis), kidney (pyelone-
phritis). Complicated and uncomplicated UTI.
Symptoms of benign prostatic hyperplasia (BPH).
Types and symptoms of urinary incontinence and over reactive bladder.
Prostate cancer screening is prostate specific antigen (PSA), and Digital rectal exams.
The urinary system includes two kidneys, two ureters, the bladder, two sphincter muscles, and the urethra. Uri-
nalysis is a test that studies the content of urine for abnormal substances such as protein or signs of infection.
Urodynamic tests evaluate the storage of urine in the bladder and the flow of urine from the bladder through
the urethra.
Urinary Tract Infection: The name of the UTI depends on its location in the urinary tract. An infection in the
bladder is called cystitis. If the infection is in one or both of the kidneys, the infection is called pyelonephritis.
This type of UTI can cause serious damage to the kidneys if it is not adequately treated.
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to re- 9-1
produce without permission. This manual is being used during review sessions conducted by PharmacyPrep.
Pathological defense mechanism of UTI:
Organ Infection Treatment

Urethra Urethritis
Bladder Cystitis. The most common UTI Cotrimoxazole 3d, nitrofurantoin 5d, trimethoprim.
Ureter Ureteritis
Kidney Pyelonephritis (Symptoms: flank pain, dysuria, Ciprofloxacin, amoxi+clav, 3rd gen cephalosporin’s
pain at costovertebral angle, and same symptoms
as cytitis)
Urine pH 6.5 to 7 (slightly acidic in morning, slightly base by evening)
Physiological Factors that increase risk of urinary tract infections.

Decrease resistance of mucus membrane. (e.g. menopause)
Increase in vaginal pH
Colonize colon spread to UTI
Colonization of urethra and peri-urethral tissue.
Causative agents of UTIs. E. coli is the most common in community acquired (80%), and hospital (50%).
Uncomplicated UTI: Occurs in females with normal genitourinary tract. Cystitis, the most common infecting
organism is E. coli (80-90%). Usual presenting symptoms. Internal dysuria, frequency, suprapubic discomfort and
urgency.
Complicated UTI: occurs in individuals with functional or structural abnormalities of genitourinary tract. Virtually
all episodes of UTI in men are complicated. E. coli (50%). Patient with cystitis.
Uncomplicated UTI Complicated UTI
Internal dysuria, frequency, su- High fever, blood in urine (turbid urine or cloudy,
prapubic discomfort, urgency, and hematuria), vomiting and sepsis.
fever. Burning upon urination. Nau- Burning upon urination. Nausea & vomiting
sea & vomiting
Cotrimoxazole, nitrofurantoin, Ciprofloxacin+amoxi
Benign prostatic hyperplasia (BPH) is a condition in men that affects the

prostate gland, which is part of the male reproductive system. The prostate is Question Alerts!
located at the bottom of the bladder and surrounds the urethra. BPH is an What is NOT a symptom of
enlargement of the prostate gland that can interfere with urinary function in BPH?
older men. It causes blockage by squeezing the urethra, which can make it Jet urination (stream)
difficult to urinate. Men with BPH frequently have other bladder symptoms
including an increase in frequency of bladder emptying both during the day and at night.
Symptoms: Urine obstructions symptoms includes frequent urine, drop by drop, incomplete voiding, nocturea
and also include irritation symptoms.
Treatment. The drug of choice to decrease prostate size Finasteride 5 mg. Alpha blocker tamsulosin, alfuzosin,
terazosin is used to treat symptoms.
Bladder neck/sphincter contraction is due to alpha agonist activity.
Painful bladder syndrome/Interstitial

cystitis (PBS/IC): is a chronic bladder
disorder also known as frequency-
urgency-dysuria syndrome. In this
disorder, the bladder wall can become
inflamed and irritated. The inflammation
can lead to scarring and stiffening of the
bladder, decreased bladder capacity,
pinpoint bleeding, and, in rare cases,
ulcers in the bladder lining. The cause of
IC is unknown at this time.
Kidney stones is the term commonly used to refer to stones, or calculi, in the urinary tract system. Stones form
in the kidneys and may be found anywhere in the urinary system. They vary in size. Some stones cause great
pain while others cause very little. The aim of treatment is to remove the stones, prevent infection, and prevent
recurrence. Both nonsurgical and surgical treatments are used. Kidney stones affect men more often than
women.
Stones (calculi) can form anywhere in urinary tract and pain radiates in flank area, sharp, sudden severe pain,
may be intermittent depends on stone movement, Nausea, vomiting, bleeding (hematuria), obstruction of flow
of urine, or an infection. Depending on the site of stone it is referred as kidney stone, ureteral stone, or bladder
stone. The process of stone formation is urolithiasis, renal lethiasis, or nephrolithiasis.
Risk factors: Infections, urinary stasis, immobility, hypercalcemia, hyperuricemia, high urinary oxalate levels.
Increased incident in men over age 40.
List of drugs associated with urolithiasis/ nephrolithiasis Causes/recommendation

Sulfa drugs (antibiotics/sulfonylureas) Drink lots of fluids/water
Fibrates Avoid use in renal stones.
Topiramate Drink lots of fluids/water
Vit. D overdose
Bisphosphonates
Calcium supplements
Allopurinol
Prostatitis is inflammation of the prostate gland that results in urinary frequency and urgency, burning or painful
urination, a condition called dysuria, and pain in the lower back and genital area, among other symptoms. In
some cases, prostatitis is caused by bacterial infection and can be treated with antibiotics. But the more com-
mon forms of prostatitis are not associated with any known infecting organism. Antibiotics are often ineffective
in treating the nonbacterial forms of prostatitis.
Proteinuria is the presence of abnormal amounts of protein in the urine. Healthy kidneys take wastes out of the
blood but leave in protein. Protein in the urine does not cause a problem by itself. But it may be a sign that your
kidneys are not working properly.
Nephropathy associated with high albumin urine.
Urinary incontinence: Uncontrollable loss of urine or involuntary leakage of urine. There are many causes and
types of incontinence, and many treatment options. Treatment range from simple exercises to surgery. Women
are affected by urinary incontinence more often than men. To treat incontinence, anticholinergic drugs oxy-
butynin is the drug of choice.
Detrusor muscle contraction due to parasympathetic activity (voiding). Detrusor muscle relaxation and tighten-
ing of sphincter is due to anticholinergic activity (storage).
Bladder relaxation is due to beta agonist activity.
Bladder neck/sphincter contraction is due to alpha agonist activity.
Overflow incontinence Stress incontinence Urge incontinance

Urethral blockage. Relaxed pelvic or leakage with - abdominal pressure, Neurological problems, Parkinson’s,
Bladder overfull cough/sneezing. sensitive to infection.
Men à surgery Feeling urgency
Women à hypomobility of spincter
Diuretics Estrogen vaginal cream, suppositories, ovule. Anticholinergic drug: Oxybutinin,
tolterodine
Tips
· Urinary incontinence symptoms àNO control on bladder or urination, urine leakage.

· Drugs that are used for treatment of urinary incontinenceà Oxybutynin or anticholinergic drugs.
· Drugs that are avoided in-patient with overflow urinary incontinence à anticholinergics
· Enuresis (bed wetting) drug of choice à ADH (vasopressin) or imipramine.
· Benign prostatic hyperplasia (BPH) is à enlargement of prostate
· Benign prostatic hyperplasia symptoms are --> dysuria, frequent urination, urine by drop by drop, nocturia,
and irritation (NOT a symptoms, stream (Jet urination).
· Drug of choice to treat benign prostatic hyperplasia à Finasteride (Proscar 5 mg), and also Propecia 1 mg to
treat baldness.
· Saw palmetto is herbal product is used for --> benign prostatic hyperplasia.
· Pyuria and dysuria is symptoms of à complicated UTI
· Hypertrophy: Increased size of an organ or tissue by increase in size of its cell.
Hyperplasia: increase in size of an organ or tissue by increase in number of its cells. Can cause tumor (can-
cer).
www.pharmacyprep.com The Eye and Ear
10
The Eye and Ear
Questions Alerts!
1) Photoreceptors rods are sensitive for dim light and cones cells sensitivity to daylight and colors.
2) Cornea is upper layer of eye is rate determine step in ophthalmic drops.
4) Eye disorders like conjunctivitis (red or pink eye), blepharitis, and sty (hordeolum), Age related macular
degeneration, Cataract, and glaucoma.
5. External and middle ear problems.
produce without permission. This manual is being used during review sessions conducted by
PharmacyPrep.
Question Alerts!
1) More sensitive photoreceptors for dim light in eye? Rods
2) Color sensitive photoreceptors are? cones
3) Rhodopsin is red photosensitive pigment in the retinal "rods" important vision in dim light.
4) Iodopsin is pigment present in the retinal “cones” important in daylight.
5) What arteries supply blood to eye? External carotid arteries.
Optic nerve from both eye merge at optic chiasm and become optic tract. This optic tract connect to thalamus
then goes to right and left brain. Primary visual area in occipital lobes of cerebral cortex.
· Cornea: In the front of the eyeball is a transparent opening known as the cornea. RATE LIMITING STEP FOR
OPHTHALMIC DROPS.
· Pupil: After light passes through the cornea, a portion of it passes through an opening known as the pupil.
· Iris: Pupil opening can be adjusted by the dilation of the iris.
· Ciliary muscles: The lens is attached to the ciliary muscles.
· Ciliary gland: secrete aqueous humor.
· Retina: The inner surface of the eye is known as the retina.
· Macula: Small central area of retina.
· Optic nerve: The network of nerve cells is bundled together to form the optic nerve on the very back of the
eyeball.
· Optic disk: The nerve cells is bundled at very back of eyeball, is also known as blind spot. Rods and cones
are NOT present on the optic disk, therefore blind spot.
· Myopia: If the incoming light from a far away object focuses before it gets to the back of the eye, that eye’s
refractive error is called “myopia” (nearsightedness).
· Hyperopia: If incoming light from something far away has not focused by the time it reaches the back of the
eye, that eye’s refractive error is “hyperopia” (farsightedness).
The retina contains two types of photoreceptors, rods and cones. These rods are responsible for night vision,
our most sensitive motion detection, and our peripheral vision. The rods are more numerous, some 120 million,
and are more sensitive than the cones. However, they are not sensitive to color.
· The 6 to 7 million cones provide the eye's color sensitivity and they are much more concentrated in the cen-
tral yellow spot known as the macula.
· The image forms in eye at retina. Ophthalmic drug rate limiting step is cornea.
Eye anatomy Functions

Cornea
Retina (photoreceptors)
Rhodopsin
Idopsin
Optic disk
Optic nerve
Celiary gland
PharmacyPrep.
Myopia
Hyperopia
Mydriatic pupils
Miotic pupils
Vitreous humor Gel like fluid filled between retina and lens.
Aqueous humor Fluid Filled between cornea and lens.
Beta carotene --> Retinol (vitamin A) --> 11-Cis retinal-> opsin
RODS CONE
Rhod”opsin” (retinal) Iod”opsin”
Rhodopsin is rod cells pigmentation. Respon- Iodopsin is retinal cone cells responsible for day light
sible for dim light vision. vision color vision
More sensitive in dark Less sensitive in dark
Higher in number Less in number
Rods: Light on the retina converts 11-cis retinal to all Trans retinal. The retinal is a vitamin A is essential for the
regeneration of 11-cis retinal. Deficiency of vitamin A causes night blindness.
Carotenoids
Aqueous humor is present in anterior eye chamber

Vitreous humor is present in posterior eye chamber
Glaucoma: Due to angle closure increasing intra ocular pressure

(IOP) cause glaucoma. This is due to;
· Increase aqueous humor production cause increase IOP.
· Decrease aqueous humor secretion from shlemn canal.
Aqueous humor is secreted from ciliary tissue (ciliary gland).
Treatment of glaucoma
Beta blockers (Timolol). They decrease IOP by inhibiting formation of aqueous humor.
Prostaglandin analogues ("prost"). Lower IOP by increase outflow of aqueous humor through uveoscleral path-
way.
Topical CA inhibitors (Acetazolamide, Dorzolamide): is diuretics. Decrease IOP by inhibiting enzyme that involved
in formation of aqueous humor.
Cholinergic agonist (Pilocarpine, carbachol): Directly stimulate muscarinic receptors to contract ciliary muscle
and increase trabecular outflow.
PharmacyPrep.
Age related macular disorder (AMD): It is due to gradual deterioration of macular in central vision. It is two
types;
1) Dry. This is characterized by drusen (white to yellow spots in the central retina). May or may not cause
vision loss.
2) Wet. Caused by presence of choroidal neovascular membrane (CNM). This is common cause of severe
vision loss.
The Amsler grid is useful for self-monitoring by patients.
Multivitamins without carteronoids are used prophylaxis of AMD.
Lutein & Zexanthin are two types of carotenoids, which are yellow to red pigments found widely in vegetable.
These may contain in multivitamin that are used for AMD prophylaxis.
Cataract: When the eye lens becomes cloudy, decrease acuity, and no pain, and this obstruct the vision is
referred as cataract.
Cataract surgery postoperative care: Antibiotics, Dilators and anti-inflammatory drugs.
Antibiotics: Fluoroquinolones 7-10 d (besifloxacin, ciprofloxacin, gatifloxacin, moxifloxacin and ofloxacin).

Aminoglycosides 7-10 d. Gentamicin, neomycin, tobramycin
Dilators and cycloplegic: used to keep iris away from implant during early healing period and improve comfort
by decrease ciliary muscle spasm.
Cyclopentolate, phenylephrine, tropicamide.
Anti-inflammatory 3-4 wks: Dexamethasone, prednisolone, diclofenac, and ketorolac.
Combination eye drops: Ciprodex (ciprofloxacin+ dexamethasone).
EYE CONDITIONS SUMMARY

Glaucoma
Cataract
AMD
Eye drops Technique: tilt head backward, place drop in conjunctiva sac; put pressure on inner cantus.
Terms: OD = OS = OU =
Ear (outer ear, middle ear and inner ear)

Otitis externa (outer ear) and Acute bacterial externa
Eczematous otitis externa: Drainage resulting from mild otitis externa may be self treated. (Ear pain associated
with ear drainage, the patient should be referred to a physician).
Otitis media with perforation of the tympanic membrane or drainage from the middle ear, the patient should
be referred to a physician.
OTITIS EXTERNA OTITIS MEDIA
Self-treated by non-prescription Require referral to physician
When to refer? Wax buildup, foreign objects in ear Fluid is indicator of infection of ear bones or tympanic mem-
canal. brane.
Child presents with fever and ear pain?
1) Ceremonious gland produce? earwax The drug of choice for otitis media? Amoxicillin or azithromy-
2) Earwax is removed by carbamide peroxide and min- cin/clarithromycin
eral oil.
Inner ear: Noise, drug exposure, such as ASA, ototoxic drug, vestibular toxicities and Meniere’s disease.
PharmacyPrep.
EAR CONDITIONS SUMMARY

Otitis externa What symptoms to refer?
Otitis media
Meniere’s disease
Ear drops admin Technique:
For infants and toddlers pull ear down and back
For adults and older children pull ear up and back
Lie on unaffected side
Stay on side for 5-10 min after drops instilled.
Can put cotton moistened with medication in ear to keep drops in place.
Terms: AD = AS = AU =
Dental anatomy and physiology
· There are 20 primary teeth and 28 to 32 permanent teeth. The last 4 is being wisdom teeth.
· In adult, there are 16 teeth in maxilla and 16 in the jaw.
· Wisdom teeth may or may not grow in.
· Incisors 8, canine 4, premolar 8, molar 8, wisdom (third molar) 4=32.
· Baby teeth start to grow during intrauterine first trimester (8 weeks).
· Teeth are made of enamel, dentin, and cement.
· Dentin composes most of the root.
· Crown is covered by the enamel.
· The root embedded inside the maxilla and jaw bones has a bulb canal.
· The bulb canal contains blood supply and nerve terminals.
· The root teeth may be single in number or multiple.
· Gingival or gums consist of mucosal tissue lies over the alveolar bone.
· Oral hygiene is practice of keeping mouth and teeth clean, to prevent bad breath, and dental problems.
· Plaque is yellow sticky films that form on the teeth and gums.
· Bacteria in plaque release acid that harm the enamel.
· Brushing and flossing daily the teeth will prevent tartar forming.
· Fluorides are a primary protector against dental cavities.
PharmacyPrep.
· Fluorides make teeth surface more resistant to acids.

· Drinking water contains enough fluorides.
· Sugar free gum increases salivation and help to clean teeth surface.
· Good food items for teeth; green tea, milk and yogurt, cheese, apples, onion.
· Smoking and chewing tobacco causes multiple dental diseases.
· Bulimia nervosa and repeated vomiting causes significant damage to enamel.
· Bad dental hygiene shows direct link to systemic diseases;
· Cardiovascular disease.
· Bacterial pneumonia.
· Low birth weight.
· Complication of diabetes.
· Osteoporosis.
Tips
· Blind spot is à optic disc
· Age related macular degeneration cause due toà retinal detachment
· Glaucoma occurs due to à abnormal increase IOP in eyeball
· Drugs that are used to treat glaucoma are à sympathetic blockers (B-blockers), Prostaglandin analogs (Lat-
anoprost), CA diuretics (acetazolamide).
· Photoreceptor sensitive to daylight? cones
· Photoreceptor sensitive to dark or dim light? rods
· What are the most sensitive photoreceptors? rods
· Age related macular degeneration cause due toà retinal detachment
· Glaucoma occurs due to à Increase IOP
· What are the mechanism of Drugs that are used to treat glaucoma are à inhibitor formation of aqueous
humor or increase outflow of aqueous humor.
· Meniere's disease is characterized as? Vertigo, hearing loss and tinnitus.
Vitreous humor is? The clear gel fills the space between the lens and the retina of eyeball of human.

· The retina contains two types of photoreceptors, rods and cones. (True/False)
· These rods are responsible for night vision, our most sensitive motion detection, and our peripheral vision.
(True/False)
· The rods are more numerous, some 120 million, and are more sensitive than the cones. However, they are
NOT sensitive to color. (True/False)
· The 6 to 7 million cones provide the eye's color sensitivity and they are much more concentrated in the cen-
tral yellow spot known as the macula. (True/False)
· Cones are sensitive to color vision(True/False)
PharmacyPrep.
Pharmacyprep.com Blood and Anemia
11
Blood and Anemia
This chapter reviews blood cells and functions. Types of anemia and their morphological changes.
Terminology
Questions Alerts!
· Blood cells such as platelets, red blood cells, and white blood cells
· Hemostasis
· Morphological changes of anemia. Iron deficient microcytic anemia and megaloblastic anemia.
· Elemental iron supplements (ferrous fumerate > dried ferrous sulfate > ferrous sulfate>ferrous
gluconate).
· Iron supplement drug interactions, thyroid hormone, tetracycline and quinolones, cholestyramine.
· Vitamin B12 and Folic acid supplements
Question Alerts!
· Agranulocytosis: Decrease in number of neutrophil 1) The highest number of blood cells?
· Neutropenia. Decrease in neutrophil 2) The second highest number of cell?
3) Reticulocytes are?
· Neutrophilia. Increase in neutrophil
4) Life of thrombocytes (platelets) ?
· Esinophilia. Increase in esinophil
5) Life of erythrocytes (RBC)?
· Thrombocytopenia. Reduced platelets to less than 150 x 109/L
Myelosuppresion is?
· Parasthesias: Abnormal tingling sensation as described as tingling &
needles.
· Hemocromotasis: Excessive iron
· Polycythemia: excessive hemoglobin or RBC concentration.
· Function of blood include transportation of gases, nutrients, hormones, metabolic wastes regulates body
temperature, pH, electrolyte balance, fluid volume protects, prevents blood loss (clotting), and prevents
infection (WBC and antibodies).
Blood
55% Fluid 45% Cells
Water containing salts Erythrocytes (RBC)= 5-6 mil/mL (44%)

Proteins Leukocytes + Platelets = (1%)
Antibodies
Hormones
Electrolytes
Fats and lipids
Sugar (carbohydrates)
Erythrocytes Leukocytes Platelets
Mineral
Vitamins
Blood constitute 55% fluid and 45% cells.

Blood proteins
· Blood proteins (albumin, glycoprotein, and fibrinogen).
· Albumin is the most common blood proteins (55%) in blood. Question Alerts!
Which is carrier of, buffer, osmotic pressure, transport lipids, The major protein in blood?
fatty acids and acidic drugs.
Globulins carry ions, hormones, and steroids and bind base drugs.
Fibrinogen changes to fibrin, helps in blood clotting.
Electrolytes: The Electrolytes present in blood are Na+, K+, Ca2+, Mg2+, Cl- and CO3
Extracellular ion Na+, Cl- and Ca2+.
The most common extra cellular cation is sodium (Na).
The most common extra cellular anion is chloride (Cl).
Intracellular ions K+, Mg2+ and phosphate.
Antibodies (Immunoglobulin) IgG, IgM, IgE, IgA, and IgD.
Erythrocytes (Red blood cells):

RBC is composed of globin (protein), iron (metal), phospholipid (lipids), potassium phosphate (salt),
hemoglobin (contain porphyrin ring system) bind loosely to oxygen and carbon dioxide. In the overdose of
carbon monoxide, the hemoglobin binds with carbon monoxide.
RBC synthesis (Erythropoiesis): Pre-erythrocyte is the first step in the synthesis of RBC series.
· The normal value of the RBC in adult men would be 4.7 million.
· Erythrocytes are originated in sequence of cells Hemocytoblastà Megaloblastà Erythroblast
(normoblast) --> Reticulocytesà Erythrocytes
· Erythropoietin, a glycoprotein is a key hormone for the production of RBC. In the absence of
erythropoietin. Hypoxia is unable to stimulate the production of RBC. The kidney is a principal organ
for the synthesis of erythropoietin, therefore, kidney failure would result in severe anemia.
RBC destruction: Life span of RBC is 120 days (4 months). RBCs are destroyed in the spleen (spleen also referred
to as "grave yard" of RBC).
Hemoglobin (Hgb): Blood protein-containing iron metal, carries oxygen in blood.

· Hemoglobin content 14.5 g/100 ml. Hemoglobin consists of porphyrin ring. Oxygen binds with
porphyrin ring. Porphyrin ring present in haemoglobin is tetramer.
· The metabolic degradation of hemoglobin takes place principally in the reticuloendothelial system
(endoplasmic reticulum).
The non-protein portion of hemoglobin is a "ferrous" complex of porphyrin. The O 2 binds the ferrous form (Fe2+)
of iron present in hemoglobin to form oxyhemoglobin. During this process one electron is transferred. (Ferrous
= Fe2+; Ferric = Fe3+). Methemoglobinemia: Abnormal state of hemoglobin contains oxidized iron as Ferric Fe3+
· The protein portion of hemoglobin is globin.

· Glycine is an aminoacid is precursor of hemoglobin.
· Myoglobin. Protein present in tissues, which is essential for oxygen transport in tissues. Carries oxygen
in tissue. The porphyrin ring present in myoglobin is monomer.
· Methemoglobin: Nitrite ions react with hemoglobin and produce methemoglobin, which has a low
affinity for oxygen and a high affinity for cyanide ions. This forms iron CN complex, it is referred as
cyanomethemoglobin.
Hemoglobin Myoglobin Cytochrome oxidase

Transport oxygen in blood Transport oxygen in tissue Catalyzes phase I metabolism
Porphyrin tetramer Porphyrin monomer Porphyrin
Has affinity and binds with Has affinity and binds with Has affinity and binds with O 2 ,
O 2 , CO, CO 2 and CN. O 2 , CO, CO 2 and CN. CO, CO 2 and CN
2+ 2+
Ferrous ion (Fe ) Ferrous ion (Fe ) Ferrous ion (Fe2+)
Death due to cyanide poisoning results from cyanide binding to hemoglobin, myoglobin and inhibiting
cytochrome oxidase.
Glycine is precursor of -CH 2 - in porphyrin ring.
Carboxyhemoglobin: Carbon monoxide bound hemoglobin.
Platelets (Thrombocytes): Platelets are referred to as thrombocytes. Platelets help in the process of blood
clotting. Platelets lack nuclei and platelets are produced in bone marrow. Platelet life span is 7 to 10 days. Range
in blood 150,000 to 300,000 mm3. Deficiency of platelets is referred as thrombocytopenia.
Leukocytes (WBC)
· Leukocytes produced in bone marrow like RBC’s. Leukocytes consist of clearly defined nuclei. About
30% are lymphocytes and about 60% are neutrophils and 8% are monocytes. Normal range of WBC’s
(white count) in blood is 4000 to 11000/mm3 (4000 to 11000/ cmm).
· Neutrophils: About 60% of white blood cells are neutrophils. Responsible for immune defence
phagocytosis.
· Monocytes: About 8% of white blood cells are monocytes.
· B-lymphocytes and T lymphocytes are primary cell of specific immune response.
· Basophils: Responsible for inflammatory response.
· Eosinophils: Defence against parasites.
· Monocytes: Immune defence (precursor of tissue macrophage) also called big eaters.
· B-lymphocytes. Antibody production (precursor of plasma cells).
· T-lymphocytes. Cellular immune response.
Granulocytes are Neutrophils, eosinophils, and basophils, cells that stain.

· Neutrophils gives stain with acidic or basic dyes
· Eosinophils gives stain with acidic dye
· Basophils gives stain with basic dye
Agranulocytes
Cells that do not stain are agranulocytes. There are 2 types of cells lymphocytes and monocytes.
Rh factor: Agglutinogens in human RBCs are known as the Rh factor blood with this factor is described as Rh +ve
(90% of population). Blood without this factor is described as Rh (-) negative. In Rh-negative mother, Rh-positive
antigens may transfer from Rh-positive fetuses to the mother via placenta. This may lead to production of Rh-
positive antibodies in the mother’s blood. These same antibodies may transfer back from the mother’s blood
into fetus via the placenta, and produce antigen antibody reactions. This leads to lysis of red blood cells in the
fetus, and miscarriage. Rho gram prevents the formation of anti-Rh antibodies in a mother who bears Rh
positive fetus.
Rh- women who have + babies get a Rhogam shot.
Blood Groups
Surface of RBC's have antigen Question Alerts!
A RBC has A antigen, plasma has B antibodies What blood group can be given to anyone?
B has B antigen, A antibodies
AB has A and B antigens, no antibodies.
O (universal donor) has no antigens, has antibodies against A and B, transfusion reaction can lead to kidney
failure.
Qualities of Blood DONOR

o o
· Temperature. 38 C (100.4 F), warfarin O A B AB
(anticoagulant) added in blood storage AB a� a� a� a�
Viscosity: 5xH 2 O sticky, cohesive, and B a� a�
resistant to flow pH 7.35 to 7.45 A a� a�
volume: 4 to 6 litres (7% body weight in
kg) (2.2 lb/kg).
O a�
· Transport O 2 and CO 2 2% of cells in whole blood males: 40-54 (androgens stimulate production)
females: 37-47 (estrogens inhibit production).
· Hemoglobin (Hb): binds transports O 2 and CO 2 (280 million/RBC) Hemoglobin - Fe+2 males: 14 to 18
g/100ml; females: 12 to 16 g/dl, fetal hemoglobin has a higher affinity for O 2 .
Anemia
Anemia has categorized based on morphological changes of RBC.
Mean cell volume (MCV): The MCV detects changes in cell size. Decrease in (↓) MCV indicates a microcytic cell
anemia, which is due to iron deficiency. Increase in (↑) MCV indicates macrocytic anemia (megaloblastic
anemia), which is due to deficiency of vitamin B 12 and folic acid.
Mean cell hemoglobin concentration (MCHC): Weight of hemoglobin in average red blood cell. In microcytic
anemia decrease in (↓) MCHC. This is not significant in determining megaloblastic anemia.
Serum ferritin: Iron stores are measured by serum ferritin. The concentration of ferritin is proportional to iron
stores.
Total iron binding capacity (TIBC). Increased in microcytic anemia.
Anemia is characterized as deficiency of red blood cells and this can occur in three forms.
Microcytic (Hypochromic) Macrocytic (Megaloblastic) Normocytic
Morphological changes (Deficiency of Fe) (Deficiency vit. B 12 or folic acid) (Normochromic)
in anemia (Sickle cell anemia)
MCV ↓ ↑ No change
MCHC ↓ No change No change
Serum ferritin ↓
TIBC ↑
Transferrin saturation ↓
Cyanocobalamine ↓
↓ Fe ↓B 12 or Folate Aplasia
Chronic diseases Chronic alcohol Renal disease
Lead poisoning Inflammation
Thalassemia
Bleeding.
Transferrin: Free Fe2+ circulates binds transferrin and transports it from small intestine to its storage sites in the
liver and from the liver to the bone marrow for the synthesis of hemoglobin.
Hematocrit: (Hct) this is ratio

of the volume of RBC to Question Alerts!
volume of whole blood. 1) What is the common cause iron deficient anemia is?
2) What type of anemia is the most common in pregnancy?
Serum ferritin: The major iron 3) What is common cause anemia in pregnancy?
storage in protein in blood. 4) In microcytic anemia? MCV and MCHC and serum ferritin decrease.
· Iron storage is measured 5) What test is used to diagnose iron deficient anemia?
by serum ferritin (The
concentration of ferritin is proportional to iron stores).
· Response to oral and parenteral iron occurs at the same rate in normal circumstances.
· Good reticulocyte response indicates active red cell production.
Microcytic (hypochromic) anaemia: Symptoms fatigue or dyspnea on exertion may occur during pregnancy and
in infants. Mainly occurs due to iron deficiency. This is could be due to.
· Low mean cell volume (MCV)
· Impaired heme (protein) synthesis
· Deficiency of serum iron
· Increased total iron binding capacity (TIBC)
· Decreased serum ferritin
Iron supplements
Iron salt Elemental iron TIPS
Ferrous fumarate 33%; 100 mg Fe/300 mg Salt with Highest elemental iron
Ferrous sulfate 20% 60 mg Fe/300 mg
Ferrous gluconate 12% 35 mg Fe/300 mg Highest GI absorption
Polysaccharide-iron (150 mg Fe/150 mg) Iron polysaccharide complex.
complex
Iron dextran inj.
Iron base suspension
Iron supplements are regulated as schedule 2 drugs (behind the counter). Iron containing <30 mg dose is
schedule III (over the counter).
· Food decrease iron absorption thus iron given on empty stomach. Vitamin C (ascorbic acid) enhances non-
heme iron absorption. Whereas polyphenols, and naphtates found in tea and coffee can inhibit non-heme
iron absorption.
· The most common side effect of iron supplement is constipation. Take with food to decrease GI side effects
like nausea and epigastric pain. However, absorption is better on empty stomach. Iron ↓ absorption by
food and antacids, Ca, Mg, Al, levodopa, methyldopa, tetracycline, NaHCO 3 , separate admin by 2 hr.
Separate thyroxin & quinolones and bisphosphonates.
· Separate antacids from iron supplement, because antacids decrease absorption of iron.
· Antidote for iron overdose is deferoxamine.
· Enteric coated and time released iron preparation is intended to reduce SEs but may be ineffective because
of failure to release iron in the gastric environment.
The usual target dose is 105-120 mg/day elemental iron in TID divided.
Parenteral iron is reserved for patients with malabsorption or true intolerance to oral iron therapy.
Food rich in heme iron is liver, lean red meats, seafood (oysters, clams, salmon, sardine, and shrimp).
To begin iron store, replenish may take 6 to 9 mo and can be monitored by measuring serum ferritin.
Megaloblastic Anemia (macrocytic anemia) Mean cell volume is increased. (MCV >100 fL)
· The main source of vitamin B 12 is meat and dairy product.
· Deficiency of vitamin B 12 or folate due to decreased of DNA synthesis. Megaloblastic anemia (large
abnormal form or precursors to RBC). Impaired DNA synthesis usually due to folate or vitamin B 12 deficiency.
· Major causes of megaloblastic anemia include folate or vitamin B 12 deficiency this is due to, chemotherapy
and alcoholism and seniors.
· Drugs that cause megaloblastic anemia are acyclovir, alcohol, antiepileptics (carbamazepine, valproic acid),
methotrexate (dose dependent), nitrofurantoin, oral contraceptives, proguanil, sulfasalazine, trimethoprim
(usually due to worsening of pre existing folate deficiency).
Vitamin B 12 deficiency: Pernicious anemia is a type of autoimmune disorder. This occurs due to deficiency of
intrinsic factor. The intrinsic factor helps in absorption of vitamin B 12 in stomach/ileum.
· Treatment. Parenteral vitamin B 12 supplement. Oral vitamin B 12 supplements are NOT effective in pernicious
anemia due to deficiency of intrinsic factor.
· Schilling Test: To detect pernicious anemia that caused by deficiency of vitamin B 12 . Urinary excretion test is
used to diagnose deficiency of vitamin B 12 caused by decreased vitamin B 12 absorption (lack of intrinsic
factor cause pernicious anemia).
Vitamin B 12 available as oral, im/sc 100 mcg daily for 1 wk or 200 mcg weekly sc/im until Hb normalized. The
daily requirement of cyanocobalamine or hydroxycobalamine 6-9 mcg.
Vitamin B 12 only nutrient need gastric secretion (intrinsic factor) to be absorbed from GIT.
Vitamin B 12 deficiency cause enlargement of bone marrow, RBCs, WBCs and platelets. It effects all proliferating
cells.
Folate Deficiency: The most often occurs in chronic alcoholics, pregnancy and drug induced folic acid deficiency
by drugs such as carbamazepine, phenytoin, sulfonamides, methotrexate, dapsone, and oral contraceptives.
Intestinal malabsorption caused by Giardia lamblia infection.
Folic acid (folate) supplements: The daily requirement is 200 mcg. For therapy 1 mg, 5 mg is used. Folinic acid
(Lucovarin) is synthetic form of folate. The folate available in natural product. In pregnancy prophylaxis folic
acids 1 mg supplements should begin 1 month before conception. Folic acid supplements in pregnancy 5 mg
daily po x 10-12 wks with history of neural tubule (NTD) defect reduce the risk of neural tubule defect. Certain
medical conditions like type 1 DM, seizure in pregnancy therapy with valproic acid, carbamazepine, BMI >35
kg/m2, and malabsorption disorder.
Folic acid: Pteridine nucleus is bonded to nitrogen of p-amino benzoic acid, and p-amino benzoic acid is bonded
to glutamic acid through an amide linkage.
Question Alerts!
H2N N N Pteridyl ring bind with enzyme
O COOH
Pteridyl group PABA analog
N N
N N
H Glutamyl moity analog
Pteridyl group
Methotrexate Trimethoprim/sulfonamides
COOH Sulphamethoxazole
p-amino benzyl
group (PABA)
. Folic acid
Erothropoetins
· Erythropoetins are glycoprotein produced through recombinant DNA technology. Epoetin is same with
natural erythropoietin.
· Therapeutic use of erythropoietins such as Epoetin and Darbepoetin are anemia. associated with cancer
chemotherapy and renal disease. Oprelvekin therapeutic use is thrombocytopenia.
Filgrastim. It is glycoprotein produced through recombinant DNA technology.
Therapeutic. Neutropenia associated with cancer chemotherapy.
Oprelvekin (IL-11). A recombinant DNA produced non-glycosylated polypeptide growth factor.
Drug that cause folic acid deficiency Folic acid dose

Methotrexate 5 mg once week
Carbamazepine in pregnancy 1 to 5 mg daily
Sulfonamide antibiotics As needed
Phenytoin As needed
Dapsone
Normocytic (Normochromic)
· In normocytic anemia MCV is normal.
· Due to acute hemorrhagic or RBC hemolysis due to immune or non-immune mediated.
· Examples of normocytic anemia includes hemolytic anemia, sickle cell anemia, and thalassemia.
Question Alerts!
1) The most common cause folic acid deficiency is diet, drugs and alcoholism.
2) Oral folic acid supplements recommended at childbearing age to decrease neural tubule defects.
3) The common source of vitamin B12 is meat and dairy products. (can be deficient in vegans in
pregnancy).
4) Elderly are commonly deficient in Vitamin B12 and can cause? Megaloblastic .
Hemolytic anemia: The sickle cell anemia disease is an inherited disorder caused by a defect in the gene for
hemoglobin. Sickle cell anemia and thalassemia are hemolytic anemia associated with abnormal hemoglobins.
Due to poor solubility of such abnormal hemoglobin in a reduced state, semicrystalline bodies are formed inside
of RBC. These crystalline bodies are pointed and elongated inside of the cell, and rupture the red blood cells.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency hemolytic anemia: The enzyme G6PD necessary to
maintain the reduce glutathione level (GSH) in red blood cells. This enzyme is necessary to prevent the
hemolysis. The deficiency of this enzyme may cause severe hemolytic anemia in patients with the use of certain
oxidant drugs such as primaquine, sulfonamide, nitrofurantoin, nalidixic acid, probenecid, chloroquine, and
dimercaprol. Glutathione is an antioxidant, which prevents the oxidation of hemoglobin to methemoglobin.
Coombs test: The coombs test is used to distinguish immune mechanism or glucose 6-phospho dehydrogenase
(G6PD) deficiency anemia. In autoimmune hemolytic anemia, coombs test is positive. Example of drugs that
cause false positive coombs test penicillin's, cephalosporin's and methyldopa.
Aplastic anemia: (Total or partial destruction of the bone marrow). Reduced red blood cell and white blood cell
and platelets (thrombocytopenia) counts is decreased. Aplastic anemia is due to inadequate production or
release of myeloid stem cells.
Drugs that cause cell aplasia: Azathioprine, phenytoin, isoniazid, penicillamine, chlorpropamide,
chloramphenicol, erythropoietin, cephalosporin's, penicillin's, tetracycline's, insulin. Methotrexate, isoniazid,
quinidine, quinine, rifampicin, sulphonylureas, methyldopa, mefenamic acid, drugs with oxidant effect on cell
membrane (particularly in G6PD deficiency).
Agranulocytosis
Agranulocytosis is profound reduction of blood cells such as neutrophil, this can cause symptoms like fever,
mouth, throat ulcers and this can lead to prostration and death. Recovery usually 2 to 3 weeks after the drug is
withdrawn. Repeat exposure to causative drug is not recommended due to sensitization.
Drugs that can cause agranulocytosis: Antibiotics (penicillin's, cephalosporin's, cotrimoxazole, chloramphenicol,
sulphonamides), antidepressants (imipramine, clomipramine, desipramine, mianserin), antiepileptics
(carbamazepine, phenytoin), anti-inflammatory (gold, penicillamine, leflunomide, sulfasalazine, NSAIDs),
antipsychotics (chlorpromazine, thioridazine, clozapine), antithyroid drugs (methimazole, propylthiouracil),
captopril, procainamide, and ticlopidine.
Thrombocytopenia (reduced platelets to less than 150 x 109/L). May present as easy bleeding, bruising or
purpura. Prolong bleeding time but INR remains normal. Usually occurs 7 to 10 days after drug administered.
Stimulation of erythropoiesis: The most nutritional deficient anemia (iron, vit.B 12 and FA), have elevated levels
of endogenous erythropoietins.
Pharmacologic stimulation of RBC production using erythropoiesis stimulating agents such as Epoeitin alpha
(Eprex), and Darbepoetin alpha (Aranesp). Used in chronic renal failure, cancer chemotherapy, HIV, hepatitis C
patient receiving ribavarin.
Tips
1. Vit C& E 2. Anemia associated 3. Parietal cells in
chronic renal disease stomach
4. Vit B12 5. Intrinsic factor 6. Skin cell cancer
7. Neurotubule defect 8. thrombocytopenia 9. pernicious anemia
10 megaloblastic anemia 11 iron 12 proximal convoluted tubule (PCT)
13 Methotrexate 14 Sulfa drugs 15 OCP
16 Phenytoin 17 Ferrous gluconate 18 Breathlessness
when lying down
19 Microcytic anemia 20 Sickle cell anemia 21 Folic acid
22 Empty stomach 23 constipation 24 ferrous gluconate
25 diarrhea 26 melena 27 vomiting
28 bronze disease, excessive 29 Deferoxamine 30 Penicillin's
absorption and storage of iron
31 Primaquin 32 Use straw
· Anemia due to deficiency of iron ( )
· Vitamin supplements recommended in elderly ( )
· Intrinsic factors secreted from.. ( )
· Deficiency of intrinsic factors cause.. ( )
· Megaloblastic anemia is due to ( )
· Oprelvekin (interleukin 11) is approved for ( )
· Epoietin alpha are used to ( )
· Deficiency of folic acid supplements in pregnancy can cause ( )
· What is the meaning of melanoma? ( )
· Drug that gives folic acid deficiency ( )
· Vitamin that decrease oxidative degradation ( )
· Anemia in pregnancy is due to ( )
· The most abundant metal in the body ( )
· Site of calcium reabsorption ( )
· Characteristic of both vitamin B 12 and folic acid deficiency ( )
· Which component is required for vitamin B 12 absorption ( )
· What is orthopnea? ( )
· What iron salts have higher GI absorption? ( )
· A patient G6PD deficiency, sulfa drug can cause… ( )
· Moon shaped RBC are seen in.. ( )
· The highest elemental iron present in…( )
· A patient taking methotrexate for cancer treatment, to treat bucal ulcers give…( )
· How do you take iron supplement? ( )
· Common side effect of iron supplement ( )
· Overdose symptoms of iron ( )
· Iron supplement antidote ( )
· Liquid iron is taken by using.. ( )
· What type of anemia can cause G6PD deficiency? ( )
· Drugs that induce hemolytic anemia? ( )
· What is hemochromatosis? ( )
· Excessive bleeding like menorrhea cause the type of anemia --> ( )
www.PharmacyPrep.Com Biochemistry
12
Biochemistry
This chapter reviews basic and essentials of biochemistry topics such as, intermediary metabolism,
carbohydrates, lipids, proteins, enzyme kinetics and porphyrins.
Question Alerts!
· Primary metabolism of glucose (glycolysis, glycogenesis, gluconeogenesis, glycogenolysis).
· Proteins, and aminoacids. Examples of non-essential and essential amino acids (PVT TIM HALL)
· Example of essential fatty acids (Omega 3, 6 and 9).
· Fatty acid oxidation, formation of ketone bodies.
Catabolism: This pathway convert pyruvate (glycolysis), acetyl Co-A (fatty acid degradation), and amino acid to
carbon dioxide and water with release of energy. This cycle is strictly oxygen dependent (aerobic). Catabolism
examples includes glycogenolysis and glycolysis.
Anabolism: This pathway forms amino acid such as aspartate and glutamate from cycle intermediates also the
porphyrin ring of the heme (hemoglobin, myoglobin and cytochrome) is formed from intermediates cycle.
Anabolism examples includes Glycogenesis and gluconeogenesis
Fermentation: The formation of ethanol and lactate from glucose are examples of fermentation.
Carbohydrates
Classification
· Monosaccharide's (C 6 H 12 O 6 ) Examples glucose, Fructose.
· Disaccharides (C 12 H 22 O 11 ) Examples. Sucrose, lactose, and maltose
· Polysaccharides. More than two monosaccharides. Examples. starch, cellulose
· Oligosaccharides. 2 to10 monomers.
Carbohydrate digestion and absorption: Dietary carbohydrate is digested in the mouth and intestine and
absorbed from the small intestine.
Disaccharides (e.g. sucrose, lactose), oligosaccharides (e.g. dextrins), and polysaccharides (e.g. starch) are
cleaved into monosaccharide's (e.g. glucose, fructose).
Question Alerts!
1) What is an end product of anaerobic glycolysis?
2) What is an end product of aerobic glycolysis?
3) Definition of Gluconeogenesis is? glucose formation from non carbohydrate sources.
4) Glucose is stored in liver cells and tissue as?
Carbohydrate metabolism. Glycogenesis, Glycogenolysis, Glycolysis, Gluconeogenesis.
Glycogenesis (glycogen synthesis): Glycogen (glycogenesis is synthesis of glycogen from glucose. This glycogen is
stored in liver and muscle.)
Glycogenolysis (glycogen breakdown): Glucose (glycogenolysis is break down of glycogen to glucose).
Glycolysis: Glucose à CO 2 + H 2 O
Glycolysis is breakdown of glucose to water and carbon dioxide. Glycolysis occurs in the cytosol and
mitochondria in most organs of the body.
Cystosolic process
Aerobic Mitochondria
Glucose Pyruvate --------------------à CO 2 + H 2 O
anaerobic
Lactate
Mitochondrial Process
Pyruvate Oxidative phosphorylation CO 2 + H 2 O
Under anaerobic conditions (absence of O 2 ): Glycolysis involves the conversion of glucose to lactate (lactic acid).
This can occur in cells without mitochondria.
Under aerobic conditions (presence of O 2 ). Glycolysis involves the conversion of glucose to pyruvate (pyruvic
acid), this occurs in mitochondria.
Citric acid cycle (Krebs cycle): This citric acid cycle pathway is also known as the Krebs cycle, which serves both
breakdown and synthetic purposes, and occurs in mitochondrial compartment.
Under aerobic conditions pyruvate enters mitochondria, citric acid (Krebs cycle), where it is completely oxidized
to CO 2 +H 2 O, if the supply of O 2 is insufficient as in actively contracting muscles, pyruvate is converted to lactate.
Mature RBC lack mitochondria, hence there is no Krebs cycle activity. In bacteria use glyoxylate cycle in place of
Krebs cycle.
The glyoxylate cycle, centers on the conversion of acetyl-CoA to succinate for the synthesis of carbohydrates. In
microorganisms, the glyoxylate cycle allows cells to utilize simple carbon compounds as a carbon source when
complex sources such as glucose are not available. The glyoxylate cycle is absent in animals.
The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate
shunt) For most organisms, it takes place in the cytosol. It is a process that generates NADPH and pentoses (5-
carbon surgars). There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH
is generated, and the second is the non-oxidative synthesis of 5-carbon sugars. This pathway is an alternative to
glycolysis. While it does involve oxidation of glucose, its primary role is anabolic rather than catabolic.
Gluconeogenesis
Gluconeogenesis is the synthesis of glucose from non carbohydrate sources.
This process, which occurs primarily in the liver and kidney is the synthesis of glucose from small
noncarbohydrate precursors such as lactate and alanine.
Pyruvate
(Pyruvic Acid)
aerobic
CO2 + H2O
anaerobic
Lactic
(Citric Acid Cycle)
GLYCOLYSIS
Glycogenolysis
GLUCOSE GLYCOGEN
Glycogenesis
Gluconeogenesis
FAT & PROTEIN
Protein metabolism: Amino acid à proteins àpeptides
Amino Acids: The amino acids from proteins are precursor of compounds and energy source like converted to
acetyl CoA. Amino acids degradation eliminated -NH2- group and this converts to NH3 and this may be toxic.
Ammonia eliminates through conversion of urea in animals. The NH2 group is removed by transamination and
oxidative deamination to urea.
Urea cycle
Urea is formed from NH 3 and amino (NH 2 ) group of Asp bicarbonate (HCO 3 ) in urea cycle in liver. Five enzymes
involved in urea cycle, two enzyme are in mitochondria and three enzyme involved in cytosol, thereby the urea
cycle partially occurs in mitochondria and partially in cytosol.
Ammonia (NH 3 ) is produced in all tissue, but the urea cycle is only carried out in liver. Thus, NH 3 must be
transported to liver with non-toxic form. NH 3 is converted to glutamine (Gln) which is not toxic.
20 amino acids are converted to 7 common intermediates. Those are:

Alanine, Cysteine, Glycine, Pyruvate glucogenic and ketogenic
Serine, and Threonine are intermediate
degraded to Pyruvate
α-ketoglutarate Succinyl- Glucogenic intermediate (Form
CoA. Fumarate. glucose)
Oxaloacetate.
Acetyl-CoA. Acetoacetate Ketogenic intermediates (Form
ketone bodies)
Ketogenesis or fatty acids oxidation: It occurs when there is a high rate of fatty acid oxidation in the liver. Three
types of substances betahydroxy butyric acid (80%), acetoacetic acid (20%) and acetone (trace amounts). These
three substances are collectively known as the ketone bodies (also called acetone bodies or acetone). Enzymes
responsible for ketone bodies formation are associated with mitochondria.
Adipose tissue Blood Liver

Lipolysis Beta
oxidiation
Triglycerides → Free Fatty Acids → FFA → Acyl CoA → AcetylCoA→
Ketone bodies
FFA= Free fatty acids
Amino acid biosynthesis products: Amino acids are not only makes proteins and also precursor of severs
products such as neurotransmitters (dopamine, nor epinephrine and epinephrine), hormones, and porphyrines.
Phenylalanine à Tyrosine à levodopa à Dopamineà NorepinephrineàEpinephrine.
· Tyrosine à Thyroxine (thyroid hormone).
· Tyrosine à Catalization by tyrosinase give phenyl 3-4 quinone than polymerization gives Melanin (black skin
pigment).
· Tryptophan à 5-hydroxy tryptophan à 5-hydroxy tryptamine (5HT or serotonin).

· Tryptophan à Niacin
· Histidine àhistidine decarboxylase produce histamine (allergic response)
· Arginine à Nitric oxide (NO)à vasodilator
· Arginine à Urea
· Arginine à Creatinine
· Glutamate à catalization by glutamate decarboxylase produce Gamma amino butyric acid (GABA
neurotransmitter).
Hemoglobin: The hemoglobin is protein consist of globulin + Heme (Porphyrin + Fe2+).

Porphyrines: Amino acids are precursor of prophyrines, and these if are component of heme biosynthesis in
mitochondria and cytosol.
Porphyrins are derived from succinyl-CoA and glycine.
Glycine à Porphyrine ring à Hemoglobin

Glycine is only amino acid without chiral centre.
There are several genetic defects in heme biosynthesis.

· Uroporphyrinogen III cosynthase deficiency, congenital erythropoietic porphyria.
· Red urine, reddish teeth, photosensitive skin, and increased hair growth.
· Ferrochelatase deficiency = erythropoietic porphyria.
Essential amino acids "PVT TIM HALL" Non-essential amino acids

Arginine, Histidine, Isoleucine, Leucine, Lysine, Alanine, asparagine, Cysteine, Glutamate,
Methionine, Phenylalanine, Threonine, Tryptophan, and Glutamine, Glycine, Proline, Serine and
Valine Tyrosine
Arginine although it is produced but most degrade to urea.
Essential amino acids (EAAs) are the components of proteins that make them essential in the diet, of the 20
amino acids in proteins, 10 are essential i.e. required in the diet because they cannot be synthesized in the body.
All humans require eight EAAs. Infants require histidine.
Only essential amino acids taken through diet because they are not synthesized in body in sufficient amounts.
Essential amino acids are “PVT TIMHALL“ phenylalanine, valine, tryptophan, threonine, isoleucine, methionine,
histidine (in infants), arginine (in infants), leucine and lysine.
ACID Base properties of amino acids. At all physiological pH all amino acids have both negative and positive
charge.
When pH = pKa, there is 50% ionized and 50% unionized.
Amino acids can act either as an acid or base and are defined as amphoteric or ampholytes.
Zwitter Ion: Amino acids are ionisable +ve ions as amines, -ve ions as acid. (no net charge)
pKa values indicate the pH at which the group (acid or
amine) is 50% dissociated
All amino acids have two titration curves.
H 3 N(+)-CH 2 -COO(-)
Isoelectric Point. (pl) The pH at which there is no net

charge on the structure.
· At a pH> pl the structure has net negative charge
· At a pH < pl the structure has net positive charge.
· Every structure has one isoelectric point but can be
many pKa values.
Proteins
Proteins composed of amino acids. proteins are
formed by condensation of amino acid. Structural role
within the cell and also within the connective tissue
and skeleton of the whole organism.
Primary structure is linear sequence of amino acids.
Each position occupied by one of 20 amino acids and

linked by peptide bonds.
Secondary structure occurs with hydrogen bonds
forming between the carboxyl portion of amino acids and the amino group of another.
Alpha helix = coiling into a helix
Beta pleated sheet = a folded sheet as polypeptide folds back on itself.
Weak hydrogen bonds between amino and carboxyl groups and different amino acids form at regular intervals,
creating a regular structure. (Not from interactions between variable R-groups).
Not all of a polypeptide forms secondary structure in most proteins.
Tertiary structure: Three-dimensional structure formed by disulfide (S-S)

bonds.
· Interactions between variable R-groups forming.
· Hydrophobic interactions between nonpolar amino acids.
· Hydrogen bonds between polar amino acids
· Ionic bonds between ionic amino acids
· covalent bonds between sulfur containing amino acids.
Producing the three-dimensional folded structure of most proteins.
Quaternary structure: A protein consisting of more than 1 amino acid chain. Separate polypeptide chains that
assemble together. Aggregations of polypeptides form interactions between more than one polypeptide.
Types of proteins: There are 20 amino acids commonly found in proteins, they are linked together by peptide
bonds. Protein is generally classified into three different categories. Simple protein, conjugated protein and
derived protein.
Simple protein is naturally occurring proteins, which upon hydrolysis yield only alpha-amino acids such as
albumins, globulins, prolamines, glutelins, and albuminoids.
Plasma proteins: albumin, globulins.
Conjugated protein: Conjugated proteins are further classified on the nature of their prosthetic groups
polypeptides + non-proteinaceous Example

Polypeptides Metals (chromoprotein) Metalloprotein Iron in hemoglobin, colored group
Polypeptides Vitamins Enzyme cofactors
Polypeptides Nucleic acids Ribosomes
Polypeptides Carbohydrates Glycoproteins, mucins
Polypeptides Lipids Lipoproteins
Polypeptides Phosphoric acid Casein, ovovitellin
Derived proteins: They are formed from primary or conjugated proteins by the actions of the acid, alkali, heat,
water, enzyme or alcohol. They generally differ in physical and chemical properties from the protein they are
derived from. They are subdivided into primary derived protein (denatured protein) or secondary derived
protein.
Denaturation of proteins: A protein denaturation results in the unfolding and disorganization of the protein
structure, which does not occurs by hydrolysis.
Denaturising agents include: heat, organic solvents, mechanical mixing, strong acids or base, detergents and ions
of heavy metals such as lead or mercury. Denatured proteins are insoluble and precipitate. Denaturation
process is often irreversible.
Globular and Fibrous proteins: Globular hemeproteins. A hemeproteins are groups of specialized proteins that
contain heme as tightly bound prosthetic groups. The most common heme proteins in human are haemoglobin
and myglobin. These proteins bind oxygen reversible. These proteins have high affinity to carbon monoxide.
Hemoglobin complex of porphyrin ring and ferrous ion (Fe2+). Transport oxygen in blood only. Carbon dioxides
and carbon monoxide also binds with haemoglobin reversible.
Myoglobin. complex of porphyrin ring and ferrous ion (Fe2+). Transport oxygen in tissues.
Myoglobin present in heart and skeletal muscles.
Hemoglobinopathies. Example of hemoglobinopathies. Sickle cells anemia, haemoglobin C disease (HbC) and the
thalassemia syndrome.
Cell Membrane
· Composed of lipid bylayer with proteins embedded within the membrane
· Lipid bilayer- Phospholipids contain hydrophilic head (outer portions of membrane) and Hydrophobic
chains (inner portions of membrane).
· Membrane proteins functions are either transport mechanisms or as receptors.
· The extrinsic proteins bound to outer and inner portions of membrane, easily removed.
· Intrinsic protein strongly bound in the membrane, cannot easily removed. May extend completely
through the membrane.
Question Alerts!
1) Amino acid are linked with -CONH- peptide bond to form proteins.
2) Caseine? Phosphoprotein
3) Keratin is an albuminoid present in?
4) Sphingosine are?
Enzymes: Protein catalysts substance that alter the rate of a chemical reaction without itself being permanently
changed into another compound.
Fats and Lipids

Fatty Acid Synthesis: Palmitate is an end product. Associated with hexose monophosphate (HMP) Shunt.
Lipids can be divided into five classes according to their chemical structure
Example
Glycolipids Cerebrosides Spingosine + carbohydrate
Gangilosides sphingolipids + sialic acid or choline phosphate
Glycolipids: Also known as cerebrosides. They are isolated from the brain. Upon hydrolysis, they yield fatty
acid, galactose and sphingosine. They are also known as galactolipids due to the presence of galactose, such as
phrenosin, and kerasin. Glycosolipid metabolism takes place in cytoplasm.
Cerebrosides = sphingosine + lipids + sugars
Gangliosides = sphingolipids + sialic acid or choline phosphate
Cerebroside are? They occur in myelin sheath of nerves and white matter of the brain tissues and cellular
membrane. Important for nerve conduction. Cerebroside are glycolipids contain b-galactose (carbohydrate) +
sphingosine + fatty acid but no phosphoric acid.
Sphingolipids contains sphingosine formed from palmitoyl CoA and serine. Sphingosine forms ceramide
backbone when joined to fatty acids. The addition of sugars, sialic acid or choline phosphate forms compounds
such as cerebrosides, gangliosides or sphingomyelin found in nerve tissues and membrane.
Phospholipids: Known as phosphatides. They are esters that consist of fatty acid, phosphoric acids and
nitrogenous compounds, such as lecithin. These are important part of membrane.
Sterols (steroids): The sterols are alcohols structurally related to steroids. They are obtained from plants and
animals such as cholesterol and ergosterol. Steroid structures have 3 cyclohexane rings and 1 cyclopentane ring.
Steroids are converted to compounds such as bile acids, vitamin D and steroidal hormones. They are not broken
down completely.
Waxes: Waxes are defined as high molecular weight esters. They consist of monohydric alcohol and high
molecular weight of fatty acids.
Fixed oils and fats: They are esters of glycerol and fatty acids, such as olive oil. Fixed oils, such as hard, which are
solid at room temperature, are known as fat.
Lipid metabolism: Catabolism triglycerides stored in fat cells are hydrolyzed by hormone, sensitive liposes into 3
fatty acids and glycerol.
· Fatty acids- are broken down by B-oxidation to Acetyl CoA (2Carbon Units), which enter the Kreb cycle to
complete oxidation to CO 2 + H 2 O with release of considerable energy, too rapid breakdown of fatty acids
leads to ketone bodies (Ketogenesis) as in diabetes Mellitus.
· Glycerol enters glycolysis and is oxidizes to pyruvate and via the Krebs cycle to CO 2 + H 2 O.
· Steroids may be converted to other compounds such as bile acids, vitamin D or steroidal hormones, they are
not broken down completely.
Anabolism. Biosynthesis forms fatty acids, steroids and other terpene-related metabolites.
Fatty acids are formed in the cytoplasm and unsaturation occurs in the mitochondria or endoplasmic reticulum.
Human cannot make Linoleic acid.
Terpende compounds- are derived from Acetyl CoA via mevalonate and include: Cholesterol and other steroids,
Fat-soluble vitamins (A,D,E and K) and Bile acids.
Sphigolipids contains sphinegenine formed from palmitoyl CoA and serine. Sphingenine forms ceramide
backbone when joined to fatty acids. The addition of sugars, sialic acid or choline phosphate forms compounds
such as cerebrosides, gangliosides, or sphigomyelin found in nerve tissues and membranes.
Phosphatidyl compounds- such as phosphatidyl choline (Lecithin), phosphatidyl serine or ethandamine are also
important parts of membranes.
Biosynthesis of lipids, regulation by insulin, glucagon, and atherosclerosis: Cholesterol production is regulated by
intracellular cholesterol concentration and by the hormones glucagon and insulin. The rate-limiting step in the
pathway to cholesterol is the conversion of (3-hydroxy-(3)-methylglutaryl-CoA (HMG-CoA) into mevalonate, and
the enzyme that catalyzes this reaction. HMG-CoA reductase is a complex regulatory enzyme whose activity is
modulated over a 100-fold range. It is allosterically inhibited by as yet unidentified derivatives of Cholesterol
OMEGA Double bond

Omega 3 Linolenic acid (alpha linolenic acid) ALA 3
EPA
DHA
Omega 6 Linoleic acid (LA) 2
Gamma linoleic acid (GLA)
Arachidonic acid (ARA)
Omega 9 Oleic acid (OA) 1
and of the key intermediate mevalonate. HMG-CoA reductase is also hormonally regulated. The enzyme exists in
phosphorylated (inactive) and dephosphorylated (active) forms. Glucagon stimulates phosphorylation
(inactivation), and insulin promotes dephosphorylation, activating the enzyme and favoring cholesterol
synthesis.
HMG-CoA reductase
AcetylCoA --> B-hydroxy, B-methyl, glutaryl CoA --> --> --> Mevalonate --> Cholesterol
When the sum of the cholesterol synthesized and obtained in the diet exceeds the amount required for the
synthesis of membranes, bile salts, and steroids, pathological accumulations of cholesterol in blood vessels
(atherosclerotic plaques) resulting in obstruction of blood vessels (atherosclerosis).
Essential fatty acids: Essential fatty acids (EFAs) are required in amounts equalling 6 to 10% of fat intake
(equivalent to 5 to 10 g/day).
15 12 9 1
COOH
Alpha-Linolenic Acid (omega-3)

They include -6 (n-6) fatty acids are linoleic acid (cis-9, 12-octadecadienoic acid) and arachidonic acid (cis-5,
8,11,14-eicosatetraenoic acid) and -3 (n-3) fatty acids are linolenic acid (cis-9, 12, 15-octadecatrienoic acid),
cis-5, 8,11,14,17-eicosapentaenoic acid (EPA), and cis-4,7,10,13,16,19-docosahexaenoic acid (DHA).
EFAs must be provided by the diet. Vegetable oils provide linoleic acid and linolenic acid, and marine fish oils
provide eicosapentaenoic acid and docosahexaenoic acid. However, some EFAs can be made from others. For
example, the body can make arachidonic acid from linoleic acid, and eicosapentaenoic acid (EPA) and
docosahexaenoic (DHA) acid can be partially synthesized from linolenic acid, although fish oil is a more efficient
source.
Fats (worst to best): Trans fats > Saturated > Cholesterol > Monounsaturated > polyunsaturated (Omega).
Essential trace elements

Trace element Complication associated with deficiencies
Copper Wilson’s disease (excess), leucopenia, neutropenia (deficiency), Minks’ (defect of
Cu+).
Penicillamine is used for treatment of Wilson’s disease.
Copper present in: Cytochrome oxidase
Iron The most abundant metal in body.
Deficiency of iron microcytic anemia, and hypochromic anemia
Hemochromatosis (excess of iron).
Enzyme or proteins contain iron: Hemoglobin, myoglobin, Cytochrome oxidase,
myeloperoxidase.
Zinc Children: poor growth, impaired sexual development (deficiency)

Adults: dermatitis (alcoholics).
Selenium Selenium deficiency can cause cardiomyopathy.
Chromium Impaired glucose tolerance
Molybdenum Present in xanthine oxidase enzyme which catalyzes conversion of purine to uric
acid
Iodine Deficiency of iodine may cause goiter disease
Tips
1. linolenic (Omega 3) 2. linoleic (omega 6) 3. Arachidonic
4. Arginine 5. Oxidized hemoglobin 6 HMG Co- Reductase
7. Methylated hemoglobin 8. Prostaglandin 9. Ferrous
10 Hemoglobin 11 Myoglobin 12 Cytochrome oxidase
13 Excessive phenylalanine in 14 Tryptophan
the urine
· Glycolysis; Glucose→(gives H 2 O and CO 2 )
· Glycogenesis; Glucose→( to glycogen formation)
· Glycogenolysis; Glycogen→(breakdown to glucose)
· Gluconeogenesis: fats & proteins→(formation to glucose)
· Nitric oxide (NO) is a derivative of what amino acid? (Arginine)
· The serotonin is produced by? (Tryptophan)
· Phenylketonuria (PKU) is? (Excessive phenylalanine)
· Cholesterol synthesis rate limiting step is catalyzed by… (HMG Co Reductase).
· The most basic amino acid (Arginine).
· Zwitter ionà amino acid with negative and positive charge.
· All amino acids have two titration curve.
· Isoelectric point (pl)à the pH of solution, where an amino acid exhibit zwitter ion
· At pH>pl the structure has net negative charge
· At pH<pl the structure has net positive charge
· Energy storage form in body is? Glycogen
· Starch is composed of? Glucose
· Lecithinsà phospholipids (choline, phosphoric acid, fatty acid and glycerol).
· Sphingolipids (sphingosine) areà Cerebrosides
· End product of anaerobic glycolysis à lactic acid à CO2 + H2O
· End product of aerobic glycolysis à pyruvic acid
· End product of amino acid (proteins) synthesis à Urea
· Krebs cycle occurs in à mitochondria
· End product of purine cycle à uric acid
· Glycolysis occurs in? Cytoplasm and mitochondria.
· Arginin is precursor of?NO
www.PharmacyPrep.Com Nutrition
13
Nutrition
Questions Alerts!
Vitamin A, D, E, K and Vitamin B deficiency symptoms
Active vitamin D3 is hormone
Essential fatty acids (omega 3 and omega 6 and omega 9)
This chapter review the important feature of the vitamins is that they generally cannot be synthesized by
mammalian cells and, therefore, must be supplied in the diet.
Canada's Food Guide, eating well with Canada Food Guide provides evidence base information on nutrient
standards and the prevention of chronic diseases.
· Carbohydrate 55%
· Proteins 30%
· Fats <5%
· Fibre 30 g/day (vegetables, cereals etc)
· Minerals/vitamins
· Water 8 to 10 glass/day
· Salt <2 g/day
Infant’s nutrition:
Reference: Compendium of Therapeutic Minor Ailments (CTMA).
Motherrisk: Provides evidence-based information and guidance about safety or risk to the developing fetus or
infant, of maternal exposure to drugs, chemicals, diseases, radiation and environmental agents.
Infants nutrition
· Formula milk ( cow milk-based formula, lactose free cow milk based formula, soy protein isolate based
formula, hydrolyzed protein formula, amino acid based formula, pre-thickened formulas).
· Iron fortified formula milk (birth to 6 months).
· Vitamin D drops 400 IU/day, and not exceed 1000 IU/day (only in children who are on complete or partial
breast feeding (human milk).
· Cow milk-based formula for higher protein content.
· Most formula milk resemble casein and whey content resemble to human milk.
· The carbohydrate sources of cow milk is lactose.
· Soy protein isolate-based formula: Free of cow milk proteins and lactose. Soy formula contain soy
isoflavones, a phytoestrogen which had been linked to reduced reproductive function.
Nutrition Allergens
· Gluten is present in wheat, rye, oat, soy, cereal.
· Milk à lactose or proteins allergy.
· Peanut à peanut butter, oil, chocolates Vitamins
· Tartrazine à Yellow coloring agent
Water soluble Fat soluble

The vitamins are of Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic Vitamin A
two distinct types. Acid (B5), Pyridoxal, Pyridoxamine, Pyridoxime (B6), Vitamin D
Biotin, Cobalamin (B12) Vitamin E
Folic acid, Ascorbic Acid (C) Vitamin K
Greater possibility of
toxicity because these
All except B12 and folate wash out of body easily. vitamin can accumulate in
Vitamin B deficiencies can lead to diarrhea, dermatitis, adipose.
glossitis. Steathorhea: presents with
Vitamin ADEK.
Fat soluble vitamins absorption depends on.
· The presence of fat substance in GIT
· Hepatic function
· Bile content
Thiamine (Vitamin B 1 ): Derived from a substituted pyrimidine and thiazole, which are coupled by a methylene
bridge. It is rapidly converted to its active form thiamine pyrophosphate (TPP), and thiamine
diphosphotransferase.
Dietary requirements: If the carbohydrate content of the diet is excessive, then thiamine intake should be
required.
Deficiency: Severely reduced capacity of cells to generate energy.
· Beriberi (result from a diet of carbohydrate rich and thiamine deficiency).
· Wernicke-Korsaskoff syndrome (thiamine related disease mostly found in chronic alcoholic’s due to their
poor dietary lifestyle).
· Deficient in chronic alcoholic thereby take vitamin B 1 supplement.
Sources: Legumes, meat, green, fish and egg.
Riboflavin (Vitamin B 2 )
It is a precursor for coenzyme flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The enzyme
that requires FMN or FAD as cofactor are termed flavoproteins.
Riboflavin decomposes when exposed to visible light (photolabile). This characteristic can lead to riboflavin
deficiencies in newborns treated for hyperblirubinemia by phototherapy.
Source: Eggs, milk, meat, and cereals.
Dietary requirements. 1.2 to 1.7 mg/day for normal adults.
Deficiency. It is often seen in chronic alcoholic’s due to their poor dietetic habits.
Sign and symptoms. Glossitis, seborrhea, angular stomatitis, cheilosis and photophobia.
Niacin (Vitamin B 3 )
· Both nicotinic acid and nicotinamide can serve as the dietary source of vitamin B 3
· Niacin is required for the synthesis of the active forms of vitamin B 3 , nicotinamide adenine dinucleotide
(NAD+), and nicotinamide adenine dinucleotide phosphate (NADP+).
NIACIN DEFICIENCIES NIACIN EXCESSIVE (OVER DOSE)
PELLAGRA, DEPRESSION, DIARRHEA FACIAL FLUSHING
HYPERURICEMIA
HYPERGLYCEMIA
+ +
· Both NAD and NADP function as cofactors for numerous dehydrogenases. E.g. lactate and malate
dehydrogenases. NAD and NADP are active substances of vitamin B 3 .
· Niacin is NOT a true vitamin in the strictest definition since it can be derived from amino acid tryptophan.
Dietary requirements: Nicotinic acid (but not nicotinamide) when administered in pharmacological doses of 2 to
4 g/day lowers plasma cholesterol levels and has been shown to be useful therapeutic for hypercholesterolemia.
(¯LDL, TG, and- HDL most effective in increasing HDL).
· Nicotinic acid therapy is not recommended for diabetics or persons who suffer from gout.
· Daily requirement is min 6 mg to 45 mg (adult) min 4 mg (children).
Protein diet restriction like renal disease may cause deficiency of tryptophan. In chronic kidney disease (CKD)
protein-controlled diet (0.8-1g/kg/day) is recommended.
Question Alerts!
1) Vitamin B6 is used as antiemetic or morning sickness.
2) Parkinson's patient taking levodopa, avoid vitamin B6
3) Antiemetic effect occurs at 1 -3 mg (adult), min 0.6 mg (children).
Deficiency: Diet deficiency in niacin (as well as tryptophan) leads to glossitis of the tongue, dermatitis, weight
loss, diarrhea, depression and dementia. (4Ds: Dermatitis, diarrhea, depression and dementia).
· Severe symptoms. Depression, dermatitis and diarrhea, are associated with the condition known as
PELLAGRA.
· Several physiological conditions e.g. Hartnup disease and malignant carcinoid syndrome.
· In Hartnup disease tryptophan absorption is impaired and in malignant carcinoid syndrome tryptophan
metabolism is altered resulting in excess serotonin synthesis.
· Isoniazid therapy to treat tuberculosis may lead to niacin deficiency.
Pantothenic acid (Vitamin B 5 )

· It is formed from b-alanine and pantoic acid.
· Source. Whole grain cereals, legumes, and meat.
· Deficiency. Extremely rare for it is readily available food sources.
Vitamin B 6 (Pyridoxine, Pyridoxal, and Pyridoxamine):

Biologically active form of vitamin B 6 , and pyridoxal phosphate.
Dietary requirements: During pregnancy and lactation the requirement for vitamin B 6 increases approximately
0.6 mg/day. Therefore, vitamin B 6 used for nausea & vomiting in pregnancy.
Drugs (¯) pyridoxal isoniazid for tuberculosis, and penicillamine (for rheumatoid arthritis and cystinurias).
Diclectin (vitamin B 6 + doxylamine) is the drug of choice for the treatment of nausea & vomiting in pregnancy
(morning sickness).
Avoid vitamin B 6 with levodopa because, vitamin B 6 increases the peripheral conversion of levodopa to
dopamine thereby it gives nausea and vomiting.
Deficiency (<10nmol/L): Peripheral neuropathy, convulsions, sideroblastic anemia, and hyperirritability.
Drugs that decrease vitamin B 6 Drug avoid with vitamin B 6

Isoniazid Levodopa
Use Vit. B 6 25 mg daily to prevent peripheral Vit. B 6 concomitant use can increase nausea &
neuropathy vomiting side effect.
Sideroblastic anemia (iron stores in
mitochondria) and this caused by deficiency
VB6 deficiency.
Biotin (Vitamin B7)

Biotin is the cofactor required by enzymes that are involved in carboxylation reactions e.g. acetyl CoA
carboxylase and pyruvate carboxylase.
Source. Found in numerous foods and also is synthesized by intestinal bacteria.
Deficiency. Excessive consumption of raw eggs due to affinity of egg white protein, AVIDIN, for biotin preventing
intestinal absorption of the biotin.
Drugs (¯). Antibiotics (long therapy).
Question Alerts!
1) What vitamin is deficient in elderly?
2) Important for maintenance myeline (its damage cause neurological signs)?
3) It is only nutrient require gastric secretion (intrinsic factor) to be absorbed from GIT
4) What vitamin that is deficient in vigan diet (NO dairy and No meat)?
Cyanocobalamin (Vitamin B 12 )
· Vitamin B 12 composed of a complex tetrapyrrole ring structure (corrin ring) and a cobalt ion in the center.
· It must be hydrolyzed from protein in order to be active. Hydrolysis occurs in the stomach, and carried to
the ileum where it is absorbed.
· B 12 as cofactor during these reactions. Catabolism of fatty acids with an odd number of carbon atoms and
the amino acids valine, isoleucine and threonine.
· Following absorption, the vitamin is transported to the liver in the blood bound to transcobalamin II.
Source. Liver, meat and dairy product.
Deficiency: Megaloblastic anemia. Parietal cells produce intrinsic factors, and are essential for absorption of
vitamin B 12 . Pernicious anemia is a type of megaloblastic anemia resulting from vitamin B 12 deficiency that
develops as a result of lack of intrinsic factor in the stomach leading to malabsorption of the vitamin B 12 . For the
treatment of pernicious anemia use vitamin B 12 parenteral (IM or SC), however do not use oral supplements.
Vitamin B 12 malabsorption has been reported with amino salicylic acid, slow-release potassium iodide,
colchicine, trifluoperazine, ethanol, metformin and oral contraceptives.
All persons over 50 and elderly should get vitamin B 12 supplements of approximately 2 mcg daily. Elderly are
achlorhydric, thereby have decreased vitamin B 12 absorption.
Oral absorption is decreased by anticonvulsants, colchicine, metformin, neomycine and omeprazole.
Question Alerts!
1) Folic acid supplements prevents?
2) OTC folic acid are 1 mg and 3 mg?
3) Deficiency of folic acid can cause megaloblastic anemia.
4) Drugs that deficiency are folate antagonist such as sulfonamides, methotrexate, phenytoin
and carbamazepine.
Folic Acid (vitamin B9)

· A conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid (PABA) that
forms pteroic acid.
· Animal cannot synthesize PABA or attach glutamate residues to pteroic acid, thus requiring folate intake in
the diet.
· Source. Yeast, leafy vegetables, and animal liver.
· Dietary requirements. An increase in the daily intake of folate during pregnancy is needed, and doubled by
the third trimester of pregnancy.
· Deficiency: Folic acid deficiency in pregnancy can cause neural tubule defect.
· Drugs (¯): Anticonvulsants (Carbamazepine, phenytoin), oral contraceptives, methotrexate, 5-flurouracil,
sulfonamides, trimethoprim, sulfasalazine and dapsone.
· Folinic acid (Lucovarin) is synthetic form of folate.
H2N N N
O COOH
N N N
N Glutamyl moity
H
Pteridyl group
COOH
p-amino benzyl
group (PABA)
Folic acid
Pteridyl group analog PABA analog
Methotrexate Timethoprin/sulphamethoxazole
Sulfonamide antibiotics
Question Alerts!
1) What vitamin is deficient in smokers? Smoking severely decreases vitamin C in blood.
2) Women have more vitamin C then men.
3) Essential for the synthesis of “collagen” in connective tissues.
Ascorbic acid (Vitamin C)

Ascorbic acid is derived from glucose via the uronic acid pathway.
Q It is required for maintenance of normal connective tissue “collagen” as well as wound healing.
Hydroxylation of proline residues in collagen is the most important reaction that requires as cofactor.
Source. Citrus fruits, tomatoes, strawberries, broccoli etc.
Deficiency: Scurvy. Cause of vitamin C deficiency is poor diet and increased requirements, especially during
severe stress or trauma (vitamin C is readily absorbed).
Symptoms: Easily bruised skin, muscle fatigue, soft swollen gums, decreases wound healing and hemorrhaging,
osteoporosis, and anemia.
Ascorbic acid is a good water-soluble antioxidant.
· An acidifying agent used to treat overdose of base drugs.
· Vitamin C is deficient in smokers, thereby vitamin C supplements.
Vitamin A
With 3 active molecules. Beta carotene à retinol à retinal à retinoic acid. Beta carotene is a precursor of
vitamin A.
Rhodopsin is active form of vitamin A in vision. (11-cis retinal to 11-trans retinal).
B-carotene consist of 2 molecules of retinal linked at their aldehyde ends, also referred as provitamin A. Very
effective as antioxidant.
Deficiency: night blindness.
Overdose or excessive dose of vitamin A can cause toxicity. Excessive accumulation of vitamin A in the liver can
lead to toxicity, which manifest as bone pain, hepatosplenomegaly, nausea and diarrhea.
1) Rhodopsin is active form of vitamin A! present in Rods

2)Topical tretinoin is? 13-Trans retinoic acid
3)Oral isotretinoin is? 13-Cis retinoic acid
4) Precursor of vitamin A is ? beta Carotenoids .
5) Vitamin A overdose can cause? Toxicity
6) Patient is using Accutane for acne. Wants to buy Vitamin A supplements. What this pharmacist concern?
7) What is laboratory test is monitored patient using isotretinoin? Triglycerides and pregnancy test before
initiating therapy.
Deficiency. Xerophthalmia. Night blindness (11 cis retinoic acid) in rhodopsin pigment.
Early symptoms. Follicular hyperkeratinosis, increased susceptibility to infection, cancer, and anemia equivalent
to iron deficient anemia. Prolonged lack of vitamin A leads to deterioration of the eye tissue through progressive
keratinization of the cornea, known as xerophthalmia. Recommended vitamin A dose 2500 IU (over dose can
cause toxicity).
Isotretinoin (Accutane) is 13-cis retinoic acid and this is oral only. The Tretinoin (Retin-A) is 13-trans retinoic acid
and this is topical (cream, gel and lotion) ("TTT").
Vitamin A deficiency Vitamin A excess

Night blindness Acute toxicity: nausea, vomiting, vertigo,
Xerophthalmia blurred vision.
Immunosuppression Chronic: alopecia, hepatotoxicity, dry skin,
Bitot’s spot hepatomegaly, arthralgia.
Teratogenicity.
Vitamin D
It is a steroid hormone. Active form is 1, 25-dihydroxycholecalciferol (Vitamin D 3 ) is derived from ergo
sterol and from 7-dehydrocholesterol (produced in the skin).
In the skin 7-dehydrocholesterol is converted to cholecalciferol following UV irradiation. Ergocalciferol (D 2 ) is
formed by UV irradiation or ergosterol. Chronic renal failure can cause deficiency of vitamin D 3
Source 1 liter milk fluid/day 400 IU vitamin D 3 . Person with risk for osteoporosis and taking bisphosphonates
should take 800 to 1200 IU vitamin D 3 /day.
Dietary source: Found fish liver oil and eggs. Also produced from skin.
Deficiency: Rickets (weak bones and decaying teeth) in children and osteomalacia in adult
Symptoms: Rickets is characterized by improper mineralization during development of the bones resulting in
soft bones. Osteomalacia is characterized by demineralization of previously formed bone leading to increased
softness and susceptibility to fracture.
Drug (¯): Vitamin D supplement 400-800 IU daily. Excessive intake >1000 IU can lead to hypercalcemia and
then cause nephrolithiasis. >75,000 IU associated with osteoporosis bone resorption.
Newborn (infant) on breast-feeding should get vitamin D drops.
Diet
7-Dehydrocholesterol
Cholecalciferol Skin (ultraviolet)
↓ [ Ca2+] Liver
- PTH 25-OH-cholecalciferol (vit. D 2 ) Storage from of vitamin D
↓ [ phosphate]
(+) Kidney
1, 25-(OH) 2 -cholecalciferol 24, 25-(OH) 2 -cholecalciferol

(Active vit. D 3 ) (Inactive)
1) Vitamin D 3 is steroidal hormone

2) What vitamin is deficiency in chronic renal failure?
3) What is dose of vitamin D for > 50y ? 800 U
4) Infants on breast-feeding have deficiency of? Vitamin D drops
5) Active vitamin D is? D 3 (1,25 dihydroxy cholecalciferol)
6) Deficiency of Vitamin D? Osteomalacia, osteoporosis, rickets.
a-Tocopherol (vitamin E)
Act as a natural antioxidant by scavenging free radicals and molecular oxygen.
Storage site of vitamin E is in adipose tissue (fatty tissues).
Alpha tocopherol is the strongest antioxidant among all tocopherols. Occurs only with fat malabsorption.
Dietary requirements: Increased intake of vitamin E is recommended in premature infants fed formulas that are
low in vitamin as well as in persons consuming a diet high in poly saturated fatty acids.
Symptoms Increase in red blood cell fragility (increase cell integrity)
Deficiency: peripheral neuropathy, retinopathy, skeletal muscle atrophy.
Vitamin K
Vitamin K 1 (Phylloquinone) is derived from green vegetables
Vitamin K 2 (Menaquinone) is produced by intestinal bacteria.
Vitamin K 3 is a synthetic menadione. When vitamin K 3 is administered. It will be alkylated to one of the vitamin
K 2 forms of menaquinone.
Dietary requirements: It maintains normal levels of blood clotting protein factors 2, 7, 9, 10, and protein C, and
protein S.
Deficiency Hemorrhagic syndrome (for infant’s due to less bacterial in colon), bleeding, elevated prothrombin
time.
Drug (¯)Antidote of warfarin
Fat diet Bacteria (colon)
Inactive vitamin K (oxidized)
Liver epoxide reductase warfarin
Active vitamin K (reduced)
1) What vitamins are synthesized by bacteria? Vitamin K 2 (Menaquinone)

2) What are vit. K clotting factors! 2,7, 9, 10 (01972)
3) Vitamin K is essential for prothrombin in liver.
4) Vir. K sources? Dark green vegs and synthesis by intestinal bacteria.
5) Vitamin K? Facilitates normal blood coagulations.
6) Warfarin antidote is? Vit. K
7) Protein C and cofactor protein S? Localize blood clot
8) Some new born babies get the vitamin K injections.
Tips
1. Vitamin D 2 Vit B 12 3 Trans 1, 3 retinoic acid (Vit A)
4. Vitamin D3 5 ileum 6 folic acid
7. neurotubule defect 8 Vitamin A 9 1,25 dihydrocholecalciferol
Vit D 3
10 25 hydroxycholecalciferol
Vitamin D2 in liver
· What vitamin is found only in animal products? ( )
· The most common vitamin deficiency in United States and Canada ( )
· What is precursor acid ? ( )
· Active form of vitamin D is? ( )
· Storage form vitamin D is? ( )
· Supplement of folic acid in early pregnancy reduces? ( )
· Sun exposed skin forms the type of vitamin D is? ( )
· Retin A is topical used for wrinkles and acne is isomer of? ( )
· Vitamin A, D, E, K absorption takes place in what part of gastrointestinal tract? ( )
· All B-complex vitamin washouts from body except? ( )
· what vitamin is essential for the synthesis of nitrogenous bases in DNA and RNA? ( )
· People who do not eat from animal sources have deficiency of? ( )
· what vitamin overdose causes toxicity? ( )
· Chronic alcoholics have deficiency of? ( )
· Chronic renal disease patient should receive vitamin à ( )
Select True/False Statement

· Deficiencies in newborns treated for hyperbilirubinemia by photo therapy; Riboflavin
· Niacin is not a true vitamin. (True/False)
· Niacin; derived from the amino acid tryptophan. (True/False)
· Pellagra is due to deficiency of vitamin B 3 (niacin) (True/False)
· Pernicious anemia is due to vitamin B 12 deficiency. (True/False)
· Pteridine ring structure is present in folic acid (True/False)
· Scurvy is due to deficiency in vitamin C. (True/False)
· b-carotenoids is precursor of vitamin A. (True/False)
· Vitamin D deficiency in children is rickets and in adults is osteomalacia.. (True/False)
· Vitamin D supplements are recommended in newborn that are on breast-feeding. (True/False)
· Folic acid supplements are now recommended for pregnant women to prevent neural tube defects
(spina bifida) in their children. (True/False)
· Omega 6 is Lenoleic acid. (True/False)
· Omega 3 is Lenolenic acid à act like aspirin à Antiplatelets. (True/False)
· Lenolenic acid mainly present in fish and walnut. (True/False)
· Vitamin E toxicity à More than 1100 units (average capsule is 400 units) à Prevent the synthesis
vitamin K coagulant factors (act as anticoagulant). (True/False)
· Severe Vitamin B 1 thiamine deficiency; Beriberi and Wernicke-Korsaskoff syndrome. (True/False)
www.PharmacyPrep.com Microbiology
14
Microbiology
Questions Alerts!
· Endotoxin (pyrogen) of gram negative and exotoxins gives positive organism
· Infective organism of common infections like pneumonia, traveler's diarrhea, toxic shock
syndrome, endocarditis, cellulites, meningitis, syphilis, athlete’s foot and warts.
· Herpes virus: HSV1, HSV2, VZV, Epstein bar, and CMV
· Hepatitis: Hepatitis A, B, C
· Influenza A and B
· HIV transmission
Fungal infections: Candidiasis (yeast), Athletes foot
Bacterial Structure
· Bacteria. Contain cell membrane and cell organs
· Bacterial nucleus: Not surrounded by cell membrane
· Bacterial ribosome are 30S, 50S, and 70S.
· Cell membrane consist of cytochrome and lipids and enzymes.
· Mesosomes convoluted invagination of mitochondria.
· Plasmid (bacterial resistant) is closed circular extra chromosomal DNA.
· Endospore = Metabolically inactive cell. Contain calcium dipicolinate (resistant to sever environmental
conditions).
· External layer = Capsule (resistant to phagocytosis)
· Cell wall = Portion external to cell membrane, osmotic protection.
· Peptidoglycan = Present in cell membrane of Gram –ve & +ve
· Mucopeptide = (protein + carbohydrate) is a peptidoglycan
· Techoic acid = Water-soluble polymer. Present in gram +ve only
· Periplasmic space = Found in gram +ve cell, between cell membrane and outer cell membrane contains
proteins.
· Outer membrane = Present in Gram –ve, phospholipid layer, embedded proteins/porins.
· Lipopolysaccharide present in Gram –ve, consist of lipid A, also known as endotoxin.
· Glycocalyx present in external layer, Slime layer, and adhesive.
· Appendages: Flagella, Pili/Fimbriae, ordinary pili or sex pili.
· Bacterial growth curve lag increase in individual size (many nutrient)
· Exponential or log is increase in population.
· Stationary division. Death (accumulate toxin, decrease in nutrient).
· Obligate aerobe or facultative bacteria: Generate H 2 O 2 , act as bactericidal. Detoxification mechanism by

Superoxide dismutase. Enzyme to neutralize peroxide like hydrogen peroxide (H 2 O 2 ).
· Obligate anaerobe has no superoxide dismutase. (No detoxification mechanism so bacterial death).
· Facultative anaerobe: Most pathogenic bacteria, can shift from fermentative to respiratory metabolism.
· Aerotolerant anaerobes: Similar to facultative, remains fermentative.
· Capnophilic anaerobes: Require CO 2 example bacteroid fragilis (gram –ve anaerobe)
Oxygen requirement
· Obligate aerobe. Generate H 2 O 2 , it is bactericidal. Super oxide dismutase enzyme neutralizes H 2 O 2 .
· Obligate anaerobe. No super oxide dismutase, killed by O 2 .
· Facultative anaerobe: Most pathogenic bacteria can shift from fermentative to respiratory metabolism.
· Aerotolerant anaerobe: Similar to facultative to remains fermentative.
Bacterial shapes: Round (coccus), rod like (bacillus), and spiral (spirochete).
· Virus
§ No cell membrane and consist of DNA or RNA and proteins.
§ Some viruses have single strand of DNA.
· Fungi
§ Cell membrane contain ergosterol layer.
· Protozoa
§ Protozoa are unicellular or single cell organisms and classified based on flagellates.
· Atypical bacteria
§ Mycoplasma: Have no cell wall
§ Rickettsia: Can be transmitted by ticks, mites etc.
§ Chlamydia: Lack ATP synthesis.
· Mycobacterium
§ Cell membrane contain mycolic acid layer.
§ Acid-fast test detects mycobacteria.
Gram +ve Gram –ve

Stain blue or purple Stain red or rose pink
Techoic acid Lipopolysaccharide (LPS) in outer
membrane
Peptidoglycan layer is thick Peptidoglycan layer is thin
Exotoxin is a metabolic product Endotoxin is a metabolic product
Exotoxin is thermolabile (heat Endotoxin is more toxic than
sensitive) destroyed at a temperature exotoxin, destroyed at higher
over 60 oC temperatures.
GRAM +ve and aerobic bacteria GRAM –ve and aerobic bacteria
Gram + ve cocci Gram –ve cocci
Streptococcus (in short Strep.) Catalase (-ve) NISSERIA
S. pyogenes (Group A) N. gonorrhea
S. agalactiae (Group B) N. meningitis
S. bovis (Group D) Moraxella catarrhalis
S. pneumonia (alpha hemolytic) Gram –ve bacilli (rods)
S. viridans (alpha hemolytic) Escherichia coli (E. coli)
Staphylococcus (in short Staph.) Klebsiella pneumonia
S. aureus (Coagulase +ve) Enterobacter spp.
S. saprophyticus Shigella
S. epidermidis Proteus mirabilis
Enterococcus Salmonella
Gram +ve bacilli S. typhi
Cyanobacteria diphtheriae S. enteritidis
Listeria monocytogenes
Bacillus cereus
GRAM +VE and Anaerobic bacteria Vibrio cholerae

Clostridium Pseudomonas aeruginosa
C. perfringens Pasteurella multocida
C. tetani H. influenza
C. difficile H. duceryl
C. botulinum Legionella pneumophila
Yersinia
Y. enterococolitica
Y. pestis
GRAM –VE and Anaerobic bacteria
Fusobacterium
Bacteroides
B. fragilis
(Coagulase +ve) (Coagulase –ve)

Staph. Strep.
Strep categorized as
Non-hemolytic: S. viridians
Hemolytic:
Group A (Strep. pyogenes) (GAS),
Group B (Strep. pneumonia), and
Group C.
Infections causative organisms

GRAM +VE
BACTERIA
Gram +ve Cocci
Found on the skin and in the nose
Boils, and Septicemia
Staphylococcus aureus Food poisoning Penicillin G and Penicillin V,
Catalase positive Wound infections, skin infections cefalexin
impetigo, and cellulitis.
Toxic shock syndrome (TSS)
Tonsillitis, Cellulites, impetigo. Clarithromycin
Beta-hemolytic streptococci
Scarlet fever, Septicemia may cause Erythromycin
e.g. Strep pyogenes (Group A
immune-mediated disease (e.g. Azithromycin
Strep: GAS)
rheumatic fever). Penicillin G, cloxacillin, cefalexin
Amoxicillin
Alpha-hemolytic Pneumonia (CAP), Otitis media, Penicillin G
Streptococcus pneumonia Meningitis, Sinusitis, Pharyngitis Clarithromycin
Azithromycin
Alpha-hemolytic Endocarditis, Amoxicillin, Penicillin G,
Streptococci viridans Dental caries Clindamycin
Instrument contamination.
S. epidermidis
Catheter infections, UTI
Gram +ve bacilli
Erythromycin or penicillin's (to
Diphtheria (disease due to toxin
Corynebacterium diphtheria eliminate carrier state)
production)
Tetracycline
Clostridia sp.
Cl. tetani Tetanus,
Cl. perfringens Gas gangrene Metronidazole, or vancomycin
Cl. botulinum Botulism (NOT used aminoglycosides)
Cl. difficile Pseudo membranous colitis
GRAM -VE
Gram-ve bacilli
Uncomplicated UTI. Sulfa drugs
(cotrimoxazole), nitrofurantoin,
Urinary tract infections (90%), Trimethoprim, fluoroquinolones
E. coli
Traveler's diarrhea (cipro, norfloxacin, Ofloxacin)
Proteus sp.
Wound infection, sepsis. Normal E. coli (diarrhea). Ciprofloxacin,
Klebsiella sp
inhabitants of the gut. and Levofloxacin,
Enteric fever (typhoid), food poisoning

S. typhi Most sp. are animal pathogens (e.g. eggs Chloramphenicol (typhoid)
Salmonella sp etc). S. typhi infects man only, causes Ciprofloxacin
typhoid.
Shigella sp. Dysentery (bloody diarrhea or shigellosis). Ciprofloxacin
Carbapenems (imipenem,
meropenem)
Nosocomial (hospital acquired) and
Aminoglycosides +/-
Pseudomonas aeruginosa opportunist infections (most common S.
Ampicillin,
aureus).
Ceftazidime (3rd)
Clarithromycin,
Pneumonia, meningitis, Otitis media Azithromycin
Hemophilus influenza
Ampicillin, amoxicillin
Tetracycline
GRAM -VE COCCI

Gram -ve cocci
Penicillin G
Meningococcal meningitis +/- shock Ceftriaxone,
Neisseria meningitides
commensal of upper respiratory tract cefuroxime Na
Rifampin
Cefixime
Ceftriaxone im/iv
Neisseria gonorrhea Gonorrhea (STIs). Always pathogenic. Ciprofloxacin
Levofloxacin
Ofloxacin
Chlamydia trachomatis Chlamydia Azithromycin 1g
ACID FAST BACILLI

Acid-fast bacilli
Tuberculosis. (Weight loss, Isoniazid
coughing, fever, sweating, chest Rifampicin
Mycobacterium tuberculosis pain) Streptomycin
The most common cause of Ethambutol
infectious death world-wide. Pyrazinamide
Dapsone
Mycobacterium leprae Leprosy
Rifampicin
SPIROCHETE
Spirochetes
Syphilis (STIs) (genital ulcers or chancres), single
large ulcer, and painless.
Penetrate through broken skin or mucus Penicillin G im inj.
Treponema pallidum
membrane usually through sexual contact. Doxycycline
Genital herpes ulcers are often multiple, small
and painful.
FUNGI
Have thick, ergosterol
containing cell walls and
Fungi grow in humans as budding
yeast cells and slender tubes
(hyphae).
Nystatin
Thrush, mucocutaneous Clotrimazole
Candida albicans (yeast) infection, vulvovaginitis Miconazole
Fluconazole
Clotrimazole, miconazole
Athlete’s foot Tolnaftate (topical)
Tinea pedis
Sporotrichosis or granulomas Abscesses (puss)

Skin, nail and hair infections,
Dermatophytes Ringworm
sometimes acquired from animals.
Allergic reactions, Ubiquitous airborne filamentous
Aspergillus sp.
opportunistic infections fungus
Meningitis in
Cryptococcus neoformans Present in soil and pigeon droppings
immunocompromised
PROTOZOA
Protozoa
Malaria. Four sp. infect man
Chloroquine, Mefloquine
Plasmodia sp via biting female anopheles
Primaquine, Doxycycline
mosquito.
Low grade gastrointestinal
Giardia lamblia Metronidazole
disease: giardiasis.
Amoebic dysentery (are
Entamoeba histolytica infective when swallowed, Metronidazole
and Giardia lamblia traveler’s diarrhea). Severe, Ciprofloxacin
(intestinal protozoa) may invade and spread to the Cotrimoxazole
liver.
VIRUS
DNA viruses
Adenoviruses Conjunctivitis, Sore throat
HSV1 and HSV2 can cause oral
and genital lesions. HSV1
Acyclovir
causes cold sores and
Herpes viruses Famciclovir
Keratoconjunctivitis.
Herpes simplex virus Valacyclovir
VZV can cause (Varicella:
Herpes zoster Foscarnet
chickenpox, zoster: Shingles),
Cytomegalovirus (CMV) Ganciclovir
glandular fever,
Epstein-Bar (EB virus)
Roseola infantum (sixth
disease)
Hepatitis B Transmitted via
Hepadnavirus. Hepatitis B blood and body fluids and Interferon alpha
sexual contact.
Slapped cheek disease, (fifth
Parvovirus: parvovirus B disease, and erythema Can cause aplastic crises
infectious).
HPV vaccine. Implicated in cancer of
Papovaviruses: the cervix.
Warts, cervical cancer,
papillomavirus, Vaccine Gardasil. Quadrivalent human
Hemorrhagic cystitis.
Polyomavirus papillomavirus (types 6, 11, 16, 18)
recombinant vaccine.
Molluscum contagiosum,
Poxviruses
smallpox
RNA VIRUS
RNA viruses
Amantadine, Ribavirin, Rimantadine

Orthomyxoviruses: (influenza A).
Influenza A and B Influenza (flu) Neuraminidase inhibitors. Oseltamivir
(A and B)
Zanamivir (A and B).
Yellow fever, chronic
Flaviviruses. Yellow fever,
hepatitis
Hepatitis C
Paramyxoviruses:
Respiratory infections: Croup
parainfluenza, RSV, Measles May be severe in infants
Measles, mumps
Mumps
Picornaviruses: Enteroviruses Meningitis, Common cold
(e.g. poliovirus), rhinoviruses, (rhinoviruses) Rhino has runny nose
Hepatitis A Hepatitis
Reoviruses: rotavirus Gastroenteritis
Retroviruses: HIV-1, 2 AIDS, T-cell leukemia, NRTI, NNRTI
HTLV I, II Spastic paraparesis Protease inhibitors
Rhabdoviruses: rabies Rabies Zoonotic infection
Togaviruses: Rubella, German measles (Rubella),
Alpha viruses Encephalitis
Tips
Find answers for the tips from the following table:
1. S. pneumonia 2. Chlamydia 3. Pseudomonas aeruginosa
trachomatis
4. S. aureus 5. Treponema pallidum 6. Corynebacterium
7. E.coli 8. H. pylori 9. Borrelia burgdorferi
10. Haemophilus 11 M. catarhalis 12. Group B Strep
influenza
13. Herpes simplex 14. Cytomegalovirus 15. Rubella
virus
16. Herpes zoster 17 Influenza A& B 18. N. meningitis
19. Eptein barr 20 Shigella 21. Compylobacter jejuni
· E. coli is classified as? à

· Beta hemolytic bacteria example is? à
· Toxic shock syndrome is caused by? à
· Lyme disease is caused? à
· Techoic acid is present in? à
· Encephalitis is? à
· Chlamydia neonatrum (C. trachomatis) is? à
· Non-gonococcal infections that cause UTI are?
· Diphtheria is caused by? à
· Syphilis is caused by? à
· Antrax is caused by? à
· What bacteria catalase degrades H 2 O 2 ? à
· Examples of live attenuated vaccines?
· Example of killed vaccine -->
· Viral diarrhea is caused by à
· The most common cause of community acquired pneumonia ( )
· The most common cause of subacute endocarditis ( )
· The causative organism of syphilis ( )
· The causative organism of lyme disease ( )
· Tick born infection is ( )
· The causative organism of bacterial diarrhea ( )
· The causative organism of otitis externa ( )
· The most common pathogen isolated from middle ear ( )
· Infection when aspiration of ear is performed. ( )
· The most common cause of bacterial meningitis ( )
· The most common cause of encephalitis ( )
· Example of gram +ve bacilli ( )
· The causative organism of sinusitis ( )
· The causative organism of nosocomial (hospital) infections ( )
· A types of herpes virus include,( )
· Causative organism of shingles ( )
· Causative organism of seasonal flu ( )
· Inoculum effect?
www.PharmacyPrep.Com Cell and Molecular Biology
15
Cell and Molecular Biology
Questions Alerts!
· Cell and cell organs
· Nucleic acids DNA and RNA bases, nucleotide (phosphate, sugar and base).
· Complimentary base pair (A-T and C-G).
· Transcription (DNA to mRNA) and translation (mRNA to rRNA) in protein synthesis.
· Sequence of protein synthesis DNA --> mRNA --> tRNA --> rRNA --> protein synthesis.
· DNA recombination methods and role of plasmid. What is cDNA?
· What is gene therapy? Antisense technology
· Cloning?
This chapter reviews basics of chromosomes, gene, nucleic acids, DNA structure and functions, replication,
Mutations and recombination. RNA structure and functions, transcription from DNA and translation to
synthesize proteins. Also review topics such as recent development of gene cloning and genetic engineering.
Fig 16.1
Prokaryotic Eukaryotic
Primitive nucleus (no nuclear membrane) Have nucleus
Large single DNA molecule Animal: no cell wall but cell membrane
Contain cell wall (rigid): covalently bonded short No chloroplast
chains of amino acids. Yesà mitochondria
Cell wall contain murein (polysaccharide chain) Plantà yes cell wall
NoàChloroplast Yes chloroplast
Noà mitochondria (cell membrane)
Present in bacteria Present in: Animal, plant, fungi, parasites, algae, and protozoa
Bacteria are reproduced by type of cell division called
binary fission.
Cell organs compose of a number of tissues, and each tissue composes of cells of the same type. The individual
cell is the minimal self-reproducing unit in all-living species. It performs two types of functions, such as performs
chemical reactions necessary to maintain our life.
The second is passes the information for maintaining life to the next generation.
Since the cell is the vehicle for transmission of the genetic information in all living species, it needs to store the
genetic information in the form of double-stranded DNA.
The cell replicates its information by separating the paired DNA strands and using each as a template for
polymerization to make a new DNA strand with a complementary sequence of nucleotides. The same strategy is
used to transcribe portions of the information from DNA into molecules of the closely related polymer, RNA. The
RNA is the intermediate between DNA and protein and it guides the synthesis of protein molecules by the
complex machinery of translation, i.e. the ribosome. The resultant proteins are the main catalysts for almost all
the chemical reactions in the cell. In addition to catalyst, proteins are performing also building block,
transportation, signalling etc.
Cell Organs
Endoplasmic reticulum (ER): It is a series of membranes extending throughout the cytoplasm of eukaryotic cells.
Cytochrome P450 present in endoplasmic reticulum.
· Rough endoplasmic reticulum helps in protein synthesis.
· Smooth endoplasmic reticulum helps in lipid synthesis, this does not contain ribosome.
Golgi body (Golgi apparatus): Series of flattened sacs. Synthesize the cell’s proteins and lipids.
Lysosomes: Drop like sac of enzymes in the cytoplasm. Help digestion within cells.
Mitochondria: (power house of the cell). It releases energy in the form of ATP.
Chloroplast (chlorophyll): It is normally present in green plants. Its principal function is to absorb energy from
the sun.
Vacuoles: They are big, fluid like structures, and may occupy more than 75% of the plant cells.
· Store nutrients as well as toxic wastes.
· Flagella. It exists as single and it helps bacteria to move.
· Cilia. It exists as numerous and it helps bacteria to move.
Centrosomes: Microtubule does cell division or formation spindle apparatus during cell division.
Peroxisomes: Contains enzymes that break down fatty acids and carbohydrates and decomposes hydrogen
peroxides.
Chromosome, Gene and Genome

Genome: The genome of an organism is its complete set of DNA. All the genetic information in an organism is
referred collectively as a “genome”.
Fig 16.2
Chromosome: The 3 billion
bases of the human
genome are not all in one
continuous strand of DNA.
Rather the human genome
is divided into 23 separate
pairs of DNA, called
chromosomes.
Chromosomes are
structures within the cell
nucleus that carries genes.
A chromosome contains a continuous molecule of DNA which is wrapped around histones. Human has 22 pairs
of autosomes and 1 pair of sex chromosome, hence make up to 23 pairs of chromosomes. Autosomes are non-
sex determining chromosomes, while sex chromosomes are X and Y chromosome. Male will have XY sex
chromosomes, whereas female will carry XX sex chromosomes. The collection of chromosomes in an individual
is called karyotype. For example, the typical male karyotype has 22 pairs of autosomes, one X and one Y
chromosome.
Gene Expression
A gene is a DNA sequence that encodes a protein or an RNA molecule. Each chromosome contains many genes,
i.e. the basic physical and functional units of heredity. Each gene exists in the particular position of particular
chromosome. In human genome, it is expected that there are 30,000 to 35,000 genes. In prokaryotic genome,
one gene is corresponding to one protein. Whereas, in eukaryotic genome, one gene can correspond to more
than one protein because of the process called as “alternative splicing”.
What is functional unit of inheritance? Gene
Human genome: Mapping the entire sequence of human gene. The human genome contains approximately
three billion nucleotides bases, which code for approximately 20,000 to 25, 000 protein-coding genes. Most
nucleotides base pairs are identical from person to person, with only 0.1% contributing to individual differences.
A gene is a series of codons that specifies a particular protein.
Nucleotide structure: Consist of 3 units that is base, sugar and phosphate

Nucleic acid (DNA and RNA). Nucleotides are the building blocks of all nucleic acid molecules (such as DNA and
RNA). These structural units consist of three essential components, i.e.
· A pentose sugar deoxyribose (in DNA) and ribose (in RNA).
· Phosphate (bound to the 5’ carbon)
· Base (bound to the 1’ carbon), nitrogenous base.
Forms of Nucleotides
· Nucleotides can have 1, 2, or 3 phosphate groups. Monophosphate nucleotides
· Have only 1 phosphate, which are the building blocks of DNA. Diphosphate nucleotides have 2 phosphate
groups and triphosphate nucleotides have 3 phosphate groups, which are used to transport energy in the
cell.
Nucleoside consist of sugar and base
There are two chemically different nucleic acids deoxyribosenucleic acid (DNA) and Ribonucleic acid (RNA).
Nitrogen Bases
"Pure As Gold" Purine Bases Pyrimidine
Adenine (A) Cytosine (C) CUT Py

Guanine (G) Uracil (U)
Thymine (T)
DNA RNA
Adenine (A) Adenine (A)
Cytosine (C) Cytosine (C)
Guanine (G) Guanine (G)
Thymine (T) Uracil (U)
Double stranded Single stranded
2-Deoxyribose Ribose
Pairs of purine with pyrimidines formed by hydrogen bonds. When strands base pair, they are said to be
complementary.
· A pairs with T (2 hydrogen bonds)
· G pairs with C (3 hydrogen bonds)
· Purine can form 2 hydrogen bonds

· Pyrimidine can form 1 hydrogen bond.
Mutations: If complimentary pair incorrectly compliments other than A to T and G to C can result into
mutations. There are 3 possible mutations like purine to purine, pyrimidine to pyrimidine and purine to
pyrimidine.
Deoxyribonucleic acid (DNA): The molecule that carries the genetic information for most living systems. DNA is
present in chromosomes of eukaryotic organisms, mitochondria, chloroplast of plants. Prokaryotes are single-
celled organisms with no nuclei (e.g. bacteria). They have no distinct nuclear compartment to house their DNA
and therefore the DNA swims within the cells. Eukaryotes, on the other hand, are organisms whose cells contain
a nucleus surrounded by cytoplasm which is contained within a plasma membrane. The DNA locates within the
nucleus. Eukaryotes are organisms with single or multiple cells, for example, plant and animal.
Prokaryotic organism, which does not have nucleus but contain single chromosome. The DNA is present in single
chromosome of prokaryotic organism.
Structure of DNA: Double helix a term often used to describe the configuration of the DNA molecule. The helix
consists of two spiralling strands of nucleotides (a sugar, phosphate and base) joined crosswise by specific paring
of the bases and 3,5-phosphodiester bonds.
Some viruses contain single stranded DNA.

There are proteins associated with DNA present in eukaryotic nucleus, these proteins referred as
nucleoproteins. In prokaryotic this protein present in DNA complex present in neucleoid
The DNA molecule consists of four bases Adenine (A), Cytosine (C), Guanine (G), Thymine (T)
A sugar-phosphate backbone, arranged in two connected strands to form a double helix.
Ribonucleic acid (RNA): Nucleotide structure for RNA. Similar to the nucleotide of DNA, the nucleotide for RNA
also has Phosphate and Base. The only difference is that the nucleotide here has Ribose Sugar, instead of
deoxyribose in the DNA nucleotide. The ribose has an extra OH group at 2’, which is different from the H group
at the same place of deoxyribose. That’s why we call these two different things “ribonucleic Acid” and
“deoxyribonucleic acid” one is with the OH group, which contains the “O” molecule, yet the other one without.
RNA Polymerases: Theses enzyme helps in synthesis of rRNA, tRNA and mRNA.
There are 3 types of types of RNA based on their functions:

· Ribosomal RNA (rRNA): normally synthesize ribosome 80% of total RNA. The rRNA is present in ribosome in
cell.
· Transfer RNA (tRNA): 15% of total RNA. Each tRNA amino acid carries the specific amino acid to the site of
protein synthesis. Each tRNA molecule contain anticodon that generally recognizes all the codons on mRNA.
· Messenger RNA (mRNA): 5% of total RNA. mRNA carries the genetic information from DNA to cytosol for
protein synthesis.
Codon
· The codon are present in the messenger RNA (mRNA), they are Adenine (A), Guanine (G), Cytosine (C),
Uracil (U). These four nucleotide bases produce three base codons. There are 64 different combinations of
these bases. Sixty one of 64 codons normally produce 20 common amino acids. However, there are 3 codons
UAG, UGA and UAA, do not produce amino acids.
· The following codon do not code for amino acids, they are known as stop, nonsense or termination codons.
When one of the codons appears the synthesis of peptide chain is stopped.
Gene transcription and translation process

Translation
Occurs in the cytoplasm Post-translational Modification
at the ribosome and (Including glycosylation,
involves mRNA and tRNA phosphorylation, and
Transcription
sulfatation.
Protein Protein
DNA ---------------------à mRNA à tRNA à rRNA à à à Protein synthesis
Step 1. Transcription à DNA à mRNA

Step 2. Translation à mRNA à tRNA.
Important concept!
1) What step comes first in protein synthesis? Transcription
2) Anticodon is present on? tRNA
3) Making mRNA from DNA is called? Transcription
4) Making DNA from mRNA is? Reverse Transcription
(retrovirus)
5) Antisense therapeutic agents target mRNA
Transcription: This is first step in cell protein synthesis, during this process information from DNA copied to
mRNA.
DNA --à mRNA
Translation: This is second step in cell protein synthesis. The protein synthesis occurs in ribosomes. During
translation information from mRNA is brought to ribosomes by tRNA. This will determine the sequence of amino
acids and protein synthesis.
Reverse transcription: This begins when the viral particles (retrovirus) enters the cytoplasm of target cell.
Reverse transcriptase is an enzyme used to generate complementary DNA (cDNA) from an RNA template.
mRNA à DNA
Complementary DNA (cDNA): DNA synthesized from a messenger RNA rather than from a DNA template. This
type of DNA is used for cloning or as a DNA probes for locating specific genes in DNA hybridization studies.
Introns and exons: The coding region of a eukaryote’s gene is different from that of a prokaryote. For
Eukaryotes, each gene contains introns and exons. Intron is a segment of gene situated between exons. It is not
responsible for the coding of protein. So the introns will be ultimately spliced out of the mRNA. And exon is a
nucleotide sequence in DNA that carries the code for the final mRNA molecule and thus defines the amino acid
sequence during protein synthesis. The process of removing the introns for the mRNA sequence is called RNA
splicing. This process is done with the help of spliceosomes. Though the Introns seem “useless”, it is quite
Amazing that in eukaryotes, each gene can have many introns, and each intron may have thousands of bases.
Introns in eukaryotic genes normally satisfies the GT-AG rule that is intron begins with GT and ends with AG.
Introns can be very long.
Plasmid is extra chromosomal substance of DNA. Plasmids are often used for DNA recombination and cloning.
Restriction Endonuclease Enzymes: Restriction enzymes or restriction endonuclease is a class of bacterial

enzymes. They are DNA cutting enzymes, which recognize certain point, called restriction site, in the double-
stranded DNA with a specific pattern and break the phosphodiester bonds between the nucleotides. Such
process is called digestion. Naturally, restriction enzymes are found and isolated from various bacterial species,
which are used to break foreign DNA to avoid infection or disable the function of the foreign DNA.
Restrictive endonuclease or restriction enzyme. Enzyme that breaks DNA in a specific site in the interior of
molecule.
There are two types of restrictive enzymes lyase and lygase. The lyase split the DNA on specific site. Lygase is the
joining of DNA on specific site.
MOLECULE A MOLECULE B
C-T-A-G…5’ 5’ … G-A-T-C
C-T-A-G-G-A-T-C (Sealed with DNA ligase)
Cloning: Given a piece of DNA X, the process of duplicating it into many pieces is called
Cloning. The basic steps involve:
1) Insert X into a plasmid vector with antibiotic-resistance gene and a recombinant DNA molecule is formed.
Plasmids and DNA fragments must have compatible RE ends for ligation by T4 DNA ligase. A linear product of
DNA and the linearized plasmid is firstly formed, followed by the joining of the opposite ends to form a circular
product.
rDNA. or recombinant DNA molecules formed by lab methods of genetic recombination (molecular cloning).
2) Insert the recombinant into the host cell (usually, E. coli). This makes use of a chemical based transformed
method, where the bacterial cells are made “competent” to take up foreign DNA by treating with calcium ions.
After the recombinant DNA molecules are mixed with the bacteria cells, a brief heat shock is applied to facilitate
uptake of DNA.
3) Grow the host cells in the presence of antibiotic. Note that only cells with antibiotic resistance gene can grow.
Note that when we duplicate the host cell, X is also duplicated.
4) Select those cells contain both the antibiotic-resistance genes and the foreign DNA X. Some cells only contains
plasmid vector but without the foreign DNA due to unsuccessful ligation in step 1. The cells with foreign DNA X
can be correctly selected by the complementation of beta-galactosidase, in which the correct colony will show
blue color.
5) Kill them and extract X.
Genetic Diseases: Hemophilia, sickle cell anemia, cystic fibrosis.
Genetic diseases: Hemophilia

· Hemophilia. This is a genetic disease often associated with X chromosome only. Thus, men can hemophilic
or no hemophilic, however there is no carrier in men.
· Hemophilia causes slow blood clot formation.
· There are two types of hemophilia, that is type A and B.
· Hemophilia type A is due to deficiency of clotting factor 8 (antihemophilic factor).
· Hemophilia type B is due to deficiency of clotting factor 9 (Christmas factor).
Gene therapy
Gene therapy cures genetic diseases such as cystic fibrosis, sickle cell anemia, and hemophilia, in which defected
genes are identified and altered or by altering gene expression to prevent or cure genetic diseases and cancers,
ADA deficiency (adenosine diaminase deficiency), this cause autosomal recessive metabolic disorder that cause
immunodeficiency.
Knockout mice:
A knockout mouse or knock-out mouse is a genetically modified mouse (Mus musculus) in which researchers
have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of
DNA.
Apoptosis: In normal component of cell regulation, the suppressor gene (tumor suppressor gene), arrest
replication of a cell with damaged DNA until the DNA is repaired. Failure to repair DNA and resume normal
function will result in programmed cell death, is referred as apoptosis. In Gene therapy tumor suppressor genes
are inserted into tumor lines to stimulate apoptosis killing the tumor cells.
Necrosis: cell death due to diseases like ischemia etc.
Cirrhosis: liver cell death due to chronic liver disease.
Tips
Select answers from the following table
1. plasmid 2. lygase 3. lyase
4. gene 5. transcription 6. nucleotides
7. Uracil 8. adenine 9. guanine
10 hemophilia 11 genome 12 Intron
13 A DNA sequence of specific
organism.
· How many type of nucleic acid?
· Building blocks of all nucleic acid molecules are the ( )
· Purine bases ( )
· Pyrimidine bases ( )
· Base found only in RNA ( )
· All the genetic information in an organism is referred collectively as…( )
· DNA sequence that encodes a protein or an RNA molecule is a ( )
· This is the first step in cell protein synthesis ( )
· A segment of gene situated between exons is ( )
· Split the DNA on specific site ( )
· Join the DNA on specific site ( )
· Small circular, extra chromosomal DNA molecule called….( )
· This is a genetic disease often associated with X chromosome only. ( )
· Genome (DNA library), complete genetic information of one species.
· What is plasmid, except?
· What is genome? à

· Prokaryotes à Have cell membrane. (True/False)
· Eukaryotic à animal cell have no cell wall (True/False)
· Nucleotide à base + sugar + phosphate (True/False)
· DNA bases à A, C, G and T (True/False)
· RNA bases à A, C, G and U (True/False)
· Complimentary bases à A-T, G-C or A-U (True/False)
· Transcription is à DNA to mRNA (True/False)
· Translation is à mRNA to tRNA (True/False)
· cDNA is à complementary DNA that produced from mRNA (True/False)
· Anticodons are present on à tRNA (True/False)
· The Largest type of RNA? r-RNA (80%) (True/False)
· The Smallest type of RNA? m-RNA (5%) (True/False)
· Single strand DNA is present in? Some virus (True/False)
· RNA polymerase I make? m-RNA (True/False)
· Haploid à single chromosome (True/False)
· Daploid à double chromosome (True/False)
· DNA transferase catalyzes the transfer of various groups such as phosphate and
· amino groups. (True/False)
· DNA hydrolase’s = hydrolyses various substances. (True/False)
· DNA lyase = catalyzes the removal of various functional groups other than the process of hydrolysis.
(True/False)
· DNA isomerase’s = catalyzes various isomerisation's (True/False)
· Reverse transcriptase found in some viruses, they are referred as retrovirus, is an RNA dependent DNA
polymerase. This enzyme requires an RNA template to direct the synthesis of new DNA. Example: NRTI –
Nucleoside reverse transcriptase inhibitors. NNRTI-Non nucleoside reverse transcriptase inhibitors.
· DNA synthesis by reverse transcriptase can be inhibited by AZT (zidovudine). (Anti HIV)
· Retrovirus : Virus that contain reverse transcriptase enzyme. Example. HIV utilizes this enzyme to replicate
their RNA genome. (True/False)
· Hapten is a low molecular weight compounds that act as immunogens after chemically complexing to a
larger molecule or cell surface. (True/False)
www.PharmacyPrep.Com Pharmacogenetics
16
Pharmacogenetics
Pharmacogenetics is study of inherited genetic differences in drug metabolic pathways which can affect
individual responses to drugs.
Pharmacogenetics search for genetic variations that lead to individual differences in drug response. E.g.
examining the influence of carvedilol, a beta blocker gene on blood pressure.
Pharmacogenomics refers to entire spectrum of genes like e.g. study examines the interactions between CYP
450 and beta 1 , beta 2 , and alpha 1 receptors effects on gene that beta blocker effects.
Fast metabolizers: CYP2C19. The presence of a single “17 variant causes a slight increase in CYP2C19 enzyme
activity. CYP2D6 presence of “2 variant gene result in increase in CYP2D6 activity.
CYP2D6
Codeine ----------------------à morphine
Slow metabolizers: No enzyme activity or metabolizes certain medications at a significantly lower rate than
normal.
The pharmacogenomics is integration of pharmacology and genetics. The study of pharmacogenomics allows to
design and develop drugs that are customized to each person’s genetic mark up. The pharmacogenomics also
utilized to study cytochrome enzymes that are responsible for drug interactions.
Genetic variations: A genetic variation occur as either rare defects or polymorphism. Polymorphism are defined
as variations that occur at a frequency of at least 1% in the human population. Example the gene encoding
cytochrome CYP450 enzymes CYP2A6, 2C9, 2C19, 2D6 and 3A4 are polymorphic.
Single nucleotide polymorphism (SNP) occurs when one base pair of nucleotide replaces another. A single base
differences that exist between individual. This is the most common genetic variation in DNA.
To perform pharmacogenetics, the first step is detailed analysis of patient list of single nucleotide
polymorphism.
Defective splicing: In which an internal polypeptide segment is abnormally removed, and the ends of the
remaining polypeptide are joined.
Individual variability in drug therapy: The required daily dose of warfarin for inhibition of thrombosis and
embolism in many disease conditions varies up to 20-30 fold from patient to patient. Therefore frequent blood
www.PharmacyPrep.Com Pharmacogenetics
coagulation testing in patient receiving warfarin therapy is mandated to achieve safe and effective
anticoagulation's.
The clinical use of statins to treat high cholesterol is large and dose dependant variations in drug efficacy and
drug safety. Study suggest the genetic polymorphism of HMG coreductase and drug transporter which regulates
hepatic uptake or efflux of statins and statin metabolites contributes to the variability efficacy and the side
effects of cholesterol lowering drugs.
Tips
· What is pharmacogenetics à
· Pharmacogenetics à
· The study which allows to design and develop drugs that are customized to each person’s genetic mark up (
)
References. Made especially for you: pharmacogenomics and pharmacy practice, CPJ. Jan 2008 vol. 141, No.1
www.pharmacyprep.com
17
Immunology and Immunizations
Questions Alerts!
• Immune cells response (B cell (Humoral immune response) and T cells (Cell mediated immune
response).
• Immunoglobulin's (IgE asthma and anaphylactic reaction)
• Mechanism of inflammation (bacterial infections neutrophil and viral infections lymphocytes).
• Mechanism and Types of hypersensitive reactions (poison ivy, Hashimoto, Montaux test,
anaphylactic reactions).
THE ORGANS OF THE IMMUNE SYSTEM

The organs of the immune system are stationed throughout the body. They are known as lymphoid organs
because they are concerned with the growth, development, and deployment of lymphocytes, white blood cells
(WBC) that are key operatives of the immune system.
LYMPH NODE. Lymph nodes are small, bean-shaped structures that are laced throughout the body along the
lymphatic routes. Lymph nodes contain specialized compartments where immune cells congregate, and where
they can encounter antigens.
B lymphocytes and T lymphocytes are primary cell of specific immune response.
Innate mechanism:
Innate immunity Adaptive immunity
Immediate Delayed (gradual)
Skin, pH, mucus, saliva, temperature interferon’s, Lymphocytes (Bcells and Tcells)
cellular; neutrophils, eosinophil, basophil Lifelong immunity.
Specific to antigen (bacteria, virus etc)
First line of defense Memory cells
No memory cells
Cells are destined to die
Humoral immune response (B cells immunity): Acquired immunity (immunity that is NOT inherited) is humoral
immunity associated with antibody production.
Cells involved in the immune system: White blood cells (WBC) or leukocytes are two types, polymorphonuclear
leukocytes (granulocytes) and mononuclear leukocytes without granules in their cytoplasm. The
polymorphonuclear leukocytes (granulocytes) Neutrophils, Eosinophils and Basophils.
• Normal range of white blood cells are 4000 to 11000/cmm

• Lymphocytes. About 30% of white blood cells are lymphocytes.
• Neutrophils: About 60% of white blood cells are neutrophil.

• Monocytes: About 8% of white blood cells are monocytes
Neutrophil
• Most abundant WBC.
• Not only phagocytes but also granulocytes
• Uses its prepackaged chemicals to degrade the microbes it ingest.
• ↑ in number of neutrophil indicates bacterial infection.
Eosinophils
• Play a role in defending against parasitic worms. They secrete their granule contents onto worms, which
helps kill them.
• ↑ in eosinophils indicates parasite infection and allergies.
Basophils
• Smallest circulating granulocytes.
• Discharge the contents of their granules, releasing a variety of mediators such as histamine, serotonin,
prostaglandins, and leukotriene, which leads to inflammation and other symptoms associated with and
infections.
Question Alert!
1) Mast cells and basophiles produce

histamines!
2) Chromoglycate Na and Nidocromyl are

mast cell stabilizers
3) What cells are not distinguishable?
LYMPHOCYTES: The LYMPHOCYTES are a type of white blood cells found in the blood and many other parts of
the body. TYPES OF LYMPHOCYTES INCLUDE B cells, T cells, Natural killer cells.
B CELLS: B CELLS have thousands of identical antibodies in their membranes that allows them to bind chemically
to a small group of chemically related antigen.
VIRGIN B CELLS: never respond to an antigen since they release into the circulation from bone marrow. Their
membrane antibodies are of the immunoglobulin M and D (Ig M and Ig D).
MEMORY B CELLS: are derived from cell division form another B cell that has responded to an antigen. Their
membrane antibodies are Ig A, Ig E, Ig G
B CELLS (B lymphocytes) mature into plasma cell that secrete antibodies (immunoglobulins), the proteins that
recognize and attach to foreign substances known as antigens. Each type of B cell makes one specific antibody,
which recognizes one specific antigen.
B lymphocytes T Cell Leukocytes (granulocytes)

Bcells Helper T cells (glycoproteins CD4) Neutrophil
Cytotoxic T cell Eosinophil
Natural killer T cell Basophil
Acquired immunity or Humoral immunity Cell immunity
Classes of ANTIBODIES (Immunoglobulins, Ig): Antibodies respond to antigens by latching on to, or binding with,
the antigens. Specific antibodies match specific antigens, fitting together much the way a key fits a lock.
Ig A 10%, Ig A1 and Ig A2, present in saliva, tears, urine, and external body fluids.
Ig D Less than 1%, Functions not well understood.
Ig E 1% located on the cell surface of blood basophils and on connective tissue mast cells to trigger the
secretion of inflammatory mediators from these cells in the presence of specific antigen. IgE mediates
allergic reactions (asthma). Eosinophils and basophils have IgE antibodies receptor. Inflammation is
related to eosinophils.
Serum half is 2 to 3 days. When this bound mast cells, the serum half-life could be several months. Ig E
levels increased in allergic reactions.
Ig G 70%, most common (abundant) of all Ig’s found in all body fluids. This is secreted at the end of primary
immune response and during memory responses. IgG1 to IgG4, and can cross placenta.
IgM 20% IgM is the most potent activator of all immunoglobulins.
IgM1 to IgM2. First immunoglobulin produced in body.
Structure of immunoglobulin's
Ig A
Ig A is secreted during memory response, this accounts for 10% of serum immunoglobulins. It is secreted across
mucosal surfaces into gastrointestinal, respiratory, lachrymal, mammary, and genitourinary secretions. Where
this protects mucosa from colonization of pathogen (Bacteria) and other microorganisms.
SERUM HALF LIFE IS ~ 5 DAYS.
Subclass: IgA1 and IgA2
Ig G
Ig G is the predominant immunoglobulin, (~ 70%). This is secreted at the end of primary immune response and
during memory responses. It diffuses from blood into other extra cellular fluids, particularly in inflamed
vasculatures, and it crosses the placenta to enter the fetal circulation.
SERUM HALF LIFE IS 25-35 DAYS.
Subclass: IgG1 – IgG4
Ig E
This accounts for ~ 1%.
This binds to Ig E receptors located on the cell surface of blood basophils and on connective tissue mast cells to
trigger the secretion of inflammatory mediators from these cells in the presence of specific antigen. IgE mediates
allergic reactions (asthma).
SERUM HALF IS 2 to 3 DAYS. When this bound mast cells, the serum half life could be several months.
Ig M
It does not leave the blood in significant amount because of it PENTAMERIC STRUCTURE (molecular size 900,000
daltons). This accounts for ~ 20%. Serum halflife 9 to 11 days.
IgM is the most potent activator of all immunoglobulins.
Subclass: IgM1 and IgM2
Ig D
Accounts for less than 1%. Has no known function.
The mononuclear leukocytes without granules in their cytoplasm are Monocyte and Lymphocyte (T-lymphocyte:
Helper T-cell, Cytotoxic T-cells and Suppressor T-cells), B-lymphocytes and natural killer cells.
T CELLS
T cells contribute to the immune defenses in two major ways. Some help regulate
the complex workings of the immune system, while others are cytotoxic and directly
contact infected cells and destroy them. Chief among the regulatory t cells are
"helper/inducer" t cells. They are needed to activate many immune cells, including b
cells and other t cells. Another subset of regulatory t cells acts to turn off or suppress
immune cells.
Cytotoxic t cells help rid the body of cells that have been infected by viruses as well
as cells that have been transformed by cancer. They are also responsible for the
rejection of tissue and organ grafts.
THYMUS GLAND: T cell do not enter the circulation directly from bone marrow. But
first enter the thymus gland to mature. Most developing T cells die in thymus gland.
VIRGIN T CELLS: Release from thymus to circulation are virgin T cells.
MEMORY T CELLS: Originate through cell division and responses of other T cells.
T Cell receptors (T antigen receptors)

T Cell have two membrane proteins (alpha and beta or gamma or delta). These proteins define specificity of
each T Cell and several other membrane proteins know as CD3 complex occurs in cell mediate immune response.
TCell mediated immunity:
T cells: Helper T Cells, Cytotoxic T Cells, and Suppressor T Cells
The helper T cells. Glycoproteins. The most T cells can be classified by the presence of membrane glycoproteins.
The helper T cells (TH cells) CD4 and Cytotoxic T cells (CTL) or TC Cells CD8.
Normal CD4 count is from 500 to 1,500 cell per cubic millimeter of
blood. Question Alerts!
CD4 counts indicates?
The helper T cells (TH cells). These can be divided two type TH1 and TH2.
These cells produce lymphokines (cytokines) are small proteins that act
on other cells in autocrine, paracrine, and endocrine manner.
TH1 activate other cells, inhibit antibody production by inhibiting the formation of TH2.
TH2 Activate B cells to divide and produce antibody.
Natural Killer Cells

At least two types of lymphocytes are killer cells; cytotoxic T cells and natural killer cells. Can increase the
number of red blood cells and reduce the need for red blood cell transfusions in patients receiving
chemotherapy; and Oprelvekin can reduce the need for platelet transfusions in patients receiving
chemotherapy.
MONOCYTES are white blood cells that can swallow and digest microscopic organisms and particles in a process
known as phagocytosis. Monocytes can also travel into tissue and become MACROPHAGES, or "big eaters."
BCell Tcell
Humoral immunity or acquired. NOT Adaptive immunity
inherited.
Activate antigen-specific cytotoxic T cells that able induce
apoptosis in body.
Antibodies: Monoclonal antibodies Cytokines (lymphokines): Interferons, interleukins, and colony
stimulating factors
CELLS IN THE IMMUNE SYSTEM SECRETE TWO TYPES OF PROTEINS. ANTIBODIES and CYTOKINES
CYTOKINES (Lymphokines): Soluble protein molecules released by participating and interacting cells in the
adaptive immune system.
Substances produced by some immune system cells to communicate with other cells.
Therapeutic cytokines: Types of cytokines (Lymphokines) includes.
• Interferons
• Interleukins
• Colony stimulating factors (CSF).
Interferon: The interferons are the family of cytokines proteins, important in the immune response. Interferon
Proteins that are secreted by cells when they become infected with virus. Bind to nearby infected cells and
prevent viral infection. This increased resistance of cells to viral infection and slows the spread of disease.
There are three major types of interferon: Interferon’s inhibit viral infections and may have anticancer
properties. Interferons are indicated in hepatitis infections.
• Alpha (leukocyte) interferon is used for treatment of chronic hepatitis B. (peginterferon alpha 2a).
• Contraindications of interferon. Autoimmune disease (SLE, RA), severe depression, or psychosis,
neutropenia, thrombocytopenia and cardiac arrhythmias.
• Interferon Beta (fibroblast) is used for treatment of multiple sclerosis.
• Gamma (immune)
Interleukin (Class I cytokine receptors IL-2, IL-3, IL-7, IL-11, IL-13, IL-15): A type of lymphokine that regulates
the growth and development of white blood cells. The interleukins also called lymphokines. Twelve interleukins
(IL-1 through IL-12) have been identified to date.
Interleukin-3 (hematopoietic growth factor), Oprelvekin (interleukin-11) is a polypeptide growth factor

obtained by recombinant DNA technology. Increases platelet production via stimulation of hematopoietic stem
cells.
Therapeutic use: Chemotherapy related thrombocytopenia.
Side effects: Fluid retention, peripheral edema and dyspnea.
Secreted by Therapeutic use

IL-3 Tcells and stimulate bone marrow and causes cell Thrombocytopenia (hemopoietic growth
proliferation. factor)
IL-11 Tcell. Induce megalocyte proliferation Anemia, (hemopoietic growth factor)
Colony Stimulating factors:

Colony-stimulating factors (CSFs) also called hematopoietic growth factors. Usually do not directly affect tumor
cells rather, they encourage bone marrow stem cells to divide and develop into white blood cells, platelets, and
red blood cells. Bone marrow is critical to the body's immune system because it is the source of all blood cells.
The CSFs stimulation of the immune system may benefit patients undergoing cancer treatment. Some examples
of CSFs and their use in cancer therapy erythropoietin, epoetin alpha, and epoetin beta. Darbepoetin
(chemotherapy induced anemia occurs within weeks to months).
Therapeutic use: Treatment of anemia resulting from chronic renal failure.
Side effects: Increase BP, thus monitor blood pressure.
Granulocyte Colony Stimulating Factors. Produced by recombinant DNA technology. Filgrastim (Pegfilgrastim)
and Sargramostim. These are glycoproteins produced via recombinant DNA technology.
Filgrastim sc 5 mcg/kg QD for 7-10 days given after 24 h of chemotherapy. (Chemotherapy induced neutropenia
can occur within days to weeks).
Therapeutic use: Treatment of chronic and chemotherapy induced neutropenia.
Sargramostim is approved for myeloid reconstitution (in bone marrow transplantation).
Side effects: Skin allergies, respiratory allergies, and cardiovascular allergies.
Filgrastim and pegfilgrastim are contraindicated for patient with
Allergic to E. coli derived proteins.
Cell surface proteins types

Tcell MHC I, CD-2, CD-4, CD-8
Bcell MHC I, MHC II, B7, CD-19, CD-20
NK Cells MHC I, CD-16, CD-56
Macrophages MHC II, CD-14, CD-40
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) proteins: Recognize peptide epitopes (fragment of antigens),
combined with chemical and MHC proteins to produce two major classes of MHC proteins.
Class 1 proteins: Present on all surfaces of body cells.
Class II proteins: Present on specific antigen presenting cell (APC’s).
Hypersensitivity Reactions: Excess, inappropriate and prolonged immune responses that cause damage to
normal tissue.
HYPERSENSITIVE REACTIONS Symptoms/EXAMPLES

IgE mediated type I hypersensitivity reaction Inflammation of upper and lower
Respiratory allergies grass, animal fur, carpet mites. respiratory tract (asthma), GI and skin.
GI allergies. Dairy products, shellfish, and peanut. Atopic dermatitis, pruritis, rhinitis,
Skin allergies, topical drugs (procaine). asthma, and food allergies. Urticaria,
Type I
Intravenous allergiesinsect venoms. eczema.

IgE mediated type I: Anaphylactic reactions. It is treated Approximately 50% of patient with
by epinephrine. (Penicillin's, bee stings, latex, pea nut). asthma secret IgE.
Cytotoxic/anti-body mediated hypersensitivity: Hemolytic anemia and

Type II
Transfusion mismatches, hemolytic anemia, thrombocytopenia are more common.

Rh disease, specific autoimmune diseases Hashimoto Hyper acute graft rejection
thyroiditis, and myasthenia gravis.
Antigen-antibody (IgG/IgM) complex Lymphadenopathy, fever, and rash- first
Non-specific autoimmune disorders such as systemic lupus symptoms.
Type III
erythematous, rheumatoid arthritis. Hepatitis infections, More serious: Glomerulonephritis,

local respiratory form of fungal reactions. Penicillin and vasculitis and lupus, arthralgia and
sulfonamides. arthritis.
Delayed type reactions mediated by cell (T cells). Symptoms of type IV: Contact
Prolong action of protozoa. Mycobacterium dermatitis, microvesicle formation, and
Type IV
Tuberculin test and poison ivy. spongiosis.

Tuberculin (Monteux test) reaction
gives erythema.
Mnemonics.
Hypersensitive reaction is "ACID"

Type 1 - Allergic (<30 min)
Type 2 - Cytotoxic (5-12 hrs)
Type 3 - Immune complex deposition (3-8 hrs)
Type 4 - Delayed (24-48 hrs)
Immunodeficiency's and Immunopathology

Primary. Either hereditary or congenital and at least one basic element to the immune system does not function
properly or is absent
X-linkedaggamaglobinemia (hypogammaglobulinemia). Inherited deficiency in antibody production in which T
cell function is relatively normal but B-cells do not fully mature
Symptoms. Pneumonia, sinusitis, meningitis and septicemia
SCIDS. Heterogenous group of inherited disorders with deficiencies of T cells, B cells and serum Ig. Infections
with opportunistic organisms occur in the 1st few postnatal and survival for longer than one year is rare without
successful bone marrow transplantation.
Secondary Immunodeficiency. Invoke decreased immunologic responsiveness
AIDS: Acquired immune deficiency syndrome is a serious and most fatal condition in which the immune system
breaks down and does not respond normally to anti-infective.
Diagnosis of HIV infection (Positive HIV ELISA antibody test confirmed by western blot). Base line assessment
including CD4 and viral load.
CD4 <500 cell/microL consider initiating antiretroviral therapy.
HIV is retrovirus: The retrovirus stores it genetic information in RNA rather than DNA. When virus enter target
cells. The RNA produce cDNA and this incorporate with host DNA and this reverse pattern of human cell which
does DNA to RNA.
How is HIV transmitted?

• Sexual transmission (contraceptives like condoms can prevent).
• Transfusion of infected blood and blood products.
• Maternal transmission (breast feeding).
• HIV contaminated instruments.
Tests that are used to diagnose HIV infection.

• ELISA (Enzyme linked immunosorbent assay).
• Western blot
• Polymerase chain reaction (PCR assays)
Stages of HIV reproduction

Stage 1. HIV enters a CD cell (helper T cell)
Stage 2. HIV is a retrovirus that its genetic information is stored on single stranded RNA instead of double
stranded DNA found in most organisms. To replicate, HIV uses an enzyme known as reverse transcriptase to
convert its RNA into DNA.
Stage 3. HIV DNA enters the nucleus of the CD4 cell and inserts itself into the cell’s DNA then instructs the cell to
make many copies of the original virus.
Stage 4. With the help of the protease enzyme, new virus particles are assembled. These newly formed viruses
have the cell ready to infect other CD4 cells.
Step 5. Shortly after HIV infection, the CD4 cell count falls sharply in the early stages of HIV infection because the
virus targets and destroys CD4 cells. When the body starts to cope with the infection, the CD4 cell count rises
again. In the advance stage, the rate at which the virus reproduces or rate at which the virus reproduces or
“replicates” surpasses the rate of CD4 cell turnover, making the body more susceptible to a variety of AIDS-
defining illnesses such as Pneumocystis carinii pneumonia (PCP), as the viral load rapidly increases unchecked
and the CD4 cell counts decline these illnesses that signal late stage infection eventually lead to death.
Common opportunistic infections.

1. Tuberculosis, both pulmonary as well as extra pulmonary. This is the one the commonest presentations.
Atypical mycobacteria such as Mycobacterium avium complex (MAC) may also cause infection.
2. Oral candidiasis
3. Esophageal candidiasis
4. Herpes zoster
5. Diarrhea, which may be due to a variety of pathogens
• Protozoal – amoeba, Giardia, isospora belli, cryptosporidium
• Helmints – strongyloids
• Viral – cytomegalovirus
6. Bacterial pneumonia and Pneumocystis carinii pneumonia
7. Toxoplasma encephalitis
8. Cytomegalovirus renitis
Cancers such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma are also seen in these patients
CD4 cells /microL (µL) Type of opportunistic infections

350 M. tuberculosis
275 Kaposis sarcoma
200 Non-Hodgkins lymphoma
100 P. carinii or jerovici (pneumonia)
50 Cytomegalovirus and M. avium intracellular
Autoimmune Disease: When the immune system mistakes self-tissues for non-self and mounts an inappropriate
attack, the result is an autoimmune disease. There are many different autoimmune diseases.
Organ specific autoimmune disorders Non-organ specific autoimmune disorder.

• Rheumatic fever Sjogren syndrome,
• Antithyroid autoimmunities Systemic lupus erythromatus.
• Myxedema (hypo)
• Hashimoto thyroiditis (hypothyroidism)
• Graves disease (hyperthyroidism)
• Myasthenia gravis (weakening of muscles)
• Autoimmune pernicious anemia
• Goodpasture’s syndrome
• Autoimmune hemolytic anemia, thrombocytopenia,
neutropenia, lymphopenia
• Insulin dependent diabetes mellitus (IDDM)-type1
• Multiple sclerosis
Systemic lupus erythromatus: Drugs that provoke lupus like syndrome ("HIPPP MCQ"). Procainamide,
hydralazine, quinidine, methyldopa, isoniazid, phenytoin and chlorpromazine, penicillamine.
Treatment: Mild diseases, low fever, arthritis by NSAIDs severe symptoms by oral methyl prednisone.
Drug induced lupus like syndrome

Drugs such as procainamide, chlorpromazine, and quinidine cause the production of antinuclear antibodies
against the histone dimer H2A-H2B. Hydralazine forms antinuclear antibodies to H1 and the H3-H4 complex.
Drugs that cause drug induced lupus like syndrome usually take months to years before the associated
symptoms occur, whereas flares of SLE due to drugs may occur within hours to days.
Symptoms: butter fly rash over cheeks, erythromatous rash to areas exposed to sunlight. Fever, infections,
arthritis, weight loss, lupus nephritis.
Steven-Johnson’s Syndrome (SJS): Q Rash, HIGH FEVER, skin peeling, and BLISTERS on the mucus membrane. In
Steven Johnson’s syndrome, a person has blistering of mucus membrane, typically in mouth, eyes and vagina.
Patchy areas of rash. SJS can occur in all age groups.
Due to: “SASPAN (Sulfonylurea, anticonvulsant (phenytoin, carbamazepine, valproic acid, lamotrigine,
phenobarbital), sulphonamide, penicillin, Q allopurinol, methotrexate and NSAIDs). Topical sulfa drugs are
contraindicated because it may cause disease like SJS, this disease is life threatening. Treatment of SJS is
cortisone
Immunizations
Questions Alerts!
• Influenza (flu) viral infections. High-risk groups, flu season, and contraindications.
• Hepatitis vaccinations. Hepatitis A and B, and Travelers.
• Storage condition cold chain management. (Biologics and vaccines).
Immunization is the means of providing specific protection against common and damaging pathogens.
Natural Immunity: Occurs when the person is exposed to a live pathogen, develops the disease, and becomes
immune as a result of the primary immune response.
Artificial Immunity.
• Can be induced by vaccine, a substance that contains the antigen. A vaccine stimulates a primary
response against the antigen without causing symptoms of the disease.
• Injection of antibody containing serum or immune globulin, from another person or animal or the
injection of monoclonal antibodies.
• The use of pooled adult human immune globulin (IG) to prevent infections in people with certain
immunodeficiency diseases
• Hepatitis B immunoglobulin (HBIG) to prevent hepatitis B in those not actively immunized with hepatitis
B vaccine.
ACTIVE Immunity
• Antigen enters the body and the body responds by making its own antibodies and B-memory cells.
• Longer lives
PASSIVE IMMUNITY
• Antibodies made in another person or animal enter the body
• Short-lived
Active IMMUNITY Passive IMMUNITY

Slow onset (acting), is used for prophylaxis Fast acting. Short duration of action. Require booster
Long duration of action. dose. Administered im or iv, or sc.
Example: Flu shot takes 2 wk to be effective and Example. Hepatitis B immune globulins (HBIG).
taken annually. Prophylaxis and therapy.
Pneumococcal vaccine takes 2 wks to be Varicella zoster immune globulins (VZIG).
effective. High-risk patient can take every 5 to Rho (D) immune globulin (RhoGAM) prophylaxis for
10 years. Rh +ve fetus by Rh –ve mother receives RhoGAM).
Tetanus vaccine effective for 10 years. Prophylaxis given during pregnancy and after labor
(delivery).
Active or adaptive immunity Onset time

Flu vaccine 2 wks
Dukoral vaccine (E. coli & Cholera) 1 wk
Hepatitis A & B 2-3 wks
Biological used as active immunity: Bacterial vaccine, Bacterial antigen and Toxoids.
Live (attenuated) organism: MMR vaccine (measles, mumps, rubella), and Trivalent oral polio vaccine (TOPV).
Killed (inactivated) organism: Inactivated poliomyelitis vaccine (IPV), Rabies vaccine, Influenza vaccine, Hepatitis
B.
Live (attenuated) vaccine Killed (inactive) vaccines
Measles, Mumps, Rubella Influenza A and B, Salk Polio (injected).
Chicken pox (varicella) Pertussis, Plague, Hepatitis A and B,
Sabine polio (oral), typhoid (oral), Rabies, Typhoid (injected), and cholera.
Tuberculosis (BCG), yellow fever, small pox.
Shingles, Influenza inhaled (intranasal Mist)
Live vaccines are contraindicated in pregnancy and HIV Killed vaccine are can be given in pregnancy and
patients. Avoid with biological response modifiers immunocompromised.
(Infliximab, anakinra, Adalimumab).
Live vaccines are made from live viruses and bacteria. Inactivated vaccines consist of whole microbes
that have been killed by heat or chemicals.
Vaccines with fragments of microorganisms

• immunization for meningococcal meningitis
• Pneumococcal pneumonia
• Hemophilus influenza type B (Hib) or secreted toxins (detoxified)
Toxoid: Diphtheria and tetanus component of the DtaP and Toxoid vaccines.
• Toxoids are detoxified toxins.

• Antigens
• Available precipitated or adsorbed form of Al(OH)3, AlPO4
• Need booster dose q10 yrs (tetanus).
Flu vaccine: Influenza A&B vaccine (seasonal flu).

• Given annual
• Flu season in Canada and in “Northern hemisphere” is Oct to April AND Flu immunization season is Oct to
mid-Nov
High risk group: seniors (>65 yo), asthma, COPD, CVD, diabetics, children >6 mo to 5 yo, healthcare workers, and
pregnancy.
CONTRAINDICATIONS: Children <6 mo. egg allergies (can be given in dr. supervision), and with flu symptoms.
All flu vaccine are killed vaccine, except Flu intranasal Mist.
Hepatitis vaccine:
Hepatitis A & B (Twinrex) >1 yo can use. Give 3 doses,
Fast track 0, 7d, 21d or normally 0, 1mo and 6 mo.
Hepatitis A >1 yo, 2 doses 0, 6 to 12 mo
Traveler’s endemic hepatitis A area.
Children living in endemic states if <1yo use hepatitis A immunoglobulins.
Hepatitis B: 3 doses, can be used children age 0, 1, 6 mo.

Traveler’s to Asia and Africa recommended to take Hep A & B.
• Hepatitis A and B have vaccine.
• Hepatitis A is given anyone over 1 year age
• Hepatitis A transmits by food or oral fecal
• Hepatitis B & C are chronic, transmit by sexual contact, blood transfusion, and drugs abuse (needle sharing).
• Hepatitis B vaccine protects Hepatitis D.
Travellers diarrhea vaccine

• Dukoral oral vaccine (oral powder) for E. coli and Vibrio cholera.
• Adult and children >2y. Give 2 dose po. Administered within 7-42 d after 1st dose and at least 1 wk before
reaching destination.
• Booster 1 dose Q 3 mo if the risk is continuous.
• Taken orally an empty stomach, 1h before or 1h after eating or drinking.
• Effective after one week of 2nd dose.
Pneumococcal vaccine
Two types
Pneumococcal conjugate vaccine (7 valent-PVC7), pediatric vaccine given to infants and toddlers <2 years of age.
Pneumococcal polysaccharide vaccine (23 valent- PPV), adult vaccine given to adult and children over 2 year of
age and adult with certain chronic illness.
Pneumococcal vaccine is indicated because it can reduce common pneumococcus pneumonia infections of
community acquired pneumonia, otitis media, bacterial meningitis, and prevent strep bacteria.
Tips
• Monocytes are white blood cells that can swallow and digest microscopic organisms and particles in a
process known as --> phagocytosis
• Hashimoto is type of hypersensitivity? Type 2
• Graves’s disease is? hyperthyroid
• Type 1 DM is? Autoimmune
• Lupus (SLE) caused by “HIPPP MCQ”? (Hydralazine, INH, Phenytoin, procainamide, penicillamine,
methyldopa, chlorpromazine and quinidine.)
• Mechanism of Systemic Lupus Erythromatus? Antigen antibody complex.
• What does NOT transmit HIV? mosquito
• What is approximate life of HIV patient? 2-3 y
• When does HiV patient’s tuberculosis and PCP (pneumonia) prophylaxis should be initiated? CD4 count 300
and 100.
• If patient get in contact with HIV. What cells are the first response to HIV? CD4 lymphocytes (helper T cells).
www.pharmacyprep.com Biotechnology
18
Biotechnology
Questions Alerts!
· Biotechnology methods for manufacturing pharmaceuticals
· Examples of biological medicines produced by monoclonal antibodies (MAB).
· Chimeric antibodies or Human Antimouse Antibody (HAMA). Examples infliximab, rituximab and
trastuzumab
This chapter is focused on pharmaceutical products that are developed using recent biotechnological methods
and their storage conditions, and role of pharmacist.
Cytokines (lymphokines): Cytokines functions as the messengers of the immune system. They are secreted by
cells of immune system in response to stimulations. Interferon's, interleukins and Colony stimulating factors.
Colony stimulating factors (CSF): Glycoprotein cytokines that promote proliferation, differentiation and
activation of immune cells.
Granulocyte CSF (Filgrastim): This drug stimulates the production of neutrophil within bone marrow. It is
approved for chemotherapy related neutropenia. It does not contain preservatives it should be stored between
2 to 8 °C. It is not frozen.
Granulocyte Macrophage CSF (GM-CSF Sargramostim): This drug is indicated for acceleration of bone marrow
for patient with Non Hodgins lymphoma, acute lymphoblastic leukemia.
Erythropoietins: The Erythropoietin’s are sialic acid containing proteins secreted by kidney in response to
hypoxemia and transported to the bone marrow through the plasma. It resembles an endocrine hormone more
any other cytokines. Erythropoietin’s enhance erythropoiesis by stimulating the formation of proerythroblasts
and release of reticulocytes from bone marrow. Erytopoietins are indicated in anemia, associated with cancer
chemotherapy. It is also used to chronic renal disease associated anemia.
Epoietin alpha once week. It is approved for anemia related to cancer chemotherapy, chronic dialysis, and HIV
therapy.
Darbopoietin alpha: every 3 week.
Interferon’s
· Interferon’s inhibits viral multiplications, thus indicated for viral infections.
· Interferon's are classified into two types, type I interferon’s (alpha and beta), which share the same
molecular receptors, and type II (gamma or immune), which has different receptors.
· Interferon beta 1b-Betaseron, Interferon-beta 1b (IFNB) is effective in the treatment of relapsing remitting
types of multiple sclerosis.
· Interferon alpha 1a is used in the treatment of hepatitis viral infections.
Hepatitis B Interferon alpha (shots) 4 months
Lamivudine oral 1 yr
Adefovir dipivoxil oral 1yr
Hepatitis C Peginfterferon combination with antiviral ribavirin.
Hepatitis A No treatment (infected get well on their own).
Interleukins: synthesized by monocytes, macrophages, and lymphocytes. Interleukins are soluble messengers
between leukocytes.
· IL-1 Intensify the production of collagen, prostaglandin and antibodies. (Pro-inflammatory, stimulates
Tcells.)
· IL-2 Fusion protein (Activates T and B cells)
· IL-3 Hematopoietic growth factor
· IL 11 Operlaveukin. Indicated for thrombocytopenia
associated with cancer chemotherapy. A type of
lymphokines that regulates the growth and
development of platelets.
Hybridoma technology (Biologics)
Bcell (antibody) + Myeloma cell (tumor cell) à Hybrid

cell à large scale culture of hybrid cell
Monoclonal antibodies (MAB): Monoclonal antibodies are

ultra sensitive, hybrid, immune system derived proteins designed to recognise a specific antibodies.
Mouse Chimeric Humanized Human

100% mouse 25% mouse 10% mouse 100% human
Infliximab Trastuzumab Adalimumab
Muromonab Rituximab Omalizumab
Abciximab Daclizumab
Cetuximab
basiliximab
Human antimouse antibody (HAMA) monoclonal antibody also known as chimeric antibodies.
Chimeric antibodies: (antibodies with mixture of mouse and human component) are produced by Human
AntiMouse Antibody (HAMA) technology. Example of drugs produced by 5 chimeric antibodies: Rituximab,
abciximab, infliximab, cetuximab, basiliximab.
Mouse (Murine) antibody: Example of drugs produced by murine antibody. Muromonab (Orthoclone OKT3),
capromab
Humanized antibody: Example of drug produced by 12 Humanized antibodies (Human monoclonal antibodies
from transgenic mice). Trastuzumab, omalizumab, daclizumab.
Transgenic mice: A genetically modified organism, whose genetic information is altered using recombinant DNA
technology.
HUMAN ANTIBODY: Example of drug produced by 4 human antibody: Adalimumab
Immunoadhesin (protein): Example of drug produced by 4 immunoadhesin (protein). Q Etanercept, abatacept.
TNF alpha inh: Adalimumab, Certolizumab, etanercept, golimumab, infliximab.

Eternercept is a fusion protein that works as receptor for TNF (traps and stops TNF).
B cell depletor: Rituximab
T cell co-stimulation inh: Abatacept
Interleukin-1 inh. Anakinra
Interleukin-6 inh. Toclizumab
Type of MAB Drugs examples Therapeutic use

Chimeric Infliximab RA and Crohn's disease
Murine Muromonab
Humanized
Human
Immunoadhesion etanercept
Muromonab (Orthoclone OKT 3 ). Indicated in acute graft rejection in renal, cardiac and hepatic transplant
patients.
Omalizumab. Binds free IgE, reduces binding to mediator releasing cells (mast cells, basophil).
Tumor Necrosis Factor (TNF): It is produced mainly by activated mononuclear phagocytes, have both beneficial
and potentially harmful effects, mediating cytotoxic and inflammatory reactions. Two anti-TNF alpha
monoclonal antibodies are approved for the treatment of rheumatoid arthritis and Crohn's disease.
Infliximab (Remicade): It is chimeric IgG antibody directed against TNF alpha (selectively binds with alpha). It is
approved for Crohn's disease and for the treatment of rheumatoid arthritis. Administered iv. 3 mg/kg, at 0, 2,
and 6 weeks and then every 8 weeks after. Infliximab should be administered with methotrexate to prevent the
formation of antibodies to infliximab.
Etanercept binds with both TNF alpha and beta: The greater risk of etanercept therapy is immuno suppression
and subsequent serious infections.
Recombinant tissue:
The fibrinolytic system enzyme: This enzymes are activated in response to the presence of an intracellular
thrombus or clot. Tissue plasminogen activators (t-PA): (Alteplase, tenecteplase, reteplase). These are
substances produced in small quantities by the inner lining of blood vessels and by the muscular wall of uterus.
Tissue plasminogen activator prevents abnormal blood clotting by converting plasminogen, a component of
blood, the enzyme plasmin. The plasmin is breakdowns to fibrin, the main constituent of blood clot.
Recombinant alteplase (Activase): This drug is indicated in management of acute myocardial infarction.
VIIa
Blood
IX X
Xa X
Prothrombin (II) Thrombin IIa
Thrombolytics:
Streptokinase XII
Urokinase
Alteplase
Fibrinogen
Catalyzation
Plasminogen Plasmin Fibrin (Soluble)
XIIa
Fibrin degradation product Fibrin (insoluble)

Site of injury
Antisense therapy (Antisense Oligonucleotide therapy): Non coding base pairs (stop codons) of messenger
mRNA.
Antisense oligonucleotides are single strand of DNA or RNA that are complementary to chosen sequence. The
antisense RNA protein translation of certain "messenger RNA" by binding to them. The antisense DNA is used to
target a specific complementary RNA.
Antisense drugs inhibit gene expression by oligonucleotide.
Antisense therapy is used to treat b-thalassemia, CMV rhinitis, hemorrhagic fever virus, cancer, HIV-AIDS.
In mechanism of action of antisense therapy act on m-RNA and prevents translation.
Antinuclear Antibody Test (ANA): Detects antibodies against nuclear antigens (DS-DNA, SS-A, SS-B, histone).
Positive results indicate autoimmune disease rheumatoid arthritis.
Clotting Factors: Recombinant antihemophilic factor (rAHF). Indicated for treatment of classical hemophilia A.
The dry concentrate of rAHF should be stored between 2 to 8o C and protect from freezing.
· Hemophilia is a genetic disease. It is categorized as hemophilia A and B.
· Hemophilia A is due to deficiency of clotting factor 8.
· Hemophilia B is due to deficiency of clotting factor 9 (Christmas factor).
Human growth hormone (hGH)

· The pituitary gland secretes human growth hormones (hGH), which stimulates an individual growth.
· Systemic growth hormone. Humatrope, protropin, and somatrem.
Tips
Find answer from the table:
1 Infliximab 2. Etanercept 3 Megakaryoblast
4 Hemophilia A 5. Muromonab-CD 3 6 Erythropoietin's
Orthoclone OKT 3
7 Filgastrim 8. Epoetin alpha
· Indicated for anemia, associated with cancer chemotherapy; also used for chronic renal disease associated
anemia ( )
· What is approved for anemia related to cancer chemotherapy, chronic dialysis and AZT therapy ( )
· What is the treatment of neutropenia associated to chemotherapy ( )
· Precursor of platelets ( )
· What drug binds with both TNF alpha and beta ( )
· What drug is used to treat acute graft rejection in renal, cardiac and hepatic transplant patients ( )
· What it is approved for Crohn’s disease and the treatment of rheumatoid arthritis ( )
· Due to deficiency of clotting factor 8 cause ( )
· Infliximab is indicated for?
· Infliximab is given as?
· What drugs attacks CD 4 + T cells? à
· Muromonab (Orthoclone OKT 3 ) is used to treat?
· 1) Infliximab mechanism?
· 2) Infliximab therapeutic use?
· 3) Infliximab storage conditions?
www.Pharmacyprep.com Toxicology
19
Clinical Toxicology
Questions Alerts!
· Overdose symptoms of benzodiazepines, opioids, acetaminophen, tricyclic antidepressants and iron
supplements.
· Antidotes of overdoses of benzodiazepines, barbiturates, opioids, acetaminophen, ASA, tricyclic
antidepressants, warfarin, heparin, LMWH, digoxin, organophosphates, atropine and iron
supplements.
This chapter focuses in methods of treatment associated with overdose of drugs and overdose
symptoms, chemicals toxicity. Drugs and chemicals that commonly cause toxicities, and the role of the
pharmacist. Antidotes and treatment are presented for specific drug toxicities.
General management of toxicity

· Supportive care (ABCs)
· Gathering information of toxicity
· Evaluating toxic symptoms and refer to doctor or emergencies
· Documentation
Poison prevention strategy: Child proof containers, Constant vigilance, Labelling

· Formulation
GI Decontamination procedures
Decontamination consists of removal of any unabsorbed poison from the patient’s body.
Commonly used methods include gastric lavage or gastric gabage, emesis, ipecac, adsorbent agent
charcoal.
Gastric lavage or gastric gabage: This procedure can be used:

· Good for patient if unconscious
· Depression
· Seizures
· Coma and convulsion
Contraindicated in patients who have ingested Acids, Alkali, Hydrocarbons, Risk of GI perforation.
Emesis (vomiting): This method is used to evacuate GI tract.

Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is 19-1
PharmacyPrep.
Emesis procedure is contraindicated in

· Children less than 6 month
· Strong acid and base
· Depression
· Unconsciousness
· Seizures
· Coma and convulsion
· Extremely rapid onset of action
· Emesis following ingestion
· Sharp objects
· Hydrocarbons, petroleum products
Ipecac induced emesis and gastric lavage primarily removes substances from the stomach and their
efficacy is affected by time and quantity of ingestions. These procedures are more effective if they are
implemented within 1 hour of ingestion.
Syrup of Ipecac is administered within 60 min toxic dose ingestion (later has no benefit)
· Onset of emesis 30 min. Effect could last 2 hours.
· 3 episodes of emesis in 60 min
Dose of Ipecac for adults and children

For emesis adult 15 to 30 ml po with 1 to 2 glass of water
For emesis child 10 to 15 ml po with 1 to 2 glass of water
For expectoration adult 1 to 2 ml po
For expectoration child 0.25 to 0.5 ml po
Decontamination
Activated Charcoal
· This method is preferable method of decontamination.
· Higher the surface area of charcoal higher the adsorption.
· Heating charcoal increase adsorption.
Adsorbent agent: Charcoal is good for drug and chemicals. NOT for (because not adsorbed) methanol,
ethanol, iron, cyanide, ethylene glycol, mercury, organic solvents, potassium, strong acids and bases.
Do not use if patient is vomiting.
Dosage: Adults 25 to 100 g. Children 1 to 12 years 25 to 50 g, 0 to 1 years. 1 g/kg

Charcoal available as colloidal dispersion form.
Bowel Irrigation Method: Osmotic solution of polyethylene glycol (PEG) is used (1-2 liter /hr orally).
Enhancement of elimination. Enhancement of elimination is possible for a number of toxins, including

manipulation of urine pH to accelerate renal excretion of weak acids and bases.
Diuresis: Promotes elimination acids and bases. This can be alkaline and acid diuresis.
PharmacyPrep.
Alkaline Diuresis: Promotes the ionization of weak acids therefore prevents re-absorption by the
kidney, facilitate excretion of weak acids. Example salicylic acids, ASA, phenobarbital, and
barbiturates.
· Dosage of NaHCO 3 (sodium bicarbonate) 50 to 100 mEq
· pH 7.3 to 8.5 (urine)
· Urine output 5 to 7 ml/kg/hr
NaHCO 3 side effects: Metabolic alkalosis, hypernatremia, hyperosmolarity, and fluid overload.
Acid Diuresis: Used to promote elimination of weak bases. Example amphetamines, phencyclidines,
quinidine derivative, and alkaloid drugs.
Dosage: Ascorbic acid 500 mg to 1 g and ammonium chloride 4 g every 2 hours serum electrolyte and
pH should be monitored.
Important characteristics of the toxicology of arsenic, iron, lead and mercury

Metal From Entering Route of Target Organs for Treatment
Body Absorption Toxicity
Lead Inorganic lead Gastrointestinal Hematopoietic Dimercaprol, Edentate
oxides and salts tract, system, CNS, kidneys (EDTA), penicillamine,
respiratory, skin succimer.
(minor)
Tetraethyl lead Skin (major), GIT CNS Seizure control, supportive
Arsenic Inorganic All mucosal Capillaries, GI tract, Dimercaprol succimer,
arsenic salts surfaces hematopoietic penicillamine
system
Arsine gas Inhalation Erythrocytes Supportive
Mercury Elemental Inhalation CNS, kidney Dimercaprol
Inorganic salts GI tract Kidneys, GI tract Penicillamine, dimercaprol
Organic GI tract CNS Supportive
Iron Ferrous sulfate GI tract GI tract, CNS, blood Deferoxamine (chelation)
Agent Toxic features of specific agents

Acetaminophen Mild anorexia, nausea, vomiting, delayed jaundice, hepatic and renal failure
Max dose 4 g/day. Max dose 2 g/day for chronic alcoholic, and hepatic disease
Antidote is acetylcysteine, should be administered within 8 hours of overdose.
Antifreeze Toxic oxidized product of ethylene glycol is oxalic acid.
(ethylene glycol) Renal failure, crystals in urine, anion and osmolar gap, initial CNS excitation and
eye examination normal.
Botulism Dysphagia, dysarthria, ophthalmoplegia, muscle weakness. Incubation period 12
to 36 hours.
Carbon monoxide Coma, metabolic acidosis, retinal hemorrhages
Cyanide Bitter almond odor, seizures, coma, and abnormal ECG.
Gasoline Distinctive odor, coughing, pulmonary infiltrates on x-ray.
Iron Bloody diarrhea, coma, radiopaque material in gut (seen on x-ray), high leukocyte
count, and hyperglycemia.
Lead Abdominal pain, hypertension, seizures, muscle weakness, metallic taste,
PharmacyPrep.
anorexia, encephalopathy, delayed motor neuropathy, changes in renal and

reproductive function. Gray mouth.
LSD Hallucinations, dilated pupils, and hypertension
Mercury Acute renal failure, tremor, salivation, gingivitis, colitis, Erethism (fits of crying,
irrational behaviour), nephritic syndrome.
Methanol Rapid respiration, visual symptoms, osmolar gap, severe metabolic acidosis.
Methanol toxicity gives blindness due to formic acid.
Mushrooms Severe nausea and vomiting 8 hours after ingestion; delayed hepatic and renal
(Amanita failure
phalloides type)
Paraquat Oropharyngeal burning, headache, vomiting, delayed pulmonary fibrosis, and
death
Phencyclidine Coma with eyes open, horizontal and vertical nystagmus, hyperacusis, myoclonic
(PCP) jerks, violent behaviour
Plants Nightshade Hallucinations, mydriasis, seizures (these plants contain atropine-like alkaloids)
family,
jimsonweed
Oleander and Digitalis poisoning
foxglove
Predatory bean Delayed severe gastrointestinal distress, seizures, hemolytic anemia, death
(rosary pea)
Antidote Overdoses Management

Acetylcysteine Acetaminophen overdose. N-acetyl cysteine best given within 8 to 10
hours after overdose
Antivenin Snakes, black widow spiders
Atropine Cholinesterase inhibitors, organophosphates, carbamates.
Bicarbonate, sodium Membrane-depressant cardiotoxic drugs, e.g. Quinidine, TCA and ASA
Deferoxamine Iron salts
Digoxin-specific Fab Digoxin and related cardiac glycosides
antibodies (Digifab)
Esmolol Caffeine, theophylline, metaproterenol
Ethanol Methanol, and ethylene glycol
Flumazenil Benzodiazepines, zolpidem
Glucagon Insulin, beta-blockers
EDTA Lead
Dimercaprol Lead, gold, arsenic, and mercury
Hydroxocobalamin Cyanide
Penicillamine Copper, lead, arsenic, gold and Wilson’s disease
Q. Naloxone Opioid analgesics (blocks mu receptors): reverse respiratory depression.
Oxygen Carbon monoxide
Physostigmine Atropine (muscarinic antagonist), not tricyclic’s
Pralidoxime Organophosphate cholinesterase inhibitors
Sodium thiosulfite Cyanide (Nitroprusside)
Protamine sulfate Heparin/LMWH
Vitamin K (Phytanodione) Warfarin
PharmacyPrep.
Dabigatran idarucizumab
Fomepizol (alcohol Methanol, ethanol, and ethylene glycol
dehydrogenase enzyme
inhibitors)
Drugs cause Mydriasis Drugs that cause miosis

(y = yard) (I = inch)
Antihistamine Opioids
Anticholinergic Cholinergic –clonidine
Tricyclic antidepressants (TCA) Phenothiazines,
Pilocarpine
Tricyclic Antidepressant (TCA): Amitriptyline, Nortriptyline, imipramine, desipramine

· Overdose symptoms. TCA are extremely toxic in overdose. Consultation with poison control center
is recommended.
· Symptoms: Mydriasis and anti-cholinergic symptoms, and severe arrhythmias (AV node)
(cardiopulmonary toxicity) exhibit tachycardia.
· Treatment is symptomatic and supportive; arrhythmias and CNS involvement pose the greatest
risk.
· Toxic dose is variable but in general 10 to 20 mg/kg may result in serious toxicity and may be
lethal.
· In child 50 mg dose can manifest the overdose symptoms.
· There are 15% mortalities with overdose of TCA are reported. Toxicity begins within 2 hours of
ingestion.
· Initial symptoms are mild and can precipitate to CNS and cardiac symptoms. All cases of
accidental, pediatric or adult overdose. Should be monitored at healthcare facility.
Opioids Overdose
· Symptoms: Lethargy, sedation, coma, bradycardia, hypotension, hypoventilation (respiratory
depression), pinpoint pupils (miosis), cool skin, decreased bowel sounds, and flaccid muscles.
· Antidote is naloxone, and full opioid antagonist. Naloxone reverse respiratory depression.
· Opioids withdrawal is treated by methadone (partial agonist mu receptors and NMDA antagonist).
· Naltrexone is used for chronic alcohol withdrawal treatment.
· Naloxone is available IV, IM and SC injection. Recommended dose 0.4 to 2 mg, repeat up to every
2-3 min as needed up to 10 mg
· Naloxone IV onset ~ 2 min; IM & SC onset 2 to 5 min
Acetyl Salicylates (ASA) Overdose

· Overdose more than 4 g/day can cause toxicity.
· Symptoms of overdose. Mild rapid, deep breathing, nausea, vomiting, vertigo, tinnitus, flushing,
sweating, thirst, and tachycardia.
· Severe acid base imbalance, respiratory alkalosis (HYPERVENTILATION), metabolic acidosis, fever,
hemorrhage, excitement, and confusion.
· Acute ASA intoxication can result from single ingestion of 150 mg/kg or more chronic ASA
intoxication also known as salicylism can occur. Salicylism can occur in high dose >100 mg/kg/day
for 2 or more days.
PharmacyPrep.
· Salicylism most often occurs in elderly, being treated for chronic conditions such as rheumatoid
arthritis.
· Treatment. Acute symptoms of overdose should be treated by supportive therapy by removal of
unabsorbed ASA from gut.
Management: Decontamination, alkaline diuresis, Hemodialysis.
· ASA overdose is treated by NaHCO 3 diuresis.
Acetaminophen Overdose
· In adult hepatotoxicity may occur after ingestion of a single dose of more than 7.5 g (adults), or
150 mg/kg (children).
· A dose of 10 g or more is potentially fatal. However, reports have indicated hepatic necrosis with
single dose of 6 g and death occurring with single dose of 13 g.
· Treatment. Consider consultation with poison control centers.
· Consultation with toxicologist is highly recommended in cases of hepatotoxicity associated with
sub-acute acetaminophen overdose.
· Antidote. Acetylcysteine, it is administered within 8 hours of overdose.
Clinical presentation of acute acetaminophen poisoning.

Phase 1. Nausea, vomiting, GI bleeding and abdominal discomfort within 1 to 12 hr after ingestion.
Phase 2. Clinical improvement in seen in 6-24 hr of ingestion.
Phase 3. Metabolic acidosis, renal and hepatic failure, sepsis, pulmonary edema and death.
Ref. Pharmacotherapy, 7th ed.
Iron supplement overdose (Fe fumarate 33%, Fe sulfate 20%, Fe. gluconate 12%)
· Toxicity is based on the amount of elemental iron. Toxicity can occur at 60 mg/kg may cause GI
symptoms.
· Clinical overdose symptoms are nausea, vomiting, and diarrhea, melena, hematemesis may cause
hemodynamic instability.
· If GI symptoms does not occur within 6 hours of ingestion suggest, it is non-toxic dose.
· Management. Decontamination for iron overdose should NOT be treated by charcoal. Treat by
ipecac.
· Antidote is deferoxamine (mechanism: it works by chelation)
Benzodiazepine
Antidote: Flumazenil
Overdose: Sedation, drowsiness, sleepy, confusion and ataxia.
Withdrawal symptoms are insomnia, delirium and anxiety, autonomic hyperactivity (sweating, pulse
>100 bpm), increased hand tremor, and restless.
Symptoms begins within 1-2 d of abrupt discontinuation or 5- 10 d for long acting.
Non-toxic drugs
Amoxicillin
3 g daily maximum
Symptoms. Diarrhea
Nystatin: Nystatin cream or suspension 30 g (3 mU) or more can cause stomach upset.
PharmacyPrep.
Tips
Find answers from the table:

1. Flumazenil 2 N-acetylcysteine 3 Glucagon
4. Latanoprost 5 NaHCO 3 6 Amiodarone
7. Myopathies 8 elevated CK MM 9 Rhabdomyolysis
10 Deferoxamine 11 Glucagon 12 Vitamin K
13 Naloxone 14 Charcoal 15
· Insulin antagonist is? (Glucagon)

· Benzodiazepine antagonist is? (Flumazenil)
· Salicylates overdose may be treated by? (NaHCO 3 )
· Acetaminophen antagonist is? (N-acetylcysteine)
· Naloxone is antidote to treat overdose of (opioids)
· Vitamin K is antidote to treat overdose of (warfarin)
· Protamine sulfate is antidote to treat overdose of (Heparin)
· Aminophylline is an antidote to treat overdose of (Barbiturates)
· Glucagon is used in emergencies to treat symptoms of (severe hypoglycemia).
· Which glaucoma medication causes iris pigmentation? (Latanoprost)
· Organophosphate insect poisoning is treated by (Atropine)
· Carbon monoxide poisoning antidote? pentoxyphiline (first treated with O 2 )
· Rat poison contains? Coumarins
· Toxicity of methyl alcohol is due to? formic acid
· What if someone ingested methyl alcohol? What to do? Give ethanol.
· Iron overdose should NOT be treated by à charcoal
· Benzodiazepine Antidote à flumazenil
· ASA overdose is treated by NaHCO 3 diuresis
· What is ASA antidote? None
· What is acetaminophen antidote? N-acetylcysteine
· N-acetylcysteine should be administered within à 8 hours of overdose of acetaminophen
· Benzodiazepine overdose treatment à Removal of benzodiazepines with lavage, treatment with
charcoal and treatment with flumazenil
· Opioid antidote is à Naloxone
· Pinpoint pupil (miosis) is overdose symptoms of à opioids
· Mydriasis is overdose symptom of à TCAs and anticholinergic
· What drugs overdose can cause proarrhythmias à TCAs
· What is true about charcoal à Increase surface area increase adsorption, decrease impurities on
surface of charcoal increase adsorption? However, increase temperature on surface of charcoal
increase adsorption.
· Deferoxamine is an antidote for iron overdose, which act by à chelation
· Tricyclic antidepressant overdose symptoms àMydriasis and anti cholinergic symptoms, and
severe arrhythmias.
· Opioids overdose symptoms à Lethargy, sedation, coma, bradycardia, hypotension,
hypoventilation, pinpoint pupils (miosis), cool skin, decreased bowel sounds, and flaccid muscles
PharmacyPrep.
· Acetyl salicylates overdose over dose: more than 4 g/day can cause toxicity à Symptoms of
overdose; Mild à rapid, deep breathing, nausea, vomiting, vertigo, tinnitus, flushing, sweating,
thirst, and tachycardia.
PharmacyPrep.
Pharmacyprep.com Pharmacokinetics
20
Pharmacokinetics
Pharmacokinetics describes the
absorption, distribution, metabolism, and Questions Alerts!
excretion of drugs in patients receiving a Common questions in pharmacy exam is to ask!
drug therapy. · Absorption, Distribution, Metabolism and Elimination
(ADME)
A Absorption · Volume of distribution
D Distribution · Renal or hepatic elimination
M Metabolism · Steady state concentrations
E Elimination
important concept of calculating kinetics is find an unknown?
Distribution: Volume of distribution is a hypothetical volume of body fluid that would be required to contain the
entire drug administered so that the concentration will be the same as that found in the blood.
High distribution (blood flow) is in liver, kidney and brain. Skeletal muscle, Adipose tissue has the slowest blood
flow.
V d = A b (amount of drug in the body)/C (concentration of drug in plasma)

Some important formula involving volume of distribution. To calculate volume of distribution
V d = D/C
Units of volume of distribution is mL or L

Plasma concentration = mg/mL
Dose mg
Vd = D
Cp
To calculate initial plasma drug concentration
Cp = D
Vd
To calculate dose
D = Cp x Vd
To calculate loading dose
D L = C ss x V d
C ss = steady state concentration
D L = loading dose
To calculate renal clearance CL R = Kx V d
Vd = d/C p Dose = vd x C p Cp= d/V d

V d (L) D (mg) C p (mg/mL)
? 300 mg 20 mg/mL
3.3L ? 10 mg/L
1.5 L 100 mg ?
Factors affecting drug distribution

RATE (speed) of EXTENT (amount) of
distribution distribution
Membrane (capillary) Lipid Solubility (chemical Lipid soluble higher distribution in adipose tissue.
permeability. structure)
Blood (flow) perfusion pH - pKa (ionization) Ionized drugs = eliminate faster
Non-ionized = stays longer in blood or tissue.
Plasma protein binding Phenytoin, warfarin, digoxin,
Intracellular binding Digoxin
Example: Vancomycin
The factors affect drug excretion into breast milk?

Drug that have higher protein binding have less excretion into breast milk.
The breast milk is more acidic than plasma. So, basic drugs have more excretion into breast milk.
Lipid soluble drug have higher excretion into breast milk.
Protein binding ¯ excretion into breast milk

Acidic drug ¯ excretion into breast milk
Basic drug -excretion into breast milk Because breast milk is acidic.
Lipid solubility - excretion into breast milk
pH High pH
Plasma Protein Binding: The Plasma proteins refer to the proteins present in the plasma binding to drugs. There
are two major types of proteins in the plasma, these are albumin and glycoproteins.
Drug undergoes protein binding with three types of proteins. Acid drugs, albumin (55% major proteins),
albumin has strong affinity to for anionic drugs (weak acids) and hydrophobic drugs. Base drugs bind to alpha
acid glycoproteins, and lipoproteins. Vitamins, steroid etc binds globulins.
Questions Alert!
Clinical importance of drug displacement.
If patient is using class 1 drug tolbutamide, is give class 2 drug sulfonamide antibiotics administered. It
displaces tolbutamide and increase rapid concentration of tolbutamide.
Extensive plasma protein binding will cause more drugs to stay in the central blood compartment. Therefore
drugs that bind strongly to plasma protein tend to have lower volumes of distribution. Drugs that have high
plasma protein binding, less volume of distribution and vice versa.
Drug Interactions by plasma protein displacement

Protein bound drugs Displacing drug
Warfarin (- INR) Clofibrate, phenylbutazone,
Sulphamethaoxazole, sulphinpyrazone
Methotrexate Salicylate
Phenytoin Valproate
Tissue Binding: Generally, high degree of tissue binding implies large V d , e.g. digoxin.
% protein binding = (Total - Unbound) x 100

Total
Drug Absorption Free drug Protein Bound

in blood Drug
Drug effect at Phenytoin 90%

site of action Vancomycin 30%
Warfarin 97%
Plasma proteins concentration that changes with some conditions

Conditions Albumin Alpha 1 acid glycoprotein
Renal Failure ¯ (hypoalbuminemia) -
Hepatic Failure ¯ -
Arthritis - -
BURNS ¯ -
Pregnancy ¯ -
Stress/Trauma ¯ -
CL T = V d x (0.693/t 1/2 )
V d = CL T /K el
Kel = 0.693/t 1/2
Elimination: Removal of drug from the body may occur via a number of routes. The most important routes of
elimination are kidney into urine. Other routes of elimination are bile, intestine, lung or milk in nursing mothers.
Second most important organ for elimination is liver.
Drug Elimination
Metabolism
Bile (hepatic or Liver)
Drug
in Excretion Urine (renal or kidney)
Body
Sweat
Breast milk
Exhaled air
The rate of elimination (disappearance of the active molecule from the blood stream or body) determines the
duration of action for most drugs.
K = elimination rate constant represents the fraction of drug eliminated per unit time.
Mg/min
Kel = 0.693/t 1/2
Renal Clearance: Drugs metabolites or unchanged drugs excreted in urine.

Question Alerts!
Total clearance (CL T ) = CL R + CL NR
CLT = Vd x kel
CL T = total clearance
Vd = CLT/Kel
CL R = renal clearance
CL NR = non-renal clearance (hepatic) CLT = Vd x (0.693/t1/2)
Renal clearance. CL R = CL T -CL NR CLT = F x D/AUC
CL = Dose/AUC
CL T = F x D /AUC, where F= bioavailability, D= dose rate, AUC Area under CL = urinary recovery/AUC
the curve Css = Ro/KVd
CL= Ro/KVd (1-e-kt)
CL T = V d x K el
where V d = volume of distribution and K el is the elimination rate constant
Factors that affect renal clearance: As clearance is decreased half-life increases, changes in Vd cause
proportional changes in half-life.
CL T = V d x (0.693/t 1/2 )
t 1/2 = 0.693 /K el
K el = 0.693/t 1/2 Question Alerts!
What is unit for rate of elimination constant?
CL t = V d x K el Factor that affects on renal clearance?
Half life = 0.693 x Vd/ClT or CLT = Vd x (0.693/t1/2).
Kel = CL/Vd Longer half-life drugs have?
Kel = represents the fraction of drug eliminated per unit
time. The slope of log-scale serum level decay curve correlates to Kel.
Half life = 0.693 x V d /Cl T
Steady-State Drug Plasma Concentration Css = 1/(K el x V d ) x (FxD)/T
Urine pH
Urine pH affects drug excretion
Weak acidic drugs: alkalinize urine to excrete more drug (HA <-> A + H+ -)
Weak base drugs: acidity urine to excrete more drugs (BOH <-> B+ + OH+ ¯)
Hepatic Clearance: The volume of drug containing plasma that is cleared by liver per unit time. Measured
indirectly as difference between total body clearance and renal clearance.
Cl H = Cl T - Cl R
Cl H = Hepatic clearance
Or Cl H = Q ER
Q = product of blood flow
ER = [C a -C v ]/Ca
C a = arterial plasma drug concentration liver

C v = venous plasma drug concentration in liver
Values for ER range from 0 to 1, if the ER is 0 then no drug removed by liver, if 0.8 then 80% of incoming drug is
removed by the plasma profuse in liver.
Hepatic clearance depends on; Blood flow: Blood flow to the liver is approximately 1.5 L/min. Exercise, disease
or drugs may alter blood flow.
Intrinsic clearance (Cl int ): The ability of the liver to remove the drug independent of the blood flow (mixed-
functions oxidase enzymes biotransform drugs). Intrinsic clearance primarily occurs because of ability of
metabolizing enzymes (mixed function oxidase) as they metabolize the drugs they enter in liver.
Steady state concentrations C ss Plasma concentration at steady state (C ss ). Under the steady state conditions.
The fraction of drug absorbed equals to the fraction of drug eliminated in the body.
ko
Plasma drug
Cmax SS
200 Css = ko = rate of infusion
(peak) CL
CL = total body clearance
concentration (mcg/ml)
Cav DL = loading dose

180 SS DL = Css x Vd
DM = maintenance dose
Vd = volume of distribution
DM = Css x CL x t
t = dosing intervals
160 CminSS
(trough)
140
Important concept!
1) Rate in = Rate out means rate of absorption is equal to rate of eliminations.
2) How many half lives? takes to reach steady state concentration? 5-7 half life
Relationship between pharmacokinetic factors and eliminations. The relationship between steady state plasma
concentration and volume of distribution can be obtained by
C ss = R/(V d xK)
R = rate of infusion
K = elimination constant
V d = volume of distribution
C ss = R/V d x (0.693/t 1/2 )
C ss = R/CL
The relationship between loading dose and volume of distribution:

D L = C ss x V d
D L = loading dose
The relationship between body clearance and average plasma concentration:

C av = F x D o / CL T x t
t = dosing interval, C av = average plasma concentration, CL T = total clearance

The relationship between AUC and volume of distribution can be obtained by intravenous F is = 1
The relation between steady state plasma concentration and volume of distribution can be obtained by: C ss =
R/V d x K
R = rate of infusion
K = elimination constant
V d = volume of distribution
Important concept! Over 95% of the drug lost or eliminated in 5 half-lives. Which is typically considered to be
the completion of process.
Rate of infusion of drug is equal to the drug’s # of half life % remained % eliminated
elimination from body at Css. 1 50 50
ko 2 25 75
Css = 3 12.5 87.5
VdK 4 6.25 93.75
5 3.125 96.8
K o or R = rate of infusion 6 1.5 98.4
7 0.78 99.2
Plateau Principle
· Time to reach steady state depends only upon the t 1/2 of the drug and is independent of the size of the dose
and the frequency of dosing. The zigzag and graph represents the same data. It takes >7 t 1/2 to reach
mathematical 99.2%steady state.
· Steady state is reached when either rate in = rate out or when the values associated with a dosing interval
are the same in the succeeding interval.
Therapeutic Drug monitoring:

Drugs in renal failure; Aminoglycosides, cyclosporine A
Drugs with saturable kinetics (non-linear kinetic); Phenytoin and over dose of salicylates
Drugs with linear kinetics; Theophylline, digoxin and procainamide
Aminoglycosides: The normal half life is 2-3 hours. In renal disease patient, the half life can extend to 30-60 hrs.
· Aminoglycosides given at intervals that are much longer than one half-life.
· Phenobarbital intervals that are smaller than one half-life is slowly cleared from body, therefore their peak
concentration is relatively smaller.
Phenytoin: Linear kinetic means when the dose of drug is increased we expect that concentration at steady state
will increase proportionately i.e. if the dose rate is increased or decreased say two-fold the plasma
concentration will also increase/decrease two folds. However, for Non-Linear (Saturated or zero order) >20
ng/ml changes in dose rate can cause more or less changes in plasma concentration. This can cause problems in
dose adjustment.
After phenytoin saturation, can phenytoin toxic symptoms like nystagmus.
Linear (First orders) Non Linear (Saturated or zero order) >20 ng/ml
4h 4h 4h 4h 4h 4h
80 mg --à 40 mg à20 mg à 10 mg 80 mg à 70 mg à 60 mg à 50 mg
Rate of elimination is proportional to their Rate elimination is at constant rate
concentration
Phenytoin at low doses Phenytoin at high dose (initial dose), ethanol elimination.
Most medication are linear elimination Salicylate overdose.
Phenytoin toxicity (nystagmus), salicylates (metabolic
acidosis, respiratory alkalosis).
Theophylline: Theophylline is a narrow therapeutic index drug, which require drug serum level monitoring to
correlate with both therapeutic and toxic effects.
10-20 mg/L needed to produce bronchodilatation with minimum side effects.
>20 mg/L is toxic dose can produce higher side effects.
>35 mg/L increase incidence of seizure and cardiac arrhythmias. The clearance of theophylline is affected by
many variables which makes necessary careful individual dosage, age, smoking, and CHF and drug interactions.
The time to reach C ss

· The concentration of drug rises from zero to C ss by first order process.
· To reach 90% of the final steady state concentration takes 3.3 half lives.
· The sole determinant of the rate that a drug reached C ss is the half-life or K el and rate is influenced by only
those factors that effects half-life.
· C ss time does NOT influenced by rate of infusion. C ss concentration rises with infusion.
Clearance
· CL = rate of elimination/C
· CL = Vd x k el where V d = volume of distribution and k el is the elimination rate constant
· CL = Vd x (0.693/t 1/2 ) where 0.693 = ln 2 and t 1/2 is the drug elimination half-life note that plasma clearance
CL P include renal (CL R ) and metabolic (CL M ) components
Dosage Regimens. The number of doses to be given per day is usually determined by the half-life of the drug and
the difference between the minimum therapeutic and toxic concentrations.
t1/2 = 0.693 Vd/Clt
Summaries from the above formula
If volume of distribution increases (drug displacement from protein binding, heart failure, cadiogenic shock).
How this effect on half-life? Half-life increases because it is directly proportional to V d .
· What if clearance decreased (renal diseases, hepatic cirrhosis)? Half life increase
· What if metabolism decreases? Half-life increases.
· What if dose is increase, how the half-life effects? dose does not affect half life.
Formulas
1st order:
C = C o x 10 –kt/2.303
–kt/2.303
Log C = log C o
C = C o x e-kt
–kt
ln C = ln C o
Half life
t 1/2 = 0.693/k
t 1/2 = C o /2k
Shelf life
t 90 = 0.105/k
t 90 = 0.1C o /2k
Clearance
Cl t = Amount absorbed/AUC
Cl t = FD/AUC
C ss = R o /KV d
C = R o /KV d (1-e-kt)
Distribution
Vd = A o /C o
Home work
(CLT ) = CL R + mL/min
CLNR
V d = D /C p L
Cp = D/ V d mg/L
D = Cp x Vd mg
D L = C ss x V d mg
Clt = FD/AUC mL/min

C ss = R o/KV d Mg/L
t 1/2 = 0.693/k hrs
t 1/2 = C o/2k hrs
www.Pharmacyprep.com Rates and orders of Reactions
21
Rates and Orders Kinetics
Questions Alerts!
· First order elimination
· Half life calculations
Rate. Speed (velocity)

Order. The way in which concentration affects rate.
Kinetic orders: There is four orders of reactions are described below. Zero order, 1st order reactions, 2nd order
reactions, 3rd order reactions, and pseudo order reactions.
Zero order reactionsà

Independent of concentration (NOT dependant on DOSE)
Time dependent
-dc/dt = Ko
Slope -ko
Example. Photochemical degradations
Zero order constant expressed in units of concentration e.g. milligrams per millilitre per hour. or gram/L/hour.
Linear equation = C = -K o t +C o
K o is slope of the line = zero order constant (conc/time)
C o is initial concentration
T = time
C = drug concentration
Slope of the line is not equal to the rate constant because it includes minus sign.
The negative indicates that slope is decreasing. Rate of elimination is independent of the amount of drug to be
eliminated. The zero order elimination rate constant is K o and has the units of amount/time. A constant amount
of drug is eliminated per unit of time.
Most drugs do not follow zero order processes. In zero-order equations, a constant amount is removed for each
unit of time. This kinetics fit the following equation.
Zero order elimination alcohol, toxic doses of Aspirin, and high doses of phenytoin, amino glycosides.
A constant fraction of drug is eliminated
4 hr 4 hr 4 hr 4 hr
80 mg à 70 mg à 60 mg à 50 mg à 40 mg
The serum level curve observed from a drug elimination by a zero-

order process. X axis is Time/hr and Y axis is Cp mg/L.
Slope = -k
Units of drug
Half life = 0.5 C o /K o
Zero order process application include administration of a drug as an

intravenous infusion and controlled release dosage forms (SR, XL,
MR) and Trans dermal patches. time
First order Kinetics:

Rate of reaction is proportional to the first power of concentration.
Concentration and time dependent
Log C o /C = K t /2.303 Question Alerts!
Where 1) First order equations.
C o = concentration at t o 2) first order slope?
K = rate constant
A plot of log scale on Y axis of concentration (Cp mg/L)against time/hr produces a straight line with a slope. The
slope of straight line correlated to Kel,
Slope –k/2.303
Half-life= 0.693/k
Half life = 0.693 x V d /Cl T
A constant fraction (percent) of drug is eliminate half of the starting amount of drug is a constant and is
known as the half-life t 1/2 .
4 hr 4 hr 4 hr 4 hr
80 mg à 40 mg à 20 mg à 10 mg à 5 mg time
First order rate constant DC/dt = -kC time-1 (1/hr or hr-1)
k = first order rate constant
-kt
C = C oe
ln C = -kt + ln C o
log C = - kt/2.303 +log C o
Comparison or zero and first orders process

Zero order First Order
Slope -k (C vs t) -kt/2.303 (log C vs t)
Rate -dx/dt Rate remains constant Rate changes over time
Rate K ◦ unit mgh-1 K unit h-1
Formula C= C o -kt C = C o e-kt
Constant rate of elimination regardless ln C = -kt + ln C o
of concentration.
Rate constant K ◦ K
Rate constant Mg/min Per hour (hour-1) or min-1
unit
Half life
Concentration independent Concentration dependant (rate of elimination
proportional to conc).
Example Sustained drug deliveries, IV infusion, All drug ADME
transdermal patches
Non-linear kinetic (constant rate Linear kinetic
process)
Conc. vs time graph is LINEAR Conc. vs time graph is NON-LINEAR
Log conc. vs time graph is LINEAR
- Plasma drug concentration NO - rate - Plasma drug concentration - rate of drug
of drug metabolism. metabolism.
Rate of drug metabolism is constant. Rate of metabolism is proportional to drug
concentration. (50% less for each t 1/2 )
Second order equation. Rate of reaction proportional to the each of the two reactant concentration and time.
Dx/dt = k (a-x) (b-x)
where
a = concentration of reactant A at time t
b = concentration of reactant B at time t
dx/dt = rate of reaction
x= number of moles of reactant A and B at time t
k = reaction constant
If concentration of reactant A and B are equal:
dx/dt = k(a-x)(a-x)
dx/dt = k(a-x)2
Second order t 1/2 = 1/ka
When there is concentration of A and B not equal, secondary order equation will be:
k = 2.303/t(a-b) = log b(a-x)/a(b-x)
Examples of second order. Saponification of esters

CH 3 COOC 2 H 5 + OH- à (double arrows) CH 3 COO- + C 2 H 5 OH
Third order reaction. Rate of reaction is proportional to concentration of each of the three reactions
Dx / dt = k (a-x) (b-x) (c-x)
When a = b = c
Dx/dt = k (a-x)3
Pseudo order. Rate of reaction is proportional to the concentration of only one reactant, in two-reactant
reaction, if a reactant present in high concentrations.
Example. Saponification of esters in presence of high concentration of bases (OH-) or acids

CH 3 COOC 2 H 5 + OH- (excess) à (double arrows) CH 3 COO- + C 2 H 5 OH.
Half-life (t 1/2 ): A half-life (t 1/2 ) is time required to decrease the amount of drug in body by 1/2 during elimination
(or during a constant infusion). Plasma t ½ is the time it takes for the plasma drug concentration to fall to half its
initial value.
0.693
t1/2 =
k
No. Of half-lives 1 2 3 3.3 5 7

Concentration 50% 75% 87.5% 90% 96% 99.9%
Zero Order First Order

k 0 = amt./time k= time-1
toxicity, saturation all common situations
units of drug
Units of drug
time
time
Concentration vs time
Concentration vs time
Semi log plot Semi log plot (log C vs t)
Units of
drug
time time
t1/2
t1/2
dose dose
Tips
What is the plasma t ½ of a drug? The time it takes for the plasma drug concentration to fall to half its initial
value.
Zero order reactionsà

· Independent of concentration
· Time dependent
· -dc/dt = Ko
· Slope -ko
· Example: Photochemical degradations
Zero order constant expressed in units of concentration eg. milligrams per millilitre per hour. Or gram/L/ hour
· Linear equation = C = -K o t +C o
· K o is slope of the line = zero order constant (conc./time)
· C o is initial concentration
· T = time
· C = drug concentration
First order reactions

Rate of reaction is proportional to the first power of concentration.
Concentration and time dependent
Log C o /C = K t /2.303
Where
C o = concentration at t o
K = rate constant
A plot of log of concentration against time produces a straight line with a slope:
Slope –k/2.303
C = C o e-kt
ln C = -kt + ln C o
log C = - kt/2.303 +log C o
Half-life t 1/2
0.693
t1/2 =
k
Blood or plasma considered in equilibrium with total volume of distribution.
t 1/2 = ( 0.693 X V d ) / CL
www.Pharmacyprep.com Pharmacodynamics
22
Pharmacodynamics
Questions Alerts!
Competitive or non-competitive agonist and antagonist rates!
Pharmacodynamics is the relationship between the concentration of

a drug and the response obtained in a patient. Concepts!
Affinity, Efficacy and Potency
Drug/Receptor Interactions (Fig 27.1)
· Affinity. Measure of ability of drug to bind to receptor.
· Efficacy. Measure of how well the drug/receptor complex produces a physiological response.
· Potency. It is comparative measure. It compares the amounts of two drugs necessary to produce the same
size effect in the body. Example. Rosuvastatin 10 mg and atorvastatin 20 mg
· Agonist has affinity and efficacy.
· Antagonist has affinity and zero efficacy.
· Partial agonist is the only class of drug that can be used either as an antagonist or as an agonist.
· When only partial agonist present, it will give the response until its ceiling effect.
· When a full agonist is already present in the body, administration of partial agonist reduce the effect full
agonist, thus act as antagonist.
Physiological antagonism. Two drugs act on different receptor; cancelling effect.
· Neutralizing antagonism/chemical antagonism
· does not need receptor
· Chemicals act on the body (e.g. antacids, digoxin).
Fig 27.1 Drug A & B have equal efficacy. Drug A & B efficacy is not comparable.
Drug A has more affinity than drug B Drug A has more affinity than drug B
Competitive antagonist. Curve shifts to the RIGHT, and the shift is parallel.
Non-competitive antagonist. Curve shifts to the RIGHT, but the shift is nonparallel E max
Competitive (equilibrium) Non-competitive (irreversible)

Competitive inhibitors are molecules that bind to the same site as Non-competitive inhibitors are molecules that bind to
the substrate preventing the substrate from binding as they do so some other site on the enzyme reducing its catalytic
but are not changed by the enzyme. power
Parallel rightward shift of agonist dose response curve shift. Flattening of dose response curve
Intensity of response depends on concentration of both agonist Response depends on only on the concentration of
and antagonist. antagonist
The same maximal response is attained by increasing the dose of Maximal response is suppressed
agonist
Competitive antagonist, where both the agonist (isoproterenol) and antagonist (propranolol) bind reversibly to
the same receptor subtype (B2 receptor). In the presence of the competitive the dose response curve is shifted
to the right in a parallel manner.
Non-competitive antagonism phenoxybenzamine bind irreversibly (with covalent bond) to alpha receptors. This
reduce the fraction available receptors and reduces the maximal effect that produced by the agonist.
Reversible enzyme inhibitors: This can be categorized into competitive and non-competitive.
Competitive (Reversible) àDrug competes with the substrate for binding to the enzyme at active site, this
binding is mutually exclusive. Inhibition can be reversed in the presence of saturating substrate, since in this
case all enzyme active sites will be occupied by substrate.
Non-competitive (irreversible) à It is independent binding, both substrate and drug bind to the enzyme at
different site. This cannot be reversed by increasing concentration substrate.
Type of drug interactions; Mathematical model

Addition 1+1 = 2 (same effect): ACE inh and K+ sparing diuretics; Codeine+ acetaminophen
Synergism 1+1 = 3 (gives greater effect): Cotrimoxazole (SMX-TMP)
Potentiation 0+1 = 2 (glyburide + metformin) potentiate hypoglycemia
Antagonism 1+1 = 0 (Morpine and Naloxone); warfarin with Vitamin K
Pharmacodynamics drug interactions are those in which drugs having additive, synergism, potentiation and
antagonism effects or side effect when combine together.
Addition Beta blocker + diuretics, Diclectin (doxylamine + vit. B6); latanoprost + timolol (xalacom);
acetaminophen + ASA, amlodipine + atenolol, nitrous oxide + halothane.
Methotrexate + sulfamethoxazole cause bone marrow depression due folate inhibition.
Synergism SMX+TMP; levodopa+carbidopa, acetylcholine + physostigmine
Potentiation Warfarin+ ASA; BZD + alcohol
Antagonism Methotrexate + folic acid; Beta blocker + Beta2 agonist
Zidovudine + stavudine (antagonize by competing binding site
Zidovudine + gancyclovir (- bone marrow toxicity)
Stavudine + zalcitabine (- peripheral neuropathy)
Sulfonylureas + corticosteroids (hypoglycemic effect is opposed)
Quantal response:
· ED 50 Effective dose in 50% of test population
· LD 50 Lethal dose in 50% of test population
· TD 50 Toxic dose in 50% of test population
· TI: Therapeutic index, a measure of safety of a drug measure by LD 50 /ED 50 or TD 50 /ED 50 .
Therapeutic Window. The therapeutic window is the useful “opening” between the minimum therapeutic
concentration and the minimum toxic concentration of a drug.
The minimum effective concentration usually trough levels of a drug.
The minimum toxic concentration determines the permissible peak plasma concentration.
Narrow therapeutic index drugs that require routine plasma/serum drug monitoring.
· Therapeutic range of select medications

· Procainamide 4 – 10 mg/L
· Quinidine 2 – 6 mg/L
· Disopyramide 2 – 6 mg/L
· Lidocaine 2 – 5 mg/L
· Valproic acid 50 – 100 mg/L
· Carbamazepine 4 – 12 mg/L
· Phenobarbital 15 – 40 mg/L
· Lithium 0.4 – 1.5 mEq/L
· Theophylline 20 mg/L
Quantal Dose-Response Curve: Guassian (bell-shaped) distribution.
Graded Dose-Response Curve

Efficacy = maximum effect
Potency = different doses, same effect
Log Dose-Response Curve:

Efficacy: height of log dose-response curve (E max )
Potency: ED 50
Mechanism Of Drug Action

Interaction with receptors and Interaction with enzymes
Enzyme induction. Barbiturates, phenytoin, other anti-epileptics, rifampicin, antihistamines, griseofulvin, oral
contraceptives.
Enzyme inhibition. Chloramphenicol.
Replenishers. Replace/fill-in endogenous substances or fluids and IV fluids, vitamin supplements, and hormone
replacement therapy.
Enzyme Kinetics (Enzyme Inhibitors): Enzymes are catalyst. In biochemical reactions, reactants are commonly
known as substrates (S), enzymes (E), ES = Enzyme and substrate complex, P = product
In the following reaction

E + S <---> ES <---> ES* <---> EP <---> E + P
Enzyme substrate (ES) complex, Enzyme product

complex (EP) and the transition state (ES*)
Enzyme inhibition classified in two categories,

reversible enzyme inhibition (competitive) and
irreversible enzyme inhibition (Non-
competitive)
The Michaelis-Menten equation: By using Michaelis-

Menten equation, rate and order of enzyme reaction
can be determined. V 1 = V max [S] /{K m +[S]}
The reaction rate [v 1 ], maximum reaction rate (V max ), substrate concentration [S] and the Michaelis-Menten
constant (K m ).
The Michaelis-Menten equation first order, when the substrate concentration is much smaller than K m .
The Michaelis-Menten equation describes how the rate of the reaction (v) depends on the concentration of both
the enzyme [E] and substrate [S].
The only way to increase V max is by increasing [E] enzyme concentration.
Question Alerts!
The Michaelis-Menten equation has the same form as the equation for a
First order Km is = 1/2 Vmax
rectangular hyperbola graphical analysis of reaction rate (v) versus
Zero order Km = Vmax
substrate concentration [S] produces a hyperbolic rate plot.
First order
· Substrate concentration is much lower than K m
· K m is lower than V max
· Substrate concentration directly proportional to rate of reaction.
Zero order
· Substrate concentration is same as K m
K m = V max
· Substrate concentration do not effect rate
Km
· K m is the measure of the affinity of the enzyme for it substrate.
· K m is the intrinsic property of the enzyme substrate system and cannot be altered by changing enzyme and
substrate concentration.
· K m lower than V max indicates first order reaction.
· K m and V max approximately same at zero order reaction.
· 1st order rate linear relation with substrate concentration [S]
V max
· V max depends on [E] and [s] concentration in 1st order equation.
· V max is the maximum rate possible to achieve with given amount of enzyme.
Tips
1 physiological antagonism 2 potency of drug 3 efficacy of drug

4 dose-response curve 5 synergistic effects 6 non-competitive inhibitor
7 competitive inhibitor 8 partial agonist 9 EC 50
· Effects that are greater than additive (synergistic). Examples of synergism?
· The effect whereby two drugs acting on the same tissue or organ through independent receptors may result
in opposite effects? (Physiological antagonism). Examples of antagonism?
· A graphic representation of a quantitative response between the amount of drug given and the response of
the drug (dose response curve).
· The amount of drug necessary to produce an effect. The concentration or dose of the drug required
producing 50% of the drugs maximum effect. (ED 50 ).
· The maximal response produced by a drug (full agonist).
· The drug concentration required producing 50% of the maximum response (ED 50 ).
· An agonist, which at even higher concentrations, gives less than 100% response (partial agonist).
· A drug which compete reversibly with agonists for the same receptor site and produces no response
(Reversible antagonist).
· It is called an irreversible antagonist that binds to the receptor site or another site which inhibits the
response to the agonist (True/false)
· Examples of drug combination with additive effect?
· Example of drug combination with synergistic effect
· Examples of drug combination potentiation effect?
· Examples of drug combination antagonism effect?
www.Pharmacyprep.com Medicinal Chemistry
23
Medicinal Chemistry
Questions Alerts!
· Functional groups. Geometric (cis & Trans) isomerism, optical isomerism, calculating optical isomers 2n.
· Active chemical rings in drugs structures dihydropyridine, indole, and piperidine, pyridine, thiazolidine,
dihydrothiazine, and pteridine.
Basics of Organic Chemistry: Organic chemistry is the study of substances that contain carbon, hydrogen,
oxygen, nitrogen, sulphur etc. However, carbon is the essential element in organic chemicals.
Atomic number of carbon is 6. Valence of carbon is 4. Carbon can form only 4 bonds (not less or more than 4).
Carbon can form chains and rings and can bind to the functional groups.
Carbon can form covalent bonds (sharing of electron between two elements).
Electronic configurations of carbon are 1S 2 2S 2 Sp 2 .
Hybridization
SP 3 = Alkanes = 107 = Tetrahedral
SP 2 = Alkenes = 120 = Trigonal
SP = Alkynes = 180 = Linear
Functional groups
Alcohol (-OH) or hydroxyl group.

· Water soluble or aqueous soluble.
· More tertiary alcohol have more lipid soluble.
· Primary alcohol. Primary alcohol oxidation produces an aldehyde.
· Secondary alcohol. Secondary alcohol oxidation produce ketone.
· Tertiary alcohol. Does not undergo oxidation.
Alcohols
OH OH OH
H H R1 R2 R1 R3
H H R2
Primary (1o) Secondary (2o) Tertiary (3o)
Amines (-NH 2 ): Amines are base.

· Categorized as primary, secondary and tertiary.
· Tertiary amines are more basic than secondary.
· Base strength of amines tertiary amine>secondary>primary>aromatic.
Amines: R1
NH2 R1 NH R2 N
R1 R2 R3
Primary (1o) Secondary (2o) Tertiary (3o)
Amine are water soluble: The primary amine more water soluble than secondary and tertiary (due to increase in
Alkyl chain). Primary>secondary>Tertiary.
· Amines undergo (phase 2 metabolism) glucuronidation, sulfate conjugation and methylation.

· Primary amines also undergo oxidative deamination (MAO enzymes).
· Primary & Secondary undergo acetylation.
· Secondary & tertiary amines undergo N-dealkylation.
· Tertiary undergoes N-oxidation.
· Phenolic amines susceptible to N-oxidation on the shelf.
Carboxylic acid (COOH): Pharmaceuticals that contain carboxylic acid group are acidic.
Esters (COOCH 3 ): Pharmaceutical that contain ester functional group, are acid or base sensitive, due to
hydrolysis.
Hydrolysis of ester produce à acid + alcohol.
Example. Penicillin G and acid sensitive beta lactam antibiotics, undergoes hydrolysis when taken orally.
Amide (CONH 2 ): Amides undergo hydrolysis; however, amides hydrolysis is slower than ester hydrolysis. Amides
upon hydrolysis produce acid + amine. Amides bonds are commonly exists in proteins.
Stability of compounds
Benzene Cyclohexane Boat Tautomerism Chair

Conformation Conformation
Which is more stable
60 72 90 60
Tautomerism More Stable More stbale More Strain

Planar
Less strain Less Strain
Isomerism: Compounds that have the same molecular formula but different chemical structures are
isomers or isomeric.
Optical isomerism. The optical isomers contain at least one asymmetric or chiral carbon atom. Asymmetric
centre or chiral centre, a carbon atom attached to four different groups. Using number stereo genic centre or
chiral centres or asymmetric carbon, one can predict the number optical isomers possible in the structure. To
calculate possible of optical isomers with given chiral centres use formula 2n where n = number of chiral centres.
Enantiomer are mirror image with one asymmetric center and non-superimposable.
CH3 CH3 if 3 chiral groups in structure. How many optical isomers are
C H possible? 2n
H C
H3C CH3 23
OH HO 2x2x2=8
D (+) or L (-) or recemic (dL) or (±)
Same physical and chemical properties except in rotation of plane polarized light. Enantiomers can have large
differences in potency, receptor fit, biologic activity, transport and metabolism.
Levorphanol Dextrophanol
L(-) D(+)
Narcotic analgesic and antitussive Only antitussive
Diastereoisomers. Two asymmetric carbon atoms. They are super imposable and are not mirror images.
Diastereomers
H NH CH3 OHNH-CH3
C C CH3 C C CH3
HH
OH H
Geometrical isomers (Cis and Trans isomers): To form Tran’s isomers, it is essential to have double bond.
Examples of geometrical isomers include 2-butene, and diethyl stilbesterol (synthetic estrogens) and several
other drugs.
Structure Activity Relationship (SAR):

Lead structure: Chemical substance with therapeutic use.
Pharmacophore: The pharmacophore of drug molecule is that portion of the molecule containing the essential
organic functional group that directly interact with receptor active site thereby it shows biological activity of
interest.
Analog: Molecule with same skeletal structure with different functional groups attached.
Some examples of analogs H 1 -antihistamines (O-missing).
Homolog: Difference of –CH 2 - in identical molecules. Example. Phenothiazine’s (antipsychotic), a chlorpromazine

is a dopamine antagonist and used as antipsychotic drug and tricyclic antidepressants.
S S
N Cl N Cl
CH2CH2N(CH3)2 CH2CH2CH2N(CH3)2
Phenothiazines chlorpromazine
Bioisosters: The functional groups or atoms that impact similar physical and chemical properties on a molecule.
Example methyl, ethyl, bromine, and chlorine.
S O
N Cl N Cl
CH2CH2C(CH3)3 CH2CH2C(CH3)3
Some examples of bioisosters phenothiazines, and diethyl stilbesterol (synthetic estrogens).
Important concept!
Fundamental pharmacophores for drugs used to treat disease.
Pyridine ring Nicotinic acid is vitamin B 3 . This metabolizes to nicotinamide.

Nicotinic Acid
Nicotinamide
N
Nicotine
Isoniazid Pyridine
Dihydropyridine are molecules based upon pyridine that have
Dihydropyridine ring been semi-saturated with two substituent's replacing one
Amlodipine double bond.
Nifedipine N Particularly well known in pharmacology as L-type calcium
H
Felodipine channel blockers.
Nicaradipine Dihydropyridine
Piperidine ring Present in numerous natural alkaloids such as piperidine and
Morphine quinine, and is the main active chemical agent in black
Codeine pepper and relatives, hence the name. Piperidine is also a
Heroin N structural element of many pharmaceutical drugs such as
H
Meperidine raloxifene, minoxidil, thioridazine and mesoridazine.
Thioridazine Piperidine Piperidine ring + Pyrrolidine = Quasi ring
Haloperidol
Risperidone
Muscarinic blockers
Atropine
Ipratropium
Bromotropin
Scopolamine
Pyrrolidine ring is a cyclic amine
Muscarinic blockers H Pyrrolidine is found naturally in the leaves of tobacco and
N
Atropine carrot. Pyrrolidine ring is the central structure of the amino
Ipratropium acids proline and hydroxyproline.
Bromotropin
Pyrrolidine
Scopolamine
Imidazoline ring Imidazoline is a nitrogen containing heterocyclic derived from
N NH
Clonidine imidazole.
Imidazoline
Isoxazole: Isoxazole is an azole with an oxygen atom to the nitrogen.
Sulfonamide Isoxazole also form the basis for the COX-2 inhibitor.
N
O
Isoxazole
-Lactams H Penicillin nucleus. Beta lactam is the square at the centre.

R N
Penicillin’s S Cephalosporin's à Beta lactam
Cephalosporin O N
O
O OH
Beta Lactam
Amino penicillin's NH2 Beta lactam antibiotics
Amoxicillin
CH
Ampicillin
R
HO
Amino Penicillin's
Pyrazole Pyrazoles are used for their analgesic, anti-inflammatory,
COX II inhibitors H antipyretic, anti-arrhythmic, tranquilizing, muscle relaxing,
N
N psychoanaleptic, anticonvulsant, Monoamineoxidase
inhibiting, antidiabetic and antibacterial activities.
Pyrazole
Indole is an aromatic heterocyclic compound
Indole ring Indole is solid at room temperature. It occurs naturally in
Serotonin human feces and has an intense fecal odor. At very low
(Neurotransmitters, N concentrations, however, it has a flowery smell, and is a
H
present in CNS). constituent of many flower scents (such as orange blossoms)
Triptans and setrons Indole and perfumes. It also occurs in coal tar.
Quinolone Quinoline or benzopyridine, is a heterocyclic aromatic organic

Quinine, hydroxyl compound
quinine and It is toxic: short-term exposure to the vapour causes irritation
quinidine N of the nose, eyes, and throat as well as dizziness and nausea.
H Longer-term effects are uncertain, but quinoline has been
Quinoline
linked to liver damage
Captopril is an ACEi consist of sulfhydril group that gives rash
Proline ring in ACEi. O and metallic taste. Sulfhydryl group is active group binds with
HS - H2C
enzyme.
N
Only Captopril has Sulfhydryl group
CH3
CO2H
Captopril
GABA derivatives Gabapentin was initially synthesized to mimic the chemical
Gabapentin, H2N COOH structure of the neurotransmitter gamma aminobutyric acid
Pregabalin, (GABA), but is not believed to act on the same brain
Vigabatrin receptors. Its exact mechanism of action is unknown, but its
therapeutic action on neuropathic pain is thought to involve
GABA Group voltage gated N-type calcium ion channels.
Imidazole
Histamine, histidine N
and
N
azole antifungals H
Folic acid structure Pteridyl – PABA-Glutamate
Pteridyl ring Pteridyl ring analog is methotrexate
PABA
Glutamate
Tips
Essential functional groups in the Structure activity of drugs
1 Amlodipine, Felodipine, 2. Muscarinic blockers, 3. nicotinic acid,
Nifedipine, Nicardipine Atropine, Ipratropium, nicotinamide,
Bromotropine, nicotine,
Scopolamine isoniazid
4 Penicillins, Cephalosporin 5. Pteridyl ring 6. Morphine, Codeine,
7. Clonidine 8. Ranitidine 9. Sulfonamide
10 histamine, histidine & 11 Indole ring 12 quinolone ring
azole antifungals, ARB’s
13 combination of piperidine & 14 3 rings of cyclohexane COX II
pyrrolidine and 1 ring cyclopentane 15 inhibitors
Pyridine ring ( )
· Dihydropyridine ring ( )
· Piperidine ring ( )
· Pyrrolidine ring ( )
· Imidazoline ring ( )
· Isoxazole ( )
· Beta lactam ( )
· Amino penicillins ( )
· Pyrazole ( )
· Steroids ( )
· Folic acid ( )
· Imidazole ( )
· Imidazole ring ( )
· Serotonin ( )
· Quasi ring ( )
· Vitamin K ( )
· Ciprofloxacin ( )
· Quinidine & Quinine ( )
· Isomers ( )
· example of geometrical isomers ( )
24
Medicinal Chemistry and Pharmacology of
Autonomic Nervous System
Questions Alerts!
· Biosynthesis of catecholamine's (Tyrosine --> Levodopa --> dopamine --> norepinephrine --> epinephrine).
· Structure activity relationship of direct acting acetylcholine agonist.
· Structure activity relationship of atropine and muscarinic blockers.
· Pharmacology and structure activity relationship of sympathomimetics like pseudoephedrine, ephedrine,
and crystal meth.
· Pharmacological actions of sympathetic receptors alpha1&2 and beta 1&2. Parasympathetic receptors
like muscarinic and nicotinic.
Nervous System
Central Nervous System (CNS) Peripheral Nervous System (PNS)

Spinal cord and brain
Autonomic Nervous System (ANS) Sensory somatic nervous System

12 pairs of cranial nerves (optic & vagus)
31 pairs of spinal nerves
Cholinergic Adrenergic
Drug receptors
Generally pharmacological receptors can be categorized into 4 types
· Seven trans membrane proteins
· Ion channels
· Transcriptional regulators
· 1-Transmembrane proteins
Seven Trans membrane proteins

The G protein coupled receptors are the largest types of pharmacological receptors, which almost 200 human
receptors are known to date.
The G proteins coupled receptors are the major therapeutic significance with well-established therapeutics
studies.
Examples of G proteins coupled receptors as therapeutic targets are Acetylcholine, muscarinic, norepinephrine,
beta receptors, angiotensin AT 1 , dopamine, Serotonin, histamines, and opioids.
· Glutamic acid (glutamate) excitatory: NMDA receptor. Example. Memantine

· GABA inhibitory: Example Benzodiazepine, barbiturates, and antiseizure drugs.
· Dopamine inhibitory: G protein linked cAMP. Antiparkinson drugs and antipsychotics.
· Norepinephrine excitatory: antidepressants, and antianxiety.
· Serotonin excitatory and inhibitory. Antidepressant and antianxiety.
· Opioids peptide inhibitory neurotransmitters Enkephalins, endorphins and dinorphine
Ion channels: There are two types of ion channels
· Voltage gated: Na+ channel, Ca2+ channel, K+ channel

· Transmitter gated: neurotransmitter interact with specific receptors.
Transcription regulators: There are over 150 receptors of this family, which acts as transcriptional receptors. This
is second major class of receptors, which include steroid hormones including estrogens, androgens, and the
glucocorticoids such as corticosteroids, vitamin D, retinoic acid, and thyroxin.
One transmembrane proteins: These receptors include several growth factors such as tumor necrosis factor,
serine/threonin kinase, neurotropins, and cytokines.
Most neurotransmitters interact primarily with postsynaptic receptors, but some receptors are located on
presynaptic neurons, providing fine control of neurotransmitter release.
Post synaptic presynaptic

Alpha1 Alpha2
Beta 1
Beta 2
Serotonin Serotonin (REUPTAKE)
Receptors in autonomic nervous system:

Cholinergic receptors are classified as nicotinic N 1 (in the adrenal medulla and autonomic ganglia) or N 2 (in
skeletal muscle) or muscarinic M 1 (in the autonomic nervous system, striatum, cortex, and hippocampus) or M 2
(in the autonomic nervous system, heart, intestinal smooth muscle, hindbrain, and cerebellum).
Question Alerts!
Identify structure of Ach, Epi, NE, 5HT
Neurotransmitters Chemical structures Characteristics

Acetylcholine CH3 Is a neurotransmitter of peripheral nervous
(ACh) N O
CH3 system neuromuscular junction, parasympathetic
H3C
CH3
system, visceral motor nuclei in the brain stem,
O and basal nucleus of Meynert.
Acetylcholine (ACh)
Epinephrine OH
H
Uses a1 , a 2 or b 1 , b 2 , b 3 adrenergic receptors,
N CH3
which are G-protein linked receptors. Plays
insignificant role in CNS and is found in the
HO
Epinephrine
adrenal medulla.
OH
OH
Uses a1 , a 2 or b 1 , b 2 , b 3 adrenergic receptors,
Norepinephrine NH2 which are G-protein linked receptors is the
transmitter of post ganglianic sympathetic
HO neurons and CNS (locus ceruleus), plays role in
OH
Norepinephrine
anxiety states, panic, attacks, depression
Dopamine NH2 Uses D 1 and D 2 dopamine receptor, which are G-
protein-linked reception is depleted in Parkinson
HO Dopamine
disease and is increased in schizophrenia.
OH
Serotonin (5- NH2 Uses 5HT receptor, which is a transmitter-gated

hydroxy- HO ion channel that is permeable to Na+ and K+ ions is
tryptamine. 5HT) neurotransmitter of the raphe nuclei of the
N
H
brainstem whose neurons project to widespread
areas of the CNS.
5-HT
g-Aminobutyric COOH Uses the GABA receptor, which is a transmitter-

H2N gated ion channel that permeable to Cl- ions. Uses
acid (GABA)
Gama-Aminobutyric Acid (GABA) the GABA receptor, which is G-protein-linked
receptor is a major inhibitory neurotransmitter in
the CNS.
Glycine COOH Uses the glycine receptor, which is transmitter-
H2N H gated ion channel that is permeable to Cl- ion is
the major inhibitory neurotransmitter in the spinal
H cord. Glycine has NO chiral carbon.
Glycine
Glutamate COOH Uses the N-methyl-D-apartate (NMDA), kainite, or
H2N quisqualate. A receptors, all of which are
COOH transmitter gated ion channels that are permeable
H to Na+, K+ and Ca2+ ions.
Glutamate
Adrenergic receptors: are classified as 1 (postsynaptic in the sympathetic system), 2 (presynaptic in the
sympathetic system and postsynaptic in the brain), 1 (in the heart), or 2 (in other sympathetically innervated
structures).
Dopaminergic receptors are classified as D 1 , D 2 , D 3 , D 4 , and D 5 . The D 3 and D 4 play a role in thought control
(limit negative symptoms of schizophrenic processes), whereas D 2 receptor activation controls the extra
pyramidal system.
GABA receptors are classified as GABA A (activating chloride channels) and GABA B (potentiating cAMP
formation). The GABA A receptor consists of several distinct polypeptides and is the site of action for several
neuroactive drugs, including benzodiazepines, newer anticonvulsants (e.g. lamotrigine), barbiturates, picrotoxin,
and muscimol.
Serotonergic (5HT) receptors (with at least 15 subtypes) are classified as 5HT 1 (with four subtypes), 5HT 2 , and
5HT 3 . 5HT 1A receptors, which occur presynaptically in the raphe nucleus (inhibiting presynaptic uptake of 5HT)
and postsynaptically in the hippocampus, modulate adenylate cyclase. 5HT 2 receptors, located in the fourth
layer of the cortex, are involved in phosphoinositide hydrolysis. 5HT 3 receptors occur presynaptically in the
nucleus tractus solitarius.
Glutamate receptors are classified as inotropic NMDA (N-methyl-D-aspartate) receptors, which bind NMDA,
glycine, zinc, Mg2+, and phencyclidine (PCP, also known as angel dust) and affect the influx of Na+, K+, Ca2+ and
non-NMDA receptors, which bind quisqualate and kainate. Non-NMDA channels are permeable to Na+ and K+
but not to Ca2+. These excitatory receptors mediate important toxic effects by increasing calcium, free radicals,
and proteinase. In neurons, synthesis of nitric oxide (NO) involving NO synthase increases in response to
glutamate.
Opioid receptors and neurotransmitters are peptide type. Endorphin-enkephalin (opioid) receptors are classified
as µ 1 and µ 2 (affecting sensor motor integration and analgesia), 1 and 2 (affecting motor integration, cognitive
function, and analgesia), and 1 , 2 , and 3 (affecting water balance regulation, analgesia, and food intake).
µ = analgesic effect, respiratory depression + GI

= development of tolerance
= analgesic effect, involved in sedation + GI
Sigma receptors, currently classified as non-opioid and mostly localized in the hippocampus, bind drugs.
Autonomic Innervations and Primary Effects: Receptor type shown in parentheses (a alpha, β beta,
M=cholinergic-muscarinic). Note that preganglionic synapses for both systems are cholinergic-nicotinic. indicate
absence of direct innervations. However, receptors are present and may be stimulated by agonists.
Sympathetic Drugs
Sympathetic agonist Sympathetic antagonist
Alpha agonist Beta agonist Mixed agonist
Alpha antagonist Beta antagonist
a1 antagonist a2, antagonist a1,b2, mixed antagonist
Non-selective Cardioselective Partial alpha & Partial agonist &

Beta antagonist Beta antagonist Beta antagonist antagonist
Classification of adrenergic agonist (Sympathomimetics)
SYMPATHETIC AGONIST Question Alerts! Catechol amine type of

NON-CATECHOLAMINES CATECHOLAMINES neurotransmitters. Enzymes that catalyze formation
Amphetamine Dopamine of dopamine to norepinephrine and epinephrine
Methamphetamine Epinephrine
NH2 Tyrosine
HO COOH
Methylphenidate Norepinephrine Tyrosine hydroxylase
Ephedrine
Pseudoephedrine
Salbutamol (Albuterol)
HO NH2
L-dopa
COOH
Terbutaline
HO
dopa decarboxylase
Salmeterol
Isoproterenol NH2
Dopamine
Metaproterenol HO
OH
dopamine b-hydroxylase
Note. Phenylethanolamine OH
NH2
Norepinephrine
HO
Sympathetic agonist OH
phenylehtanolamine-N-methyltransferase
Indirect acting sympathomimetic amine. Example: (S-Adenosyl Methionine - SAM)
OH H
Hydroxy amphetamine, ephedrine or pseudoephedrine, N CH3
methyl amphetamine, and tyramine. HO

OH
Epinephrine
Indirect acting sympathomimetics amines may have one,
two, or no hydroxyl groups. The less the hydroxyl group the higher the lipophilic and the greater the absorption
and greater duration of activity after oral administration. Alkyl substitution at the alpha carbon next to amino
group reduces the destruction of phenol and phenyl compounds and increases lipophylic characters meth crystal
structure.
OH H OH H H
NH2 CH3 N CH3 N CH3 N CH3
CH3 NH2 CH3 CH3 CH3
Amphetamine Dextroamphetamine Ephedrine

Pseudoephedrine Methamphetamine
A B C D E
Alpha 2 agonist
H
N
R HN Imidazoline ring
Clonidine
CH3
OHCH3 OH
HO NH2
HO NH2
COOH
Decarboxylation
Methyl dopa - a prodrug Methyl Norepinephrine
Sympathetic agonist and antagonist share chemical features of natural ligand of epinephrine.
Sympathetic antagonists
Beta Blockers Alpha Blockers

O
CH3
CH3O N NC
O CH2CHCH2NHCH N O
CH3
N
CH3O
NH2
Propanolol Prazosin
All alpha blockers contain 4-amino-6-7-dimethoxyquinazoline ring system attached to piperazine ring. Reduction
of furan ring of prazosin to the tetrahydrofuran ring of terazosin increases the duration of action by altering rate
of metabolism. Terazosin, doxazosin, Tamsulosin have long half life and duration of and that allows once daily
dosing. Tamsulosin & Terazosin, alfazosin used for BPH.
Beta blockers
Lipophilicity: The lipophilic BBs primarily cleared by liver (Propranolol, pindolol, and metoprolol) hepatic
elimination). Hydrophilic (atenolol and Nadolol) are renally cleared.
Propranolol can penetrate into CNS thus can be used for anxiety and CNS SEs insomnia, depression, and vivid
dreams present only in propranolol.
Cardioselective beta selective blockers are 4-substituted aryloxypropranolamine.
Labetalol and Carvedilol: Alpha 1 , beta 1 , and beta 2
Timolol, betaxolol, metoprolol block B 2 receptors in ciliary muscles. The ciliary muscles (gland) produce aqueous
humor.
SAR OF SYMPATHETIC DRUGS

AGONIST ANTAGONIST
LEVODOPA, DOPAMINE, NE, EPINEPHRINE PROPRONOLOL
Cholinergic
Cholinergic Agonist Muscarinic Antagonist
Direct cholinergic agonist Indirect cholinergic Tertiary amines Quaternary amine

agonist .Atropine Ipratropium
Scopolamine Tiotropium
Acetylcholine agonist anticholinesterase Benztropine Glycopyrrolate
Trihexyphenidyl
Choline ester Pilocarpine

Bethanachol
Carbachol Reversible Reversible Organophosphate
Methanacol Quaternary alcohols Carbamate (Irreversible cholinesterase inh)
Donepezil .Physostigmine Echothiophate, Malathion
Neostigmine Parathion
Rivastigmine Sarin
Pyridostigmine
Cholinesterase
Acetylcholine -------------> Acetyl + Choline
Structure activity of direct acting cholinergic drugs

CH3
O CH3
H3C-N
ACETYLCHOLINE
Acetylcholine CH3 O Carbacholdà 1 carbamate group
CH3 Methanachol à 1 methyl group
O CH3
Methanocholine H3C-N Bethanachol à 1methyl &1 carbamate group
CH3 CH3 O
Methyl group
CH3
O NH2
H3C-N
Carbacholine CH3 O
Carbamate group
CH3
O NH2
H3C-N
CH3 CH3 O
Bethanacholine Carbamate group
Methyl group
Drugs for Alzheimer’s disease
Reversible
Acetylcholinesterase inhibitor
non specific
selective Specific
Galanthamine
Donepezil Rivastigmine
(relatively selective)
Structure activity of anti-cholinergic drugs

Muscarinic antagonist Question Alert!
Methamphetamine (street name crystal meth,
Tertiary amines Quaternary amine
glass, or ice).
Atropine Ipratropium Dehydroxylation of pseudoephedrine gives
Scopolamine Tiotropium methamphetamine
Benztropine Glycopyrrolate Pseudoephedrine has one hydroxyl group.
Trihexyphenidyl Amphetamine or dextroamphetamine gives
methamphetamine by N-methylation.
Quasi ring is present in muscarinic antagonist: It is combination of piperidine + pyrrolidine. Longer the chain on
nitrogen of quasi ring, lower antimuscarinic activity.
Tips
1. Methanol 2. Carbachol 3. Bethanechol
4. One methyl group 5. Alpha 1 6. Alpha 2
7. Beta 1 8. Beta 2 9. Scopolamine
10 phenylethanolamine N-methyl transferase 11 Quasi 12 Piperidine & pyrrolidine
ring ring
13 Competitive muscarinic blockers, it act on
vestibular system and the CNS.
· Epinephrine act on? ( )
· Norepinephrine act on? ( )
· Enzyme that catalyzes norepinephrine to epinephrine ( )
· Muscarinic drugs essential group for anticholinergic action is? ( )
· Muscarinic blockers structure contain? ( )
· Acetylcholine, methanchol, carbachol and bethanechol differs in? ( )
· competitive muscarinic blocker, that act on vestibular system and the CNS ( )
· Choose 3 examples of direct acting acetylcholine agonist? ( )
· Scopolamine mechanism is à ( )
· Methanachol is structurally similar to acetylcholine, however differs in à
· Write three examples direct acting acetylcholine agonist? ( )
· Organophosphate antidote is? ( )
· Atropine overdose is treated by ( ) can get into brain
· Myasthenia gravis is treated by ( )
25
Medicinal Chemistry and Pharmacology of
Histamines, Serotonin, Prostaglandin and Non-
Steroidal Anti-inflammatory Drugs
Questions Alerts!
· Chemical structure of diphenhydramine (lipid soluble) as sedative.
· Serotonin synthesis from tryptophan --> 5-hydroxy tryptophan -->Serotonin
· Serotonin pharmacological actions of agonist (triptans) and antagonist of 5HT3 (ondansetron).
· Structure activity of prostaglandin analogues PGE1 (misoprostol) and PGF2 (latanoprost).
· Pharmacology of leukotriene receptor antagonist montelukast and zafirlukast.
· Acetaminophen structure and metabolism that explains hepatotoxicity.
· Glutathione chemical structure.
· Acetylsalicylic acid pharmacological actions Antiplatelets, Antipyretic, Analgesic and Anti-inflammatory
actions.
Autocoids (local hormones): Chemical mediators that the body releases as a response to pathogens or noxious
substances. Produced in the body and has profound pharmacological effects.
Autocoids or chemical mediators
Amine types Endogenous type

Ecosonides
Histamines Prostaglandins
Serotonin Prostacyclin
Thromboxane
Leukotrienes
Bradykinin
Amines: No real clinical application in the treatment of diseases however antihistamines are of great
importance. Amine types of autocoids include histamines and serotonin.
Endogenous Peptides
· Site of production for endogenous peptides are GIT, kidneys, lungs, pancreas and uterus.
· Physiological actions of endogenous peptides are.

· Prostaglandins. Pain sensation, development of inflammation
· Thromboxane. Aggregation of platelets
· Prostacyclin. Inhibition of platelet aggregation
· Leukotrienes. Inflammation, chemotactic properties (pull substances to them)
Histamines: The histamine is produced from mast cells. Histamines act on three receptors, of these H1, H2
receptors are excitatory and H3 receptors.
Physiological functions of H 1 receptor typical
· Allergic and anaphylactic response to histamines.
· Gives bronchoconstriction, and vasodilatation.
· Increase capillary permeability.
· Spasmodic contractions of gastrointestinal smooth muscle.
H COOH H
N N
NH2 NH2
N N
-CO2
Histadine Histamine
-CH 2 - in histadine
Chemistry of H 1 antihistamine. Usually lipid soluble, and similar in terms of absorption and distribution.
· Good absorption after oral administration distribution with peak plasma concentration of 1 to 2 hours.
· Allows some to go to the blood-brain-barrier especially structural resemblance to histamine.
H 1 antihistamine chemical classification

· Ethylene diamines: Pyrilamine, and triplennamine
· Alkylamines: Brompheniramine, chlorpheniramine, and acrivastine.
· Ethanolamine: Diphenhydramine, dimenhydrinate, and doxylamine.
· Piperazines: Meclizine, cyclizine, hydroxyzine, and cetrizine.
· Phenothiazine. Promethazine
· Dibenzocycloheptenes. Cycloheptadienes.
· Pthalazinone. Azelastine.
Piperidine: Terfenadine, astemizole, levocabastine, loratadine, and fexofenadine.
Tertiary amine
Identify structures!
CH3 Diphenhydramine chemical structure!
O CH2CH2 N
CH3
CH N N CH3 Tertiary amine is present
Lipid soluble
Has C-O-C, C-N bonds
Diphenhydramine Cyclizine Has aromatic rings (hydrophobic)
Mechanism: Competitive antagonist of histamine
receptors. H 1 receptors are located in the brain, heart, bronchi, GI tract and vascular smooth muscle. Mast cells
and basophiles are principle histamine containing cells.
H1 Antihistamine
1st Generation (PM) 2nd Generation (AM) 3rd Generation

Ethanol amines: Piperazine derivatives Piperadine Derivatives
Cetirizine (Reactine) Desloratadine (Aerius)
Diphenhydramine
Piperidine Derivatives
Dimenhydrinate
Fexofenadine (Allegra)
Doxylamine Loratadine (Claritin)
Alkyl amines
Chlorpheniramine Once daily dose
Piperidine Derivatives
Azatadine, Cyproheptadine
Piperizines
Meclizine, Cyclizine
Hydroxyzine
Side effects: Sedation, dizziness, nausea, constipation, diarrhea, loss of appetite and anticholinergic.
Metabolism of antihistamines. Some examples of metabolites of antihistamine that are used as drugs.
· Loratadine metabolizes to desloratadine.
· Hydroxyzine metabolizes to Cetirizine
· Terfinadine metabolizes to Fexofenadine.
O
H3C
H3C
OH
CH3 CH3
CH3
HO N
HO N
OH
OH
Terfinadine Fexofenadine
N N
N COOCH2CH3 NH
Cl Cl
Loratadine Desloratadine
Histamine H1-receptor blockers
Particularly Particularly Particularly All H1- antihistamines

Diphenhydramine, promethazine cyproheptadine
promethazine
Anti Alpha Dopamine Serotonin Histamine H1 Histamine H2

Cholinergic Adrenergic receptor receptor receptor receptor
(muscarinic) receptor
Pharmacology H1-antihistamines
H 1 antihistamine pharmacological actions (drugs action) takes place by blocking blocks H 1 -histamine receptor
effect. This results in beneficial effect on, Allergic symptoms, seasonal rhinitis, conjunctivitis, rhino viral
infections (common cold) and urticaria.
H 1 -antihistamine therapeutic uses. Antihistamine may bring relief to cold symptoms, runny nose, red and itchy
eyes. Allergic rhinitis symptoms such as nasal allergies. Antihistamine sedative properties are utilized to treat
temporary relief of insomnia. Antihistamines are effective to treat nausea and vomiting.
Used for
· Allergiesà 2nd gen
· Runny noseà Diphenhydramine
· Insomnia à Diphenhydramine
· Nausea and (motion sickness): Dimenhydrinate, and doxylamine.
· Motion sickness à Dimenhydrinate, Meclizine & scopolamine, Promethazine.
GI TRACT à VOMITING CENTRE ß VESTIBULAR NUCLEI

(-5HT3 ) (MEDULLA) (H1 & M)
-
CHEMORECEPTOR TRIGGERS (D)
(OPIOIDS, CHEMOTHERAPY, HORMONE (PREGNANCY)
Side effects:
Anticholinergic. Dry mouth, constipation, tachycardia, and difficulty voiding urine.
CNS. Dizziness, drowsiness, performance impairment (memory, work performance, visual motor coordination).
GI. Constipation
Contraindications with mainly first generation anti histamines. Narrow angle glaucoma, bladder neck
obstruction, hyperthyroidism, cardiovascular disease, and benign prostate hyperplasia.
First generation H 1 antagonist Second generation H 1 antagonist

Higher sedation and anticholinergic Less sedation due to less lipid soluble and do not penetrate the
Tertiary amine (cause sedation) BBB.
Lipids soluble, and can cross blood brain barrier NO anticholinergic effect
More central anticholinergic side effect Drug interaction
Anti-serotonin Terfenadine/astemizole. Cardiac arrhythmias characterized by
Anti-bradykinin prolong QT interval (torse de pointes).
Usually QID Grapefruit juice (apple, orange) reduces oral bioavailability of
fexofenadine.
Dimenhydrinate, Meclizine, cyclizine and Cetirizine have high fatigue and somnolence (10%).
promethazine are useful for the prophylaxis of Loratadine have low fatigue and somnolence.
motion sickness and vertigo.
Promethazine is the most potent antihistamine,
and limits its use due to sedation.
Pregnancy: Bromopheniramine can cause teratogenicity. All 1st gen and 2nd generation antihistamine are used in
pregnancy except bromopheniramine due to its teratogenicity. 1st generation commonly used due to its wide
experience.
In children (less sedative) antihistamines such as loratidine or use sodium chromoglycate. First generation
impairs academic and learning abilities in children. Most antihistamine and nasal cromolyn considered safe in
children over 2 years of age. There is limited
information about fexofenadine in under 12-year-old Question Alerts!
age. Topical antihistamines like levocabastine eye
drops are used allergic conjunctivitis and
Topical antihistamines. Olopatadine (Pantanol), available as nasal spray.
Levocabastine (Livostin), Emedastine (Emadine),
Azelastine (Astelin), and Kitotifen (Zaditor).
Topical applications of H 1 receptor antagonist to the eye relieves itching, congestion of conjunctiva and
erythema. The density of mast cells are high conjunctiva and tear film.
H 2 receptor antagonist (H 2 RA) present on parietal cell, and help to produce HCl secretions: H 2 receptors
mediated functions. H 2 receptors responses to histamine such as increased secretion of gastric acid increase
pepsin and intrinsic factor (Castle’s factor).
Mechanism: Competitive inhibitors of H2-receptors on parietal cells, thus inhibit gastric acid secretion.
Therapeutic use: GERD, upset stomach (use prophylactically before meals (longer lasting episodes, night time
and predictable heartburn after trigger food.)
Ach Histamine Gastrin

Atropine Ranitidine
Muscarinic receptor H2 receptor
IP 3 C a 2+ cAMP ?
H+ secretion
PPIs
Classification of H 2 antagonist (H 2 RA: Ranitidine, Cimetidine, Famotidine and Nizatidine (drug names end with
"tidine").
Pattern of heartburn recommendation

Intermittent, short term heartburn needing fast Antacids, alginates
relief.
Longer lasting episodes (night time) needing a H2RA
longer duration of effect.
Predictable heartburn after trigger food. H2RA taken before unavoidable exposure.
Frequent heartburn or episodes needing treatment PPI
for more than few days
H2 antagonist chemistry
Cimetidine, an H2-receptor antagonist
CH3 N CN
CH2SCH2CH2 NH C NHCH3
HN N
H 2 antagonist pharmacology. H 2 receptor antagonist competitively blocks H 2 receptors thus blocking the effect
of histamines on gastric secretions.
H 2 antagonist therapeutic use. To treat heartburn, dyspepsia GERD, GI ulcers, Stress-induced gastritis.
H 2 antagonist side effects: Cimetidine can cause gynecomastia. Mild diarrhea, or constipation, headache,
myalgia, confusion, hallucination, and excitement.
Administration: all H 2 RA are available oral and cimetidine, famotidine and ranitidine are also parenteral. Oral
have rapid absorption.
Serotonin (5-Hydroxy tryptamine 5HT)
Question Alerts!
1) Serotonergic system modulates mood, emotion, sleep, and appetite.
2) Serotonin contain indole ring.
3) Tryptophan to serotonin is catalysed by? Hydroxylase & decarboxylase
Serotonin neurotransmitters involved in vasoconstriction, vasodilation, regulation of body temperature, sleep,

depression and hormonal regulations.
Tryptophan (amino acid) à 5-hydroxy tryptophan à Serotonin (neurotransmitter).

Tryptophan is precursor of serotonin and tryptophan taken up in neuron and converted to serotonin. (Increase
synthesis of serotonin)
Conversion of tryptophan to serotonin takes place in two reactions, first hydroxylation and decarboxylation
catalyzed by tryptophan hydroxylase and L-amino acid decarboxylase respectively. Serotonin contain indole ring.
NH2
NH2
HO HO CH2CH2NH2
COOH COOH
N N N
H H H
Hydroxylase Decarboxylase
Tryptophan Hydroxy tryptophan Serotonin (5HT)
HO CH2CH2NH2 Niacin
N Tryptophan Serotonin
Indole ring H
Serotonin (5HT) Melatonin
MAO (oxidative de-amination)

Serotonin-----------------------------------> 5-hydroxy indole acetic acid
Serotonin targets
· Serotonin receptors: 5HT 1 , 5HT 2 , and 5HT 3 (migraine, N&V)
· Serotonin reuptake in CNS (antidepressants)
· Break down of serotonin by MAO. (antidepressants)
Physiological functions of serotonin receptors. Serotonin group has several subtypes of receptors: 5HT 1 , 5HT 2 ,
and 5HT 3 àDeficiency of 5HT 1 , 5HT 2 and 5HT 3 gives anxiety, depression, aggression, impulsive and appetite.
· 5HT 1D ; Auto receptors inhibit presynaptic activity in both serotoninergic and adrenergic neurons in the CNS.
· 5HT 2 . Vasoconstriction, and platelet aggregation
· 5HT 3 . Excessive of 5HT 3 gives nausea, vomiting
· 5HT 4 . Release of acetylcholine in the enteric region
Subtype Clinical significance Drug Clinical Use

5HT 1a 5HT IN CNS ACTS AS Buspirone 5HT 1a agonist Antianxiety,
NEUROTRANSMITTER. antidepressant, antiaggressive,
antiemetic.
5HT 1b/1d CNS, vasoconstriction Triptan Migraine attacks
5HT 1c CNS
Platelets, smooth muscles. (5HT Ergotamine Antimigraine (acute)
5HT 2 CONSTRICTS SMOOTH MUSCLES OF Cyproheptadine
BRONCHI & GI)
CNS (-ve schizophrenic symptom).
CNS, gastrointestinal (IN GI 5HT ACT AS Ondansetron Antiemetic in chemotherapy
5HT 3 LOCAL HORMONE & TO REGULATE
PERISTALISIS MOVEMENT)
5HT 4 CNS, gastrointestinal
Serotonin
5HT1a 5HT1b/1d 5HT2 5HT3 5HT4
Agonist Agonist Non selective Antagonist Agonist

Buspirone Triptans Ergotamine (DHE) Ondansetron Cisapride
Sumatriptan are 5HT2 agonist. Alosetron
Rizatriptan Cyproheptadine Fabesetron
Zolmitriptan affects both 5HT2 Ramosetron
Naratriptan and 5HT1 (to
-appetite)
Trazadone is 5HT2A
ANTAgonist
Antagonist of 5HT2a
atypical antipsychotic
olanzapine
Clozapine
Risperidone
Quetiapine
Trazodone is a triazolopyridine derivative, chemically unrelated to other available

antidepressants. Trazodone's most potent pharmacologic activity involves antagonism at the 5-
HT2a serotonin receptor. Less potently, trazodone also inhibits the serotonin transporter, which
reduces serotonin reuptake by the presynaptic neuronal membrane. Because both of these functions
contribute to its antidepressant effect, trazodone is classified as a serotonin antagonist-reuptake
inhibitor, or SARI. Trazodone also exhibits antagonism at alpha-1 adrenergic receptors, which accounts
for its propensity to cause orthostatic hypotension, and histamine-1 receptors, which contributes to its
sedative properties.
5HT1 receptor class of drugs

5HT 1B/1D receptor agonist
Mechanism: Contraction of arterial smooth muscles, especially in carotid and cranial circulations.
Triptans (all are indole derivatives): Sumatriptan, Rizatriptan, Naratriptan, Zolmitriptan, Almotriptan, and
Frovatriptan.
TRIPTANS CH 3
NSO CH 2 2 CH CH N
CH
5HT 1D/1B receptor agonist
2 2
3
H CH3
N
H
Indole ring
Sumatriptan
5HT 1D/1B receptor agonist therapeutic uses. Triptans are used to treat migraine headache attacks.
5HT 1D/1B receptors pharmacological actions cause constriction.
5HT 1D receptor agonist side effects. Feeling of warmth, dizziness, tightness or heaviness in the chest, rarely
patient may experience chest pain.
5HT 4 agonist
Cisapride (a benzamide), and tagaseride (indole derivative). Ergotamine serotonin partial agonist. Ergot alkaloids
have agonist and antagonist properties.
Ergot alkaloids and derivatives with antagonist/partial agonist activity include ergonovine, dihydroergotamine
(DHE), methysergide and bromocriptine.
5HT 4 agonist Cisapride (a benzamide), and tagaseride (indole

Cl
O
derivative).
H2N C NH N CH2CH2CH2O F
OCH3 CH3O
Cisapride
5HT 3 receptor antagonist: Ondansetron (indole derivatives) and Granisetron (benzimidazole derivative).
5HT 3 antagonist O
CH2 N N ONDANSETRON
SETRONS N
GRANISETRON
CH3
Indole ring Ondansetron
5HT 3 receptor antagonist pharmacology act on 5HT 3 mixed receptors and can effect on nausea and vomiting.
5HT 3 receptor therapeutic use ondansetron and granisetron are used to treat chemotherapy induced or vagal
stimulation and surgery nausea and vomiting.
5HT 3 receptor antagonist side effects. Ondansetron side effects. Constipation, headache, dizziness and
granisetron diarrhea.
Prostaglandins, thromboxane’s, prostacyclins and leukotrienes are synthesized from arachidonic acid. These four
substances are naturally occurring 20-carbon cyclopentanofatty acids derivative.
Ecosonides
Ecosonides are metabolites of arachidonic acid (a fatty acid). Examples of ecosonides are prostaglandin analogs,
thromboxane’s, and prostacyclins. Arachidonic acid is derived from linoleic acid or taken from diet and esterified
to phospholipids (phosphatidylethanolamine). Site of production of endogenous peptides are GIT, kidney,
pancreases and uterus.
Arachidonic acid is derived from dietary linoleic acid (2 double bonds) or is ingested from the diet and esterified
to phospholipids.
Prostaglandin
Prostaglandin has been classified based presence and absence of keto or hydroxyl groups at 9 and 11. Subscripts
relate to the number of double bond present in aliphatic chains.
Corticosteroids Leukotrienes O
9 COOH
Lipoxygenase
Membrane phospholoipids Arachidonic acid

11
Cyclooxygenase HO
NSAID, ASA, COX-II Question Alerts!
SAR of prostaglandins? PGE1 and
Phospholipase A2
PGF2a
Prostaglandins G 1) PGE analogs have 9 keto and 11
Hydroperoxidase hydroxyl group
2) PGF analogs have 9 hydroxyl and
Prostacyclin (PGI2)
PGH2 Thromboxane A2 11 hydroxyl group
Platelet aggregation Paltelet aggregation 3) Misoprostol is? Ecosonides
Vascular tone Vascular tone 4. Misoprostol has one double bond
Bronchial tone
PGE2 & PGF2
Dipyridamole and two hydroxyl groups (11C and
Uterine tone
Uterine tone 16C)
Vascular tone
Bronchial tone
PHYSIOLOGICAL FUNCTIONS: Platelet aggregation, relaxes bronchial and GI smooth muscles, relax smooth
muscles, and inhibit gastric acid secretion, pain, edema, and inflammation.
Prostaglandin analogs
PGE1 PGE2 PGF2a PGI2 TxA2
Pyrogen elevate Bronchoconstriction Decrease platelets Increase Platelets

Protects gastric
PGE2 contraction contraction of aggregation aggregation
mucosa
of uterus uterus
Misoprostol Dinoprostone Epoprostenol Thromboxane A2

Latano"prost" Dipyridamol
Alprostadil Bronchial & Blood vessels
Bronchial & inhibits platelet
Bronchial & smooth muscle dilatation
smooth muscle aggregation
smooth muscle dilatation Inhibit aggregation
dilatation constriction
of platelets
PGE analogs
PGE 1 analogs classification: Misoprostol, and alprostadil.
PGE 1 analogs medicinal chemistry. Misoprostol is chemically belonging to Economides.
PGE1 ANALOG MISOPROSTOL

MISOPROSTOL ¯ HCL SECRETION
Consist of 2-OH and one double - MUCUS SECRETION & BICARBONATE
bond. USED FOR CYTOPROTECTIVE EFFECT.
DOES NOT PREVENT GI SYMPTOMS
PGE 1 analogs pharmacology. PGE 1 and PGH 1 can be used to produce relatively local vasodilatation.
PGE 1 analogs therapeutic uses:

· Misoprostol is used for prevention of NSAID induced GI ulcers.
· Combination products. Naproxen + misoprostol, and diclophenac + misoprostol.
· Misoprostol vaginal use is for cervical priming before endometrial procedures (dilation and curettage).
· Alprostadil. In adults it useful for the treatment of impotence due to erectile dysfunction.
· Alprostadil is used for temporary maintenance of a patent ductus arteriosus when awaiting corrective
surgery for congenital heart defects.
PGE 1 analogs side effects
· Misoprostol. Abortificient side effect. The common side effects is diarrhea. Abdominal pain, uterine
contraction (can cause miscarriage in pregnancy).
PGE 2 analogs classification

· Dinoprostone derivatives. Dinoprostone
PGE 2 analogs therapeutic uses. Dinoprostone are used for their abortificient effects and to induce cervical
ripening in pregnancy.
PGF 2 a analogs classification: LATANOPROST, TRAVOPROS, BIMATOPROST, UNOPROSTONE

PGF 2a ANALOG Question Alerts!
- outflow of aqueous humor.
PGF 2a analogs pharmacology. Lowers IOP by increasing uvescleral (aqueous humor) outflow.
PGF 2a analogs therapeutic uses.
· Latanoprost (Xalatan) 0.005% ophthalmic solution. Used topically to lower intra ocular pressure in OAG,
combination products latanoprost + timolol indicated for open and close angle glaucoma.
· Travoprost (Travatan). Topical ophthalmic drug

· Bimatoprost (Lumigan). Topical ophthalmic drug
· Unoprostone (Rescula). Topical ophthalmic drug
· Carboprost (Hemabate). Abortificient (withdrawn).
PGF 2a analogs side effects: Eye pigmentation, lengthening and thickening eyelashes.
PGI analogs. Epoprostenol (Prostcyclin)
PGI analogs (prostacylcin) chemistry
PGI analogs (prostacylcin) pharmacology

PGI analogs (prostacylcin) therapeutic use. Epoprostenol. Used in the treatment of emergency pulmonary
hypertension. It produces antiplatelets action.
Thromboxanes (TxA2).
· Increase platelet aggregation and potent vasoconstrictors.
· Dipyridamol blocks thromboxane thus produce antiplatelet action.
Leukotrienes
Leukotrienes are produced from arachidonic acid; this reaction is catalyzed by 5-lipoxygenase enzyme, which
oxidize polyunsaturated fatty acids possessing
two cis double bonds separated by a methylene
group to produce lipid hydroperoxide. Questions Alerts!
1) Leukotrienes are produced from arachidonic
Leukocytes express lipoxygenase and release acid by the catalyzation of? Lipoxygenase
leukotrienes in lungs. Plays important role in 2) LTRAs act on? LTC4 and LTD4
numerous physiological functions. 3) Leukotriene inhibitors used in children > 2yrs?
· Slow reacting substance of anaphylaxis. Montelukast
· Heart. Negative inotropic, and smooth
muscles chemotaxis.
· GI tract. Neutrophil chemotaxis.
· Pulmonary (major): Bronchoconstriction, increase permeability, and increase mucus secretion.
· Blood: Chemotactic agent for neutrophil, eosinophils, and modify lymphocyte proliferation and
differentiation.
Leukotriene antagonists’ chemistry. Zafirlukast and montelukast have peptidomimetic structure and inhibit
LTC 4 and LTD 4 receptors.
MONTELUKAST inhibit LTC 4 and LTD 4 receptors

PEPTIDOMIMETIC STRUCTURE
ZAFIRLUKAST
Leukotrienes antagonist’s therapeutic uses.

Zafirlukast: For the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and
older. Take empty stomach to enhance it absorption.
Montelukast. Can be used in children over 2-year age, Montelukast may be taken without regard of food.
Available as chewable tablet (once daily in the evening) and granules. Administer granules directly into mouth or
mix with teaspoon of cold or room temperature applesauce, carrot, rice or ice cream. Do not take Aspirin or
NSAIDs while on this medication.
Leukotriene inhibitors are drug of choice for the treatment of Aspirin induced asthma and maintenance.
Side effects. GI upset, abdominal pain, diarrhea, liver dysfunction, and headache.
Drug interactions. Terfenadine significantly reduces the plasma concentration of zafirlukast.
Non Steroidal Anti-inflammatory Drugs (NSAIDS)

Salicylates derivatives NSAIDs: Cox 1&II reversible competitive inhibitors
Acetyl salicylic acid (ASA) Antiplatelet, antipyretic, analgesic and anti-inflammatory [AAAA]
ASA is irreversible Cox I & II inhibitor.
Salicylic acid
Methyl salicylates Wintergreen oil-topical agent, counter irritant
Salsalate, sodium thiosalicylate Injectable
Choline salicylate Oral liquid
5-Aminosalicylic acid Crohn's disease and ulcerative colitis
(Mesalamine)
Olsalazine
Sulphasalazine Active product is 5ASA. Use for ulcerative colitis and Crohn's disease
Diflunisal Diflurophenyl derivative of salicylic acid
Pyrazolone derivatives
Sulfinpyrazone
Phenylbutazone
Propionic acid derivatives The order of gastric ulcerogenic activity.
Sulindac>naproxen >ASA, indomethacin, ketoprofen, ibuprofen
Ibuprofen Primarily used for pain associated with inflammation. Mild stomach upset
Ketoprofen
Naproxen Primarily Long lasting pain and migraines. Can be hard on stomach
compare to ibuprofen.
Carprofen
Fenoprofen
Acetic acid derivatives

Indomethacin The most potent. But high renal side effects, have high anti-inflammatory
Diclofenac (po, topical, spray) Voltaren
Ketorolac Toradol. NSAID used for acute pain.
Sulindac
Etodolac
Anthranilic acid derivatives
Mefenamic acid Used for menstrual pain or dysmenorrhea.
Meclofenate
Oxicams derivatives
Piroxicam Feldene
Meloxicam
Pyrazole derivatives. COX II inhibitors: induced in pathological states inducible; Cox II produce
prostaglandins at inflammation sites, macrophages, synovocytes, and
cause inflammation and pain.
Celecoxib (Celebrex) COX II Enzyme are responsible for arthritis pain, thus COX2 inh. Are long
term used for arthritis. Increase risk of blood clot, heart attack, or stroke
and CHF.
Lumerocoxib Only has no sulfa allergy, where all other Cox II inhibitors have sulfa
allergy.
Chemistry of Salicylates derivatives
F OH
COOH OH
F COOH
O
CH3 COOCH3
O
Diflunisal (Dolobid) Methyl salicylate (Wintergreen oil)

Acetyl Salicylate
Acetyl salicylic acid (ASA)

· Pharmacological actions: ASA exhibits analgesics, antipyretics, anti-inflammatory and antiplatelet actions.
ASA irreversibly inactivates both COX 1 & COX 2 , where as all other NSAIDs inactive reversible COX 1 & COX 2 .
Onset: 5-30 min, duration 3-6 hours
Analgesic action
· Prostaglandin PGE 2 thought to sensitize the nerve endings to the action of bradykinin, histamines and other
chemical mediators, thus inflammatory process may cause analgesic action. Decrease of PGE 2 synthesis
represses the sensation of pain. ASA analgesic dose 325 mg every 4 to 6 h.
Antipyretic action
· Prostaglandin PGE 2 stimulation occurs when pyrogen an endogenous fever producing agents such as
cytokines is released from the white blood cells that are activated by infection, hypersensitivity, malignancy
or inflammation. Salicylates lower temperature by decreasing PGE 2 synthesis. ASA antipyretics dose 325 to
650 mg q 4 to 6 h PRN.
· Reye syndrome: Children with flu and viral infection should avoid using ASA, because it may cause Reye’s
syndrome.
Antiplatelets action
Irreversible platelet inhibition and inhibition of Cox-I & Cox-II action gives antiplatelets action. Antiplatelets
action minimum dose is 60 to 80 mg.
Anti-inflammatory action: Cox-I, Cox-II and prostaglandin inhibition. The anti-inflammatory dose of ASA 650 mg.
Mechanism of action of ASA. COX -1 FUNCTIONS COX-2 FUNCTIONS

COOH Daily synthesis of prostaglandin Expressed only in response of
O OCH3
ASA that contribute to normal inflammation of injury.
O
homeostatic (arrest of bleeding).
Cyclooxygenenase Active Protection of the gastric mucosa
COX I & II
O through prostaglandin
O C CH3 Hemostasis through the
Cyclooxygenase (inactive)
synthesis of thromboxane.
COOH
OH
GI mucosa Cox I PGE2 - Gastric protection, NSAIDs

Arachidon - bicarbonates, - mucosal blood flow - GI bleeding,
ic acid peptic ulcer
Kidney Cox I & II PGE2 & PGI2; efferent arterial vasodilation ¯GFR & -
(-GFR) and - Na&H2O excretion Na&H2O
retention
Cardiovascu Cox I & II PGI2&TxA2 vasoconstriction, platelet - stroke and MI
lar aggregation
COX2: vasodilation and inhibit platelet
aggregation.
Problems associated with NSAID and acetyl salicylic acid.

· Respiratory depression: Toxicity respiratory alkalosis and metabolic acidosis (increase CO2 and decrease pH).
· GI effects: due to inhibition of prostaglandin PGEs. Prostacyclin PGI 2 inhibit gastric secretion. The most
common side effects of salicylate are GI disturbances like nausea, vomiting, epigastric discomfort, GI
bleeding, peptic ulcers (dyspepsia, heart burn).
· PGE 2 and PGF 2a stimulates synthesis of protective mucosa in stomach and small intestine.
· Indomethacin has the highest incidence of (35 to 50%) of GI ulcers.
· Renal problems: PGE 2 and PGI 2 are responsible for renal blood flow. NSAID ¯ RENAL BLOOD FLOW. It can
cause acute renal failure.
NSAIDS INDUCE ASTHMA BY AIRWAY RESISTANCE.
Reye's syndrome is an acute syndrome that may follow influenza and chicken pox infections in children. It is
characterized by symptoms of sudden vomiting, violent headache, and unusual behavior. The Reye's syndrome
is associated with only ASA.
Sulfasalazine chemistry
· Contains azo bond. Sulfasalazine contains a sulfonamide group, may cause allergy patients with sulfa allergy.
· In metabolism undergoes azo reduction (phase I). Metabolism produces 5-amino salicylic acid. Sulfasalazine,
olsalazine, balsalazine are metabolized in the colon by gut flora to yield 5ASA. Avoid in ASA allergic patients.
· Sulfasalazine therapeutic use drug of choice for ulcerative colitis.
· Sulfasalazine side effects: can cause megaloblastic anemia, and infertility (in men).
NH2 CO2H
Azo bond OH
5-aminosalicylic acid
O N (Mesalamine)
S
N Azoreductase +
COOH N OH
O N
N S
HO at Gut N
OH
Sulfasalazine NH2
Sulfapyridine
Azoreduction in colon
Diflunisal
· Diflurophenyl derivative of salicylic acid.
· No salicylate toxicities (does not produce salicylic acid)
· No antipyretic action
Propionic acid derivatives: Ibuprofen, Ketoprofen, Naproxen, Carprofen and Fenoprofen

IBUPROFEN Propionic acid
LOW GI SIDE EFFECT
H3C
CH COOH
Ibuprofen
ACETIC ACID DERIVATIVE

Acetic acid derivatives: Indomethacin, Diclofenac, Ketorolac, Sulindac and Etodolac
INDOMETHACIN Acetic acid
Sulindac has long half-life used daily or BID.
H3CO COOH
CH3
N
O
Indomethacin
Cl
Acidic acid derivative therapeutic uses

· Indomethacin is used for acute gout attacks treatment, more CNS effect, aplastic anemia and
contraindicated in elderly.
· Diclofenac (Voltaren)à ophthalmic drops
· Ketorolac (Toradol)à short-term use only
· Sulindac (Clinoril)à safest in renal failure
ANTHRANILIC ACID (FENAMATES) DERIVATIVES

Mefenamic and Meclofenate Anthralnic acid
Mefenamic acid is associated
acid with severe diarrhea and
H3C
associated with inflammation of
CH3
bowel.
NH
COOH
Preferred in dysmenorrhea
Mefenamic acid
Anthranilic acid (fenamates) derivatives therapeutic use: PREFERRED IN DYSMENORRHEA
Oxicams derivatives: Piroxicam (feldene), Meloxicam (Mobic) and Tenoxicam.

MELOXICAM OH
CONH
N N
S CH3
O2
Piroxicam
Oxicams derivatives side effects

· Piroxicam (Feldene)à Its mean half life is 50 hours; thus, this can be used once daily dose, more bleeding,
contraindicated in elderly.
p-Aminophenol derivatives: Acetaminophen chemistry.
ACETAMINOPHEN H3COCHN
Acetaminophen is an active
Dealkylation
metabolite of phenacetin or
acetanilide.
CH3CONH OCH2CH3
OH
Phenacetin Acetaminophen
Phenacetin or acetanilideà Acetaminophen
Acetanalide--> Hydroxylation--> acetaminophen

Acetaminophen pharmacology: Acetaminophen has antipyretic and analgesic action.
· Inhibits central prostaglandin synthesis in CNS. Less effective in blocking peripheral prostaglandin synthesis,
acetaminophen has no anti-inflammatory activity and does not effect on platelet function.
· Antipyretic action dose is 325 to 650 mg q 4 to 6 h PRN.
· Acetaminophen does NOT have Rye syndrome and may safely be able to be used in patient (child) with
varicella or an influenza type viral infection.
· Can be used in ASA or NSAID allergic patients. Can be used in children because no Rye syndrome.
Advantages are stable in liquid thus available in various solutions.
Acetaminophen side effects.

Skin rash, hemolytic anemia (long term phenacetin use), high doses renal dysfunction and tubular necrosis
hepatotoxicity if it used more than 4 g/day. With excessive alcohol max dose 2 g/day.
Acetaminophen metabolism: Acetaminophen undergoes phase I metabolism and glucuronidation, sulphate

conjugation, and glutathione conjugation. Toxic intermediate of phase I metabolism is N-benzoquinoneimine,
which is catalyzed by glutathione conjugation leading to cysteine and mercapturic acid.
Acetaminophen Metabolism
Question Alerts!
O
1) Acetaminophen structure?
CH3 C NH OH
2) Phenacetin dealkylation gives acetaminophen.
3) Acetanilid hydroxylation gives acetaminophen
e Acetaminophen 4) Common Side effects of acetaminophen? Skin
sf e r as UDP-GT
tran rash
S ulfo
Glucoronidation 5) Acetaminophen can cause? Hepatotoxicity
Sulfate conjugation 6) Acetaminophen metabolism occurs in? Liver
Cytochrome CYP 450 7) Toxic metabolite intermediate produced by
acetaminophen in liver is? N-Benzoquinoneimine
N-benzoquinoneimine 8) Toxic metabolite N-benzoquinoneimine is
catalyzed by? Glutathione conjugation
Glutathione conjugation 9) Glutathione conjugation end product is ?
Mercapturic acid
Mercaptopurine
Glutathione saturation causes hepatotoxicity. Antidote N-acetylcysteine binds with glutathione and activate
metabolism of N-benzoquinoneimine.
HS
O Glutathione is consisting of glutamic acid, cysteine, and
H glycine
HOOC N COOH Antidote of acetaminophen is N-acetylcysteine
N (CH3CONH-CH-(COOH)-CH2SH)
H
NH2 O NAPB. N-acetyl p-benzoquinoneimine.
Glutatione UDP-GT. Uridinyl diphosphate glucuronidase
transferase.
COX-2 INHIBITORS
Celecoxib (Celebrex), Celecoxib (cerebrex) CELECOXIB IS USED FOR ARTHRITIC PAIN
SO2NH2
PYRAZOLE DERIVATIVES Question Alerts!
F3C N
N Drugs that have sulfa allergy?
Celecoxib, hydrochlorothiazide, sulfonamide
CH3 antibiotics, acetazolamide, Furosemide,
sulfasalazine, rosuvastatin.
· COX 2 inhibitors Side effects: Arrhythmias, GI upset, diarrhea, back pain, respiratory problems, and
nephrotoxicity. Celebrex contain sulfa group; therefore, celecoxib has sulfa allergy.
· Celecoxib and valdecoxib have sulfonamide functional group.
OPIOIDS STRUCTURE ACTIVITY

Benzomorphan Pentazocine. HCl Weak mu antagonist and potent kappa
derivatives Pentazocine lactate
agonist action
Pentazocine-kappa agonist, given with
naloxone to prevent abuse.
Phenyl piperidine Fentanyl citrate Structure activity of opium alkaloids.

Meperidine. HCl 5) Meperidine metabolizes to
Derivatives (pethidine) normeperidine and this can cause seizures.
Sufentanil citrate 6) Fentanyl short half-life and lipid
Loperamide solubility helps to transdermal action.
Morphinan Butorphanol tartrate Butorphanol. A kappa agonist, mu

Nalbuphine. HCl antagonist more potent but less efficacy
Derivatives
than morphine and not orally active.
Natural opium Codeine phosphate 1) p-phenyl N-methyl piperidine is

Hydromorphone.HCl essential.
alkaloids Morphine.HCL 2) Morphine diacetylation gives heroin.
Morphine sulfate 3) Codeine demethylation gives morphine
Oxycodone.HCl by CYP 2D6.
Oxymorphone.HCl Buprenorphine a mixed analgesic, more
Buprenorphine potent than morphine but less efficacy.
Phenylethylamine Methadone Methadone and propoxyphene structurally

Derivatives related to phenylethylamine
Propoxyphene.HCl
Propoxyphene
napsylate
NALOXONE Naloxone is antidote has “N-allyl group”.
CH3 Acetyl groups CH3

CH3
9 N N
N
1
O O
CH3O O OH O
HO 3 O 6 OH H3C C O O C CH3
Morphine Codeine Heroin
CH3 CH3
N CH3 H3C CH2 O
N H3C
N CH2CH2 C O C CH2CH3
N
HO CH3
H3C O
HO O O CH3O O O
Oxycodone Propoxyphene
Hydromorphone Methadone
CH2CH CH2 CH3

Allyl group CH2CH C CH2
N CH3
N N
HO CH3 HO
CH3
HO O O HO HO
Pentazocine Butorphanol
Naloxone
CYP2D6 (DEMETHYLATION)
CODEINE ----------------------------------------> MORPHINE
HYDROCODONE ---------------------------------à HYDROMORPHONE
OXYCODONE ------------------------------------à OXYMORPHONE
Morphine structure activity

· Reactive metabolite of morphine is morphine 6-glucuronide
· Phenolic hydroxyl is important for activity. Analgesic activity is depending on p-phenyl-N-alkylpiperidine
moiety (4-phenylpiperidine). Piperidine ring is chair-form conformation and perpendicular aromatic ring. It
has tertiary amine group (methyl).
· Codeine, heroin, morphine, meperidine, hydromorphone is structurally same class and have cross allergy.
Hydrocodone is derivatives of codeine, hydromorphone is derivative of morphine.
· Meperidine is piperidine analgesics, meperidine metabolizes to toxic metabolite normeperidine this can
cause seizures in renal disease patients.
· Partial agonist/antagonist characteristics replacement of methyl moiety on the nitrogen atom with larger
substituent's.
· Allyl substitution is present in naloxone. This allyl group is associated with opioid antagonist action.
· Substitutions at the C 3 and C 6 morphine hydroxyl group’s pharmacokinetic properties altered.
· Methyl substitution at C 3 reduces first-pass hepatic metabolism by glucuronide conjugation as a
consequence codeine and oxycodone have a higher oral, and parenteral potency.
· Acetylation of both morphine hydroxyls gives heroin (more rapid access across the blood-brain barrier
compared morphine) in the brain heroin is rapidly hydrolysed to monoacetylmorphine and morphine.
Opioids as antidiarrheal drugs

· Loperamide (Imodium). Has low abuse potential. Used as antidiarrheal. Maximum dose 16 mg/day.
· Diphenoxylate + Atropine: Lomotil
Opioids as antitussives drugs:

· Codeine is used extensively as cough suppressants.
· Hydro codeine bitartrate is 3 times more effective as antitussive.
· Dextromethorphan HBr is the (+) isomer of the 3-methoxy form of the synthetic opioids levorphanol.
Tips
1. PGF2a analog 2. Ecosonide PGE1 analog 3. Tryptophan
4. histadine 5. LTC 4 and LTD 4 6. N-acetyl-p-benzoquinoneimine
7. Mercapturic acid 8. proton pump inhibitor 9. Pyroxicam
10. Misoprostol 11. Tertiary amine 12. Lipid soluble
13. Crosses BBB 14. GI bleeding 15. Renal diseases
16. 5HT3 antagonist 17. 5HT1B/1D agonist 18. peptide opioid neurotransmitter
19. Diacetyl morphine 20. cysteine 21. glycine
22. glutamic acid 23. pinpoint pupil 24. respiratory depression
25. constipation 26. Type 1 PG analog 27. steroid sparing agents
28. analgesic 29. antidiarrheal 30. antitussive
· Histamine precursor is? ( )

· Serotonin precursor of? ( )
· Misoprostol is? ( )
1st generation antihistamines often cause sedation, this is due to? ( )
· Ondansetron is classified as? ( )
· Triptans is classified as? ( )
· Latanoprost is classified as? ( )
· Montelukast and zafirlukast act on? ( )
· Endorphins are? ( )
· Acetaminophen hepatotoxicity is due to? ( )
· Glutathione conjugation produce? ( )
· The most common side effects associated with NSAIDs ( )
· What NSAID has highest GI bleeding? ( )
· Drug of choice to treat NSAID induced GI ulcer ( )
· Drug of choice to prevent NSAID induced GI ulcer? ( )
· Glutathione consist of? ( )
· Ibuprofen, indomethacin, mefenamic acid are? ( )
· Leukotriene antagonist also referred as? ( )
· Opioids can be used as? ( )
· Heroin structure ( )
· Morphine overdose symptoms; ( )
· Glutathione ( ) is a tripeptide that contain unusual tripeptide linkage between amino acids of L-
Glutamaic acid, L-Cysteine and Glycine
26
Medicinal Chemistry and
Pharmacology of Cardiovascular
Drugs
Questions Alerts!
· Mechanism of diuretics and site of actions. Hydrochlorothiazide chemical structure.
· Structure activity relation ACEi. and captopril structure
· Structure activity relation ARBs.
· Statins or HMG Co-A reductase inh. and structure activity relation
· Calcium channel blocker (CCBs) structure activity relationship
· Vasodilators: Hydralazine, dizoxide and CCB,s
Thiazide Loop diuretics K+ Sparing CA inhibitors Osmotic

Chlorthalidone Ethacrynic acid Amiloride Acetazolamide Mannitol
Hydrochlorothiazide Furosemide Spironolactone Dorzolamide Urea
Indapamide Triamterene
Metolazone Eplerenone
Distal convoluted Ascending loop Collect duct Proximal tubule Proximal

tubule tubule
Hyper GLUC OH DANG HyperKalemia
Loops loose Ca
Metabolic alkalosis Metabolic Metabolic acidosis Metabolic
alkalosis and intracellular acidosis
alkalosis
Diuretics
In general, the opposite findings of serum electrolytes are seen in urine.
Type of Site of Ca Mg Na K Uric Blood Lipids Metabolic Disturbances

diuretic action acid sugar
Thiazide Distal - ¯ ¯ ¯ - - - Hypokalemic metabolic alkalosis
convoluted "HYPERGLUC"
tubule
Loop Loop of ¯ ¯ ¯ ¯ - - _ Hypokalemic metabolic alkalosis
henle
K- Early _ - ¯ - - _ _ Hyperchloremic metabolic acidosis
sparing Collecting (↑CO 2 )
duct Intracellular alkalosis
CAI Proximal _ _ _ ¯ - - _ Hyperchloremic metabolic acidosis
tubule
Osmotic Glomerular ¯
Thiazide diuretics: Chlorthalidone, hydrochlorothiazide, indapamide hemihydrate, and metolazone.
Thiazide diuretics chemistry: Benzene ring with sulfonamide in position 7, and halogen or trifluoro methyl group
in position 6. The electron withdrawing group at position 6 is necessary. Saturation of 3, 4 double bonds
(increases potency with hydrochlorothiazide).
Methyl group at position 2, or lipophylic substituents at position 3, enhance the potency and prolong the
activity. Replacement of sulfonyl in position 1 by a carbonyl group prolongs the activity.
H No Doble bond
Cl N on position 3 - 4 Cl N
NH NH
Essential NH2SO2 S NH2SO2 S
O2 O2
Hydrochlorothiazide Chlorothiazide
Cl
O N CH3
NH2SO2 NH
Cl S
N CH3 O2
Indapamide (Lozol) Diazoxide (Hyperstat)
Hydrochlorothiazide Chlorothiazide
Tablets Liquid
The duration of action up to 18 The duration of action is 6-
hrs 12 hrs.
Thiazide diuretics pharmacology

· Thiazide act on distal tubule of nephron and ↑ H 2 O, Na, Cl, K, excretions (↓ levels in body), hyperuricemia
and retain calcium (Ca). long term use of thiazides can cause hypokalemia and hypomagnesemia thus K
and Mg supplement may require.
· May cause alkaline urinary pH by effecting on carbonic anhydrase.
· Metabolic alkalosis (Hypochloremic alkalosis).
Thiazide diuretics therapeutic uses
· Thiazides are the drug of choice for uncomplicated hypertension.
· Especially useful in elderly and African populations and with chronic renal diseases.
· Not effective in patient renal clearance less than 50 ml/min.
· Not preferable in diabetic and hyperlipidemic patient.
Thiazides diuretics side effects (Hyper GLUC)

· Hypokalemia, hypomagnesia, hyponatremia, hypercalcemia, hyperuricemia, hyperglycemia, metabolic
alkalosis, photosensitivity rashes, acute pancreatitis, libido, difficulty with erection and ejaculation (long
term).
Loop Diuretics: Furosemide, ethacrynate sodium, and ethacrynic acid. Also known as high ceiling diuretics. i.e.
produce a peak diuresis much greater than other diuretics.
Loop Diuretics chemistry: Anthranilic acid derivatives with sulphonamide substituent, or aryloxyacetic acids
without sulphonamide substituent.
LOOP DIURETICS
FUROSEMIDE 2-Aminobenzoic acid derivative
Sulfa allergy
Reversible ototoxicity
ETHACRYNIC Phenoxy acetic acid derivative

ACID NO Sulfa allergy
Irreversible ototoxicity
Loop diuretics pharmacology

· Increase H 2 O, Na, Cl, K, Ca excretion (decrease levels in body) and Increase Ca2+ ion excretion
(hypocalcemia) (Loops Lose Calcium).
· No change in urinary pH. Metabolic alkalosis (hypochloremic alkalosis)
· Act in the thick ascending loop of henle and inhibit the sodium/potassium dichloride co-transport system.
Potent agent can excrete up to 25% of filtered Na+. No ions come into the cell therefore the sodium pump
and Na/Cl symport do not work.
Loop diuretics therapeutic use: Furosemide is the drug of choice in renal disease (CrCl is less than 50 ml/min),
acute pulmonary edema, and hypercalcemia.
Loop diuretics side effects: [OH DANG] Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfa), except ethacrynic
acid, Nephritis (intestinal), and Gout arthritis.
Sequence of ototoxicity (ethacrynic acid > furosemide > bumetanide)
Ototoxicity: Ethacrinic acid ototoxicity is irreversible (permanent hearing loss). Renal disease increase risk of
ototoxicity.
Furosemide ototoxicity is reversible sensory neural hearing loss, i.e. discontinuing drug can be normal.
Loop diuretic onset in 30 min and last 6 hrs.
Carbonic anhydrase inhibitors: Acetazolamide, dorzolamide, brinzolamide.

Carbonic anhydrase inhibitor chemistry: Acetazolamide. Aromatic or heterocyclic sulfonamides with a
thiadiazole ring.
CARBONIC ANHYDRASE INHIBITORS

ACETAZOLAMIDE All CA inhibitors the sulfonamide l group is
essential for CA inhibitory activity.
DORZOLAMIDE
Carbonic anhydrase inhibitor pharmacology. Increase water, sodium, and potassium and bicarbonate excretion.
Cause alkaline urinary pH, and gives metabolic acidosis.
Carbonic anhydrase inhibitor therapeutics: Used in treatment of glaucoma (not chronically). Acute mountain
sickness (respiratory alkalosis) also high altitude sickness (mountain sickness). Because of the alkaline diuresis it
produces, acetazolamide has been used for the treatment of overdoses of acidic drugs.
Carbonic anhydrase side effects

· Because of the alkaline Electrolytes à Hyperchloremic metabolic acidosis (loss of HCO 3 -), hypokalemia.
· Formation of renal stones (phosphaturia & hypercalciuria).
· CNS à depression, drowsiness, sedation, fatigue, and disorientation.
· GI à Nausea, Vomiting, and Constipation
· Blood related à Bone marrow depression, thrombocytopenia (reduction of number of platelets in blood),
hemolytic anemia, leucopenia (reduction in number of WBC), agranulocytosis (acute deficiency of
neutrophils). Sulfa drugs antibiotics type allergies.
Osmotic diuretics. Mannitol and Urea

OSMOTIC DIURETICS
MANNITOL Mannitol is a carbohydrate, monosaccharide
UREA
Osmotic diuretics chemistry

· Water-soluble with low renal threshold, and highly polar.
· They limit tubular reabsorption of water.
· Promote diuresis.
· Increase in urinary pH
Osmotic diuretics pharmacology

· This drugs limit tubular reabsorption of water and promote diuresis.
· Increase excretion of H 2 O, Na, Cl and HCO 3 (decrease levels in body), increase alkaline urinary pHàIncrease
excretion of HCO 3
Osmotic diuretics therapeutic use

· This drugs limit tubular reabsorption of water and promote diuresis.
· Mannitol used in treatment of shock, to treat drug overdose and to decrease intracranial or intraocular
pressure.
· Prophylaxis of acute renal failure.
Osmotic diuretics side effects. Pulmonary edema, dehydration and contraindicated in CHF, and anuria (renal
failure).
Potassium sparing diuretics: Spironolactone, eplerenone, amiloride, and triamterene
Potassium sparing diuretics chemistry

Competitive inhibitor of aldosterone Blocks Na uptake at the luminal membrane and blocks
excretion of K+
Spironolactone, Eplerenone Triamterene and Amiloride
Aldosterone hormones increase K+ excretion in
collecting duct and reabsorb Na+ and Cl-
· Spiranolactone binds at the receptors at the late distal tubule and collecting tubules thus prevents the
reabsorption of Na+ and Cl- ions. Inhibits potassium secretion thus increase K+ levels.
· Pteridine or pyrazine derivatives or steroid analogue antagonist of aldosterone.
· Triamterene, amiloride contain pteridine or pyrazine derivatives.
· Spironolactone: Contain sterol structure + lactones.
CH2 CO
H3C CH2
O NH2
H3C N
N
H2N N N NH2
O SCCH3
O
spironolactone(Aldactone) triamterene(Dyrenium)
Spironolactone metabolized to main active metabolite canrenone by first pass metabolism in liver. This
metabolite has hepatocarcinogenic effect. Canrenone is responsible for 80% of its activity.
Metabolism in liver.
Spironolactone ------> Canrenone-------> canrenoic acid anion
Eplerenone is a new aldosterone antagonist. Metabolized by CYP450.

Eplerenone has no hormonal side effects like gynecomastia.
Eplerenone is derived from spironolactone by substitution of the 17-alpha thioacetyl group of spironolactone
with a carboxymethoxy group.
Potassium sparing diuretics pharmacology

· Act in the early collecting duct to inhibit the electrogenic reabsorption of Na+ by blocking the Na channels
and hence the exchange of sodium for potassium.
· After administration: ↑ Na+, Cl- elimination, ↓K+, Ca2+ (amiloride).
· Increase Na, H 2 O, HCO 3 excretion (decrease levels in body), decrease K+, H+ excretion.
· Alkaline urinary pH, and increase excretion of HCO 3 .
· Potassium sparing diuretics gives the intracellular alkalosis.
Potassium sparing diuretics therapeutic use

· Amiloride, spironolactone and triamterene act as competitive antagonists of aldosterone in the kidney.
Because they are weak diuretics when given alone, they are often used in combination with
hydrochlorothiazide.
· Spironolactone is the drug of choice for the treatment of ascites.
· Spironolactone is antiandrogenic and has been used to treat hirsutisms in doses of 200 mg/day.
· Amiloride used in nephrogenic diabetic insipidus
· Spironolactone is the drug of choice for the treatment of ascites.
Potassium sparing diuretics side effects

· A side effect may be hyperkalemia, an increase in potassium levels, so that potassium supplements are
usually not taken with these drugs. If they are needed, the dose of potassium is frequently administered
three times a week instead of daily.
· Side effects of spironolactone include endocrine à Gynecomastia, menstrual irregularities, Electrolytes à
Hyperkalemia, irregularities, CNS à mental confusion
Vasodilators
Vasodilators cause the smooth muscle in blood vessels to relax. Relaxed or dilated blood vessels allow more
blood to flow through, causing a reduction in blood pressure by decreasing peripheral resistance. As vasodilators
work, the blood vessels become dilated causing a drop in pressure because there is less blood volume to fill the
vessel. The body can compensate for this by retaining enough fluid to fill the blood vessel sufficiently to raise the
blood pressure again.
Hydralazine and minoxidil are direct vasodilators not usually used a sole therapy for high blood pressure, as their
effect is usually short-lived when administered alone. Minoxidil is available in tablets and also as a topical lotion
(Rogaine) for treatment of male-pattern baldness).
NH2
HN
hydrazine group
NH (Basic)
NH
Hydralazine
ACE Inhibitors
Captopril, benazepril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, and trandolapril.
Question Alerts!
1) Sulfhydryl in captopril is active group, where as other ACEi, carboxylic acid is active group.
2) All ACEi are primarily eliminated by renal, except. Fosinopril (50:50). (dose adjustment not require
renal impairment).
ACE Inhibitors chemistry

Sulfhydril containing inhibitors. Captopril. Sulfhydryl group leads to shorter duration of action.
O
HS - H2C
N
CH3
CO2H
Captopril
Dicarboxylate containing inhibitors. all ACEi
Phosphonate containing inhibitors. Fosinopril
Captopril and Lisinopril are acidic drugs while all other are amphoteric.
The carboxylic attached to N-ring is common structural feature in all ACEi. The sulfhydryl group of captopril is
proved to responsible for excellent activity of captopril, and this also responsible of its two most common side
effects skin rashes and taste disturbances (example metallic taste and loss of taste). The sulfhydryl group also
present in another drug penicillamine, which attributes to its metallic taste.
Free acid group or sulfhydryl or phosphonate groups essential for the activity.
O O-CH2-CH3
O Esterase O OH
NH O
N HN N
CH3 CH3
HO2C
Bioactivation of Enalapril
Captopril and LISinopril are acidic drugs while all other ACE inhibitors are amphoteric.
ACE Inhibitors that are NOT prodrug captopril and LISinopril.
All ACEi are once daily used, except captopril (2-3 times) daily.
Enalapril is prodrug of Enalaprilate.
Lisinopril is a lysine analogue of Enalaprilate.
Fosinopril is phosphate containing ACEi.
What enzyme polymorphism effect ACEi? Angiotensin converting enzyme (ACE)
ACEi lowers nephropathy mechanism
Proteinuria
Aldosterone Na&H2O retention
Angiotensin II -------------------àKidney ¯GFR
ACEi ¯proteinuria
& ¯ Na & H 2 O retention
ARBs - GFR (renal perfusion well maintained)
No rebound hypertension
ACE Inhibitors pharmacology

· ↓ sympathetic output
· Increase vasodilatation of smooth muscles
· ↑ levels of bradykinin cause dry cough
· By reducing circulating angiotensin II levels ACEi ↓ the secretion of aldosterone, resulting ↓ retention of Na
and H 2 O retention leads to decrease in cardiac output (CO).
· ↓ in preload and after load
· Dilation of venous blood vessels leads to decrease in cardiac preload by ↑ venous capacitance.
· Arterial dilator reduces systemic arteriolar resistance and ↓ after load.
· Lower blood pressure by reducing peripheral vascular resistance with reflex increasing cardiac output rate.
ACE Inhibitors therapeutic use

· ACE inhibitors are used to treat uncomplicated hypertension and pre-hypertensive patient. However, if
Angiotensin is not the contributing factor for the hypertension, the chances of ACE inhibitors working are
diminished.
· These drugs represent a major advance in hypertensive treatment and have most displaced digoxin as the
drug of choice in congestive heart failure. 1st line treatment for: Heart failure.
· ACE inhibitors also tend to protect the kidneys of diabetics from developing renal failure when used in the
early stages of diabetic nephropathy. Diabetes nephropathy, post MI.
· LVH (Left ventricular heart failure).
· Prior CVA/TIA (Cardiovascular Attacks/ Transient Ischemic attacks) & in renal disease.
ACE Inhibitors side effects

· Profound low pressure (hypotension), taste abnormalities, dry cough (5 to 15%), blood cell abnormalities,
and kidney problems such as proteinuria (presence of protein in urine). They are contraindicated in
pregnancy. A persistent dry cough may necessitate discontinuing the drug. ACE inhibitors increase the risk
of hyperkalemia. Allergic reactions angioedema (rare). Reversible neutropenia and fatigue.
Dry cough Due to - bradykinins
Hypotension
Hyperkalemia
Angioedema
Proteinuria in renal
stenosis
- serum creatinine
Reversible
neutropenia
Pregnancy
contraindicated
Angiotensin Receptor Blockers (ARBs)

Losartan, telmisartan, valsartan, irbesartan, and candesartan.
ARBs are analogs of imidazole ring attached with 5–CH 2 -OH group (imidazole-5-acetic acid).
N
Cl
Question Alerts! N
Imidazole ring (essential)
1) Structure activity of Angiotensin receptor
blockers imidazole is essential.
2) Telmisartan and Candesartan cilexitil have Tetrazole ring OH
benzimidazole. This enhances hydrophobic binding
and increase potency (peak/trough ratio). N N
3) Candesartan is prodrug. N
4) all ARBs have tetrazole ring N
5) All ARBs have renal and fecal elimination (avoid H
telmisartan (fecal 97%) in hepatic dysfunction)
Losartan
Angiotensin receptor blockers, block the effects of angiotensin II, a naturally occurring substance that causes
blood vessels to narrow (constrict). When these drugs are administered, blood vessels dilate, thereby lowering
blood pressure and decreasing the workload of the heart. These drugs appear to have the same benefits as ACEi,
without or less producing the common side effect of a dry cough.
Pharmacological actions
· Angiotensin binds to its own receptors are found on vascular muscle and in the adrenals.
· Stimulation leads to vasoconstriction and release of aldosterone in the adrenal gland.
· It blocks aldosterone secretion.
Side effects
Less dry cough (cough associated with ACEi does appear with these drugs), Bradykinin causes vasodilation of
arterioles and venules results ↓ TPR, less dry cough. Dizziness, hypotension/syncope, renal dysfunction
(reversible renal failure), hyperkalemia and angioedema.
Contraindications. Pregnancy (renal fetal toxicity), and bilateral renal artery stenosis (stenosis; abnormal
narrowing of passage or opening, such blood vessels or heart valve.
Pharmacokinetics. Losartan may increase the effects of potassium supplements, potassium-sparing diuretics, and
cyclosporine, leading to raise of potassium in the blood.
Antihyperlipidemic Drugs
ANTIHYPERLIPIDEMIC DRUGS LDL TG HDL
STATINS 3- Atorvastatin calcium (LIPITOR) ¯¯¯¯ ¯¯ --
Hydroxy-3- Fluvastatin sodium (LESCOL
Methylgluteryl Lovastatin (MEVACOR)
(HMG)-CoA
Pravastatin sodium (PRAVACHOL)
Reductase
Inhibitors
Rosuvastatin ( CRESTOR)
Simvastatin (ZOCOR)
FIBRATES Bezafibrate (BEZALIP) ¯ ¯¯¯¯ ---
Fenofibrate (LIPIDIL
Gemfibrozil (LOPID)
Clofibrate
NIACIN Niacin ¯¯ ¯¯¯ ----
RESINS (Bile Cholestyramine resin ¯ MINIMAL MINIMAL EFFECT
Acid (QUESTRAN) EFFECT
Sequestrants) Colestipol HCl (COLES)
Antihyperlipidemic drug chemistry. Categorized into non-absorbable agents and absorbable agents.
Nonabsorbable agents: Resins (Polystyrene resins). Anion-exchange resins bind with the enzymes in
intestine and prevent the synthesis of cholesterol. It decreases LDL 15 to 30%, increase HDL 3 to 10%, however
no change or increase in TG (disadvantage).
Pharmacological actions
GIT Blood Adipose tissue
Cholestyramine chloride
· A basic anion-exchange resin made of trimethylbenzylammonium groups in a large copolymer of styrene

and divinylbenzene.
· Act on small intestine.
· Available as powder only
· Mixed with juice, water or non-carbonated beverages
Colestipol hydrochloride
· A copolymer of diethylpentamine and epichlorodrin
· Available as granules or tablets (1 g)
· Do not crush, chew or cut and should be taken with plenty of water.
· Hygroscopics
· Water insoluble
· Do not absorb orally
· Do not metabolized and excreted in feces
All resins do not change triglycerides or may increase TG. Avoid in cholelithiasis or complete biliary obstruction
due to impaired secretion of bile acids caused by these conditions.
All oral medication should be administered 1 hour before and 4 to 6 hour after resins.
Absorbable agents
· Niacin.Nicotinic acid (Niacin or vitamin B 3 )
· Fibrates. Clofibrate and Fenofibrate (aryloxyisobutyric acid derivatives)
· Probucol (sulfur containing bis-phenol)
· Statins. Lovastatin (3-hydroxy-3methylglutaryl-coenzyme A)
· Fatty fish oil. Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA)
Nicotinic acid
Administered orally, it converted in body to nicotinamide, NAD+ and NADP+. The later two are coenzymes
essential for biochemical oxidation, reduction reactions. Participation in tissue respiration oxidation, reduction
reactions, which decreases hepatic LDL and VLDL production. At high doses lowers LDL, VLDL and raises HDL.
Strongly inhibits lipolysis in adipose tissues. Inhibits tubular secretion of uric acid, causes gout or hyperuricemia.
COOH Question Alerts!

1) NAD+, NADP are active products of niacin but Nicotinamide
N has NO activity.
Niacin 2) Niacin causes flushing is due to?
In Liver
Adipose tissue Fatty acids Triacylglycerol VLDL LDL
Triglycerides
The most common side effect and often dose limiting is cutaneous vasodilatation that gives flushing and
pruritus. Taking ASA 325 mg and take with food can manage the flushing.
Hepatic dysfunction (elevate LDH, AST, and ALT) is another serious side effect of niacin at higher doses and
avoids alcohol. GI side effects such as nausea, vomiting, and diarrhea can be minimized be taking with meals.
Usual dose of niacin if tolerated 500 mg to 4 g/day divided TID po after meal.
Nicotinic acid produced from plant.

Nicotinamide (reduced) produced from animal sources.
Statins
Question Alerts!
Statins structure activity?
1) essential group for statin action is 3,5 dihydroxycarboxylate.
2) lactone ring in lovastatin and simvastatin have bioactivates to 3,5 dihydroxycarboxylate.
2) Where does cholesterol is synthesised? Liver
3) All statins have similar onset, duration, dosing intervals and plasma protein binding. Differ in
structure, kinetics, and potency.
4) peak plasma conc. in 1-4 hrs however take 2 weeks to lower plasma cholesterol.
5) Primary route of elimination is fecal. Have high hepatic metabolism and increase liver enzyme
(liver trans aminases) therefore active liver disease contraindicated.
6) Atorvastatin does NOT require dose adjustment in renal disease patients therefore used in
renal diseases (precaution <60 ml/min).
7) Atorvastatin is the longest half life of all statins AND CAN BE TAKEN ANYTIME
OF THE DAY. Administer antacids 2h after rosuvastatin.
Blocks the action of enzyme HMG CoA reductase, this enzyme needed for the synthesis of cholesterol, mainly in
the liver. Decrease LDL receptors (18 to 55%), and lower cholesterol synthesis (cholesterol pills).
HMG-CoA reductase à Mevalonic acidàcholesterol
Statins Structure Activity Relationship. HMG-CoA reductase inhibitors are statins are chemical component is a
prodrug lactone ring, and activates to 3, 5 dihydroxy acid. The 3,5-dihydroxycarboxylate is essential for
inhibiting HMG Co reductase action. Lovastatin and simvastatins are prodrugs have lactone structure, it requires
in vivo hydrolysis. Statins may increase blood transaminase (ALT & AST) and creatinine kinase (CK-MM) activity
associated with myopathy, especially when combined with fibrates or cyclosporine. Lovastatin and simvastatin
are prodrugs. It has lactone structure and it becomes active liver.
Lactone ring
O
CH3
O
CH3CH2CH-C-O
OH
CH3
H3C
Lovastatin
Statins metabolized in hepatocytes, thus increase liver enzyme.
Statin
Atorvastatin Fluvastatin Lovastatin Pravastatin Rosuvastatin Simvastatin
Metabolizing CYP3A4 CYP2C9 CYP3A4 not known CYP2C9 CYP3A4
Enzyme (s)
Grapefruit juice Avoid Avoid Avoid
Take Anytime At night At night Anytime Anytime At night
Food With or With or With or With or With or With or
without after after without without without
(↑50%)
Statins (A= atorvastatin, L=lovasatin, F=fluvastatin, S = simvastatin, P = pravastatin); FLS = take at bed time
(night); ALS = avoid grapefruit juice (because grape fruit juice inhibit CYP 3A4); ALS = avoid grapefruit juice
(substrate CYP3A4); FLS = take at bedtime; FL = take with food; A = any time of the day; PF = can take with
grapefruit juice; P = least drug interaction
The 3,5-dihydroxycarboxylate, bicyclic ring, and ethylene bridge is essential for activity.
· Lovastatin should be always administered with food to increase bioavailability, otherwise it can decrease
30%-50 bioavailability.
· Atorvastatin can be taken anytime of the day, because has long half-life.
· The best agent for renal disease patient is atorvastatin, because it has minimal renal elimination, thus do not
require dose adjustments.
· Pravastatin is the ring opened dihydroxy acid with 6-hydroxyl group is more hydrophobic than lovastatin. It
has low penetration into peripheral tissue and less side effects.
Fibrates
Clofibrate and fenofibrate (aryloxyisobutyric acid derivatives): Decrease TG levels, increase HDL levels
(moderately), decrease LDL levels inhibit cholesterol synthesis.
Peroxisome proliferator activated receptor alpha agonist (PPAR a agonist)
Isobutyric acid group is essential for activity.
Fenofibrate has uricosuric effect thus this can be used to treat hyperuricemia.
Bile acid sequestrants (Cholestyramine)

Copolymer consisting primarily of polystyrene with small amount of divinyl benzene as cross-linking agent. It
contains fixed quaternary ammonium group, these positive charge group function as binding site for anions by
ADSORPTION mechanism.
Antianginal agents
Chemistry of Nitrates
· Nitrates: Nitroglycerin and isosorbide nitrates are organic esters of nitric acid.
· Nitrites: Amyl nitrites are organic esters of nitrous acid.
· Inorganic nitrate: Nitroprusside Sodium
Question Alerts!
Pharmacology of nitrates Nitroglycerin are? Nitrates
· Nitrites and nitrates: Directly relax vascular smooth
muscle by formation of free radical nitric oxide. Nitric oxide (NO) activates guanylyl cyclase to increase
synthesis of cGMP within smooth muscle.
· Vascular effects. Peripheral pooling of the blood (venous pooling), reduced preload decreased systemic
vascular resistance, reduced after load. Reduce myocardial oxygen demand, redistribution of coronary flow.
Vascular smooth muscle
Nitrates - Nitrites - Nitric oxide (NO) relaxation
Nitrates therapeutic use: Relieve acute anginal attacks, as prophylaxis, for long-term management of recurrent
angina pectoris.
Nitrates side effects
· Nitroglycerin (sublingual). Headache (usually resolves if patient persists with therapy), hypotension,
tachycardia, flushing, and edema.
· Nitrate tolerance: Nitroglycerin transdermal patches associated with nitrate tolerance, to minimize the
tolerance “nitrate free period” is used. Patients should have a 10 to 12 h nitrate-free period each day to
prevent tolerance.
· Nitroglycerine (transdermal) patch may cause contact dermatitis at site of patch.

· Nitrate drug interactions. Avoid concomitant use of PDE 5 inhibitors such sildenafil, verdanefil, and tadanafil
within use of 5 days, because can cause severe hypotension.
· Nitroglycerin SL spray and tablets Stored at room temp. It is hygroscopic, and stored original tightly closed
container.
Calcium Channel Blockers

Calcium channel blockers can be characterized in two types’ non-dihydropyridine and dihydropyridines.
Dihydropyridine (DHP) Non-Dihydropyridines (NDHP)
Phenylalkylamine Benzothiazepines
Nifedipine, Amlodipine, Nicardipine, Verapamil hydrochloride Diltiazem hydrochloride
Felodipine
¯ Vascular resistance thus ¯ Myocardial oxygen demand Have both cardiac depress
vasodilatation and hypotension may and reverse coronary vasospasm and vasodilator.
lead to reflex tachycardia. Bradycardia Bradycardia
R1
CO2R2 4 3 CO2R2
5 2
CH3 6 N 1 CH3
H
General structure of 1,4 dihydropyridines
1,4-dihydropyridine ring Pyridine ring
H H3C N CH3
H3C N CH3
CYP3A4 H3CO2C CO2CH3

H3CO2C CO2CH3
NO2
NO2
Oxidized analog
Nifedipine
(inactive)
(active)
Question Alerts!
1) SAR Dihydropyridine ring is essential
2) Primary elimination is renal. Dose reduction
is requiring.
3) Verapamil is primarily metabolite is nor -
verapamil (N-methyl verapamil). This prolongs
the PR interval, this more common with iv
verapamil.
4) Only nifedipine, nicaradipine, verapamil and
diltiazem are available as IR and SR.
CYP3A4 inhibitors: Erythromycin &clarithromycin, Cimetidine, Grape fruit juice, Gemfibrozil

Verapamil, Amiodarone, Azole antifungals, Protease inh. and Cyclosporine
CYP3A4 inducers: St. John wort and rifampin, phenobarbital and carbamazepine
Calcium blockers pharmacology: These agents are used to treat hypertension and are effective in treating
angina as well. All muscles, including the smooth muscle of the blood vessels, require calcium inorder to
contract. If the CCB block the entrance of the calcium into the muscle, the muscle will not contract. This will
allow the muscle to relax and subsequently reduce the blood pressure. Other therapeutic uses angina, migraine,
and antiarrhythmic.
Non-dihydropyridine
Verapamil: phenylalkylamines
Diltiazem: Benzothiazepine
Verapamil is similar to beta-blockers in effect, verapamil can cause bradycardia. The effect on Heart is graded
from higher to lower: verapamil > diltiazem > nifedipine.
Verapamilà avoid using in CHF (cause –ve inotropic effect) and constipation.
Dihydropyridine
Dihydropyridine are similar to Nitrate in effect. Act on peripherally by decrease afterload (good for vasospastic
angina) or decrease total peripheral resistance. Dihydropyridine can cause reflex tachycardia in response to
hypotension caused by decreased in total peripheral resistance. Dihydropyridines relax and dilating arteries. The
sequence of effect on vascular smooth muscles is high to low nifedipine > diltiazem > verapamil.
Calcium channel blockers therapeutic uses

Calcium channel blockers are used to treat hypertension and are effective in treating angina as well. All muscles,
including the smooth muscle of the blood vessels, require calcium in order to contract. If the calcium-channel
blocking agents block the entrance of calcium into the muscle, the muscle will not contract. This will allow the
muscle to relax and subsequently reduce the blood pressure. Other therapeutic uses: angina, migraine, and
antiarrhythmic.
Non-dihydropyridine side effects

Flushing, profound low blood pressure, swelling of legs and feet, constipation and stomach upset. If edema
(swelling) of the legs and feet occur, a diuretic may be added to the regimen.
Dihydropyridine side effects. Blood pressure will fall too low and sometimes causes reflex tachycardia. The other
side effects include, flushing, headache, dizziness, orthostatic hypotension, and edema.
Anticoagulants
Anticoagulants classification
Heparin (long chain Catalyzes the inhibition of Heparin pentasaccharides are natural
pentasaccharide) thrombin by clotting factors products, long chain pentasaccharides are
responsible for heparin induced
thrombocytopenia.
Low molecular weight Heparin Selective to factor Xa and IIa Dalteparin sodium (Fragmin)
(LMWH) Enoxaparin sodium (Lovenox)
(fractionated heparin) Nadroparin calcium (Fraxiparine)
Tinzaparin sodium (innohep)
Warfarin sodium Vitamin K Antagonists oral
Dabigatran Direct thrombin (factor II) oral

inhibitor
Rivaroxaban, Apixaban Direct factor Xa inhibitor oral
Fondaparinux Indirect factor Xa inhibitor SC Synthetic polysaccharides has no
thrombocytopenia.
Anticoagulants chemistry
Heparin Large, highly acidic mucopolysaccharide made up of sulfated D-glucosamine
and D-glucuronic acid molecules

LMWH Low-molecular weight heparin fragments (1-10 kDA), enoxaparin, dalteparin,
tinzaparin, and ardeparin, are being produced through controlled
depolymerization of Heparin
Heparinoids: A low-molecular weight heparinoid that are glycosaminoglycans
danaparoid, lipirudin extracted from porcine mucosa. Danaparoid sodium is a mixture
and ancrod. of non-heparin low molecular weight sulfated
glycosaminoglycuronans derived from porcine intestinal
Danaparoid mucosa. Danaparoid is also indicated for the treatment of
patients with an acute episode of Heparin-Induced
Thrombocytopenia (HIT), and for prophylaxis in patients with a
history of HIT. Mechanism. has a much higher anti-factor
Xa/anti-IIa ratio (more than 20:1)
Lepirudin A recombinant DNA-derives 65 amino acid polypeptides (nearly identical to

hirudin).
Coumarin derivatives Warfarin, and dicumarol chemically related to vitamin K, are water-insoluble,
weakly acidic 4-hydroxycoumarin lactones.
Phenindione are indanedione derivatives.
Warfarin is racemic structure: The S-isomer is 3-5 times more potent than the R-isomer. The S-isomer is a
substrate of CYP 2C9 and inducers or inhibitors of this enzyme have the most effect on the INR. Warfarin has a
narrow range for efficacy and toxicity and inducers or inhibitors of either isoform can be significant. CYP450 drug
interactions with warfarin are the most common cause of an INR increase or decrease.
Warfarin is substrate of
CYP2C9........... S isomer O
OH
CYP1A2............R isomer
CYP3A4............R isomer O O
CYP2C19..........R isomer
Coumarin ring
Structural formula of coumadin derivative oral anticoagulants (Warfarin) Coumarins is

CYP2C9 rat poisons.
Warfarin ………………………………> metabolite
Onset of action: Anticoagulation effects 2-3 days. The delay is due to factor V turnover if 5 hours and factor 2
(thrombin) is 2-3 days.
Anticoagulant pharmacology
· LMWH. These agents are not interchangeable with heparin in their actions and use. Because these highly
acidic. These administered parenteral as sodium salt. Because poorly absorbed from GI tract.
· Heparin: Heparin is mucopolysaccharide. Enhances the serum protease antithrombin III results in
inactivation of factors 2a, 9a, 10a, 11a, 12a, and 13a. Maximum effect occurs within minutes. Heparin stops
the expansion of thrombi by preventing fibrin formation. Antidote of heparin is Protamine sulfate: Works by
acid base neutralization. Heparin act In vitro and In vivo. It has faster onset of action
· Warfarin: Inhibits the hepatic synthesis of vitamin K dependent factors 2, 7, 9 and 10. Warfarin antidote is
Vitamin K. This agent act only in vivo (in liver). Onset of action is slower (8 to10h). Warfarin is
contraindicated in pregnancy.
Anticoagulant therapeutic use

· LMWH: Used in prevention of deep vein thrombosis (DVT) or pulmonary embolism (PE).
· Heparin: Major antithrombotic drug for DVT and pulmonary embolism. To prevent postoperative venous
thrombosis in-patient undergoing surgery.
· Warfarin: used to prevent blood clots, mainly in areas where blood flow is slowest, particularly in the leg and
pelvic veins.
Anticoagulant side effects

· LMWH: Hypersensitivity reaction (chills, fever, urticaria etc), Bleeding, Heparin induce Thrombocytopenia
(HIT), Osteoporosis.
· Heparin: Hypersensitivity reaction (chills, fever, urticaria etc), Bleeding and heparin induce
Thrombocytopenia (HIT).
· Warfarin: Bleeding; hair loss; Skin necrosis (rare), blue fingers and toes (uncommon) this also referred as
purple toe syndrome
Add table of comparison of anticoagulant

Cardiac glycosides
Digoxin is the most widely used cardiac glycoside increase myocardial contractility ad efficiency, improve
systemic circulations, improve renal perfusion and reduce edema
Cardiac glycosides Chemistry

· Consist of one or more sugars (glycine portion) and a steroidal nucleus (aglycone or genin portion) bonded
through an ether (glycosilic) linkage. Have an unsaturated lactose substituent (cyclic ester) on the genin
portion.
· Digoxin has an additional hydroxyl group at position 12. Duration of action is inversely proportional to the
number of hydroxyl groups, which increase polarity.
DIGOXIN O O
OH
CH3 Question Alerts!
Position 12 hydroxyl group
CH3H
OH is present digoxin
CH3 H3C H OH
OH O O O
O O O H
OH OH OH
O O
CH3
CH3H
CH3 OH H3C
O O H OH
OH O
O O O H
OH CH3 OH
DIGITOXIN
Cardiac glycosides Pharmacology

· Cardiac glycoside at therapeutic doses produce. Positive inotropic effect (+ve inotropic). negative
chronotropic effect (-ve chronotropic), and increased vagal tone of the sinoatrial (SA) node (vegomimetic).
Digoxin mechanisms of action
Electrolyte ‘ rearrangement ’ Increased Vagal tone

(Mechanism) (Mechanism)
- Ca i
- Inotropic Tachyarrhythmias Brady arrhythmias ¯ Heart Rate

(Desired) (Side effect) (Side effect) (Desired)
· Inhibit the membrane bound Na+/K+ activated ATPase increase intracellular sodium concentration, reduce
calcium transport form cell, and facilitate calcium entry via voltage gated membrane channel.
Cardiac glycosides Therapeutic use

· Cardiac glycoside at therapeutic doses produce: Myocardial contractility and efficiency, improve systemic
circulation, improve renal perfusion and reduce edema thereby it indicated in treatment of:
· Congestive heart failure, atrial fibrillation, atrial flutter, paroxysmal atrial tachycardia
Contraindications: Digoxin is contraindicated in ventricular arrhythmias
Thrombolytic Drugs
Streptokinase Anistreptase (Aminase) Urokinase

t-pa
(Strepto protein from Prodrug of streptokinase (Abbokinase)
(tissue type
Group C-B-hemplytic plasminogen activator)
steptococci bacteria Alteplase (activase)
Directly degrade
fibrin and Reteplase (Retevase)
fibrinogen very high affinity to
plasminogen, bound to
thrombus
Thrombolytic chemistry
Alteplase, Recombinant DNA-derived plasminogen activators (t-PA) with 527 and 355 amino
reteplase, and acids.
Tenecteplase
Streptokinase Nonenzymatic 47-kDa. Derived from b-hemolytic streptococci cultures.
Anistreplase APSAC is a complex of human lys-plasminogen and streptokinase with an anisoyl group
blocking the catalytic site.
Urokinase A two chain serine protease obtained form human kidney cell culture.
Thrombolytic pharmacology
· Facilitate conversion of plasminogen to plasmin that subsequently hydrolyzes fibrin to dissolve clots.
Thrombolytic therapeutic use

· Acute MI (STEMI), stroke and acute massive pulmonary embolism (PE), and deep vein thrombosis (DVT).
Thrombolytic side effects

· Hypersensitivity reactions, Internal GI bleeding, retroperitoneal bleeding, superficial bleeding at catheter
injection site. nausea and vomiting.
Antiarrhythmic agents
Antiarrhythmic drugs are classified as follows:
· Class IA: Procainamide, quinidine, disopyramide
· Class IB: Phenytoin, lidocaine, mexiletin, tocainide
· Class IC: Propafenone, Flecainide, Moricizine
· Class II: All the beta-blockers
· Class III: Sotalol, Bretylium, Amiodarone, dronedarone
· Class IV: All the calcium channel blockers
Antiarrhythmic drugs Chemistry

Cinchona alkaloids, natural products (Example: quinidine, it is an optical isomer of quinine)
Amides type of local anesthetics (Example: procainamide, flecainide, disopyramide)
Xylyl derivatives (Lidocaine, xylocaine), Mexilitine.
Quaternary ammonium salts (bretylium)
Diiodobenzyl oxyethylamines (amiodarone)
b-blockers (nadolol, propranolol, esmolol)
Non-dihydropyridine type calcium antagonist (diltiazem, verapamil)
Hydantoins (phenytoin)
Amiodarone chemical structure
Amiodarone Dronedarone
Two iodine in structure No iodine in their
structure
No sulfonamide group Sulfonamide group is
(no sulfa allergy) present (sulfa allergy)
NO 4 P side effects.
Antiarrhythmic drugs pharmacology

Class Ia: Quinidine (Biquin durules), and Procainamide (Procaine SR), Disopyramide (Norpace CR): Slow the
phase 0 (slow entry of Sodium ion), Prolonged re-polarization, Prolonged effective refractory period
Class Ib: Lidocaine, Tocainamide, and Mexiletine: Minimal effect on Phase 0 Slow phase –III repolarization
(decrease K pump out).
Class Ic: Encainide (Enkaid), Propafenone (Rhythmol), and Flecainide (Tambocor); Very effective on slowing
phase 0 depolarization, Little effect on repolarization.
Class II: Beta blockers: Propranolol, Atenolol, and Timolol: Competitively block catecholamine induced
stimulation of Beta receptor thereby suppressing phase IV depolarization
Class III K+ channel blockers: Amiodarone, Bretylium, Sotalol: Prolong Phase III repolarization (Prolong QT
interval)àTorose de pointes
Class IV Ca2+ channel blockers: Verapamil, Diltiazem, And Nifedipine: Shortens action potential
Digoxin: affects vagotonic response (vegomimetic) thereby increasing AV nodal refractoriness. It is
contraindicated in ventricular fibrillation. Ventricular tachycardia may result from digitalis toxicities
Antiarrhythmic drugs therapeutic use

Class Ia: Quinidine (Biquin durules), Procainamide (Procaine SR), Disopyramide (Norpace CR): indicated to treat
SVT, VT.
Class Ib: Lidocaine, Tocainamide, and Mexiletine: indicated in the treatment of VT, VA
Class Ic: Encainide (Enkaid), Propafenone (Rhythmol), and Flecainide (Tambocor); Indicated in the treatment of
VA
Class II: Beta blockers: Propranolol, Atenolol, and Timolol: Indicated to treat AT, SVT, VT, VA
Class III K+ channel blockers: Amiodarone, Bretylium, Sotalol: Prolong Phase III repolarization (Prolonged QT
interval can cause dangerous ventricular tachycardia )àTorose de pointes.
Class IV Ca2+ channel blockers: Verapamil, Diltiazem, and Nifedipine: Indicated in the treatment of SVA, VA
Digoxin: Effects vagotonic response (vegomimetic) thereby increases AV nodal refractoriness. It is
contraindicated in ventricular fibrillation. Ventricular tachycardia may result from digitalis toxicities.
Antiarrhythmic drugs side effects

Class Ia. Quinidine, procainamide, disopyramide; Torsades de pointes.
Amiodarone: blue skin, photosensitivity, photophobia, Respiratory. Pulmonary toxicity which including
interstitial pneumonitis; Respiratory muscle impairment, pigmentation. GI: nausea, anorexia, constipation,
hepatitis and cirrhosis, hypothyroidism, hyperthyroidism.
Blue skin color, corneal deposits, hepatic toxicity, optic neuritis, and erectile dysfunction.
Structure of amiodarone, dronedarone and levothyroxine.
Amiodarone inhibits CYP3A4 and 2C9.
Antiplatelet drugs
Antiplatelet Drugs
ASA Dipyridamole Ticlopidine Glycoprotein Prostaglandin

& inhibitors analogs
Clopidogrel
Epoprostenol
Eptifibatide
Tirrofiban
Change chart
ASA, clopidogrel (Plavix), ticlopidine (Ticlid), dipyridamole

dipiperdino-dinitro pyrimidine and theonopyridine.
ADP inhibitors. Ticlopidine and clopidogrel, prasugrel
Fab fragments of human monoclonal antibody to the glycoproteine (GPIIb/IIIa) receptors (Abciximab, tirofiban,
eptifibatide).
Antiplatelet drugs pharmacology

ASA Inhibits platelet cyclooxygenase production of thromboxane A 2 , thus
preventing platelet aggregation or clumping.
ASA act as antiplatelet action at dose 60 to 80 mg
Ticlopidine & Interfere ADP-induced membrane-mediated platelet-fibrinogen
Clopidogrel binding.
Fab fragments Monoclonal antibodies act against the glycoprotein IIb/IIIa-receptor
thus prevent platelet-platelet aggregation.
GPIIb/IIIa-receptor Reversible antagonist of fibrinogen, von Willebrand’s factor
antagonist
Antiplatelet drugs therapeutic use

· Platelets of the elements of blood cells, tend to clump together. The antiplatelet drugs interfere with the
coagulation by inhibiting platelet aggregation. Heart attacks and strokes occur when a blood clot that forms
in a narrowed portion of an artery blood flow and cuts off the supply of oxygen and nutrients to the tissue
that lies beyond the site of the clot.
Antiplatelet drugs side effects

· ASA: Bleeding (epistaxis to major GI bleeds), Serious GI bleeding less common with lower doses (80-
325mg/day)
· Clopidogrel. Bleeding, diarrhea, rash, and thrombocytopenia.
· Ticlopidine: Neutropenia, bleeding, diarrhea, rash, thrombocytopenia (2.5%) that is generally reversible
with drug discontinuation. Monitor neutrophils every 2 wk for 1st 3 months
Tips

1. Nitroglycerin 2. ALS 3. APR
4. Fluvastatin and Lovastatin 5. Contain sulfhydryl 6. CYP3A4
group
7. increase HDL 8. decrease LDL 9. decrease TG
10 act on distal collecting 11 intracellular alkalosis 12 Sulfonamide and
tubules halogen at position 6 & 7
13 angina 14 MI 15 CHF
16 Nitrates
· Spironolactone (act on collecting tubules, intracellular alkalosis)

· Hydrochlorothiazide (thiazide), essential functional group (sulphonamide and halogen at position 6 & 7).
· Dihydropyridine are used for the treatment of? (angina, MI, CHF)
· Essential functional group that are present in thiazide diuretics? (sulphonamide at position 7)
· What diuretics cause intracellular alkalosis? (Potassium sparing)
· Nitric oxide (NO) is a neurotransmitter that acts as? (vasodilator)
· Drugs that cause venous pooling? (Nitroglycerin)
· Nitroglycerin is classified as? (Nitrates)
· Fibrates? (increase HDL, decrease LDL, decrease TG)
· Statins that should be avoided with grapefruit juice (ALS)
· Statins that should be taken with meals (FL)
· Statins that can be taken anytime of the day (APR)
· Dihydropyridine oxidized to pyridine by enzyme? (CYP3A4)
· Drug that contain sulfhydryl group (Captopril)
· Treatment of systolic+/- diastolic BP is used? ALL antihypertensive.
· Treatment isolated systolic BP (180/80) is used? CCB
· Which antiarrhythmic drug cause pulmonary toxicity? (Amiodarone).
· Amiodarone (4Ps. phototoxicity, pigmentation, pneumonitis, ↓peripheral conversion of T4 to T 3 )
· Which antimalarial drug causes retinopathy side effect? (hydrochloroquine)
Write the examples of drug that affects systolic and diastolic blood pressure.
· Norepinephrine à ↑ SBP & ↑ DBP
· Epinephrine à ↑ SBP & ↓ DBP
· Dopamine à ↑ SBP & ↑ DBP
· Dobutamine, isoproterenol à ↑SBP & ↓ DBP
· Reserpine à ↓SBP & ↑ DBP
· Phenylephrineà↑ SBP & slightly ↑ DBP
www.pharmacyprep.com Medicinal Chemistry of CNS Drugs
27
Medicinal Chemistry and Pharmacology of Psychiatric and
Neurological Disorder Agent
Questions Alerts!
Common questions in pharmacy exam are to ask!
· Phenothiazine structures activity relation. Benzazepine (clozapine, olanzapine, quetiapine) structure
activity.
· Pharmacological actions of SSRIs and dual acting antidepressants and serotonin syndrome, Structure
activity of TCAs.
· Structure activity antipsychotic drugs.
· Structure of activity antiepileptics carbamazepine, phenytoin, gabapentin
· Structure activity and classification of benzodiazepine and half-lives.
· Conversion to levodopa to dopamine. Selegiline and rasegiline, tolcapone
· Structure activity of CNS stimulants (pseudoephedrine formation to meth amphetamine.
Classification of Antidepressants
Monoamine Oxidase Amine reuptake a2 receptor blockers

(MAO) Inhibitors inhibitors drugs Mirtazapine
Irreversible MAOI
Phenelzine
Non-selective 5HT only
Tranylcypromine
5HT, NE, D Selective serotonin
Reversible MAOi (RIMA)
Reuptake inhibitors (SSRI’s)
Moclobemide
Fluoxetine, Fluvoxamine
Paroxetine, Sertraline
5HT, NE Citalopram, Escitalopram
Tertiary amine type
(5HT > NE) Dual action
Amitriptyline SNRI
Imipramine Venlafaxine
Doxepin Duloxetine
Desvenlafaxine
Secondary amine type
NDRI
(5HT = NE)
Bupropion
Desipramine
Nortriptyline
Abbreviations. 5HT = 5hydroxy tryptamine (Serotonin), NE = Norepinephrine; SNRI = Serotonin Norepinephrine

Reuptake Inhibitors, NDRI = Norepinephrine Dopamine Reuptake Inhibitor; RIMAs = reversible inhibitors of
monoamine oxidase. TCA = Tricyclic
Antidepressants
Classes of antidepressant drugs include: tricyclic compounds (TCAs), monoamine oxidase inhibitors (MAOIs),
selective serotonin re-uptake inhibitors (SSRIs) and reversible inhibitors of monoamine oxidase (RIMAs).
Monoamine oxidase inhibitors (MAOis) chemistry

Irreversible MAO inhibitors: Phenelzine, Tranylcypromine
Selegiline and Rasagiline (MAO-B selective) used for the treatment of Parkinson's disease.
Reversible MAO inhibitor type A (RIMA): Moclobemide

Monoamine oxidase inhibitors (MAOis) pharmacology
These drugs inhibit the destruction of these brain chemicals, which leads to increased concentrations of these
neurotransmitters, which may account for their antidepressant activity.
Monoamine oxidase inhibitors (MAOIs) therapeutics

The monoamine oxidase inhibitors (MAOis) were the first class of compounds used to treat depression. They are
also used as anti-anxiety and narcolepsy. Selegiline is used for the treatment of Parkinson’s disease.
Monoamine oxidase inhibitors (MAOIs) side effects

· Patients, taking these drugs, must monitor their diet for tyramine, an amino acid present in many foods that
are fermented, aged or smoked e.g. cheese. There are a number of foods containing tyramine and such`
drugs must be avoided. Monoamine oxidase is an enzyme, which inactivates the neurotransmitters,
epinephrine, nor epinephrine and dopamine. CVS affects à Orthostatic Hypotension, Tachycardia,
Arrhythmias, Stroke.
· CNS effects à Sleep disturbances, CNS stimulations. Weight Gain, Sexual Dysfunction
· Anticholinergic àless than TCAs.
Tricyclic antidepressants (TCA) chemistry
Secondary amine type: Dibenzocycloheptadine (Example Nortriptyline) and dibenzapines (Example

Desipramine).
Tertiary amine type. Dibenzocycloheptadine (Example Amitriptyline and Dibenzapines (Example Imipramine).
Tertiary amine Secondary

Amitriptyline Nortriptyline
Imipramine Desipramine
Doxepin
High anticholinergic effect Less anticholinergic
NE/5HT More NE
Dibenzocyclohepatadiene Derivatives
Tertiary Amine type Secondary Amine type of TCA
CHCH2CH2N(CH3)2 CHCH2CH2NHCH3
Amitriptyline Nortriptyline
Dibenzapine Derivatives
N N
CH2CH2CH2N(CH3)2 CH2CH2CH2NHCH3
Imipramine (tofranil) Desipramine (Norpramin)
Question Alerts?
1) If patient is allergic to amitriptyline can cause cross allergy with? CBZ
2) TCA structures are similar to phenothiazines (antipsychotics)
3) TCA half lives are > 15 hrs. Taken once daily
4) Tertiary amine TCA have more Anticholinergic SEs.
Tricyclic antidepressants (TCA) pharmacology

These drugs inhibit reuptake of NE and 5HT at receptor site, which leads to increased concentrations of these
neurotransmitters, which may account for their antidepressant activity.
Tricyclic antidepressants (TCA) therapeutic use

These drugs are used for the treatment of major depression. Clomipramine is the drug of choice for anxiety
disorder (OCD).
Amitriptyline also used in migraine prophylaxis and treatment of neuropathic pain, fibromyalgia, and post
herpetic neuralgia, insomnia. Imipramine was used to treat enuresis in children (Bedwetting).
Tricyclic antidepressants (TCA) side effects

· CVD effects: Orthostatic Hypotension, Tachycardia (AV blockade); CNS: Confusion/Delirium. Weight Gain,
Sexual Dysfunction, seizure, and Bone marrow depression.
· Anticholinergic side effects (Constipation, Blurred vision, Urinary retention, Dry mouth, MYDRIOSIS).
Selective Serotonin Reuptake Inhibitors Chemistry (Aryloxypropyl amine is essential for serotonin selectivity).
The amine group shows maximum potency when in secondary form i.e tertiary amine, reduce potency for 5HT
transporter.
NHCH3
F3C O O Cl
N
N CH2CH2CH2 N N N
N
Fluoxetine (Prozac) Trazodone (Desyrel)
Fluoxetine S-isomer is 100 times more potent

than R-isomer
Question Alerts!
Fluoxetine metabolised to norfluoxetine, t1/2
200h. It has 5 weeks wash out period and may
not require dose tapering.
Fluoxetine à N-demethyl metabolite
(norfloxetine), has weaker effect but is
responsible for long half-life.
Selective Serotonin Reuptake Inhibitors pharmacology

The SSRIs are selective in blocking the reabsorption of serotonin by nerve cells by acting at the 5-HT receptors,
and therefore, increasing the amount of serotonin available in the brain.
Selective Serotonin Reuptake Inhibitors therapeutic use

This class of antidepressants has fewer side effects than MAOI’s or TCA’s. They are also used for bulimia,
obsessive-compulsive disorder and panic attacks.
Selective Serotonin Reuptake Inhibitors side effects

GI. Nausea (most common), headache, insomnia, nervousness, and fatigue. Sexual dysfunction (orgasmic delay).
SSRI SIDE EFFECTS TCA SIDE EFFECTS

NAUSEA, DIARRHEA, DRY MOUTH, HYPOTENSION, ANTICHOLINERGIC,
CONSTIPATION, SUICIDAL IDEATION, SEXUAL DYSFUNCTION, SEDATION.
INSOMNIA, SEXUAL DYSFUNCTION. Cardiovascular (AV node blockade).
Serotonin syndrome? When combined with MAOi plus SSRI or MAOi plus TCA.
Antipsychotic drugs
Antipsychotics are used to treat schizophrenic individual is out of touch with reality, hallucinates, hears voices
and exhibits bizarre behaviour. These symptoms are only one aspect of schizophrenia. Other symptoms are
social withdrawal, and an inability to communicate or to concentrate.
Typical or 1st generation
Phenothiazine Thioxanthenes Butyrophenones Diphenylbutyrylpiperidine Dibenzoxazepine Dihydroindolone

Chlorpromazine Chlorprothixene Haloperidol Pimozide Loxapine Molindone
Fluphenazine Thiothixene Droperidol
Trifluoperazine
Thioridazine
Phenothiazines: Chlorpromazine, thioridazine, and prochlorperazine,

Must contain nitrogen containing side chain substituents on nitrogen for antipsychotic activity drug. The ring
and nitrogen must be separated by three-carbon chain such as chlorpromazine (Thorazine).
Phenothiazines. Such as thioridazine in which the ring and S

side chain nitrogen are separated by a two-carbon chain has Side chain
only antihistaminic or sedative activity. Difference of one - N X
CH 2 - in side chain referred as homolog. R

Side chain containing piperazine derivatives have the greater R = CH2CH2CH2N(CH3)2
potency and highest pharmacological activity.
Substituents on X increase anticholinergic activity. Phenothiazine skeleton
Thioridazine piperidine ring in side chain low EPS risk but
central muscarinic and QT prolongation.
Butyrophenones: Haloperidol
Butyrophenones are chemically NOT related to phenothiazines but have similar activity. Haloperidol produces a
high incidence of extra pyramidal side effects and less sedative, anticholinergic effect than chlorpromazine and
produce less autonomic effect like mild hypotension at high doses.
Thioxanthene’s: Thiothixene, chlorprothixene: Lack of ring nitrogen and side chain is attached through double
bond.
Atypical or 2nd generation: Clozapine, olanzapine, risperidone, paliperidone, quetiapine, ziprasidone, laurasidone
and aripiprazole.
Benzazepine derivatives
2nd generation antipsychotics such as benzazepine derivative act on less on D 2 , and high on 5HT 2A. Where as in
typical antipsychotic haloperidol binds equally high affinity to D 2 , serotonin and putative alpha 2 receptors.
Dibenzazepine: Clozapine and quetiapine

Clozapine acts less potent D 2 , more potent 5HT 2A, (D 2 /5HT 2 ratio is very low) H 1 , a1&2 , low on M.
Olanzapine acts potent D 2 and 5HT 2A .
Quetiapine acts less potent D 2 , Most effectively binds 5HT 2A , H 1 , a 1&2 , low on M (D 2 /5HT 2 ratio is low).
Risperidone blocks 5HT 2 greater than D 2 receptors. , (D 2 /5HT 2 ratio is very low)
Paliperidone: Active metabolites of risperidone. This is not metabolized in liver thus have low drug interactions.
Available as PO daily dose (taken in morning due to insomnia), and prolong released injectable suspension.
Ziprasidone: Agonist of 5HT 1A and moderate inhibition of synaptic reuptake of 5HT and NE. (D2/5HT1a ratio is
low). Thus ziprasidone has potential efficacy in –ve symptoms and depression. Take with high calorie food.
Aripiprazole: partial agonist at 5HT 1a and D 2 receptors. (D2/5HT1a ratio is medium) Thus has potential efficacy in
–ve symptoms and depression. Available oral single daily dose. Taken with or without food.
· D 2 inhibitory effect effective produce more pharmacological benefit to treat positive symptoms.
· 5HT 2A inhibitory effect effective in producing more pharmacological benefit to treat negative symptoms.
D2 5HT 2 M1 H1 Alpha 1 Alpha 2 5HT 1A QT Weight glucose

Clozapine least high +/- high + + +++ +++
(less)
Olanzapine +++ +++
Risperidone + +
Quetiapine least high +/- high + ++
(less)
Paliperidone + +
Ziprasidone + yes yes +/- +/-
Aripiprazole + yes +/- +/-
Antipsychotic drugs pharmacology

· 1st generation antipsychotic mainly binds to D 2 thereby block dopamine receptors in cortical and limbic
areas of brain. Blockade in dopamine at basal ganglia leads to side effects such as Parkinson’s (Extra
pyramidal side effects).
· 2nd generation antipsychotics bind and inhibit serotonin receptors and dopamine receptors. Some examples
clozapine 5HT 2 , D 1 and D 2 , D 4 , muscarinic, and alpha-adrenergic receptors. Risperidone blocks 5HT 2 greater
than D 2 receptors. Quetiapine, Least effect on dopamine.
Antipsychotic drugs therapeutic use

The antipsychotic agents are used to treat schizophrenia and other psychoses (major mental disorders).
1st generation antipsychotics are preferred to treat positive schizophrenia symptoms. 2nd generation
antipsychotics preferably used to treat negative schizophrenia symptoms.
Antipsychotic drugs side effect: Extra pyramidal Symptoms (EPS), Parkinsonism, sexual dysfunction,
anticholinergic side effects, tardive dyskinesia, and sedation. The first-generation antipsychotics have high extra
pyramidal side effects, and second generation have high weight gain side effects.
Question Alerts!
Tardive dyskinesia (abnormal, involuntary movements of the eye, face, and tongue) is NOT a symptom of
Parkinson’s disease.
WEIGHT GAIN DYSLIPIDEMIA T2DM EPS

OLANZAPINE +++ +++ +++
CLOZAPINE +++ +++ +++ 0
RISPERIDONE ++ ++ ++
ZIPRASIDONE 0 0 0
ARIPIRPRAZOLE 0 0 0
Drug interactions: Smoking inducer CYP 1A2. Smoking increase clearance (40%) of haloperidol and decrease
serum concentration (70%).
Olanzapine and clozapine metabolism is increase by smoking by inducing CYP1A2.
CNS stimulants: Methylphenidate, amphetamines

Methylation: Amphetamine --> Methyl amphetamine
Dehydroxylation: Ephedrine or pseudoephedrine --> Methyl amphetamine

OH H OH H H
NH2 CH3 N CH3 N CH3 N CH3
CH3 NH2 CH3 CH3 CH3
Amphetamine Dextroamphetamine Ephedrine

Pseudoephedrine Methamphetamine
A B C D E
(meth amphetamine street name crystals meth, glass, ice)
SAR of CNS stimulants

Pseudoephedrine and ephedrine are optical isomers
Pseudoephedrine have one C-methyl, one N-methyl, one OH group
Amphetamine and dextroamphetamine are optical isomers (enantiomers).
Amphetamine and dextroamphetamine have one C-methyl
Methamphetamine have one C-methyl and one N-methyl
Benzodiazepines
Neurotransmitters that play important role in sleep or hypnotic actions are GABA, histamine, acetylcholine,
catecholamine and adenosine.
2
N
1
9 1
O 10 D X3
N
Short Intermediate Long acting 8
N
2 9
A B 4
acting acting 7
A B 3
8
N5
Midazolam Alprazolam Diazepam 6 5
N 4
7 6
Triazolam Lorazepam Flurazepam 1'
6'
1'
6'
Oxazepam Clonazepam C 2' C 2'
Temazepam Chlordiazepoxide 5'
3'
5'
3'
4' 4'
5-Phenyl-1,4-benzodiazepine Annelated benzodiazepine
Annelated benzodiazepine. Example. Alprazolam, and triazolam
The ring B in benzodiazepine is "diazepine"
Dealkylation
· Diazepam and chlordiazepoxide. Metabolized to desmethyl diazepam or desmethyl chlordiazepoxide have
long half life (>50 hr).
· Flurazepam metabolized to desalkyl flurazepam.
Oxidation
· Alprazolam and triazolam oxidized to short and intermediate acting.
Rapid conjugation
· Oxazepam and lorazepam metabolite have no intrinsic activity.
· Benzodiazepines such as lorazepam, Oxazepam and temazepam (LOT) have OH group at position 3 easily
undergo phase II glucuronidation conjugation, and have short half-life.
· Benzodiazepine without OH group at position 3, must undergo phase I hydroxylation reaction and then
phase II metabolism thus have long half life (long acting).
Benzodiazepine pharmacokinetics
Long acting benzodiazepines include Diazepam (longest half-life), flurazepam, clonazepam, chlordiazepoxide.
Intermediate acting: Alprazolam, Lorazepam, Oxazepam, temazepam and nitrazepam.
Short acting: Triazolam, midazolam (shortest half life). Short acing benzodiazepine have no phase I metabolism,
or extra hepatic metabolism.
Benzodiazepine pharmacology
Benzodiazepine receptors BZ 1 and BZ 2 are found in brain, benzodiazepines bind to BZ 1 and BZ 2 that are parallel
to GABA receptors.
Benzodiazepine therapeutic use

Benzodiazepine are minor tranquilizers are used to treat insomnia, anxiety and seizure. Benzodiazepine are used
to help panic attacks and insomnia, benzodiazepines should be administered for short-term use only as they
become ineffective and cause memory loss. Continuous R.E.M. sleep deprivation makes people more irritable
and less able to concentrate.
Benzodiazepine side effects: The benzodiazepines in some patients, especially with long-term use, experience
drowsiness; tolerance dependency and withdrawal symptoms can be problematic. Even with short-term use,
some patients experience tolerance and dependency.
Barbiturates
Ultra-short action Short acting Long action

Thiopental Amobarbital Phenobarbital
Secobarbital
Pentobarbital
Barbiturates chemistry
· 5, 5-disubstituted derivatives of barbituric acid, a saturated diketopyramidine.
· Two side chains in position 5 are essential for sedative hypnotic activity and long acting has a phenyl and an
ethyl group in position 5. Barbiturates have structural similarity with hydantoins (phenytoin), however,
hydantoins have five membered ring structure.
· Primedone is prodrug, and active metabolite is phenobarbital.
R1 R2
O O
O
HN NH N
N CH2CH2CH2CH2 N N
O N
O
General Barbiturate Structure
Buspirone (Buspar)
Barbiturates pharmacology
Barbiturates interfere with Na+ and K+ transport across membrane potentiates GABA A action on Cl- entry. These
drugs do not bind to BZ 1 and BZ 2 benzodiazepine receptors.
Barbiturates Therapeutic Use

They are effective only for a few weeks since they alter the length of time spent in R.E.M. sleep. They should
only be used for short-term therapy as sedative or hypnotics. Tuinal (a combination of secobarbital and
amobarbital), and secobarbital are reportable controlled drugs. Phenobarbital is used to control seizure
disorders, often in combination with primidone and/or phenytoin.
Barbiturates Side effects

Drowsiness the next morning, tolerance, and dependence.
Non benzodiazepine GABA-A agonist
· Act at GABA A receptors and have high affinity than benzodiazepines.
· Short acting
· No rebound effect on withdrawal
· Low physical dependence
Imidazopyridines
· Zopiclone
· Zolpidem (ambien)
· Pyrazolopyridine
· Zeloplon (Sonata)
Anti-Parkinson’s Drugs
Drugs to treat Parkinson’s disease
Dopamine COMT Dopamine MAO B Anticholinergic

precursor inhibitors agonist inhibitor
Anti-viral drug
Peripheral dopa Entacapone Amantadine
Selegiline, rasagiline
decarboxylase
inhibitor
Benztropine
D2 Selective Ergot alkaloids
Levodopa Carbidopa Pramipexole D1 and D2 Non-selective
Ropinirole Bromocriptine
Combination Pergolide
Levodopa/carbidopa
(Sinemet)
COMT = Catecholamine O-Methyltransferase Inhibitors: DA= Dopamine

Anti-Parkinson’s drugs chemistry
Question Alerts!
1) Levodopa to dopamine is catalyzed by?
HO COOH NCH2CH2 OH
Dopa decarboxylase (decarboxylation).
2) Levodopa to 3-O-methyldopa is catalyzed
NH2
HO by?
Levodopa Trihexyphenidyl 3) Example of COMTi ?
S 4) Selegiline and Rasagiline are?
5) Pramipexole and Ropinirole are? S
N CH2CH3
N CH3 O CH2CH N
CH2CH3
CH3
Benztropine Ethopropazine
Direct acting dopamine agonist: (Bromocriptine, Pergolide, Pramipexole, and Ropinirole), Direct acting D 2
agonist. Inhibiting the secretion of the hormone prolactin from pituitary gland.
Dopamine precursors (levodopa): High protein content meals interfere with transport of levodopa into the CNS.
Levodopa should be taken on an empty stomach, typically 45 min before a meal. Dopamine precursors and
decarboxylase inhibitors: Levodopa (L-dopa)/carbidopa is the single most effective anti-Parkinson drug. It is
changed into dopamine in the brain. Antiviral agent with antiparkinsonian properties (Amantadine). Indicated in
drug induced Parkinson’s Disease because levodopa will reverse the beneficial effect of the drug.
Anti-Parkinson’s drugs therapeutic use

Anti-Parkinson’s drugs side effects
· Levodopa /carbidopa. Nausea, vomiting, orthostatic hypotension, dyskinesia, hallucinations, confusion Long
term use of levodopa/carbidopa therapy can produce mydriasis & precipitation of glaucoma, and
melanoma.
· Amantadine. anticholinergic side effects, hallucinations, edema of feet & ankles.
· Anticholinergic drugs, avoid in elderly. It aggravates glaucoma, memory impairment

· COMT inhibitors. dyskinesias, nausea, sleep disorders, anorexia, diarrhea, hallucinations.
Direct acting dopamine agonist. (Bromocriptine, Pergolide, Pramipexole, Ropinirole)

nausea, vomiting, orthostatic hypotension, psychosis, pleural fibrosis (chest x ray before initiating therapy).
Non selective dopamine agonist. Bromocriptine and pergolide are ergot alkaloids that have effects on partial
dopamine (D 1 ) and full on D 2 receptors and other receptors.
Selective (Full) dopamine agonist. Pramipexole, and Ropinirole selective full agonist on D 2 and D 3 receptors.
These drugs do not have effect on non-dopaminergic receptors; thereby there are no peripheral effects
associated with these drugs.
Catechol-O-methyl transferase (COMT), (entacapone, and tolcapone) an enzyme that helps metabolize
levodopa, is found in both the brain and in the peripheral nervous system. prevent peripheral metabolism of
levodopa, which increases its availability to the brain.
Antiseizure drugs by mechanism of action
Reduces NMDA Affect GABA Reduce Na+ Reduce Ca2+

Receptor activation receptors conductance in current
hyperactive neurons through T-
channels
*Felbamate Phenobarbital
Primidone
Ethosuximide
Carbamazepine
Diazepam Phenytoin
Vigabatrin Fosphenytoin
Topiramate Lamotrigine
Tiagabine
Gabapentine
Valproate
Pregabalin
Valproic acid
Anti-epileptics chemistry
Anti seizure drugs (Antiepileptics, anticonvulsants) Question Alerts!
· Phenytoin (Dilantin). Hydantoins Phenytoin structurally related
· Carbamazepine . Iminostilbenes (hydantoins) to phenobarbitals
· Valproic acid Dialkylacetate. divalproex and valproic
acid are related chemicals. Divalproex is a mixture of valproic acid and sodium valproate. In the body, they
are metabolized to separate compounds, and both exert anticonvulsant effects.
· Primidone. Phenobarbital and primidone are chemically related. Primidone is metabolized to phenobarbital
and another compound in the body, both of which have anticonvulsants properties.
· Ethosuximide (Zarontin). Suxinamides
GABA analogs: Gabapentin, vigabatrin, pregabalin and baclofen (a muscle relaxant).

Gabapentin (structurally similar to GABA neurotransmitter), Lamotrigine. Phenyltriazine derivative.
NH2
O
Gabapentin OH
NH2
H
O
Pregabalin OH
carbamazepine is an iminostilbene derivative that is related chemically to the tricyclic antidepressants and is
structurally similar to phenytoin.
Oxcarbazepine: It is prodrug of carbamazepine.

Oxcarbazepine is has minimal drug interaction with OCP. (It is not autoinducer).
O CH3
O CH2CH3 Question Alerts!
HN NH
HN 1) Phenytoin is metabolized by p-
O hydroxylation followed by conjugation similar
O
Ethosuximide (Zarontin)
to phenobarbital.
Phenytoin (Dilantin)
2) Fosphenytoin is phosphate ester of
H2N COOH
phenytoin, rapidly hydrolysed to phenytoin in
vivo. Fosphenytoin is neutral (pH-7) so it is
N
CONH2
less irritating.
GABA
3) Phenytoin Na must be buffered to an
Carbamazepine (Tegretol) Gabapentin (Primary amine) alkaline pH to maintain solubility thus very
irritating when injected.
Anti-epileptics pharmacology
Anticonvulsants are CNS acting drugs that are used to treat seizures. Epilepsy is a disorder of electrical
conduction in the brain and results in loss of consciousness, seizures and convulsions. The electrical activity
causes nerve cells to become hyper-excitable and to discharge uncontrollably. Phenytoin decreases the sodium
content of nerve in the brain and thereby decreases the hyper excitability of the cells that are involved in
initiating seizures.
Carbamazepine blocks Na channels thereby reducing abnormal impulses in brain.
Anti-epileptics side effects

Phenytoin: can cause overgrowth of the gums (gingival hyperplasia) and proper mouth hygiene is necessary for
people taking this drug. Encephalopathy, blood dyscrasias, Nystagmus (toxic symptoms), Hirsutism. Birth
defects like cleft palate, and Stevens Johnson syndrome.
Phenytoin structure has hydantoins. Thus, it gives hydantoins syndrome. This can give congenital defect in
children as cleft palate.
Carbamazepine: Rash, ↑ liver enzymes, neutropenia, aplastic anemia.
Chronic: drowsiness, vertigo (sensation of dizziness and confused, disoriented state of mind). Aplastic anemia,
Stevens Johnson syndrome (skin hypersensitivity reactions). Acute intoxication: Coma, hyperirritability,
convulsions and respiratory depression.
Topiramate. Cognitive dysfunction, headache, kidney stones, and weight loss.
Clobazam. Tolerance to therapeutic effects, insomnia, depression, dizziness, drowsiness, Light headedness,
ataxia.
Local anaesthetics
Local anaesthetics chemistry. Most local anesthetics are structurally similar to the alkaloid cocaine; however,
these structures consist of a hydrophilic amino group through ester or amide functional groups.
Ester Type: Cocaine, procaine, chloroprocaine, and benzocain.

Short acting due to rapid hydrolysis. Ester type of local anesthetic hydrolysis produces para amino benzoic acid
(PABA).
Amide Type: Lidocaine, dibucaine, prilocaine, mepivacaine, bupivacaine, and etidocaine. Long acting, and
metabolized in liver. Procainamide is long acting amide type local anesthetic than procaine an ester type,
because isosteric replacement of ester oxygen with a nitrogen atom.
Lidocaine (tertiary amine) Procaine (aromatic amine)
CH3 CH2CH3 CH2CH3

O O
N N
N CH2CH3 O CH2CH3
H
H2N
CH3
Ester Type
Amide Type
Question Alerts!
Local anesthetics pharmacology What type of local anesthetics gives PABA
Inhibit sensory nerves that carry stimuli to CNS, block metabolites? Benzocaine, Procaine and
nerve fibre conduction. Blockade is reversible, must tetracaine
continue administration of the drug for effects to
continue.
Local anesthetics therapeutic use

Procainamide à Antiarrhythmic drug (Na+ channel blocker).
Lidocaine is used for à antiarrhythmic drug and amide type local anesthetic.
General anesthetics
Add classification from pharmacology
General anesthetics chemistry
O
Cl
NH
O O NH2CH3 Cl-
O
HN N H2C6H5O7- N+
- H CH2CH2
S Na+
Thiopental Sodium Ketamine Hydrochloride Fentanyl Cytrate
General anesthetics pharmacology
Ketamine. Short acting non-barbiturate anesthetic induces a dissociated state in which the patient appears
awake but is unconscious and does not feel pain.
Propofol. Sedative or hypnotic action, used in induction and maintenance of anesthesia. Fast onset (40 seconds
of administration).
Thiopental is rapid acting barbiturates.
General anaesthetics therapeutic use

· Halothane is used in pediatric anaesthesia; it is infrequently used in adults.
· Isoflurane (Forane), enflurane, sevoflurane and desflurane are frequently used in adults.
· Enflurane is used as an inhalation agent for adults, but is not widely used for pediatric cases.
· Isoflurane may be the most widely used inhalation agent.
· Fentanyl is a narcotic, available as transdermal patch. Good analgesic property
General anaesthetics side effects

Ketamine. Causes sedation, immobility, amnesia, and nightmares.
Halothane. is associated with malignant hyperthermia.
Tips
· SSRI onset of action is à
· Fluoxetine washout period à
· Depression with sexual dysfunction à
· To treat depression in insomnia patient à
· Depression with diabetes à
· Venlafaxine at higher dose act on à
· Higher dose of venlafaxine (225 mg/day) have effect on à
· Patient on antidepressants and shows with dilated pupil, may be due toà
· TCA onset of action is à
· A substance found commonly in fermented foods, which can be toxic when MAO inhibitors are, usedà
· MAO is classified as à
· Avoid taking cheese with à
· Milk + MAOI à
· St. Johns wort is à
· Selegiline and Rasagiline à
· Venlafaxine is classified as à
· Drug of choice against bipolar disorders and manic depression à

· Lithium toxicity symptoms -->
· CNS-->
· Thiopental à
· Lithium blood levels in adults à
· Serotoninergic syndrome à
· Fast or quick acting benzodiazepine is à
· GABA analogs are à
· Antiseizure drugs that gives Stevenson Johnson syndrome à
· What antiseizure drugs that is also used as weight loss therapy?
· Nystagmus à
Select TRUE OR FALSE Statements______________

· Lithium concentration varies with Na+ ions (T/F)
· Li+ conc. increases with decrease Na+ (T/F)
· Li+ conc. decreases with increase in Na+( T/F)
· ACEI decrease Na+ and increase Li+( T/F)
· NSAID decrease Na+ renal perfusion is less (T/F)
· Thiazide deplete Na+( T/F)
· Fluoxetine (SSRI) increase Li+ toxicity (T/F)
· Renal dysfunction à Li+ increase( T/F)
· Dehydrationà Li+ increases (T/F)
28
Pharmacology of Endocrine
Drugs
Questions Alerts!
· Insulin structure activities and duration of action and peak effect.
· Structures activity of steroidal hormone such as estrogen (phenolic group), progesterone (ethinyl
group) and testosterones.
· Thyroid hormones thyroxine (T4) and triiodothyronine (T3)
· Structure activity of Adrenal corticoids mineral corticoids and glucocorticoids such as hydrocortisone
(11- position hydroxyl group). Topical glucocorticoids ranking of potency.
· Classification hypoglycemic drugs like 1st & 2nd gen sulfonylureas. The second generation such as
glyburide, gliclazide and glimipride.
· Insulin and incretin hormones functions and analog liraglutide and Exenatide.
· DPP-4 inhibitors such as sitagliptine and saxigliptine.
Antidiabetic drugs pharmacology

Sitagliptine. Prolong the half life of an endogenously produced glucagon like peptide-1 (GLP-1). In DM-2, the
GLP-1 levels are deficient. GLP-1 are inactivated by DPP-4. Thereby DPP-4 inhibitors partially reduce the
inappropriately elevated glucagon post prandially and stimulate glucose dependant insulin secretion.
Sulfonylureas (Chlorpropamide, Gliclazide, Glimepiride, Glyburide, Tolbutamide). Increased secretion of insulin

by action on β-cells of pancreas. Glyburide may produce a mild diuresis by enhancing renal free water clearance.
Question Alerts!
1) Glyburide all action is due to insulin secretion (most hypoglycemic).
2) Glimepiride is quick onset of action and long acting. It has extra pancreatic activity thus has
less hypoglycemia SE. Binds to different proteins in the putative sulfonylurea receptors. Exerts
hypoglycemic effect with less secretion of insulin.
Chlorpropamide has antidiuretic activity possibly due to potentiating of antidiuretic hormone (ADH) in the renal
tubules.
First generation: Tolbutamide, Chlorpropamide,
Second generation: Glyburide, Gliclazide. Glyburide all action is due to insulin secretion (most hypoglycemic).
Third generation: Glimepiride

Glimepiride is quick onset of action and long acting. It has extra pancreatic activity thus has less hypoglycemia
SE. Binds to a different protein in the putative sulfonylurea receptors. Exerts hypoglycaemic effect with less
secretion of insulin.
Second generation agents have larger R 1 substituent's, because of large substituent's these are more lipids
soluble and more potent compared to first generation. Sulfonylureas areas acidic compounds attached to
aromatic ring.
O H H
R1 HS N N
R2
O O
General Sulfonylurea srtucture

T 1/2 Duration
Glyburide 1.5 – 3 h Up to 24 h Highest hypoglycemia, Pancreatic action
Gliclazide 2-4 h Up to 24 h
Glimepiride 5-9 h Up to 24 h Pancreatic and Extra pancreatic (delta cell).
Faster onset of action and less hypoglycemia
R1 = Halogen, amino, acetyl, methyl, trifluro groups potentiate activity

R2 = governs the duration of activity
Meglitinides (Nateglinide, Repaglinide): Increased secretion of insulin by action on β-cells of pancreas.

Structurally similar to sulfonylureas but substituted by benzoic acid derivatives (meglitinides).
Has no sulfa allergy.
Greater decrease in post prandial blood glucose.
Safer in renal disease patient.
Metformin is basic compound. Meglitinides are acidic compounds. Rosiglitazone and pioglitazone are acidic
compounds.
Repaglinide Half-life is 1 hrs and rapidly eliminated. Thus, used for post prandial blood glucose levels.
Alpha-glucosidase Inhibitors (Acarbose)

Inhibits alpha glucosidase in intestinal border thus decreasing the absorption of starch and disaccharides.
Biguanides (Metformin hydrochloride): Increased peripheral utilization of glucose by decreased

gluconeogenesis. Do not cause hypoglycemia in monotherapy.
METFORMIN ¯ GLUCONEOGENESIS (LIVER)

¯ GLYCOGENOLYSIS (LIVER)
- GLUCOSE UPTAKE
TATOMERISM
Thiazolidinedione’s (Pioglitazone and Rosiglitazone): Decreases insulin resistance in the periphery and liver.
Improves glycemic control while reducing circulating insulin levels.
THIAZOLIDINEDIONE ¯ GLUCONEOGENESIS (LIVER)

¯ GLYCOGENOLYSIS (LIVER)
- GLUCOSE UPTAKE
Orlistat. Blocks the action of stomach and pancreatic enzymes (lipases) that digest fats, so fats and other fat-
soluble vitamins ADEK are not absorbed in the body but pass through and excreted in the feces.
Antidiabetic drug Therapeutic uses

Sulfonylureas (Chlorpropamide, Gliclazide, Glimepiride, Glyburide, Tolbutamide)
Disulfiram like reaction is caused by which type of antidiabetic drugs, when taken with alcohol.
Chlorpropamide has antidiuretic activity possibly due to potentiating of ADH in the renal tubules; there is some
evidence that chlorpropamide may actually stimulate ADH secretion.
Meglitinides (Nateglinide, Repaglinide): Nateglinide used for type 2 diabetes. It is imperative that there be rigid
attention to diet and careful adjustment of dosage. When metformin is combined with a sulfonylurea, instruct
the patient on hypoglycemic reactions and their control. If vomiting occurs, withdraw drug temporarily, exclude
lactic acidosis, then resume dosage cautiously.
Biguanides (Metformin). Metformin can be of value for the treatment of obese diabetic patients. May cause
hypoglycaemia when combined with sulfonylureas (glyburide).
Metformin: basic compound. Meglitinides; acidic compounds. Rosiglitazone and pioglitazone; acidic compounds
Alpha-glucosidase Inhibitors (Acarbose). For type II Diabetes Mellitus in combination with other antidiabetic
drugs. In combination oral hypoglycemic therapy, always use agents from different class of oral hypoglycemics.
Thiazolidinedione’s (Pioglitazone, Rosiglitazone): These agents depend on the presence of insulin for its
mechanism of action. Contraindicated in patients with serious hepatic impairment, acute heart failure.
Increasing insulin sensitivity in type 2 diabetes. It improves sensitivity to insulin in muscle and adipose tissue and
inhibits hepatic gluconeogenesis.
Agonist of the peroxisome-proliferator activated receptor- g (PPAR g). The PPAR g binds to DNA activating
transcription of wide variety of metabolic regulators (antihyperglycemic).
THIAZOLIDINEDIONES ¯ GLUCONEOGENESIS (LIVER) - EDEMA AND CHF

AGONIST OF PPAR g ¯ GLYCOGENOLYSIS (LIVER)
- GLUCOSE UPTAKE
Side effects:
Rosiglitazone + Metformin: Indicated for use when diet, exercise, and metformin or rosiglitazone alone do not
result in adequate glycemic control. Rosiglitazone+metformin is the combination used in case of insulin
resistance.
Rosiglitazone + Metformin: If acidosis of any kind develops, Avandamet should be discontinued immediately.
The use of rosiglitazone in combination therapy with insulin is not indicated due to its side effects, therefore,
Avandamet is not indicated for use in combination with insulin.
2,4-thiazolidinedione is pharmacophore of glitazones.
Orlistat (Xenical). Reduces fats stores and produce weight loss. It is an intestinal lipase inhibitor.
DPP4 Inhibitors are Quinozolinone or cyanopyrrolidine based structures.
Sitagliptine, saxigliptine linagliptine.

Safe in renal disease
DPP4 - INSULIN
GLP-1 ------------------------------à PANCREATIC ISLET CELL ¯ GLUCOGON
¯ POST PRANDIAL BLOOD
GLUCOSE
GLP-1 RELEASED FROM GI ¯ FASTING GLUCOSE
DPP4, INACTIVATES GLP-1
Antidiabetic drugs Side effects

Sulfonylureas (Chlorpropamide, Gliclazide, Glimepiride, Glyburide, Tolbutamide).
GIT disturbance (metallic taste), hypoglycemia, weight gain, hepatic x renal insufficiency. (Jaundice), tachycardia,
headache, rash, increased ADH.
Structure activity of biguanide (metformin)

Biguanides (Metformin hydrochloride)
· GI: Diarrhea, nausea, vomiting, abdominal bloating, flatulence, and anorexia (weight loss) are the most
common reactions to metformin and are approximately 30% more frequent in patients. Occasionally,
temporary dose reduction may be helpful.
· Decreased vitamin B 12 (cyanocobalamine) absorption thus can cause megaloblastic anemia.
· Unpleasant or metallic taste, which usually resolves spontaneously.
· A rare and serious side effect is lactic acidosis.
Alpha-glucosidase Inhibitors (Acarbose): GI. Flatulence, diarrhea, abdominal pain, cramps, nausea.
Thiazolidinediones (Pioglitazone, Rosiglitazone): Weight gain, fluid retention, congestive heart failure and
hemodilution, varying effects on lipids, increase HDL, increase LDL, pioglitazone decrease TG. As a consequence
of their improved insulin sensitivity, these patients may be at risk of pregnancy if adequate contraception is not
used.
Orlistat. Stethorrhea (oily leakage), and abdominal discomfort.
Increase glucose excretion in urine. Act as Sodium-glucose transport protein 2 (SGLT 2 ) inhibitor. Canagliflozin
(Invokana), Dapagliflozin and Empagliflozin
DPP4 inh GLP-1 analog SGLT2
Sitagliptine Exenatide Canagliflozin
Saxigliptine Liraglutide (long acting) Empagliflozin
Linaglptine Dapagliflozin
Oral only SC injection only Oral only
Weight neutral Weight loss Weight loss
Nasopharyngitis Pancreatitis DKA, Hyperkalemia,
polyuria, polydipsia.
Renal/hepatic Renal elimination Renal elimination
Linagliptine is safe in renal Suppress glucagon release
disease and reduce appetite.
Ketoacidosis: Mainly Type 1DM

Acetyl CoA (produced in liver) --> acetoacetic acid Beta-hydroxybutyric acid
Acetone
Thyroid disorders
Thyroid gland secretes levothyroxine, liothyronine or triiodothyronine and calcitonin
Medicinal chemistry of thyroid disorders
Drugs Used In Thyroid Disease
Hypothyroids Hyperthyroids
Thyroxine (T4)
Synthroid Triidothyronine (T3)
Eltroxin
Thioamides: Iodide 131 Ipodate

I
Methimazole Lugol solution:
Propylthiouracil (KI+I)
Important Concept!
1) levothyroxine (T4) have 4 iodines and Levothyronine have 3 iodine.
2) Deiodination reaction is catalyzes T4 to T3 by deiodinase enzyme which takes place in peripheral
tissues and liver.
3) Lugol's solution is 10% KI + 5% I, is taken as oral drops. It can stain.
4) Drugs that affects thyroid functions? Warfarin, heparin, lithium, amiodarone.
5) Amiodarone structure is similar to thyroxine. Thus amiodarone interferes with peripheral conversion
of T4 to T3. Where as dronedarone has NO iodines.
Deionidation
HO HO
I I
I H NH2 H NH2
I COONa I COONa
O O
I I
Sodium Levothyroxine (T4) Sodium Liothyronine (T3)
3,5, 3’, 5’ thyroxine (T 4 ) 3,5,3’ Triiodothyronine (T 3 )
5-monodeiodinase enzymes found in extra thyroidal peripheral tissues catalyzes T 4 to T 3 .
Thyroid hormone pharmacology: Levothyroxine a major hormone of thyroid gland is liothyronine and thyroid,
desiccated.
Thyroid hormones therapeutic use. Levothyroxine, liothyronine, thyroid, desiccated is used for the treatment of
Goiter and thyroid cancer.
Thyroid hormones Side effects. Levothyroxine. Rare side effects such as anxiety, diarrhea, weight loss, sweating,
insomnia, and muscle cramps.
Thyroid hormones drug interactions Important Concept!

1) Overdose symptoms of thyroid hormone
Thyroid hormones increase catabolism of vitamin K cause hyperthyroid symptoms
dependent clotting factors thereby increase the effect of 2) Levothyroxin taken empty stomach.
warfarin. Glycemic control may decline with initiation of 3) Hypothyroidism: Increase serum TSH,
levothyroxine, potentially requirement of decrease FT4 and TT3
antihyperglycemic agents. Antiepileptic, cholestyramine,
and sucralfate may reduce the absorption of levothyroxine because these agents bind with levothyroxine.
Drug and Food interactions. May decrease absorption of levothyroxine by iron salts, cholestyramine, colestipol
and sucralfate.
Thyroid hormones monitoring

Levothyroxine: Periodic tests of thyroid function, monitor serum TSH levels to adjust initial Dosage after 6 to 8
weeks then as required or annually adrenal insufficiency may adrenal insufficiency may have to be increased
during pregnancy to maintain TSH in desired range, check TSH each trimester and 4 to 6 wk after any dosage
adjustment.
Treatment of hyperthyroidism: Question Alerts!

Mechanism of antithyroid drugs
Antithyroid drugs Chemistry: Thioamides such as methimazole, and
propylthiouracil. The iodides, Lugol's solution (KI+I) oral drops and
radioactive iodine.
Antithyroid drugs Pharmacology

Antithyroid drugs such as methimazole and propylthiouracil (PTU) act by.
· Decreasing thyroid hormone production
· Decreasing response to thyroid hormone
Antithyroid drugs structure: thiocarbamide (R-(C=S)-NH-R) is essential group for antithyroid activity.
Thiocarbamide are similar to thiourea.
Antithyroid drug mechanism:

TPO
Iodine transport into thyroid gland ------> thyroglobulins ----> T 4 , T 3 released into blood
TPO; THYROID PEROXIDASE ENZYME.
· Inhibit the synthesis of T 3 and T 4 by inhibiting the iodination of tyrosine in the thyroglobulin. (Inhibits
thyroid peroxidase or TPO).
· Blocks the coupling of the iodo thyroxin.
· Inhibits the conversion of T 4 to T 3 thereby thyroid hormone synthesis is decreased.
· Obvious effects are very slow since it takes 3 to 4 weeks before the hormone levels show a decrease.
· Do not prevent the uptake of IODINE by the gland (do not effect the extensive amount of hormone stored in
thyroidal thyroglobulin).
THIOAMIDES INHIBIT TPO

INHIBIT COUPLING OF IODOTHYROXIN
INHIBIT DEIODINATION (T 4 àT 3 )
DO NOT AFFECT ON IODINE UPTAKE
Propylthiouracil. Manage the overactive thyroid gland

Iodides. (Lugol's solution)
· Lugol solution is KI+I
· Inhibits the uptake of I 2 by a tyrosine.
· Inhibit hormone release by inhibiting thyroglobulin degradation.
· Decrease the size of the gland, decrease blood supply to the enlarged gland therefore it is used in
preparation for surgery
Radioactive iodine
· Effects of iodide on the thyroid gland.
· Emission of B rays.
· Gets incorporated into the storage facility
· Very effective as it concentrates in the thyroid destroys the gland within a few weeks
Antithyroid drugs side effects

Antithyroid drugs (Methimazole and propylthiouracil). Reduction in white blood cells leading to the risk of
infection, nausea and vomiting, joint pain, headache, rashes and itching, Jaundice, fever.
Iodides: Uncommon, reverses when the drug is discontinued, outbreak of acne
Swollen salivary gland, ulceration of the mucous membranes, conjunctivitis, rhinorrhea, and metallic taste,
bleeding disorder, anaphylactic reaction.
Radioactive iodide: induced genetic damage, leukemia, neoplasia. Cannot be administered to pregnant and
nursing mothers cross placental barrier secreted into the breast milk
Therapeutic uses
· Antithyroid drugs (Methimazole Propylthiouracil)
· Methimazole: used to treat hyperthyroidism
· Propylthiouracil: used to treat hyperthyroidism
· Iodides: Used in the treatment of thyroid storm
· Radioactive iodine: I131 isomer of iodine is used in the treatment of thyrotoxicosis
Antithyroid drugs Contraindications / Precautions
· Propylthiouracil: Prescribed with caution in pregnant women. There is a risk of goiter and hypothyroidism in
the newborn infant if too high dose is used. Reduce dose to infant and children
· Iodides: Should be avoided in pregnancy as it crosses the placental barrier thus causing fetal goiter.
Antithyroid drugs Pharmacokinetics

Methimazole: Well-absorbed, Slow excretion, t 1/2 is 6 hours
Propylthiouracil
· Propylthiouracil – rapid absorption after oral administration
· Peak serum levels seen after 1 hour, and t 1/2 is only 2 hours
· Extensive first pass metabolism
· Excreted by the kidneys as glucuronide (inactive)
· Preferred in pregnancy for it does not cross the placental barrier
· Strongly protein bound. Secreted in breast milk less than methimazole
Radioactive iodine: Sodium I131 given orally and well absorbed from the GIT, t 1/2 is 5 days
Medicinal Chemistry Steroid Hormones: The hormones that consist of fused 17-carbon atom ring system are
classified as steroids. Examples of hormones that have steroidal structure. Vitamin D, adrenocorticoids or
corticosteroids, and gonadal hormones or sex hormones (estrogen, progesterone, and testosterones).
Chemically these are derivatives of cyclohepanoperhydrophenanthrene, which also similar to aromatic
phenanthrene ring structure. Steroid skeleton consist of three 6 member cyclohexane rings and 1 cyclopentane
ring.
17
11
1 C D Question Alert!
16 All steroid hormones like estrogen, progesterone, testosterone,
7
A B aldosterones, adrenal corticoids and vitamin D have 3 cyclohexane rings,
3
and 1 cyclopentane ring.
4 6
Steroid Skeleton
Adrenocorticoids: Derived from C-21 pregnane steroidal nucleus. Cortisone and hydrocortisone.
Adrneocroticosteroids are classified as glucocorticoids and mineral corticoids.
· Glucocorticoides formed and secreted from the middle layer of adrenal cortex.
· 17-b-keto side chain (COCH 2 OH), the 4-ene, and the 3-ketone structures.
· Oxygen atom at C-11 is essential for glucocorticoid activity.
· Double bond between C-1 and C-2 increases glucocorticoid activity without increasing mineral corticoid
activity.
· Fluorination at C-9 increases both mineral corticoid and glucocorticoid activity.
· Fluorination at C-6 increases glucocorticoid activity and less on mineral corticoid activity.
· Hydroxyl group at C-17 and methyl group at C-16 enhances glucocorticoid activity and abolishes mineral
corticoid activity.
· An acetate ester at C-21 or 16a, 17a-isopropylidenedioxy groups enhances topical absorption.
O O
OH OH
OH OH
O HO
Cortisone Hydrocortisone
O O
Mineral corticoids are aldosterone

· Desoxycorticosterone acetate and fludrocortisone acetate. Formed in the outer layer of the adrenal cortex,
a prototypical mineral corticoid (aldosterone) and middle layer gives cortisones.
O O
OAc OAc
OH
HO HO
Desoxycorticosterone F Fludrocortisone
O O
CH3
Glucocorticoids potency ranking

Topical glucocorticoids potency ranking Inhaled and intranasal corticosteroids
· Very high potency. Betamethasone (0.05%) · Beclomethasone
dipropionate, Clobetasol (0.05) · Budesonide (highly potent nonhalogenated
· High potency. amcinonide, Triamcinolone steroid)
0.5% · Flunisolide
· Medium potency. Betamethasone benzoate · Triamcinolone
(0.025), Triamcinolone 0.025 to 0.1 · Fluticasone
· Low potency. dexamethasone, and · Mometasone (quick onset, more local
hydrocortisone absorption and lowest systemic absorption,
consequently fewest systemic SEs).
Gonadal Hormones
O
OH OH
Question Alert! Phenolic ring
C CH
1) Estrogen has phenolic
ring.
2) Presence of 17
ethinyl group results in HO O O
orally effective drug by
Estrogen Progesterone Testosterone
preventing formation of
estradiol to estrone. Although there is a new chiral group at C 7 . It is considered antiestrogen since
there is no functional group at carbon 7.
Gonadal Hormones
Testes
Ovary
Testosterone
Estrogen
Progesterone
Estradiol Norethidrone Testosterone Testosterone

Ethinyl estradiol Norgestrel Anabolic Antagonist
Mestranol (prodrug) Norethynodrel steroids
Norgestimate Finasteride
Desogestrel Dutasteride
Medroxy proge Cyproterone
Estrogen antagonist acetate
Tamoxifen Nonsteroidal
Clomiphene Progesterone antagonist Flutamide
Estrogen agonist + Mifepristone (RU-486) Bicalutamide
antagonist (SERM) nilutamide
Raloxifine
Estrogens
Estrogen chemistry: Ovaries produce 17b estradiol and estrone. These hormones have 18 carbons for four rings.
Three 6 membered rings and one 5-member ring. Estrogen exist as estradiol in body in equilibrium with oxidized
form of estrone and further biochemically modifies water soluble of estriol that let excrete estrogen. Estrogen A
ring is phenolic ring (aromatic), basic nucleus is known as estrane with methyl group designated as C-18 on
position C-13 cyclopentano-perhydrophenanthrene. Ethinyl estradiol à 17 alpha estradiol.
Naturally occurring estrogen is estradiol
Synthetic estrogen is ethinyl estradiol
Diethylstilbestrol à Non-steroidal synthetic estrogen (stilbene derivatives)

OH OH
O
Phenolic ring OH
HO HO HO
Estradiol Estrone Estriol

Estrogen Pharmacology
Estrogens are female sex hormones that are used primarily to decrease bone loss and to treat the symptoms of
menopause. Estrogen is used to reduce or prevent osteoporosis in susceptible women. Estrogens decrease the
frequency and severity of hot flashes as well as the dryness in the vagina that many post-menopausal women
experiences.
Estrogen therapeutic uses

Estrogen is the component of all brands of oral contraceptive pills. Estradiol and conjugated estrogens are
available in tablet form; estradiol is available in a patch and injection. Conjugated estrogens are available in a
vaginal cream. Estrogen is component of Diane 35 and Alesse oral contraceptive that are used for the treatment
of acne.
Estrogen side effects. Feminization (Breast tenderness), GI: Nausea, stomach upset, depression, weight gain,
CVS: increased blood clotting (Increased risk of thromboembolism diseases), edema, hypertension, stroke, and
MI. The most frequent adverse effect is nausea. Prolonged used of unopposed estrogens (estrogen given
without progesterone) in postmenstrual women increases the risk of endometrial cancer.
Antiestrogens
The two-drug tamoxifen and clomiphene are categorized as full antiestrogens. Raloxifene is a Selective estrogen
receptor modulator (SERM) has partial antiestrogen and estrogenic actions.
Antiestrogen chemistry. These drugs are non-steroidal antiestrogenic compounds equally effective in oral or
injection forms.
N O N O N O
OH
Cl S
HO
Tamoxifen Raloxifen
(NOLVADEX) Clomiphene (EVISTA)
Tamoxifen and clomiphene are bioisoster.

Tamoxifen is an example of geometric isomer.
Antiestrogen pharmacology
Tamoxifen competes for binding to the estrogen receptors thereby inhibits the action of estrogen.
Clomiphene Interferes with negative feedback of estrogen on hypothalamus and pituitary thereby increases the
secretion of gonadotropin releasing hormone (GnRH) and causes stimulation of ovulation.
Antiestrogen therapeutic use: Tamoxifen is indicated in advanced breast cancer in postmenopausal women.
Clomiphene is used to treat infertility associated with anovulatory cycles.
Antiestrogen side effects: Tamoxifen: hot flashes, vaginal bleeding, menstrual irregularities, risk of endometrial
cancer, nausea, vomitingà Least nauseating anticancer drugs.
Clomiphene: ovarian enlargement, vasomotor flushes, visual disturbances.
Raloxifene Pharmacology: Reduces bone resorption thereby decrease bone turnover. Exhibit estrogen like
(agonist) effect on bones and lipid metabolism. Exhibit estrogen antagonist action on uterine and breast tissues.
Raloxifene therapeutic use: Used in prevention of osteoporosis.
Raloxifene side effects: Hot flushes
Progesterone
Progesterone chemistry. Progesterone is a C-21 steroid, its basic nucleus is known as pregnane.
Two types of progesterone
· 17-alpha hydroxyprogesterone such as Question Alert!
medroxyprogesterone acetate and megestrol acetate. 17-alpha ethinyl androgen are potent
17-alpha ethinylandrogens (more potent). Norethindrone and progesterone.
Norethynodrel are commonly used in OCs, because potent oral
activity, more lipids soluble and less first pass metabolism.
17-alpha hydroxyprogesterone 17-alpha ethinyl androgens (androgenic progesterone's)

Injections Oral stable
Potent
Medroxyprogesterone, megestrol acetate Norgesterol, norethindrone, levonorgesterl
Progesterone therapeutic use

Progesterone is used alone for the treatment of amenorrhea, abnormal uterine bleeding, and endometriosis.
Levonorgestrel is progesterone, which is available as a sub-dermal implant for long-term contraception. Six
capsules are implanted on the inside of the upper arm. Contraception begins within 24 hours and may last up to
5 years. Side effects nausea, depression, liver failure, cancer and high blood cholesterol. Medroxyprogesterone
acetate (Depo-Provera injection) is used to treat amenorrhea (cessation of menstrual periods) and abnormal
uterine bleeding. It is also used as a contraceptive. As a contraceptive, 150 mg is injected once every three
months.
O
(no aromatic ring O
C OC - CH3
and ketone at position 3 O
C
O
O CH3
Progesterone Medroxy Progesyterone Acetate

HO C C-H
Noethindrone
O
Progesterone products
Prometrium (micronized progesterone) 100 mg capsules powder is suspended in peanut oil, glycerine.
Progesterone side effects

Medroxyprogesterone acetate unexpected or increased flow of breast milk, depression, loss or changes in
speech, coordination, stomach pain, swelling of face, ankles or feet, headaches, mood changes, and unusual
fatigue.
Anti Progestins
Anti Progesterone: Mifepristone (RU – 486)
Anti Progesterone pharmacology
Progestin antagonist with partial agonist activity. Mifepristone also has anti glucocorticoid property. Causes
abortion if administered in early pregnancy (85%) due to interference with progesterone and decrease in
production of human Chorionic Gonadotropin (hCG).
Anti Progesterone therapeutics use

Abortifacient: Administration of mifepristone used as contraceptive given once a month when progestin levels
are high (Prostaglandin E 1 and misoprostol orally after single dose of mifepristone effectively terminates the
gestation.
Androgens
Danazol, Nandrolone, Stanozolol, and Fluoxymesterone
Testosterone. C-19 steroid. All androgens have anabolic activity.
Androgenic effect. Testosterone 17-enantahne, resemble estradiol esters that increases duration of action when
given I.M. Agents with 17-methyl or ester groups are orally active
O
OH O C (CH2)5 CH3
O O
Androgen Testosterone enanthate
Testosterone (no ester or ethinyl group)
O
O R
C C
O CH2CH3
H3C
O N H Finasteride (presence of Heterocyclic ring)

O H
Dromostanolone Antiandrogen
Androgen pharmacology
Testosterone is the androgen that leads to the development of male secondary sexual characteristics and
maintains the male reproductive system.
AROMATASE 5-ALPHA REDUCTASE

17 B ESTRADIOL<---------TESTOSTERONE--------à DIHYDROTESTOSTERONE
AROMATASE INHIBITORS: ANASTROZOLE. Used as anticancer drug for breast cancer.
5-ALPHASE REDUCTASE INHIBITORS: FINASTERIDE
AROMATASE INH. ¯ESTROGEN 5-ALPHA REDUCTASE INH. ¯TESTOSTERONE

ANSTROZOLE FINASTERIDE
DUTASTERIDE
USED TO TREAT BREAST CANCER USED FOR BPH AND PROSTATE CANCER
CAUSE OSTEOPOROSIS.
Androgen therapeutic use

Testosterone is commonly prescribed in the treatment of female breast cancer, androgen deficiency, and for
stimulation of growth, weight gain, and red blood cell production. Commonly known as "anabolic steroids"
because they promote muscle growth. They are also commonly used to help patients recover from a surgery
and cancer treatment that resulted in damage to muscle tissue. Androgens orally ineffective.
Anabolic effects are seen with all androgens.
Danazol: Danazol also possesses weak, dose-related androgenic effects. And is used in endometriosis
(ectopic growth of the endometrium).
Androgen side effects
· In males. Priapism (continuous erection), impotency, and gynecomastia.
· In females. Masculinization, acne, hirsutism, deepening of voice, menstrual irregularities. Contra indicated in
pregnancy.
· Increase LDL, decrease HDL levels, and increase coronary artery disease, fluid retention (edema).
Increased anabolic activity with Nandrolone, and oxandrolone.
Anti-androgens
Finasteride, Dutasteride, Flutamide, and Cyproterone acetate. Antiandrogen nonsteroidal in nature (example:
Flutamide, bicalutamide, and nilutamide).
O R
OH C
O N H
O H
Antiandrogen
Androgen
Testosterone (no ester or ethinyl group) Finasteride (presence of Heterocyclic ring)
Anti-androgens pharmacology: Inhibit the synthesis of androgen.

· Finasteride: Competitively inhibits 5-alpha reductase this alpha reductase catalyses testosterone to
dihydrotestosterone (DHT). Because prostate growth is dependent on DHT, rather than testosterone. This
drug is used for treatment of BPH, it suppress (shrink) the prostate size.
· Finasteride is effective in 3 to 6 months.
Anti androgens therapeutic: Finasteride is steroid like drug approved for benign prostate hyperplasia treatment.
Anti-androgen side effects

· Sexual dysfunction. Decrease libido, testicular pain breast tenderness and hirsutism.
· Hypersensitive reactions like rashes, pruritus, swollen face and lips.
· Contraindications. Pregnancy.
· Absorbs from skin avoid contact in pregnancy.
Tips
· What drug shows it action by acting on cell surface? à
· Insulin has pharmacodynamic effect on à
· Insulin is stored at -->
· Insulin hormone antagonist à
· Glucogan hormone causeà
· Diabetic ketoacidosis (DKA) mainly occurs in à
· Sulfonylureas: Chlorpropamide, Gliclazide, glimepiride (Amaryl),glyburide and tobutamide.
· Chlorpropamide + alcohol can cause à
· Meglitinides – Nateglinide, repaglinide
· Biguanides - metformin
· Dose adjustment in renal impairment, SE: lactic acidosis, diarrhea (most), VB 12 ↓
· ONLY oral, NO Wt↑ → good for obese Pt, NO hypoglycaemia on its own
· DI: alcohol (potentiates hypoglycemic effect)
· CI: hepatic impairment, renal impairment, CHF, hypoxemic states Pts
· Metformin + glyburide may causeà
· Thiazolidinediones (TZDs) pioglitazone, rosiglitazone and combination rosiglitazone with glimepiride or
metformin.
· Thiazolidinediones SEs: Wt↑(most), fluid retention, ↑ HDL, NO hypoglycaemia on its own
· DIs: gemifibrozil ↑repaglinide concentration thereby avoid combination. CIs: congestive heart failure.
Can use renal impairment patients.
· Alpha-glucosidase Inhibitors: Acarbose, SE: flatulence, diarrhea
· With meal, NO use as monotherapy.
· Incretin hormone or glucagon like peptide-1 (GLP-1) are inactivated by? Dipeptidyl peptidase-4 enzyme
(DPP-4s).
· Sitagliptine inhibits? DPP-4
· Sitagliptine SEs: Nasopharyngitis, DI: low potential (NO inhibit CYP P450),
· Take with metformin, with or without food, NO potentiates hypoglycaemia
· Intestinal Lipase Inhibitors – orlistat, SE: Diarrhea, Stethorrhea, abdominal discomfort, and oily leakage.
Take with food; impair absorption of fat-soluble vitamins (A, D, E, K)
· Thyroid Hormones-levothyroxine (Eltroxin, Euthyrox, Synthroid): T4
· Dosage: 1.6 µg/kg/day (adults), 12.5-25 µg/day (pts with coronary artery disease or elderly)
· Example of antithyroid drugs à
· Myxedema is malfunction of à
· Antithyroid Agents - methimazole: MMI (Tapazole), propylthiouracil: PTU (Propyl-Thyracil).
· SE: agranulocytosis, monitor WBC or CBC
· Stop about 5days prior to a thyroid scan, RAIU or treatment with 131I
· Increase in cortisone cause (Hypercorticoids) à
· Decrease in cortisone cause (Hypocorticoids) à
· Glutathione is à
· During ovulation increase of à
· Corpus luteum is stimulated by à
· What steroidal hormone structure have phenolic ring à
· Finaseride is à
· Vitamin D 3 acts as à
· The effect of vasopressin on kidney à
· Deficiency (absence) of ADH cause à
· Glutathione protectsà
· The endocrine gland plays important rule in calcium metabolism à
· The major factor that controls Na excretion in kidneyà )
· The effect of the antidiuretic hormone is to à
· In postmenopausal therapy, which drugs have, risk of endometrial cancer à
· Oral contraceptives completely contraindicated inà
· Oxytosin is used à
· Calcium reabsorption of distal convoluted tubule due toà
· Testosterone to 5-hydroxy testosterone is catalyzed by? à
· Example of antiandrogenic drug à
· Finasteride mechanism of action à
· Steroid structures are common in hormones, such estrogen, progesterone, and testosterones. Steroid
contain how many cyclohexane and cyclopentane respectively in it skeleton.
www.Pharmacyprep.com
29
Pharmacology of Respiratory
Drugs
Questions Alerts!
· Pharmacology of beta2 agonist
· Side effects of oral steroids like prednisone
· In children asthma use short acting steroids like prednisone and avoid long acting
dexamethasone. Short acting have less side effects on growth suppression.
Asthma
Chronic inflammatory disorder of the airways, ↑ airways responsiveness, causes reversible obstruction. In
asthma esinophils, mast cells and T lymphocytes plays significant role. ↑ Sensitivity, and hypersensitivity of
airways to specific and non-specific stimuli, such as air, odour, allergens, and virus etc.
Asthma COPD
Airway (Bronchus) Progressive, partially reversible airway limitation. Increases frequency and severity
of exacerbations. COPD is preventable and treatable. The cardinal symptoms are
SOB and activity limitation, fatigue, and barrel chest.
Terminal alveoli
Inflammatory disease Emphysema (permanent enlargement of Chronic bronchitis
alveoli)
Esinophilic Neutrophil Neutrophil
Coughing with wheezing SOB (dyspnea), fatigue SOB (dyspnea) + sputum
during breath, and SOB.
DOC for acute asthma attacks DOC bronchodilator ipratropium, tiotropium, Antibiotics are used to manage
is salbutamol, anti- salbutamol, salmeterol, formoterol (LABA). exacerbations of pneumonia.
inflammatory Inhaled Inhaled corticosteroids are LEAST likely used. Corticosteroid PO for less than
corticosteroids (ICS). PSO2 <90% oxygen therapy <2wks.
Drugs that cause bronchodilation Drugs that cause bronchospasm

Examples of beta 2 agonist Beta blockers
(sympathomimetics) à Salbutamol,
salmeterol, formoterol
Examples of mixed alpha & beta à
Examples of muscarinic antagonistsà
Beta 2 Adrenergic Agonist

MOA. Beta2 stimulation causes increase camp in smooth muscle leading to bronchodilation.
Short acting beta 2 agonist (SABA). (only for rescue as needed)

· Inhaled. Salbutamol (Albuterol) 1-2 puff tid-QID maximum 8 puffs (each puff 100 mcg).
· Terbutaline maximum 6 inhalations/day
· Onset. within 5 min
· Therapeutic use. Relieve bronchoconstriction, the acute symptoms of cough, wheezing and chest tightness,
asthma emergencies and exercise induced asthma.
· Side effects: Tremors, nervousness, tachycardia, palpitation, weakness, flushing of face or skin, insomnia,
nausea and vomiting.
· Regular use can lead to decline in lung function.
Oral beta 2 agonist. The oral beta 2 agonist have more SEs, and less bronchodilation effect than inhaled
preparations.
Long acting beta2 agonist (LABA) (Maintenance or daily): In asthma LABA combined with ICS.
· Inhaled. Formoterol (full B 2 agonist), salmeterol (partial agonist)
· Onset. 14 min and duration up to 24 hours. Regular BID treatment.
· Therapeutic use. Maintenance therapy and EIA. Used in patients already taking corticosteroids. Formoterol
can be used for acute and maintenance.
Formoterol has faster onset of action 3 to 5 min.
Anticholinergic: used as bronchodilators:

Ipratropium bromide is short acting bronchodilator and is used as alternative for patients who are already
susceptible to tremors or tachycardia from B 2 agonist.
Tiotropium DPI (Spiriva, Handihaler, and RESPIMAT inhaler) 18 mcg/daily capsule for inhalation. Long acting
anticholinergic taken once daily, it is administered by handihaler.
Sid effects: Dry mouth, metallic taste, mydriasis, and glaucoma if released into eye.
ANTICHOLINERGIC BRANCHODILATORS
Ipratropiun (Atrovant) Ipratropium 2puffs Q6-8h
Tiotropium (Spiriva handilaer, Respimat) Once daily
Glycopyrronium (Seebri Neohaler) Twice daily
Aclidinium (Tudorza Pressair) Twice daily
Umeclidinium (Incruse Ellipta) Once daily
Combinations: ICS + LABA.
Symbicort = budesonide/formoterol
Advair = Fluticasone/salmeterol
Zenhale = mometasone/formoterol
BREO = FLUTICASONE + VILANTEROL
Corticosteroids
Inhaled corticosteroids (ICS): Fluticasone, mometasone, budosenide, beclomethasone and ciclesonide.
Used for mild to moderate asthma. Benefit ↑ lung function, ↓ airway hyper responsiveness, ↓ symptoms of
exacerbations. Max clinical effects in 2 to 4 wks. Fluticasone in few days, given 2 to 4 pf BID.
Side effects: Sore mouth and sore throat. Oral pharyngeal candidiasis (oral thrush), dysphonea (hoarseness)
from vocal cord myopathy and cough. Rinsing mouth and using spacer (aero chamber) can minimize side effects.
High dosages. Check bone densitometry, patient with glaucoma check IOP.
Oral corticosteroids (Po CST): Prednisone and prednisolone.

· Therapeutic use: Severe asthma with intensive airway inflammation.
· Side effects: Hyperglycemia, osteoporosis, hypothyroidism, hypertension, weight gain, ulcers, edema, and
susceptible to infections.
Leukotriene antagonist: Montelukast and zafirlukast.

The montelukast and zafirlukast have anti-inflammatory action, however LTRAs are not as effective as low dose
inhaled corticosteroids for improving symptoms or exacerbations. It is considered as ad-on therapy with ICS.
· Therapeutic use: Asthma maintenance (steroid sparing agents), and the drug of choice for ASA induced and
beta blockers induced asthma.
· Montelukast 10 mg QHS po tablets is used in children >2 yr age, available as granules and 4 mg, 5 mg
chewable tablets.
· Zafirlukast 20 mg BID po at least 1 h before and 2hr after meals is used in over >12 yr age and only oral
available.
Advantage of combinations. More convenient, enhance adherence, less expensive.

Disadvantage. Loss in dosing flexibility
Chronic Obstructive Pulmonary Diseases
Chronic obstructive pulmonary diseases (COPD) is due to chronic obstruction of airway passage. COPD is two
types. Emphysema (high altitude sickness) and chronic bronchitis.
Emphysema is a disease in which the small air exchange sacs (alveoli) in the lungs become permanently
enlarged and damaged (alveoli walls destroyed) decreasing oxygen absorption and resulting in shortness of
breathe.
Chronic bronchitis is an inflammation of the airways in the lungs that causes lungs to produce excessive amounts
of mucus (phlegm), associated with chronic productive cough. This reduces the flow of air to the lungs.
Drug used for the treatment of COPD: Anticholinergics. Ipratropium and tiotropium are muscarinic blocker and
act as bronchodilator. Beta adrenergic agonists, Corticosteroids and theophylline.
Community acquired pneumonia (CAP) without risk factors:
Pneumonia in COPD patient is treated by amoxicillin, doxycycline, cotrimoxazole, azithromycin, or

clarithromycin.
COPD with risk factors (FEV 1 <50%, Ischemic heart diseases, use of home O 2 , chronic use of steroids, antibiotic
use <3m, >4 exacerbation/yr). Amoxi/clav, cephalosporin's (1st , 2nd, and 3rd) or fluroquinolones (levofloxacin
and moxifloxacin).
Inhalational Drug delivery devices:

Aerosolized medications drug delivery depends on:
Drug formulation properties (particle size distribution, selected the delivery system)
Selection of appropriate device: with appropriate particle size and lung delivery.
Inhalation technique: inspiratory flow rate, inspiratory volume, and breath holding time determines the dose of
inhaled drug that deposits in lung.
Tips
1. B 2 receptor 2. Cough 3. Wheezing
4. permanent enlargement of 5. Salbutamol 6. Emphysema
alveoli
7. chronic bronchitis 8. emotional stress 9. cold air
10. dust pollen 11. ASA 12. Animal dander
13. mold 14. humid>50% 15. exercise
· Emphysema is characterized as? ( )
· COPD is? ( )
· asthma symptoms( )
· Asthma triggers include? ( )
· The drug of choice to treat allergen induced bronchospasm ( )
· What action of adrenergic agonist action is selected treatment of asthma? ( )
· A young patient having asthma and allergic to air conditioners. What will be the pharmacist recommend? à
· What is the drug of choice in allergy induced bronchospasm? à
· What action of adrenergic agonist action is selected treatment of asthma? à
· Formoterol is can be best described asà
· Theophylline clearance is increased by à
30
Pharmacology of
Musculoskeletal Drugs
Questions Alerts!
· Allopurinol (purines) structure and drug interactions with azathioprine. Allopurinol associated with skin
rash, alternatively use Febuxistat.
· Bisphosphonates are pyrophosphates. SAR of bisphonates
· Structure activity of methotrexate and biological response modifiers.
Rheumatoid arthritis (RA). Inflammation of joints with frequent acute attacks.

· Rheumatoid arthritis occurs when body’s immune system attacks the tissue lining and results in the
joints causing cartilage to erode.
Osteoarthritis (OA):
Causes.
· RA. Autoimmune
· OA. aging of cartilage and trauma
Sex distribution
· RA. More common in females
· OA. Equal in both sex
Symptoms
· RA. Joint stiffness in the morning, painful and swollen joints, weight bearing and non-weight bearing
joints. Affects on soft tissue.
· OA. Painful joints, restricted joint movements. Mainly weight bearing joints.
Diagnosis
· RA. Rheumatoid factor, erythrocyte sedimentation rate (ESR), x-ray, antinuclear antibody (ANA)
· OA. X-ray only
Treatment
Rheumatoid arthritis à NSAID’s and DMARD’s
Osteoarthritis à Acetaminophen, NSAID’s
Symptoms Osteoarthritis Rheumatoid arthritis

Stiffness Morning or after inactivity (last 30 min) In the morning (last 1 hour)
Limited affected joints. Does not affect Affects on Soft tissue
Localized soft tissue. Not localized
Pain Worsens with activity or Worsened with prolonged inactivity. (Usually
after prolong use, (weight bearing activity) improves with activity).
Generally weight bearing joints (hip, knee, Affects on weight bearing and non-weight
ankle) bearing joints
Inflammation Uncommon Common
Risk factor >65 years Autoimmune
Treatment Acetaminophen 650 mg q4-6 hr à NSAIDS Methotrexate (for pain prednisone po) à add
à add topical à prednisone infliximab
Osteoarthritis
A degenerative joint disease caused by a breakdown of the cartilage of the bones. Degradation of articular
cartilage in synovial joints.
Non-prescription
· Acetaminophen is initial drug of choice for symptom relief. Maximum therapeutic dose should be tried for 2
to 3 weeks.
· Acetaminophen 650 mg 4 to 6 times a day.
· ASA/NSAIDs/Ibuprofen is 2nd line therapy.
· Acetaminophen + caffeine + codeine
· Glucosamine and chondroitin
· Topical counter irritants (Methyl salicylate/Menthol/Capsaicin).
Prescription Medication
· COX-2 inhibitors as effective as NSAIDs but lower incidence of GI side effects.
· Intraarticular corticosteroids (3 to 4 injections year)
· Hyalunon injections only for those who failed other therapies
· Narcotic analgesics
Rheumatoid arthritis
A chronic systemic, autoimmune inflammatory Question Alert!
condition. Symmetric synovitis affecting similar Lab investigations of RA.
joints bilaterally. 1) Erythrocyte sedimentation rate (ESR)
· It is non-organ specific autoimmune 2) C-reactive proteins (CRP)
disease. 3) Rheumatoid factor (RF)
4) Antinuclear antibody test (ANA)
· Type III hypersensitive reaction
· Blood contain rheumatoid factor
· Stiffness occurs in the morning.
· Large of areas of joints are effects.
Question Alert!
· Not associated with frequent of use of joints.
1) Methotrexate weekly dose max 25/wk.
· It effects on weight bearing and non-weight
2) Lab tests before initiating methotrexate
bearing joints.
Pharmacological Choices
Disease modifying anti-rheumatic drugs.
· Methotrexate is the drug of choice rheumatoid arthritis.
· Should be started within 3 months of disease onset (max effect in 3 to 6 months).
· Initial dose of 20 to 25 mg po/wk, do not exceed >25 mg/wk.
· Minor SEs oral ulcers can be reduced by concurrent use of folic acid.
· Should be avoided in patients with hepatitis B and C, renal insufficiency, or lung disease, serious SEs are
cytopenia, and hepatic toxicity.
· Hydroxychloroquine. SEs corneal and retinal deposition.
· Leflunomide. Can be used in combination with methotrexate (Contraindicated in pregnancy) or in place of it
for patients who have failed or have contraindications to methotrexate.
· Should be stopped in both males and females at least 3 months before attempting conception (patient must
undergo drug elimination by taking cholestyramine 8 g TID for 11 days.
· Azathioprine a purine analog immunosuppressive agent.
· Cyclosporine
· Minocycline
· Penicillamine
· Gold sodium thiomalate
NSAIDs. The NSAIDs are used in conjunction with DMARDS. The analgesic effect of NSAIDS and salicylates is
prompt but reduction of inflammation can take 2 to 4 wks. Avoid NSAID with methotrexate.
If patient experiences in RA flare, use lowest possible dose of short term glucocorticoids.
Glucocorticoids: Prednisone/Triamcinolone safest therapy during pregnancy and lactation.
If RA not controlled, combination of DMRDs or TNF alpha inh are used.
Biological response modifier: Infliximab, etanercept, adalimumab.
Rituximab and trastuzumab, infliximab Produced by human antimouse antibody (HAMA). Monoclonal
antibodies, these antibodies also known as chimeric antibodies.
Infliximab, adalimumab, certolizumab, etanercept, golimumab. Tumor necrosis factor TNF is key mediator of
inflammatory synovitis and bone cartilage destruction.
Side effects: TB infections, psoriasis, increased risk of lymphoma, leukemia. Avoid live vaccines.
Contraindication. SLE, , CHF.
· Only available as iv. Store in refrigerator.
· Approved for ulcerative colitis. It is always used with methotrexate.

· Side effects: The most common SEs is headache, fever, chills, fatigue, diarrhea, pharyngitis upper respiratory
tract and UTIs.
Toclizumab. An interleukin (IL-6) inhibitor
Abatacept. A natural inhibitor of Tcell
Rituximab: a chimeric antibody removes memory B-cells.
Anakinra. Blocks interluekin-1 (IL-1)
Azathioprine: A cytotoxic agent and effective immunosuppressant.

Sulfur analog of mercaptopurine.
GST XO
Azathioprine ---------------à 6-MP ------------- à 6-THIOURACIL
Gout Arthritis
OH
N
N
H2N N N
H Guanine
Guanine deaminase
NH2 OH
OH
N N
N N N
Adenine Xanthine N
deaminase Oxidase
N N N
H N H HO N
N H
Adenine Hypoxanthine H
Xanthine
Xanthine
Allopurinol Inhibit oxidase
OH
O N N
O O H2N Uricase N
H2N-C-NH2 + HO-C-C-H OH
O N N HO N N
Glyoxylic acid H H
Urea H
Allantoin Uric acid
Formation or uric acid, urea and glyoxylic acid from purines
MERCAPTOPURINE AND AZATHIOPRINE ARE THIOGUANINE ANALOGS.
Gout is a disease in which monosodium urate monohydrate (MSU) crystal deposit in joints, soft tissues such as
cartilage, tendon and bursa or renal tissues such as glomeruli, interstitium tubules.
Gout is associated with increased body stores of uric acid. Acute

Question Alert!
attacks involve joint inflammation caused by precipitation of
1) Purine bases such as adenine and
uric acid crystals. guanine produce Xanthine.
Hyperuricemia à Urate crystal in joints à inflammatory 2) Identify structure Xanthine oxidase
response inhibitor?
Acute gout arthritis

Abrupt onset of excruciating pain and inflammation of joint during the night or early morning. Patient cannot
tolerate even light pressure such as a bed sheet on the affected joint. Attacks often resolve spontaneously over
3 to 10 days.
OH3C
NHCOCH3 (C3H7)2N-SO2
OH3C CO2H
OH3C O
CH3O Probenecid
Colchicine
Colchicine
· It produces an anti-inflammatory and analgesic effect
· It not used as analgesic action
· The most common SE is GI irritation
Antihyperuricemic agents
Allopurinol. Inhibit xanthine oxidase.
NON-PURINE STRUCTURE. HAS NO EFFECT ON OTHER ENZYME PURINE AND PYRIMIDINE PATHWAYS. SOME OF
THE SIDE EFFECTS ASSOCIATED WITH ALLOPURINOL MAY BE DUE TO NON-SELECTIVITY AND STRUCTURAL
SIMILARITY TO NATURALLY OCCURING PURINE OR PYRIMIDINES.
· Xanthine oxidase enzyme is metabolizing enzyme of mercaptopurines. This enzyme is inhibited by
allopurinol.
· Side effects: The major SEs are dermatological (skin rash, exofoliative lesions), GI (nausea, vomiting, and
diarrhea).
· Can form urate crystal in kidney and take with plenty of fluids.
Xanthine oxidase enzyme activate allopurinol into oxypurinol (a transition state analog) that binds very tightly to
the molybdenum-sulfide (Mo-S) complex at the active site of xanthine oxidase.
XO XO
PURINE ---àHYPOXANTHINE----------------à XANTHINE ------------- URIC ACID
ALLOPURINOL ALLOPURINOL
FEBUXOSTAT FEBUXOSTAT
Febuxostat is a xanthine oxidase inhibitor: Allopurinol associated with skin rash, alternatively use Febuxostat.
Structurally different than allopurinol, thus can be used in patient allergic to allopurinol. Febuxostat is consist of
thiazole ring.
Can be used in renal diseases. OH OH
ALLOPURINOL FEBUXOSTAT N
N Xanthine N
N
SIMILAR PURINE NON-PURINE N
Oxidase
N
N
THIAZOLE HO N
H
Protein binding is High protein binding
H
Alloxanthine
negligible (99%) Allopurinol (oxypurinol)
Allopurinol 1-3 hr, Long half-life 8 hr ALLOPURINOL ----------------à OXYPURINOL
oxypurinol up to 20 hr
Sulfinpyrazone
· Increase uric acid excretion
· SEs. Can form kidney stones
· Drink plenty of fluids
Probenecid
· SEs. can form kidney stones
Fenofibrate and losartan are used as uricosuric agents and for treatment of hyperuricemia.
Osteoporosis
Calcium homeostasis (serum concentration of ionic calcium)
Three hormones parathyroid, calcitonin and vitamin D control calcium homeostasis.

Osteoblast. Formed in bone marrow, stimulate bone formation.
Osteoclast. Responsible for carrying out the bone resorption or destroying process.
Bisphosphonates: Inorganic Pyrophosphates (P-O-P group) and bisphosphonate (P-C-P)

Alendronate, residronate, etidronate, pamidronate and zoledronic Acid
R1 = OH group binding to bone is

enhanced
R2 = site determines antiresorptive
potency including effects on binding to
hydroxyapatite.
Bisphosphonates are two types simple bisphosphonate and aminobisphosphonates

Simple: Etidronate
Amino (containing nitrogen): alendronate, residronate, Pamidronate, Zoledronate,
Bone remodeling:
ACTIVATION à RESORPTION à REVERSAL à FORMATION à MINERALIZATION
(osteoclast) (osteoblast)
Tips
1 Anti hyperuricemia drugs 2 GI irritation 3 Allopurinol

4 Sulfinpyrazone 5 Probenecid 6 Alloxanthine or oxypurinol
7 Acetaminophen 8 Renal failure
· Drink plenty of fluids while taking…( )
· Side effect of colchicine ( )
· Colchicine is contraindicated in? ( )
· What analgesic is not used in gout arthritis? ( )
· Example of drug that decrease uric acid production or formation (3, febuxostat)
· Example of drug that increase uric acid renal secretion ( )
· What drug is not used for acute gout attack? ( )
· The major metabolite of allopurinol( )
· The most important risk factor for osteoporosis is? Low bone density.
· Penicillin's and probenecid drug interaction occurs due to competing secretion in nephron.
· Drugs that has uricosuric effects (↓ uric acid) are? Fenofibrate and losartan.
· The new xanthine oxidase inhibitor Febuxostat is an option for patient with sever renal insufficiencies.
Allopurinol dose adjustment in renal insufficiency.
31
Pharmacology of Antimicrobial
Drugs
Questions Alerts!
· Structure activity of penicillin's and cephalosporins and mechanism of penicillin resistance.
· Quinolones mechanism of action and structure activities.
· Structure activity Tetracycline epimerization gives 4-epitetracyclin.
· Macrolides side effects explain by structure activity.
Antibiotics classifications
Cell Wall synthesis inhibitors Penicillin's, Cephalosporin's, Vancomycin
Protein Synthesis inhibitors Aminoglycosides, Macrolides, Tetracycline’s, Lincosamide
DNA Synthesis inhibitors Quinolones/Fluoroquinolones, Metronidazole
Folate Inhibitors Sulfonamides, Trimethoprin.
Penicillin's
6-Aminopenicillanic acid
b-lactam ring
H H
H R N N S
R N S
S R R
O N N
N O O R
O
COOH COOR
COOH Dihydrothiazine
C Thiazolidine
D
C = Bond cleavage by beta-lactamases Penicillins Cephalosporins

D=Susceptible to hydrolysis
R = Substitution of R effects in solubility's salts are given orally, R = benzyl penicillin = Pen G. R = Phenoxymethyl
= Pen V
A chemical drug-drug incompatibility between gentamycin C 2a and beta lactam. Two drugs react with each
other so that N-acylation of C 1 of gentamycin by the beta lactam bond takes place, thus inactivates both
antibiotics.
Question
R = Benzyl amineAlerts!
= Amoxicillin and ampicillin (Amino penicillin's)
1) Rings structures present in penicillin's and cephalosporin's. ? Thiozolidine and dihydrothiazine ring
2) Site of beta lactamase reaction on lactam ring?
3) Site of acid hydrolysis in beta lactams?
Protein Synthesis Inhibitors
50 S Antibacterial Agents 30 S Antibacterial Agents
Macrolides Chloramphenicol Aminoglycosides Tetracycline's

Erythromycin Lincosamides Gentamycin Demeclocycline
Azithromycin Clindamycin Streptomycin Doxycycline
Clarithromycin Lincomycin Kanamycin Minocycline
TEST CC: T = tetracycline, E = erythromycin S = Sulfadrugs, T = trimethoprin, C = clindamycin C =

Chloramphenicol, are bactereostatic.
Macrolides: Erythromycin, clarithromycin Question Alerts!

and azithromycin. 1) Erythromycin and clarithromycin produce "KETAL"
Mechanism. Protein synthesis inhibitors. metabolite. It is responsible for GI irritation.
Structure. Large lactones ring of 12 or 14 2) Ery and Clarithromycin are potent CYP 3A4 inhibitors.
or 16 atoms are attached to amino sugar Whereas Azithromycin is weak inhibitor of CYP 3A4
(hexose) & neutral sugar by glycosidic 3. Macrolides cause QT segment prolongation
link.
Macrolide are contraindicated in hepatic failure.

Erythromycin
· Lactone ring + desoamine (amino sugar) + cladinose (neutral sugar).
· Common SEs. Gastric upset is due to conversion of erythromycin to ketal. QT prolongation.
· The macrolides are generally unstable to acids, bases & high temperature.
Azithromycin
· Stable to acids, bases & high temp, thus less gastric upset.
· Long half life, greater and longer tissue penetration and covers H. influenza.
Clarithromycin: The enhanced lipophilic allows for lower or less frequent doses.
Erythromycin and tetracycline cross placenta in appreciable amounts and also appear in breast milk.
CYP3A4 INH CYP 3A4 SUBSTATE
ERYTRHOMYCIN ¯¯¯
CLARITHROMYCIN ¯¯¯
AZITHROMYCIN ¯¯
ALS (STATINS) ***
CCB ***
SILDENAFIL ***
Tetracycline’s: Tetracycline, doxycycline and minocycline.
Chemical instability: Tetracycline a-stereo orientation of the C4 dimethylamino-moiety is essential for the
bioactivity. Epitetracycline is inactive drug by epimerization.
H N(CH3)2
N(CH3)2 H N(CH3)2
OH
4 OH OH
Base H+ 4
NH2
H+ NH2 Base NH2
OH
O O OH OH
O O O O
Tetracycline
4 Epi- Tetracycline
Epimerization of Tetracyclines
OH OH
OH O O M HO OMO
H
M= di or trivalent metal ion
Metal chelation with the tetracyclines

Photo toxicity: Tetracycline with C7 chlorine, absorb light in the visible region leading to free radical generation
and potentially cause severe erythema to sensitive patient on exposure to sunlight.
Tetracycline Doxycycline Minocycline

Less SEs. Less SEs High SEs. Has reactive amino acid. Causes
Hepatitis, liver necrosis from serum sickness (discoloration of nail, bones,
iv, avoid in pregnancy. teeth).
Pediatric (<8y) tooth Vestibular toxicity (vertigo, ataxia, nausea),
discoloration. dizzy, headache
Empty stomach With or after food but With/without
empty better absorbed
Renal safe
Effective acne Effective acne More effective for acne due to lipid soluble.
Used in RA.
Dis with bi, tri valent Less Dis. More Less DI
photosensitive
Once daily, bioavail 90-100%
Expired tetracycline cause Funconi like syndrome (renal tubular necrosis, diabetes like symptoms) and
extreme cases has been fatal.
Quinolones & Fluoroquinolones

Nalidixic acid (urinary disinfectant)
Fluoroquinol 1st gen. Nalidixic acid, Norfloxacin
ones 2nd gen. Ciprofloxacin, Oflaxacin
3rd gen. Gatifloxacin, Moxifloxacin, Levofloxacin (respiratory tract)
4th gen Travofloxacin, basifloxacin
Inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV makes cell inaccessible and leads to cell death.
Different quinolones inhibit different extent of topoisomerase II and IV. DNA gyrase seems more important in
gram –ve. Topoisomerase IV in gram +ve.
Nalidixic acid is primary effective against gram –ve.
Quinolones chelate with polyvalent ions such as Fe, Al, Mg, Ca to form less water-soluble and complexes and
thus decrease considerable potency.
Nitrofurantoin
Nitrofurontoin inhibits bacterial DNA and RNA.
· Not used in renal diseases or contraindicated in CrCl <60 ml/min
· The drug of choice in urinary tract infection and also used as prophylaxis for UTI in pregnancy 100 mg BID
for 7 days.
NITROFURONTOIN RAPID GI ABSORPTION & HIGH URINARY CONCENTRATION

Pseudomonas and Proteus spp. are naturally resistant.
Folate antagonist sulfa drugs (Cotrimoxazole):

Dihydroteroate diphosphate + PABA à dihydroteroic acid à tetrahydrofolic acid à thymidine à DNA
Oxazolidinones: Linezolid (po, parenteral).

Mechanism. Binds to bacterial ribosomes to inhibit protein synthesis.
· Side effects: Reversible thrombocytopenia.
· Drug interactions: It can cause serotonin syndrome with antidepressants.
· Therapeutic use. Methicillin resistant S. aureus (MRSA) infections
Tips
Cell wall synthesis inhibitors
1 Amoxicillin 2 Penicillins 3 Ampicillin

4 Type 1 allergy 5 Type 2 allergy 6 Cloxacillin
7 Penicillin V 8 Clindamycin 9 Penicillin G
10 Doxycyclin 11 Macrolide 12 vancomycin
· Methicillin is only IV and IM

· Penicillin G benzathine has long half life à 24 to 60 hrs
· Naficillin is mainly hepatic elimination.
· Beta lactamase sensitive drugs Pen G, Amoxi, Pen V and Ampicillin
· Endocarditis prophylaxis is (Dental extraction prophylaxis) à 1
· A child less than 2 y allergic penicillin, what is the drug choice for otitis media treatmentà11
· A patient has heart diseases and underwent prostatic valve surgery. Dentist plan to tooth extraction, what
antibiotic is suitable for endocarditis prophylaxisà1,6,8
· Chewable antibioticsà1
· Beta lactams that should be taken empty stomach à
· Aminopenicillins are ( )
· What is the alternate drug of choice in patient allergic to penicillin? ( )
· Penicillins are ineffective in treatment of bacterial infections associated with à
· MRSA infections are treated by à
· P. colitis associated diarrhea is treated by à
· Bacteria is inhabitant in GI, what location of GI tract is commonly found à
· Type of bacteria mainly present in colon is à
· If allergic penicillins the best alternate choice of antibiotics is macrolide.
· What type hypersensitive reaction caused by Penicillins à
· Drug of choice Pseudomonas aeurigunosa? Penicillin, cephalopsprins (4th gen), carbepenams (imepenam,
merepenem), ciprofloxacin.
· What bacteria is not present in CAP infections?
Macrolides Tips
1 Erythromycin 2 Clarithromycin 3 Azithromycin
4 Type 1 allergy 5 Tetracycline 6 Gastric upset
7 Room temperature 8 Refrigerator 9 H. influenza
10 Doxycyclin 11 Ciprofloxacin 12 Cotrimoxazole
· Azi & Clarithromycin suspension stored at à 7
· Which macrolide suspension have to refrigerate after reconstitution (1)
· What antibiotics should caution and require monitoring in patient receiving warfarin (2)
· What antibiotic potentiate the effect of digoxin and can cause digitalis toxicity à 1,2 and tetracycline 5
· Azithromycin is the drug of choice in traveler diarrhea for patient traveling to à Thailand (south east Asia)
Tetracyclin Tips
1 Tetracyclin 2 Doxycyclin 3 Minocyclin
4 Photosensitive 5 Must take empty stomach 6 With food
10 Calcium supplements 11 Dairy products 12 Cartilage toxicity
13 Bi & tri valent 14 renal tubular necrosis 15 prophylaxis
· Tetracyclin are contraindicated are contraindicated in pregnancy and children. (T)

· Tetracyclin can stain teeth causing discoloration. (T)
· Oral tetracycline is drug of choice for acne treatment (T)
· Tetracyclin MUST BE taken on empty stomach. (T)
· Tetracyclin binds à
· Macrolides àGI distress (abdominal discomfort, diarrhea) are most common SE. This can be prevented by
taking with food or decreasing dose.
· Expired tetracycline can lead à
· Doxycyclin is the DOC àCAP
· Doxycyclin should be taken à
· Minocyclin maybe taken with or without food. (T)
· Phototoxic reactions (sever skin lesions) can develop with exposure to sunlight. Photoxicity is the most
common side effect of doxycyclin or demeclocyclin.
· Epimerization of tetracycline produce à epitetracyclin.
Clindamycin Tips
1 Clindamycin 2 Diarrhea 3 P. colitis
4 Photosensitive 5 Anaerobic 6 Fever
infections
7 Room temperature 8 Bloody diarrhea 9 metronidazole
10 Calcium 11 Dairy 12 Vancomycin
supplements
· Most common complication of clindamycin is à2
· Clindamycin is active against à5 and gram +ve, & -ve
· Pseudomembranous colitis symptoms include fever, abdominal pain, bloody stools.
· Clindamycin can cause à
· Clindamycin drug associated diarrhea is treated byà
· Clindamycin suspension can be stored at à 7
· Clindamycin should be taken à full glass of water
Quinolone and fluroquinolone Tips

1 Ciprofloxacin 2 moxfloxacin 3 Norfloxacin
4 Photosensitive 5 Must take empty stomach 6 Cartilage erosion
7 Room temperature 8 Crystalluria 9 UTI
10 Calcium supplements 11 QT Prolongation 12 Cotrimoxazole
· Fluroquinolones are indicated for UTI, Infectious diarrhea (Travellers diarrhea), lower respiratory tract
infections, bone and joint infections (osteomylitis).
· Gatifloxacin, Moxi, levofloxacin SE are à 11
· Fluroquinolones contraindicated in children, under 18 y, pregnant women are due to à6
· Antacids, bivalent and trivalent ions significantly decrease absorption of àtetracycline
· Fluroquinolone increase INR in patient receiving warfarin, therefore monitor à PT
· Fluroquinolones can cause hyperglycemia, therefore monitor à Blood glucose in diabetics
· Fluroquinolones at higher alkaline pH can cause àCrystallurea
Metronidazole Tips
1 Metronidazole 2 Alcohol 3 Trichomonas
4 Amoeba 5 GET A metro, P. 6 With or without food
colitis
7 Room 8 Refrigerator 9 Anaerobic bacteria
temperature
10 Ca supplements 11 H. pylori 12 Disulfiram like reaction
· Alcohol with metronidazole can cause à
· Metronidazole is classified as Antiprotozoal drug
· Metronidazole is effective against à
· Metronidazole discolor urine (T)
· Metronidazole caution in pregnancy (T)
Sulfadrugs Tips
1 Cotrimoxazole 2 Sulphamethoxazole 3 Steven Jhonson Syndrome
4 Photosensitive 5 Synergistic effect 6 Pneumocyctis carinii pneumonia
(PCP)
7 Drug fever and 8 Skin rash, 9 UTI
serum sickness exofoliative
dermatitis
10 Hemolytic anemia 11 Trimethoprim 12 Pregnancy
· Sulfamethoxazole+trimethoprim has à synergistic effect
· A 22-year-old patient currently using cotrimoxazole for UTI, reported sever rashes on arms, neck and back,
what are the possible reactionsàallergic reaction
· What are the folic acid synthesis inhibitorsà Sulfa drugs, methotrexate, 5-FU, trimethoprin,
pyremethamine, and dapsone.
· Patient with G6PD deficiency, takes sulfadrugs can cause à 10
· Hypersensitive reactions of sulfadrugs most commonly involve àskin, mucus membrane.
· Life threatening hepatitis caused by sulfadrug toxicity or sensitization rare SE, the signs and symptoms
includeàheadache, N&V, Jaundice
· Sulfamethoxazole have high frequency of skin hypersensitive reaction in patient with (AIDS)
· If used in last trimester of pregnancy, can cause kernecterus in new born.
· Cotrimoxazole suspension stored at room temperature in amber color glass bottle.
1 Vancomycin 2 Penicillins 3 Tetracycline

4 Clarithromycin 5 Streptomycin 6 Azithromycin
7 Minocycline 8 Clindamycin 9 Metronidazole
· What drugs to treat infection of gram -ve anaerobic bacteria Bacteroid fragilis (abdominal infection) (8,9
)
· What antibiotic suspensions should be stored at room temperature (4,6,8)
· What antibiotics are not effective for Mycoplasma bacteria (2)
· What drugs increase warfarin INR, digoxin & theophylline levels (3,4 )
· What antibiotics are effective H. pylori infections (used along with PPIs in triple therapy (2,3,4,9)
· What antibiotics are used in treatment of acne (3,7,8, and 10)
· The drug for treating methicillin-resistant Staphylococcus aureus infections (1 & 9)
· What antibiotic has the highest ototoxicity (5)
· What macrolide antibiotic is more active against gram-ve H. influenza than erythromycin (6)
· What antibiotic is used for acne and rheumatoid arthritis (7)
· Must avoid alcohol while on this drug because it cause disulfiram like reactions (9 )
· What drug is used as prophylaxis in traveller’s diarrhea (11)
· What is the drug of choice for UTI & traveller’s diarrhea ( 11)
· What drug is used in chronic treatment of UTI (11 )
Tips
1 Folate antagonist 2 Nalidixic acid 3 Thiazolidine
4 epimerization 5 DNA gyrase & 6 Antacids
topoisomerase II
7 Ca (bi and 8 Dihydroteroic acid 9 Dihydrothiazine
trivalent)
10 Tetrahydrfolic acid
· The chemical ring present in penicillin's ( )
· The chemical ring present in cephalosporin's ( )
· Tetracycline at 4 position undergoes…( )
· Tetracycline chelate with.. antacids, Ca and Iron ( )
· Sulpha drugs act on? ( )
· Sulpha drugs action prevent formation of? ( )
· Quinolone antibiotic are bactericidal act by inhibiting…( )
· What is an example of urinary tract disinfectant? ( )
1 Amoxicillin 3 Penicillin G and V 5 Tetracycline
2 Cephalexin 4 Cefuroxime 6 Ceftriaxone
10 Ciprofloxacin 11 Ofloxacin 12 Clindamycin
13 Trimethoprim- 14 Metronidazole 15 Vancomycin
sulfamethoxazole
· is commonly causes dose-related GI tract disturbances, including nausea, vomiting, and diarrhea ( )
· raises blood levels of theophylline and potentiates terfenadine in producing ventricular arrhythmias. ( )
· have enhanced activity against Haemophilus influenza ( )
· Inhibit the activity of DNA gyrase ( )
· are effective in bacterial prostatitis and bacterial diarrhea except that caused by C. difficile ( )
· What drug act as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle ( )
· It is used primarily for the treatment of Trichomoniasis, Amebiasis, Giardiasis (14)
· and P.colitis ( )
· Stevens-Johnson Syndrome is a severe form of erythema multiforme ( ) characterized by bullae on the
oral mucosa, pharynx, anogenital region, and conjunctiva; target-like lesions; and fever
· Antacids containing Mg or aluminum interfere with absorption if taken within 4 h ( )
www.pharmacyprep.com Metabolism
32
Metabolism
Questions Alerts!
· Phase 1 or functional group metabolism, example oxidative deamination reactions.
· Cytochrome CYP450 (major CYP3A4) substrates, inhibitors and inducers.
· Phase II or conjugation metabolism like glucuronidation, glutathione conjugation, and acetylation.
· Alcohol metabolizing enzymes.
· 1) Glucuronidation is catalyzed by? UDP GT
· 2) Amino acids present in glutathione? glycine +Cysteine + glutamic
· 3) Mercapturic acid is product of? Glutathione conjugation
· 4) Norepinephrine to epinephrine is catalyzed by? N-methyl transferase
· 1) Site of hydrolysis of penicillin's and cephalosporin's? GI tract
· 2) Local anesthetic hydrolysis that gives PABA? Benzocaine, Procaine, and tetracaine.
· 3) What type of metabolic reactions are the most common in GI tract? Hydrolysis
· Biotransformation: Biochemical reactions that are catalyzed by enzymes.

· Bioactivations: Metabolic reactions that produce active metabolite.
· After metabolism of drugs. Drugs become more water soluble, excreted faster and toxicity can increase or
decrease.
· Reactive metabolites are breakdown to other active or toxic metabolites.
Biotransformation Bioactivation (Pro-drugs) Reactive metabolites

Phase 1 metabolism Cefuroxime axetil Meperidineà nor-meperidine
Phase 2 metabolism Methyldopa Acetaminophenàbenzoquinoneimine
ACEi: Enalapril, Ramipril Furosemide à Furosemide epoxide
Valacyclovir --> valacyclovir Sulfamethoxazole à Nitroso sulfamethoxazole
triphosphateàacyclovir Cyclophosphamide à Acrolein
Famciclovir --> penciclovir Spironolactone à canrenon.
Methanolà Formic acid
Ethylene glycol à oxalic acid
Enzyme sites Phase I Phase 2

Endoplasmic reticulum (Hepatic CYP450, prostaglandin Hepatic non-microsomal enzymes:
microsomal enzymes) the primary Acetylation, sulfate, GSH, alcohol
location for drug metabolizing dehydrogenase, hydrolysis
enzymes
Cytosol (soluble fraction of many water soluble enzymes.
cytoplasm)
Mitochondria MAOi, aldehyde UDPGT
dehydrogenase, CYP450
Lysosomes: Phase I peptidase
Nucleus: UDPGT
PHASE 1 PHASE II
Functional groups metabolism (OH, NH 2 , COOH, SH Conjugation (ADDITION) metabolism
etc)
Oxidation, reduction, hydroxylation, deamination, Glucuronidation, glutathione conjugation,
dealkylations, demethylation, oxidative deamination sulfonation, acetylation, glycine conjugation and
methylation.
Cytochrome oxidations (CYP450), reductase, aminase
and monoamino oxidase (MAO).
Phase 1 Metabolism
Phase I metabolism (Functional group metabolism or mixed function oxidase metabolism).
Reactions that convert the parent drug into more polar (water-soluble) molecules by introducing a polar
functional group, such as -OH, or-NH 2 , COOH, SH. Phase I metabolism mainly occurs in liver, kidney, GI tract and
other tissues. These reactions are catalyzed by cytochrome (CYP450). Cytochrome is mainly found in
ribosomes, specifically endoplasmic reticulum.
Drugs in phase 1 metabolism undergoes the following reactions oxidation (most common phase 1 reaction),
hydroxylation, dealkylation, deamination, reductions, hydrolysis, and de-sulfuration.
Oxidative metabolism
The most common phase I reaction is oxidation. Oxidation metabolism most commonly occurs in liver. Less in
intestine, lungs and kidney catalyzed by CYP450 with different routes 3A4, 2C9, 2C6 and others oxidizing
enzymes. Example substrate, enzyme inducers and enzyme inhibitor.
Alcohol oxidations Ethanol
· Primary alcohol oxidation à aldehyde à acid. Alcohol dehydrogenase

· Secondary alcohol oxidation à ketone
· Tertiary alcohol à no oxidation Nausea and vomiting
· Ethylene glycol à oxaldehyde à oxalic acid (toxic). Acetaldehyde headache
Hypotension
· Ethylene glycol is used as antifreeze. Thiamine decrease
bioavailability
· CH 3 OH (methanol) àHCHO (formaldehyde) Acetaldehyde dehydrogenase
Acetic acid
àHCOOH (formic acid) à formic acid is toxic can cause blindness.

· CH 3 CH 3 à CH 3 CH 2 OH (ethanol)à CH 3 CHO (acetaldehyde) à CH 3 COOH
Reduction Reactions: on metabolic reactions are azoreduction, nitro reduction and carbonyl reductions.
Reduction: Bacteria resident in the GI tract are known to be involved in azo and nitro reductions. Reactions
catalyzed by reductase. Both mechanism of oxidation and reduction is to create a polar substrate to be excreted.
Azoreduction: As in sulfasalazine and olsalazine. Reducing enzymes called reductase, such as azoreduction is
catalyzed by azoreductase enzyme, which catalyzes reduction reaction. Example of azo (-N=N-) reduction
sulfasalazine undergoes azoreduction in gut (colon) and produces 5-aminosalicylic acid (5ASA) and sulfpyridine.
NH2 CO2H
Azo bond OH
5-aminosalicylic acid
O N (Mesalamine)
S
N Azoreductase +
COOH N OH
O N
N S
HO at Gut N
OH
Sulfasalazine NH2
Sulfapyridine
Azoreduction in colon
Nitro reduction: Nitro (NO 2 ) group upon reduction produce amine (NH 2 ) group. Drugs that undergo nitro
reductions e.g. nitro reduction takes places in the metabolism of chloramphenicol and clonazepam. Carboxylic
acid upon reduction produces aldehydes and then alcohol.
Carbonyl (ketone or aldehyde) reduction example: acetohexamide.
acetohexamide undergoes carbonyl reductions.
Hydrolysis
Hydrolysis is a metabolic reaction that most commonly occurs in gastrointestinal tract. Hydrolysis is catalyzed by
enzyme called esterases. There are two functional groups commonly undergo hydrolysis are esters and amides.
Esters (hydrolysis) produce à acid + alcohol.
Amide hydrolysis products à acid + amine.
Amide hydrolysis is catalyzed by amidases. Fixed oils consist of ester functional groups, metabolized by ester
hydrolysis and produce glycerol + fatty acid. Esters (esterases) present in plasma and various tissues.
HYDROLYSIS
VALACYCLOVIR -------------à ACYCLOVIR --à ACYCLOVIR TRIPHOSPHATE
HYDROLYSIS
FAMCYCLOVIR -------------à PENCYCLOVIR-à PENCYCLOVIR TRIPHOSPHATE
Ester hydrolysis Hydroxylation

CH3 CH3
N NHCOCH3 NHCOCH3
N
OC2H5 OH + C2H5OH
O O OH
Meperidine Acetanilid Acetaminophen
Hydroxylation
Acetanilid hydroxylation gives acetaminophen

Phenacitin de ethylation (dealkylation) gives acetaminophen
ACETAMININOPHEN ------------à N-BENZYLQUINONEIMINE
Question Alert!
1. Example of oxidative deamination reaction? Norepinephrine metabolism by MAO.
2. ASA and Salicylic acid metabolism includes Glucuronidation, and glycine conjugation (major)
hydrolysis, and hydroxylation
3.ACEinh activated by esterases. (Ester à ACID)
Deamination: Examples of deamination include amphetamine and dopamine.

Oxidative Deamination
H2 H H2 O
C NH2 C NH3
CH3 CH3
MAO
Serotonin ---------------------------------> 5-hydroxy indole acetic acid (5HIAA)
Oxidative deamination
MAO
Dopamine -----------------------------------> 3, 4-dihydroxy phenyl acetic acid (DOPAC)
Oxidative deamination
CYCLOPHOSPHOMIDE --------à ACROLEINE + PHOSPHORAMIDE MUSTARD
DEHYDROXYLATION
ADEFOVIR ----------------------------------àCIDOFOVIR
Cl Cl (-) O Dehalogenation. (Halothane, Chloramphenicol)

CF3 - C - H CF3 - C Halothane immunological reaction produce
H hepatotoxicity
Br
Br (-)
Phase 2 Metabolism
Phase 2 metabolism reactions are referred as conjugation reactions, parent drug or its metabolite with certain
natural constituents such as glucuronic acid, glycine, glutamine, sulfate, and glutathione. There are 6 major
conjugation pathways.
Factors affecting Drug Metabolism

Chemical structure (functional group)
Species differences. Quantitative (presence of enzyme inducers or inhibitor) phase I, qualitative in phase II
reaction
Physiological or disease state: liver disease, CHF, renal disease, Hypo & hyperthyroidism. Also alteration in
albumin production as in elderly.
PHASE 2 REACTION Enzymes Drugs

Glucuronidation (addition Uridenyl Diphosphate Acetaminophen, morphine, diazepam,
of glucuronic acid) Glucuronyl sulfathiazole, digoxin, and salicylic acid.
Transferase (UDP GT)
Acetylation (addition of N-acetyl transferase Sulfonamides, isoniazid, clonazepam, and
acetyl group) (NH 2 , OH) dapsone (Primary amines undergo acetylation).
Glutathione conjugation Glutathione S- Ethacrynic acid, reactive phase 1 metabolite of
(addition of glutathione) transferase (GST) acetaminophen mercapturic acid is produced.
(glycine + Cysteine +
glutamic acid)
Glycine conjugation (Amino Acetyl transferase Salicylic acid (75% of salicylic acid is excreted
acid conjugation) after glycine conjugation, nicotinic acid (Niacin),
Addition of glycine deoxycholic acid.
Sulfate conjugation Sulfotransferase Acetaminophen, methyldopa, estrone
Methylation N-Methyltransferase Epinephrine, norepinephrine, dopamine,
histamine
Genetic factors: Acetylation rate by N-acetyltransferase, which may result in fast acetylators or slow acetylators
(pharmacogenetics).
Nutritional status. Low protein diet decreases oxidative drug metabolism, vitamin C deficiency decreases
oxidative pathways. Vitamin E deficiency retards dealkylation and hydroxylation
Age: Infants, children, elderly. Circadian rhythms, nocturnal plasma levels of theophylline and diazepam are
lower than the diurnal plasma levels. Drug administration route (first by pass) for oral only, iv, sublingual no first
by pass.
Elderly person have less phase I metabolism.
Infants: ¯oxidative enzymes, and glucuronide conjugation but well developed sulfate conjugation. (Phenytoin &
phenobarbital have low half-life in infants). Theophylline neonates t 1/2 13-26 hr but children 3-4 hr.
Young children: - drug metabolism, - capacity for methylation.
Cytochrome classification: The cytochrome P450s enzymes are located in the endoplasmic reticulum and are
highly concentrated in the liver (microsomal hepatic enzymes) and small intestine. Additionally, CYP P450s are
also found in the mitochondria membrane. CYP 450s encompass a highly diverse "superfamily" of hemoproteins
and one of their most relevant functions is that of metabolizing drugs in humans. Cytochrome oxidase enzymes
have porphyrin ring so susceptible with CO, O 2 , and CN. CYPs in endoplasmic reticulum in liver and small
intestine and also mitochondrial membrane. Monooxygenase catalyzers (oxidizing) need NADPH as co-enzyme
to use O 2 .
CYP 1,2,3,4, isoforms involved in drugs and xenobiotics. CYP 7,11,17,19,21,27 involved in steroids and bile acids.
Steroid and bile acid metabolism (primary): CYP7. CYP11, CYP 17, CYP19, CYP21 and CYP27 enzymes
metabolize steroids, and bile acids, is referred to as primary metabolism.
CYP11A
STEROIDS ¬ CYP11B ¬ ----- CHOLESTEROL --- (CYP7A1)à BILE ACIDS
¯ CYP21
CYP3A
CYP2A
CYP2B
¯ Acetyl-CoA
METABOLISM & EXCRETION
Drug metabolism (secondary): CYP1, CYP 2. CYP3, and CYP4 subtype of enzyme catalyze drugs, or exogenous
chemicals. CYP3A is the most common enzyme that catalyze phase 1 oxidative reactions.
Cytochrome P450 classified into subtypes. CYP = Cytochrome, 1 or 2 or 3 number, family. A, B, C,

indicate subfamily and 1, 2, 3 indicate individual genes.
CYP1 CYP2 CYP3
CYP1A1 CYP1A2 (3%) CYP2D6 (25%) CYP3A4 (52%)
CYP1B2 CYP2C9 (18%) CYP 3A5
CYP1C3 CYP2C19
CYP2E (1%)
Potential enzyme drug metabolism
Enzyme SUBSTRATES INHIBITORS INDUCERS Examples

CYP3A4 Benzodiazepines Nefazodone Phenobarbital Generally, all anticonvulsants
Dihydropyridine CCBs SSRIs Phenytoin are inducers + Rifampin
Carbamazepine Azole antifungals Carbamazepine
Ethynyl estradiol Cimetidine Prednisone CYP3A is the most abundant
Statins (ALS) Macrolides (E,C) Toglitazone CYP3A4 is most next CYP3A5
Terfenadine Protease inhibitors Rifampin
Theophylline Verapamil Cisapride and terfenadine can
Protease inhibitors Omeprazole (PPI) St. Johns Wort have cardiotoxic levels with
PI:Ritonavir, Saquinavir,
Triazolam Nelfinavir, Lopinavir Azoles and Clarithromycin
Amitriptyline
Lidocaine
Cyclosporine
Digoxin
Caffeine
Non-sedative
antihistamine
CYP3A4 Grapefruit; Flavanoids D-F interaction
CYP3A5 Nifedipine Glucocorticosteroids

Cyclosporine
Steroid hormones (i.e.,
sex hormones)
CYP2D6 TCAs SSRIs None a potential D-D interaction as

SSRIs Nefazodone 2 drugs from 1 therapeutic class
Antipsychotics Venlafaxine TCA and SSRI as well as other
Antipsychotics
Beta blockers (Haloperidol) Psychotherapeutics
Narcotics (codeine) Quinidine
Venlafaxine Ritanavir 2nd most CYP Enzyme
CYP1A2 TCAs Quinolones (ciprofloxacin) Omeprazole

Propranolol Grapefruit Phenobarbital D-F interaction
Warfarin Nefazodone Phenytoin
Theophylline Fluoxetine Rifampin
Acetaminophen Smoking D-C interaction
Clozapine Charbroiled meats
Olanzapine Carbamazepine
CYP2C9 Phenytoin Azole antifungal Rifampin

Warfarin Metronidazole Carbamazepine Fatal D-D interaction
NSAIDs Ritonavir Phenytoin
Losartan Clopidogrel
Amitriptyline Fluvastatin
CYP2E1 Alcohol D-F interaction

Examples of metabolic pathways
Drug Pathway
CH3
a Deamination (followed by oxidation and reduction of the ketone formed)

b
NHR N-oxidation
N-dealkylation
Hydroxylation of the aromatic ring
Hydroxylation of the b-carbon atom
Conjugation with glucoronic acid of the phenol products from the ketone formed by
Amphetamines
deamination.
R5 R5' Oxidation and complete removal of substituents at carbon 5.
O 6 O
5
4
N-dealkylation at N1 and N3
Desulfuration at carbon 2 (thiobarbiturates)
R1N 2 NR3 Scission of the barbiturate ring at 1:6 bond to give substituted malonylureas
1 3
O
Barbiturates
N-dealkylation in the N10 side chain
N-oxidation in the N10 side chain
Oxidation of the heterocyclic S atom to sulfoxide or sulfone
5
6 S
4 Hydroxylation of one or both aromatic rings
7 3
Conjugation of phenolic metabolites with glucuronic acid or sulfate
8 10 2 Scission of the N10 side chain
N
9 R 1
Phenothiazines
SO2NHR
1
Acetylation at the N4 amino group
2 6 Conjugation with glucoronic acid or sulfate at the N4 amino group
3 5
Acetylation or conjugation with glucoronic acid at N1 amino group
4 Hydroxylation and conjugation in the heterocyclic ring, R
NH2
Sulfonamides
Tips
Tips practice format 02: Find answers from the table:

1. UDP-gluconyltransferase 2. CYP3A4 3. UDPGT
4. formic acid 5. alcohol dehydrogenase 6. oxidation
7. inhibit metabolism and increase 8. in the liver 9. drug metabolism is impaired
concentration by protein deficiency
10. levels of some cytochrome 11. Phenobarbital, Phenytoin, 12. Codeine & Fluoxetine
P450 isoenzymes will vary Carbamazepine, Rifampin, St.
between individuals John’s wort
13. CYP 450 14. Increased metabolism of drugs 15. it becomes more inactive, more
polar, larger and more easily
excreted in the bile & urine)
16. Benzodiazepines, statins (ALS), 17. Erythromycin, Clarithromycin, 18. Acetylation
Digoxin, Sildenafil grapefruit juice, Ketoconazole,
Cimetidine, Protease INH
19. Sulfasalazine 20. Glutathione conjugation 21. CYP 1,2,3 and 4

22. endoplasmic reticulum 23. decreased in elderly 24. Glucoronidation
25. hydrolysis
· Where does the majority of drug metabolism take place? (in the liver)
· What is the primary enzyme system involved in drug metabolism? (CYP 450)
· What is the significance of induction of drug metabolism (increased metabolism of drugs).
· What is meant by inhibition of drug metabolism and what is its significance? (Inhibit metabolism and
increase concentration).
· What happens to the drug after conjugation? (it becomes more inactive, more polar, larger and more easily
excreted in the bile & urine).
· What enzyme catalyzes most common conjugation reactions? (UDP-glucoronyl transferase).
· How does age affect drug metabolism? (Decreased in elderly and infants)
· What type of nutritional factors affect drug metabolism? (Drug metabolism is impaired by protein
deficiency).
· How does genetics affect drug metabolism? (Levels of some cytochrome P450 isoenzymes will vary between
individuals). Pharmacogenetics studies
· The most common metabolic reaction in the GI (hydrolysis).

· The most common phase I metabolic reaction is? (Oxidation)
· The most metabolic reaction in human (Glucuronidation)
· The most common drug metabolizing cytochrome subtype enzyme is? (CYP3A4)
· Benzodaizepines are metabolized by? (CYP3A4)
· Glucuronidation reaction is catalyzed by? (UDPGT)
· Cytochrome is commonly located at? (Endoplasmic reticulum)
· What enzyme is responsible for drug metabolism? (CYP 1,2,3 and 4)
· Acetaminophen detoxification mechanism involves, what type of metabolic reaction? (Glutathione
conjugation)
· Azo reduction occurs in? (Sulphasalazine)
· Primary amine undergoes what type of metabolism? (Acetylation)
· What are the most common CYP3A4 inhibitors? (Ery, Clari, gfj, Ketoconazole, Cimetidine, Protease inh, INH).
· What are the most common CYP3A4 substrates? (Atorva, Benzodiazepines, statins (ALS), digoxin, estrogen,
terFinadine, Sildenafil).
· What drugs is the most common CYP2D6 substrate? (Codeine)
· What are the most common CYP3A4 inducer? (Phenobarbital, Phenytoin, Carbamazepine, Rifampin, St.
John’s wort)
· What is not a drug-metabolizing enzyme? (Alcohol dehydrogenase).
· Methanol toxicity can lead to blindness due to? (formic acid).
· Mercapturic acid are s-derivatives of N-acetylcysteine synthesized from? Glutathione
CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A4

Significant Theophylline s-warfarin Clopidogrel Codeine
substrate Haloperidol Phenytoin Amitriptyline
Olanzapine Atomoxetine
Clozapine
Significant Fluvoxamine Fluconazole PPIs Fluoxetine
inhibitor bupropion
Significant CBZ, CBZ, CBZ, Amiodarone
inducers phenytoin, phenytoin, phenytoin, Duloxetine
phenobarbital phenobarbital phenobarbital
Rifampin Rifampin Rifampin
Smoking
www.Pharmacyprep.com Biopharmaceutics
33
Biopharmaceutics
Questions Alerts!
Common questions in pharmacy exam are to ask!
· Relative bioavailability and absolute bioavailability.
· Drug interchangeability
· Partition coefficient (octanol/water)
· Factors effecting ionization and unionization like pH, and pKa
This chapter review on the concepts of physicochemical properties of oral drugs and dosage form, and the effect
of route of administration on absorption. Emphasis is on bioavailability and bioequivalence studies.
Biopharmaceutics is the study of the relationship between the physiochemical properties of a drug to those of
dosage form in which contained
Bioavailability: The fraction of unchanged drug reaching the systemic circulation following administration by any
route. The rate and extent of absorption from administered dose can be figured out by using bioavailability.
Absolute bioavailability: Calculated by comparing the bioavailability of the product to that of an IV bolus dose.
Absolute bioavailability is “F’ which is the fraction of drug systematically absorbed from the dosage form. Always
AUC of iv is 100% or 1.
AUC po /AUC iv
Relative bioavailability: Calculated by comparing similar data for the product to another drug product of the
same dose and dosage form.
Relative Bioavailability. AUC of the dosage form/dose
AUC of the reference/dose
To determine the AUC? AUC = [F x Dose]/V d x K
Bioavailability is rate and extent

RATE (SPEED): “C MAX ” AND “T MAX ”
EXTENT (AMOUNT): Area under the curve (AUC) or the total amount of an unchanged drug excreted in urine.
C MAX PEAK CONCENTRATION AND T MAX IS TIME THAT TAKE TO REACH C MAX .
BIOEQUIVALENT ARE PHARMACEUTICAL EQUIVALENT + RATE AND EXTENT ARE EQUAL.
RATE EXTENT
CMAX & TMAX AUC
AUC = area under the curve
CL = dose/AUC
CL = amount eliminated/AUC
First pass effect: Extent to which a drug is removed by the liver during its 1st passage in the portal blood through
the liver to the systemic circulation. In simple words it is the amount loss during metabolism in the liver.
Factors that influence bioavailability: First pass hepatic metabolism, solubility of drug, chemical stability, and
drug formulation.
DOSAGE FORMS WITH FIRST PASS EFFECTS

Oral (tab, cap, susp, sol) High first pass
Sublingual No first pass
Rectal Less first pass
Injections No
Bioequivalence or bioequivalent drugs: Bioavailability of the active ingredients in the 2 products are not
statistically different under suitable test conditions. Example generic and brand.
Bioavailability and Bioequivalence

Time of Onset; is the time from drug administration to MEC.
Intensity; is proportional to the number of receptors occupied by the drug to exhibit a maximum
pharmacological effect.
Interchangeability of drugs.
Generic substitution: Brand or different unbranded product over the prescribed drug. Generic substitution can
occur only in pharmaceutical equivalent.
Pharmaceutical equivalent: Same active drug ingredient, identical strength or concentration, dosage form and
route of administration and bioequivalent. Examples Ramipril generic and Altace brand. Pharmaceutical
equivalent can differ in color, flavour, shape, scoring, configuration, packing, preservative, expiration time and
labelling.
Pharmaceutical equivalent (generic brand substitution)

Dimicron MR Gliclazide
Synthroid Levothyroxine
Cymbalta Duloxetine
Lipitor Atorvastatin
Crestor Rosuvastatin
Lyrica Pregabalin
Pharmaceutical substitutes or alternates: Pharmaceutical alternative for the prescribed drug product. Two
products containing same therapeutic moiety, e.g. tetracycline HCl and tetracycline PO 4 , cefuroxime Na and
cefuroxime axetil, erythromycin base and erythromycin estolate or pantoprazole Na and pantoprazole Mg,
metoprolol succinate and tartrate.
PHARMACEUTICAL ALTERNATE
Docusat Na Docusate Ca
Cefuroxime Na Cefuroxime axetil
pantoprazole Na (pantolac) pantoprazole Mg (Tecta)
metoprolol succinate Metoprolol tartrate.
Erythromycin base Erythromycin estolate
Therapeutic equivalent: Two chemical equivalent have same therapeutic effects (efficacy and safety).
Therapeutic equivalent
Amoxicillin Ampicillin
Ramipril Lisinopril
Therapeutic alternate: Products of different active ingredients having same therapeutic or clinical response. E.g.
antihistamines.
Home work Examples

Pharmaceutical equivalents
Pharmaceutical alternates
Therapeutic equivalents Amoxicillin suspension/capsules
Therapeutic alternates
Predicting water solubility:

Partition coefficient (P): Refers to the ratio of the concentration of drug in octanol (lipid) to that of water.
Partition Coefficient (P) = (Drug) lipid /(Drug) aqueous

P = solubility in octanol/solubility in water
P=1
A drug is hydrophobic if partition coefficient is >1
A drug is hydrophilic if partition coefficient is <1
Mechanism of drug absorption.

Transport process across membrane
Passive paracellular Carrier

Glycoprotein
Diffusion Diffusion mediated
mediated
(transcellular)
Efflux
Cell membrane (phospholipids layer). Drugs high in lipids move faster in a phospholipid bilayer and this means
that water soluble drugs used carrier proteins for transport.
Types of absorption. Four types of absorptions occur across membrane 1. Passive absorption (passive diffusion),
2. Active transport, 3. Facilitated diffusion, and 4. Endo/exocytosis.
Passive absorption (diffusion): It is also referred as simple absorption or diffusion. The movement of drugs
across lipid membranes driven down by their concentration gradient. Characteristics
· There is concentration gradient (high à low) is essential for passive absorption
· No energy is needed for passive absorption
· There must be semi permeable membrane
· Fick’s Law can determine rate of diffusion of absorption
Primary Active transport: An energy dependent movement of compounds across membranes against
electrochemical gradient that is carrier mediated and requires metabolic energy e.g. multi drug resistant
transporters.
Characteristics:
· Active transport also referred as active absorption
· Need energy
· No need of concentration gradient
· Can go against concentration gradient if facilitated by energy.
· Example of active absorption includes: tubular secretion.
Examples of primary active transport ion channels:

· Na+, K+, ATPase (Na+, K+ pump) in cell membrane transport Na+ from intracellular to extracellular fluid and K+
extracellular to intracellular. Examples of drugs (digoxin) that blocks Na K ATPase.
· H+, K+, ATPase (proton pump) in gastric parietal cells transports H+ into the lumen of the stomach against the
electrochemical gradient. Drugs that block proton pump: Proton pump inhibitor such pantoprazole.
· Ca2+ ATPase (Ca2+ pump) in the sarcoplasmic reticulum or cell membrane transport Ca2+ against
electrochemical gradient.
Facilitated diffusion. The carrier-mediated transport of compounds down an electrochemical gradient. e.g. the
cation transporters in the kidney.
Characteristics
· Require carrier (proteins)
· Similar to passive absorption because do not require metabolic energy.
· Examples of facilitated diffusion. Glucose uptake into muscle and adipose cells facilitated by insulin. If
impairs this can lead to diabetes mellitus.
Endo/exocytosis --> Internalization of drug molecules (cell drinking)
PASSIVE DIFFUSION ACTIVE TRANSPORT FACILITATED ENDO/EXOCYTOSIS

CONCENTRATION No concentration
GRADIENT IS ESSENTIAL gradient
Topical drugs, eye drops, Tubular secretion Glucose uptake
placenta Calcium & vit.D by insulin
Factors that determines the absorption

Oral drug
Question Alerts!
1) Ficks Law determines "rate
of absorption". Disintegration
2) Noyes-Whitney determines
"rate of dissolution".
Dissolution Rate of Dissolution
Noyes-Whitney
Absorption
Ficks Law - Rate of absorption
Hasselback & Factors that affect the rate of absorption

* pH effect
Handerson
* ionization & unionization
Question Alerts!
Ranking of various oral dosage (fastest → slowest) The fastest oral dosage form?
· Solutions (ready for absorption) Solution
· Suspensions (wetted and ready for dissolution)
· Powder [(dispersed + GI fluid → wet) absorbed]
· Capsules (dissolve gelatine cap first → then powder)
· Tablets (disintegrate from tablet to smaller granulate then → powder.
· Sustained release tab (barrier of coating materials).
The rate of absorption of solid drugs.

Solid drug -->(disintegration) and then (dissolution) --> Drug in solution --> (absorption) in to blood.
Dissolution is the rate-limiting (slowest) step in sequence.
· Disintegration. Breaking down of drug so as to facilitate dissolution. This usually occurs in oral routes.
· Dissolution. Dissolving substances in the GIT fluids to facilitate absorption of the drug.
· Rate limiting step. It is the time it takes for a drug to dissolve and become available for absorption.
Factor that effect rate of absorption: Degree of ionization, solubility, pH (acidity or alkalinity of the substance).
Degree of ionization: Drugs will pass thru a membrane at a faster rate if they are unionized. The size of an ion
increases due to dipole-to-dipole attraction especially water. Ionized portion of drug is less soluble in lipid but
more in water.
DRUG IONIZED EXCRETE
DRUG UN-IONIZED REABSORBS (EXCRETE SLOWLY)
Solubility
· Extremes of either water or oil solubility is associated with poor absorption.
· Hydrophilic = water soluble (water lover), poorly absorbed. Removed faster from the body.
· Hydrophobic or lipophilic = oil or lipid soluble, or oil and lipid lover.
pH (acidity or alkalinity of the substance)

· Most drugs are weak acid or weak bases. Dissociation of weak acids or bases is directly affected by pH
therefore absorption is directly affected by pH.
· As pH rises (H+ decreases), the amount of weakly acidic drug in the non-ionized state decreases
· As pH falls (H+ increases) the amount of weakly acidic drug in the non-ionized state increases; i.e. diffusion
pressure increases.
· For weak bases the effect is opposite.
NOTE. One changes the pH by 1 unit, the ratio of non-ionized to ionized changes by factor of 10. The direction of
change and ration can be calculated in one’s head when the pH changes are 1 full unit
Henderson-Hasselbalch Equation. Helps to determine pH effect on absorption. (Determining the drug absorption
by pKa). If the pKa of drug and pH of the medium are known, the fraction the molecules in the ionized state can
be predicted by means of the Henderson-Hasselbalch equation. How much of drug is found on either side of
membrane.
For an acid:
pH = pKa + log (Salt)/ (Acid)
pKa = pH – log (Salt)/ (Acid)

For base:
pH = pKa + log (Acid)/ (Salt)
You may also see the above as:
pH = pKw – pKb + log (base)
(salt)
Since pKw = pKa + pKb
Weak acid RCOOH (Cross membrane) à RCOO + H+

Weak Base R-NH 3 à RNH 2 + H+ (cross membrane)
Predicting Percent ionized (To calculate percent of a weak acid or base that is ionized).
Where charge -1 if acid drug or 1 if basic drug

Notes on ionization
· Ionized drugs are water soluble and poor absorption through
stomach, blood brain barrier, and placenta, no reabsorption
across membrane and excrete faster.
· Non-ionized (unionized) are lipid soluble and absorbed well in
membrane (cell membranes are composed of lipids), and have
higher reabsorption.
· An acid in an acid solution will not ionize (acid + acid = non-
ionized).
· An acid in a basic solution will ionize (acid + base = ionized).
· A base in a basic solution will not ionize (base + base = non-
ionized).
· A base in an acid solution will ionize (base + acid = ionized).
· PKa = pH drug exists as 50% ionized and 50% unionized.
· If pH-pKa = 0, then 50% of drug is ionized and 50% is unionized.
· If the acid/base ratio is 1:1, then the log of that number will be zero, and pH = pK a .
· If pH - pKa = 0.5, then the solution is 75% ionized/25% unionized or 75% unionized/25% ionized.
· If pH - pKa >1 then the solution is 99 to 100% ionized or 99 to 100% unionized.
· If pH - pKa >2 then the solution is 100% ionized or unionized.
Surface area (Ficks law of diffusion)

Ficks law predicts the rate of movement of molecules across barrier.
Formula:
Rate of diffusion = D x A x (C 1 – C 2 )
L
D = Diffusion coefficient
A = Surface area of solid
C 1 = Concentration near to stagnant layer
C 2 = Concentration of solute to other side
of stagnant layer
L = The length of the stagnant layer
This relationship demonstrates the drug absorption is faster from organs with large surface areas. The rate of
diffusion is directly proportional to the area of the solid, the concentration difference between the
concentration of solute in the stagnant layer at the surface of solid and its concentration on the farthest side of
the stagnant layer and diffusion coefficient. It is inversely proportional to the length of stagnant layer. The
driving force behind the movement of the solute molecules through the stagnant layer is the difference in
concentration of solute at C 1 and its concentration at C 2 .
Solubility
Defined as the concentration of solute in a saturated solution under specific conditions of temperature and
pressure. It may be viewed as an equilibrium condition in which solute molecules are leaving the solid (or
undissolved phase) at the same extent as solute returning to it.
Saturated solution: Is a state in which solute is at equilibrium with solid phase
Supersaturated Solution: Contains more dissolve solute then it normally would contain at a specific temperature
if there were undissolved solute present. If upon cooling, the excess solute fails to crystallize from the lower
temperature, the solution is supersaturated.
Unsaturated solution: Contains dissolved solute in a concentration below that necessary for complete saturation
Compendia expressions of approximate

· Very soluble………………………..Less than 1 part
· Freely soluble……………………...1-10 parts
· Soluble…………………………….. 10-30 parts
· Sparingly soluble ………………… 30-100 parts
· Slightly soluble …………………… 100-1,000 parts
· Very slightly soluble ……………… 1,000-10,000 parts
Types of Solvents
Polar solvents
These consist of strongly dipolar molecules having high dielectric constants, e.g., water, and methyl alcohol,
ethyl alcohol.
Semi polar solvents
These are strongly dipolar molecules, but which do not form hydrogen bonds. Examples are ketones and certain
alcohols. They may induce a degree of polarity in nonpolar solvent molecules.
Nonpolar solvents
These solvents have a small or no dipolar character. Theses include hydrocarbons, fixed oils, and mineral oil.
They have a low dielectric constant and possess little tendency to reduce the attractive forces between ions of
strong and weak electrolytes.
Factor Affecting solubility and Rate of Solution

Noyes-Whitney Equation
A thin layer of solvent, which behaves as an integral part of the particle and is referred to as the diffusion layer,
C 1 -C 2 , surrounds a particle of solute dispersed in a solvent medium. The diffusion layer remains a part of the
solute particle regardless of extent of agitation of the bulk solution. The dissolution rate of the solute is
expressed by the Noyes-Whiteney equation:
Dc/dt = KA (C 1 -C 2 )
Where dc/dt is the change in concentration of solute in solution with respect to time.
Effect of Temperature
Solubility of a solid in a liquid is dependent on the temperature. If heat is absorbed in the solution process,
solubility of solute will increase with increase in temperature.
Effect of electrolytes on the solubility of non electrolytes

Salting out and salting in. The addition of a salt may either increase or decrease the solubility of nonelectrolyte.
When the solubility is decreased, the effect is referred to as “salting out”. When the solubility is increased, it is
known as “salting in”.
Action potential across cell membrane: Neuronal excitability depends on the influx of ions through specific
channels in membranes.
Membrane depolarization: Excitation = increase Na entry (influx), decrease K exit (efflux)
Membrane repolarization. Inhibition = increase Cl- enter in and increase K+ exit.
Agent Action Results

Botulinus toxin Blocks release of ACh from Total blockade
presynaptic terminals
Curare Competes with ACh for Decrease size of end plate potential: maximal
receptors on motor end plate doses produce paralysis of respiratory muscles
and death.
Neostigmin anticholinesterase Prolongs and enhances action of ACh at muscle
end plate
Hemicholinium Blocks reuptake of choline into Depletes ACh stores from presynaptic terminal.
presynaptic terminal
Tips
1. Oral 2 rectal 3 in the stomach and intestine but mainly in the
liver
4. first pass metabolism 5 sublingual 6 lungs
7. nasal mucosa 8 intramuscularly 9 intravenous
10 transdermal
· The metabolism of the drug before the drug reaches the general circulation ( )
· Where does the first pass metabolism occur? ( )
· Which route of administration is most likely to subject a drug to a first-pass effect? ( )
· What sites of absorption have low first pass metabolism? ( )
· What factors affect the bioavailability of a drug? ( )
· What is responsible for the different phases of a two-compartment model of drug elimination? ( )
· What is meant by first pass metabolism? Drugs are metabolized before reaching systemic circulations
· Where does the first pass metabolism usually occur? liver
· Which routes of administration are most likely to subject a drug to a first pass effect? Oral (drug that by pass
liver have no first pass metabolism).
· What sites of absorption have low first pass metabolism? Rectal.
· Bioavailability of sustained release and immediate release preps, what is the same! AUC.
· Fick's law describes? ( rate of absorption)
· The rate limiting step in ophthalmic drops? (cornea)
· Partition coefficient is described as? ( predicting drug solubility)
· Write the sequence of surface area in GIT (small intestine>stomach> large intestine).
TRUE OR FALSE
· Sustained release and immediate release formulations of a drug have different rate of bioavailability
however the same extent.
· After oral administration of iron, it is absorbed from duodenum by an active transportation (T/F)
· Whenever a drug is more rapidly and more completely absorbed from a solid form, the rate-limiting factor
is the dissolution process (slowest).
· Write sequence of absorption for oral dosage, from higher to lower: solution > suspension > liquid gel caps
> powder>
www.Pharmacyprep.com Physical Pharmacy
34
Physical Pharmacy
Questions Alerts!
· United States Pharmacopeia/National Formulary (USP/NF) standards of alcohol and temperatures,
Compounding Formula
· Colligative properties. Osmotic pressure AND OSMOLARITY CALCULATIONS.
· Arrhenius equation
· Polymorphism
· Critical solution temperature
State of the matter
Gases Liquids Solids

· Changes in state. Increase in temperature of a substance increases its heat content, or enthalpy.
· Melting. Solid to liquid state.
· Vaporization. Liquid to gaseous state. Question Alerts!
· Volatile liquids used as inhalation anesthetics e.g. ether, halothane, and Sublimation is?
methoxyflurane also used in vasodilatation in acute angina e.g. amile nitrite.
· Sublimation: Solid heated directly to gaseous or vapor state without passing through the liquid state e.g.
camphor and iodine. Examples of process like lyophilisation (freeze drying).
· Deposition. The reverse process to the sublimation i.e. direct transition from the vapor state to the solid
state. Example colloidal silicon dioxide and some form of sulphur.
Solids.
Polymorphism: Polymorphism is the occurrence or existence of the same substance in different crystalline
forms. Ability of a substance or drug to exist in different crystalline forms. Different properties such as melting
points, solubility, dissolution rate, density, and stability. Examples of polymorphism include theobroma oil or
cocoa butter exhibit polymorphism.
Amorphous materials. Solids and liquids differ from crystals in that they do not possess long-range periodicity of
packing. They will therefore be isotropic. Window glass, basically SiO 2 is a common example. Many plastics like
PVCs are also amorphous.
Crystalline versus amorphous form. The amorphous form of a compound is usually more soluble than the
crystalline form. Different polymorphic forms of the same compound may demonstrate different physical
properties including water solubility.
Question Alerts!
Interfacial Phenomena Wetting Phenomenon?
The Interface: Interfacial phenomena are attributable to the effect of the
properties of molecules located at or close to the boundary between
immiscible phases. The region of influence is referred to as the interface. Interface may exist between a liquid
and a gas (a foam) between two immiscible liquids (an emulsion), between a solid and liquid (a suspension),
between solids, solid and gas, etc.
Wetting Phenomena: A solid is said to be wetted by a liquid if the liquid spontaneously spreads over the solid.
A solid is not wetted by a liquid if the latter cannot spread over the former spontaneously. The contact angle is
an important parameter reflective of the degree of wetting of a solid by a liquid. This is the angle that a droplet
of the liquid makes with the solid surface at the point of contact.
Liquids: With few exceptions, most organic solvents are irritating or toxic. Aromatic hydrocarbons cause
paralysis of the central nervous system and are irritating to the skin.
Methyl alcohol (methanol) and isopropyl alcohol, ethylene glycol is toxic, and butyl and amyl alcohol are
irritating. Volatile ethers paralyse the central nervous system, and are irritating to mucous membrane increases.
Ketones are mildly irritating and the low molecular weight esters are irritating. Toxicity and irritation limit the
many solvents internal use except, Glycerine, ethyl alcohol, and propylene glycol can be employed for internal
use as pharmaceutical solvents.
Aliphatic hydrocarbons, ether, and glyceryl esters of aliphatic acids can be employed for external use as
pharmaceutical solvents.
Propylene glycol has been employed as a solvent for oral and parenteral solutions of drugs such as
antihistamines, barbiturates and vitamins.
Hydrogen bonding (H….N or H….O) increases the likelihood of cohesion in liquids and further affects their
physiochemical behaviour.
Van der Waals forces impose regular arrangement among molecules.
London forces in molecules are weak intermolecular forces in liquid hydrocarbon are not true chemical bonds.
Critical solution temperature: It is the maximum temperature above which homogenous liquid is formed
regardless to any concentration of phenol.
Viscosity is an internal property of a fluid that offers resistance to flow. Not, all liquids are the same. Some are
thin and flow easily. Others are thick and gooey. Honey or corn syrup will pour more slowly than water. A
liquid's resistance to flowing is called its viscosity.
Gases: The intermolecular forces of attraction in gases are virtually non existence at room temperature.
Pressure. Random collision of molecules with boundaries of the system is responsible for pressure.
Ideal gas law: The interrelation among Volume (v), pressure (P) and the absolute temperature (T) is given by
ideal gas law: PV = nRT, where n = number of moles of gas and R = molar gas constant (0.08205 L atm/mole deg).
Pharmaceutical gases:
· Anaesthetic gases: Nitrous oxide and halothane
· Compressed gases: Oxygen, nitrogen, carbon dioxide
· Liquefiable gases: used as propellants in aerosol (pressurized package) products, eg: ethylene oxide is gas
used to sterilize or disinfect heat-labile objects.
Chemical kinetic & Drug stability

Factors that affect chemical stability: The factors that affect chemical stability include: temperature, pH,
moisture, air (oxygen) and light. Effect of temperatures on drug degradation. The Arrhenius equation describes
the effect of temperature on the rate of drug degradation reaction. Heat increases rate of chemical reaction.
Every 10oC increase normally 2 to 3 times rate of reaction increases.
Arrhenius equation
k = S x e-Ea/RT
Ea =Arrhenius activation energy
T = absolute temperature
e-Ea/RT = Boltzman factor
S = Frequency factor Question Alerts!
R= Gas constant Arrhenius equation determine factors
effecting on chemical stability
Logarithm
Log k = log S-Ea/2.303 RT
Integration between two limits k 1 and k 2 at temperature T 1 and T 2
Log K 2 /K 1 = Ea/2.303 R x (T 2 -T 1 /T 1 T 2 )
Change pH effect on degradation of drugs. The magnitude of the rate of hydrolytic reaction catalyzed by acid
(H+) and base (OH-) can change with pH. Acid (H+) catalysis predominates at lower pH, whereas base (OH-)
catalysis operates at higher pH.
To determine the effect of pH on degradation kinetics, decomposition is measured at several H+ concentrations.

The pH of optimum stability can be determined by plotting the logarithm of the rate constant (k) as function of
pH. The point of inflection of the plot is the pH of optimum stability. The value is useful in the development of a
stable drug formulation.
At pH 1 to 3 (strong acidic) more susceptible to H+ (acidic). At pH 5 to 14 (weak acid and base) more susceptible
to OH- (base).
Change in pH: Hydrolysis reactions are catalyzed by H and OH ions, can change with pH
· Acid (H+) catalysis predominates at lower pH
· Base (OH-) catalysis predominates at higher pH
The effect of pH on degradation kinetics, decomposition is measured by plotting the log of the rate constant as
function of pH. The point of inflection on the plot is the pH of optimum stability. This value is useful in
development of stable drug formulation.
Modes of pharmaceutical degradation:
Hydrolysis, Oxidation and free radicals results in degradation and photolysis. Antioxidants prevents free radical
propagation (hydrogen peroxide, .OH, and benzoyl peroxides).
Antioxidants:
· Water soluble: Ascorbic acid, sodium bisulfate, and sodium sulfite.
· Lipid soluble: Butylated hydroxyl anisole (BHA), butylated hydroxyl toluene (BHT), propyl gallate, and the
tocopherol (vitamin E 1 ).
Photolysis: Exposure to light wavelength less than 400 nm. Protect using amber glass or opaque storage. Sodium
nitroprusside has a shelf life only 4 hour, if exposed to normal room light, when protected form light, the
solution is stable for at least one year.
Stability, kinetics and shelf Life: Most commonly zero order and first order reactions are encountered in
pharmacy.
Zero order
-dC
= ko
dt
Where Ko is zero-order rate constant [C/t]
C = -Kot + Co
Where Co is the initial concentration of drug
t = C-Co
-Ko
First order
-dC
= kC
dt
Where C is concentration of intact drug remaining, t is time, (-dC/dt) is

the rate at which the intact drug degrades, and k is the specific reaction
rate constant.
-kt
log C = +log Co
2.303
Where Co is the initial concentration of drug
In natural log form: Question Alerts!

Shelf life t10% or t90% = 0.105/k
In C = -Kt + In Co
Shelf life t 10% or t 90% = 0.105/k
Buffers and Buffer Calculations: A buffer is a compound or a mixture of compounds that has the ability to resist
changes in pH when limited amounts of acid or base are added to the solution of the buffer or when the solution
is diluted with solvent.
Generally, a buffer system consists of a weak acid and its salt of the weak acid, or a weak base a salt of the weak
base. An example of the former is acetic acid and sodium acetate and of the latter is ammonium hydroxide and
ammonium chloride.
Mechanism of action: In the example of the acetic acid-sodium acetate buffer combination the acetic acid is
essentially unionized and the sodium acetate is completely ionized. When acid is added to the buffer system,
the hydronium ion reacts with acetate ion to form more unionized acetic acid
CH 3 COOH + H 3 O+ -------> CH 3 COOH + H 2 O
And when base is added to the buffered solution, it will react with acetic acid to form more acetate ion.
CH 3 COOH + OH- --------> CH 3 COO + H 2 O
Other Types of Systems: The combination of certain salts may function as a buffer system, as for example, the
combination of monobasic potassium phosphate and dibasic potassium phosphate in the appropriate molar
ratio. A study of the mechanism will reveal that the buffer behaviour is essentially the same as the previous
cases mentioned above.
Buffer Calculations; The calculations involving buffer systems are based on the Henderson-Hasselbalch equation.
pH = pKa + log [base]/ [acid]
The above equation applies to all buffer systems involving a single proton transfer (conjugate acid-base pair).
If a buffer system, for example, is composed of 0.1 molar acetic acid and 0.1 molar sodium acetate (Ka for acetic
acid is 1.75 x 10-5). The pH of a solution will be pKa is 4.5
pH = pKa + log [base]/[acid]
pH = 4.75 + log (0.1/ 0.1) = 4.75
pKa = -log of Ka
If the concentrations of acetic acid and sodium acetate are equimolar, the pH of the solution will always be the
same, 4.74. However, the higher the concentration of buffer compounds, the greater will be the buffer capacity
or the greater the ability to resist change in pH.
Buffer Capacity: This is a quantitative expression of the ability of a buffer system to resist change in pH.
β = ∆A/∆ pH
where β is the buffer capacity and ∆ A is the addition in gram equivalents per litre of strong acid (or strong base)
to buffered solution to produce a pH change of ∆pH.
Colligative properties: The Colligative properties depend primarily upon the number of particles in solution.
Example adding solute to solution of these properties includes.
· Lowering vapor pressure
· Increase in boiling point Question Alerts!
· Decrease in freezing point 1) Examples of colligative properties?
· Osmotic pressure 2) Freezing point depression is used to calculate
molecular weight of non-ionic molecule.
· Lowering of vapour pressure. When a solute is added to a liquid, it will decrease the vapor pressure of the
liquid.
· Increase in boiling point. The effect on the boiling point is just the opposite. That is the boiling point of a
liquid is increased if something is dissolved in it. Boiling is the vapour pressure of liquid not more than the
atmospheric pressure.
· Decrease in freezing point. When a solute or salt is added to liquid, it will decrease the freezing point.
· Osmotic pressure.
· Isotonic. The solute concentration is the same on both sides of the membrane. The solutions are said to be
isotonic compared to one another.
· Hypotonic. The clinical significance of all this is to insure that isotonic or iso-osmotic solutions do not
damage tissue or produce pain when administered.
Tips
· Arrhenius equation is used for? à
· Water-soluble antioxidants? à
· Fat-soluble antioxidants? à
· Theobroma oil and cocoa butter are? à
· Polymorphs have à
· Arrhenius equation is used for? à
· Water soluble antioxidants? à
· Polymorphs are different in crystalline forms of the same drug, will differ in à
· USP official temperature is à
· Protect from light indicates storage in light resistant container that reduces light transmission in the range of
à
· Pycnometer is used for à
· Hydrometer is used for à
· Boric acid is à
· Tannic acid is à
· Acetic acid is à
· Freon is à
USP (United States Pharmacopea):

· Alcohol USP 94.9% ethanol V/V
92.3% ethanol W/V
· Diluted alcohol 49% ethanol V/V
· Rubbing alcohol 70% V/V absolute alcohol (denatured)
www.Pharmacyprep.com Pharmaceutical Excipients
35
Pharmaceutical Excipients
Questions Alerts! Question alerts!
Common questions in pharmacy exam is to
ask! 1) What type of water is used to
· Types of water in parenteral preps manufacturing parenteral preps?
· Examples of alkalinizing agents,
antioxidants, surfactants, levigating 2) What type of water is used for multiple use
agents, bacterial and fungal containers?
preservatives.
Water for injection USP

· Prepared by double distillation or reverse osmosis
· Free from pyrogen
· Used as solvent for parenteral solutions in manufacturing.
Sterile water for injection USP

· not >1 liter
· Sterilized and packed in single dose container of type I and II glass.
· Limitation of total solids depends on size of the container.
· For compounding
Bacteriostatic water for injection USP

· Not >30 ml
· Contain 1 or more antimicrobial agent
Packed in single or multiple use dose containers.
Sterile water for irrigation USP

à >1 liter
Sterilized and suitably packed
It contain no antimicrobial agents or other added substance
Purified water USP

Prepared by distillation, reverse osmosis, or ion exchange
Should not contain 10 ppm solid particle
Should have pH between 5 and 7
Used in prescription and finished manufactured product
Not used in parenteral and ophthalmic products
Sterile purified water USP

It is purified water sterilized and packed
It does not contain antimicrobial agents
It is NOT intended for parenteral preparations
Water for injection USP STERILE water for Bacteriostatic Distilled water
injection
Manufacturing Parenteral or IV Multi dose container Oral, topical and all other
admixture, ophthalmic preps
Compounding
IV, IM, SC and Single dose containers Vitamin B12 inj
ophthalmic
The method of preparation of purified water USP must be indicated on the label. [Sterile water for injection
(USP method)].
Excipient Type Use Example

Acidifying agent Used in liquid preparations to Acetic acid
provide medium for product Ammonium chloride
stability. Ascorbic acid
Citric acid
Fumaric acid
Hydrochloric acid
Nitric acid
Alkalizing agent Used in liquid preparation to provide Ammonia solution
alkaline medium for product Ammonium carbonate
stability. Also used for acidic drug Diethanolamine
(ASA) overdose. Monoethanolamine
Potassium hydroxide
Sodium borate
Sodium carbonate
Sodium hydroxide
Triethnolamine
Trolamine
Sodium bicarbonate
Adsorbent An agent capable of holding other Powdered cellulose
molecule onto its surface Activated charcoal
(adsorption) by physical or chemical
(chemsorbtion) means.
Aerosol propellant An agent responsible for developing Carbon dioxide
the pressure within an aerosol Dichlorodifluoromethane,

container and expelling the product Dichlorotetrafluoroethane,
when valve is opened. Trichloromonofluoromethane (CFCs) also
Ozone oxidation mechanism is? free known as freon gas, it is not safe.
radical formation. Hydrofluroalkenes (HFA) are safe.
Topical sprays are n-butane and propane.

Air displacement An agent which is employed to Nitrogen or inert gases (Ar, Ne, Xe, He)
displace air in a hermetically sealed
contained to enhance stability.
Antifungal preservative Used in liquid and semi solid Benzoic acid
preparations to prevent the growth Butyl paraben
of fungi. Ethyl paraben
Methyl paraben
Propyl paraben
Sodium benzoate
Sodium propionate
Antimicrobial Used in liquid and semi solid Benzalkonium chloride
preservative preparations to prevent the growth Benzothonium chloride
of microorganisms. Benzyl alcohol
Cetylpyridinium chloride
Ophthalmic preps use benzalkonium Chlorobutanol
chloride concentration 0.004%. Phenol
Phenylethyl alcohol
Phenylmercuric nitrate
Thimerosal
Antioxidant An agent which inhibits oxidation Water soluble (aqueous):
and thus is used to prevent the Ascorbic acid
deterioration of preparations by Sodium ascorbate
oxidative process. Sodium bisulphite
Sodium formaldehyde
All of the following are antioxidants, Solfoxylate
except? Sodium metabisulfite
a. vitamin C (ascorbic acid) Hypophosphorous acid
b. vitamin E (Tocoferal)
C. EDTA Lipid soluble (non aqueous):
d.Sodium bisulphite Ascorbyl palmitate
E. Sodium benzoate Butylated hydroxyanisole (BHA)
Ans. E Butyllated hydroxytoluene (BHT)
Monothiglycerol
Propyl gallate
Tocoferal (vitamin E 1 )
Buffering agent Used to resist change in pH upon Potassium metaphosphate
dilution or addition of acid or alkali. Potassium phosphate Monobasic
Buffers are made with Acid and salt Sodium acetate
of acid or base and salt of base. Sodium citrate anhydrous and dehydrate
Chelating agent A substance that forms stable, water EDTA

soluble complex (chelates) with Edate disodium
metals. Chelating agents are used in Edetic acid
some liquid pharmaceuticals as
stabilizers to complex heavy metals,
which might promote instability. In
such a case they are also
sequestering agents.
Colorant Used to impart color to liquid FD&C
Caramel
Ferric oxide gives red color
Tartazine gives yellow color
Clarifying agent Used as filtering aid because of Bentonate
adsorbent
Emulsifying agent Used to promote and maintain the Acacia
(Surfactant) dispersion of finely subdivided Cetomacrogol
particles of a liquid in a vehicle in Cetyl alcohol
which it is immiscible. The end
product may be a liquid emulsion or Anionic
semisolid emulsion (e.g. cream). Sodium lauryl sulfate
Emulsifying agents also known as
surfactants. Non ionic
Tweens (Polyoxyethylene 50 stearate)
Glycerl monoestearate
and
Spans (Sorbital monooleate)
Cationic
Benzalkonium chloride
Encapsulating agent Used to form the shells for the Gelatin
purpose of enclosing a drug Cellulose acetate phthalate (CAP), enteric
substance or drug formulation for coated.
ease of administration. Sorbitol
Flavorant Used to impart a pleasant flavor and Anise oil
often odor. Cinnamon oil
Cocoa
Menthol
Orange oil
Peppermint oil
Vanillin
Strawberry
Humectants Used to prevent the drying out of Glycerin
preparation, particularly ointments Propylene glycol
and creams due to the agent’s ability Sorbitol
to retain moisture.
Levigating agent A liquid used as an intervening agent Mineral oil
to reduce the particle size of drug Glycerin
powder by grinding together, usually

in mortal.
Ointment base The semisolid vehicle into which Water soluble base
drug substance may be incorporated Hydrophilic ointment
in preparing medicated ointment. Rose water ointment
Polyethylene glycol (PEG) ointment
Lipid soluble
Lanolin
Propylene glycol
Petrolatum (Occlusive base)
Hydrophilic petrolatum
White ointment
Yellow ointment
Plasticizer Used as a component of film coating Diethyl phthalate
solutions to enhance the spread of Glycerin
the coat over tablets, beads and Sorbitol
granules.
Solvent An agent used dissolves another Solvent that are used in parenteral prep.
pharmaceutical substance. Olive oil
Corn oil
Canola oil
Cottonseed oil
Peanut oil
Water for injection USP
Question Alerts!
Sterile water for injection USP
1) What solvents are NOT used in parenteral
Normal saline, D5W, Ringer solution.
preps? Mineral oil, theobroma oil
Solvent in oral prep.
Purified water
Sterile water for irrigation
Ethyl alcohol
Glycerin
Mineral oil
Oleic acid
Stiffening agent Used to increase the thickness or Cetyl alcohol
hardness of ointment Cetyl esters wax
Microcrystalline wax
Paraffin
Stearyl alcohol
White wax
Yellow wax
Surfactant Substance, which absorbs to Benzylalkonium chloride

surfaces or interfaces to reduce Nonoxynol 10
surface or interfacial tension. May Oxtoxynol 9
be used as wetting agents, Polysorbate 80
detergents or emulsifying agents Sodium lauryl sulfate
Sorbitan monpalmitate
Suspending agent A viscosity increasing agent used to Agar
reduce the rate of sedimentation of Bentonite
particles dispersed throughout a Carbomer
vehicle in which they are not soluble. Carboxymethylcellulose sodium (CMC)
Hydroxymethyl cellulose
Question Alerts! Hydroxypropyl cellulose
SUSPENDING AGENT Hydroxypropyl methyl cellulose (HPMC)
- VISCOSITY Kaoline
¯ SEDIMENTATION Methyl cellulose
Tragacanth
Veegum
Tablet anti adherent Agent, which prevent the sticking of Magnesium stearate
tablet formulation ingredients. Talc
Silicon dioxide
Tablet coating agent Used to coat a formed tablet for the Sugar coating:
purpose of protecting against drug Liquid glucose
decomposition by atmospheric Sucrose
oxygen or humidity to provide Film coating:
desired release pattern for drug Hydroxethyl cellulose
substance after administration, to Hydroxypropyl cellulose
mask the taste and odor or the drug. Hydroxyproply methylcellulose
The coating may be various type: Methylcellulose (e.g. Methocel)
Sugar coating Ethyl cellulose (e.g. Ethocel)
Film coating or enteric coating
Sugar coated is water based and Enteric coating
results thickened covering around a Cellulose acetate phthalate
formed tablet. Sugar coating Shellac (35% in alcohol, “pharmaceutical
generally starts to break up in glaze”).
stomach. A film coated is thin cover Methacrylic acid
around a formed tablet or bead.
Unless it is an enteric coated the film
coat will dissolve in the stomach. An
enteric-coated tablet or bead will
pass through the stomach and break
up in the intestine. Some coating
that is water insoluble may be used
to coat tablets or bead to slow the
release of drug as they pass through
the gastrointestinal tract.
Tablet direct Used in direct compression tablet Dibasic calcium phosphate (e.g. Ditab)
compressing exipient formulation
Tablet /Capsule Used to render a capsule of a tablet Titanium oxide

opaquant coating opaque. May be used alone
or in combination with colorant
Tablet polishing Used to impart an attractive sheen Carnauba wax
to coated tablet White wax
Tonicity agents Used to prepare isotonic solutions in Sodium chloride and dextrose.
parenteral, ophthalmic and irrigation
solutions.
Filler/ Filler functions: Increases the bulk volume so that the final product has the proper volume for
diluents patient handling.
Filler requirements: inert, compatible, non-hydroscopic, soluble, cheap, compactable, and
tasteful.
Fillers: Lactose, sucrose, glucose, mannitol, sorbitol, calcium phosphate, calcium carbonate,
and cellulose.
Binder Binders cause the adhesion of the powdered drug and inactive ingredients. Dry powder added
to the mixture prior to the wet granulation process solution that is used in the wet granulation
process.
Binder types. Wet/Solution Binders. Gelatine, cellulose, cellulose derivatives, polyvinyl
pyrrolidone (PVP), starch, sucrose, and polyethylene glycol.
Dry Binders: Cellulose, methyl cellulose, polyvinyl pyrrolidone, polyethylene glycol, and starch.
Disintegrant Disintegrant are used to ensure that when tablets are in contact with water, they are rapidly
breaking into smaller fragments, facilitating their dissolution.
Disintegrates facilitate water uptake, rupture the tablets.
Disintegrate: Starch, cellulose, crosses linked polyvinyl pyrrolidone, sodium starch glycolate,
sodium carboxymethyl cellulose.
Glidants To improve the "flow" ability of the powder or granules or both. Example Corn starch, silica
derivatives (silicon dioxide colloidal), and talc.
Glidants properties are measured by “Angle of repose” and X-ray photo electron.
Lubricant To ensure that tablet formation and ejection can occur with "low friction" between the solid
and the die wall. Example polyethylene glycols, stearic acid, stearic acid salts (calcium, zinc and
magnesium stearate).
Anti- It is used to "reduce the adhesion" between the powder (granules) and the punch faces and
adherent thus prevent tablet sticking to the punches. Example talc, and starch.
Sorbent Limited fluid sorbing in dry state.
Tips
1 Anti-adherent 2. Polysorbate 3. alkalizing agent
4 lubricant stearic acid 5. Water for injection USP 6. Anionic surfactant
7 improve flow ability 8. ascorbic acid 9. Sodium bisulfate

of granules
10 sorbic acid ester 11. hydrofluoroalkenes HFA
· Triethanol amine is? ( )

· Prevent sticking in die wall is referred as? ( )
· Glidant is? ( )
· Example of water soluble antioxidants are? ( )
· Sodium lauryl sulfate is? ( )
· The type of sterile water used in parenteral preparation in manufacturing? ( )
· In aerosol propellant action is given by? ( )
· Magnesium stearate is? ( )
· Tween is? ( )
· Span is? ( )
www.Pharmacyprep.com Rheology
36
Rheology
Rheology is study of deformation and flow of matter.
Questions Alerts!
Newtonian Fluids Common questions in pharmacy exam is to ask!
· The rate of shear (flow) should be the directly · Thixotropy systems (gel to solution)
proportional to the shearing stress. · Antithixotropy systems (solutions to gel)
· The reciprocal of viscosity is defined as fluidity.
· The units of viscosity are poise. (gm/cm sec).
Non-Newtonian Fluids
The fluids that do not obey the Newton’s law are
described as non-Newtonian fluids.
Non-Newtonian flow is characterized into three types:

plastic, pseudo plastic and dilatants.
Plastic Flow
· The substance that exhibits plastic flow and does not
pass through the origin, it normally intersects the
shearing stress axis.
· The point at which it intersects the shearing stress axis is known as yield value.
· Plastic flow is also known as Bingham bodies.
· Plastic flow materials. They do not start to flow until the applied shearing stress equals the yield value.
· At stress below the yield value, material act as an elastic material.
Pseudo plastic flow

· Most of the pharmaceutical follow pseudo plastic
flow. Pseudo plastic flow also known as shear
thinning system.
· Flow begins at the origin.
· The viscosity of material decreases with increase
rate of shear force.
· It is thixotropy. Examples suspending agents such as ethyl cellulose, carboxymethylcellulose and its
derivatives.
Thixotropy systems: Two types of systems associated with thixotropy. Products that have thixotropy with shear
stress, decrease in viscosity and increase flow ability.
· Pseudo plastic flow
· Plastic systems
Thixotropy occurs when transformation of gel to solution. Thixotropy is used in formulation of suspensions
dosage form where system remains gel form upon resting and by application of shear stress this can be
converted to solution form.
Gel-------------------->Solution
↓ Viscosity
↑ Flow
Dilatants flow
· Also known as shear thickening systems, it is just opposite to pseudo plastic flow.
· The increase in rate of shear force normally increases resistant to flow.
· Normally suspension with high percentage of dispersed solid particles does follow dilatants flow.
· Examples are suspension containing high concentration of small-deflocculated particles.
Anti-thixotropy systems (RHEOPEXY): Products that exhibit opposite action of thixotropy are referred to as anti-
thixotropy. Anti-thixotropy occurs when solutions to gel transformation. Example dilatants flow.
· Upon shear stress decrease flow and increase viscosity.
· Increase in viscosity thereby decrease flow rate.
· Example products fusidic acid ophthalmic and timolol ophthalmic drops. or Excessive suspending agent.
Solution ----------------> Gel
↑Viscosity
↓Flow
THIXOTROPY ANTI-THIXOTROPY
Pseudo plastic flow (shear thinning) Dilatant flow (shear thickening)
Gel-------------------->Solution Solution ----------------> Gel
↓ Viscosity ↑Viscosity
↑ Flow ↓Flow
↓ resistance to flow ↑ resistance to flow
Tips
1. Bentonite at high conc 2. is increase viscosity with increase 3. dilatants flow
shear stress
4. increase flow 5. decrease viscosity 6. antithixotropy
7. decrease flow 8. thixotropy increases flow and 9. Gel to solution
decrease viscosity
10 Solution to gel
· Term that referred to non Newtonian flow, increase force will increase difficulty in suspension flow? ( )
· Pseudo plastic flow ( )
· Thixotropy systems ( )
· Anti-thixotropy systems ( )
· Dilatants flow ( )
· Rheopexy is? ( )
· Agents to prepare dilatants flow ( )
· Shear thickening is? ( )
Pharmacyprep.com Pharmaceutical Dosage Forms
37
Pharmaceutical Dosage Forms
Questions Alerts!
· Tablet manufacturing methods (for ASA) and problems
· Soft gelatin and hard gelatin capsules
· Methods of powdering (levigation, trituration, pulverisation)
· Suppository calculation
· Suspending agents and flocculating agents
· HLB for w/o and o/w
Solid Dosage Coarse Dispersion Solution Dosage Miscellaneous

Dosage
Tablets Pills Internal Use

Caplets Inhalants
Suspensions Aerosols
Lozenges Gels
Powder Emulsions External Use

Lotions
Liniments
Capsules Creams
Soft gelatine shell Ointments
Hard shell Vitamin drops
Suppository
Pellet/Bead
Solid Dosage Form

Tablets Most commonly known dosage form is the tablet.
Advantages Accurate dosage
Lesser manufacturing cost
Easy to pack and ship, Easy to identify, Easy to swallow
Appropriate for special-release forms
Best for large-scale production
Most stable of all oral dosage forms
Tampered proof
Disadvantages Some drugs are hard to compress into tablet
Some drugs may be difficult to formulate to have adequate bioavailability.
Some drugs has foul odour or disgusting taste, so they are preferably done in
forms of capsules.
Methods of tablet Question Alerts!

preparation. There are 3 1) What method is NOT suitable for ASA tablet manufacturing? wet
methods of tablets granulation
preparation 2) Direct compression is used for chemical like potassium chloride
3) Wurster Process is used for coating tablets
Wet granulation method, Dry granulation method and direct compressions method.
Wet This is a widely employed method for the production of compressed tablets. This
granulation method NOT suitable for moisture sensitive drugs, like ASA, this drug can undergo
hydrolysis in moisture.
Dry In the dry granulation method the granulation is formed by compacting large
granulation masses of the mixture and subsequently crushing and sizing these pieces into
smaller granules.
By this method either the active ingredient or the diluents must have cohesive
properties in order for the large masses to be formed.
Direct Some granular chemicals like potassium chloride and methenamine possess free
compression flowing as well as cohesive properties that enables them to compress directly in a
tablet machine without need of either wet or dry granulation. Vehicle should be
compressible and have good flow. Example dried lactose, mannitol, and starch.
Important Concept!
1) Poorly manufactured tablets may have small “Pinholes” on the surface which occurs when the
tablet powder stick to punch face-picking
2) Air entrapment can causes? Lamination
3) Excessive moisture can cause? sticking
4) Too much pressure or excessive pressure in punching may cause? Capping
Problems in tablet manufacturing

Capping The partial or complete separation of the top or bottom crown from the main body of
the tablet. Too much pressure or excessive pressure in punching.
Lamination Separation of tablet into two or more distinct layers. Air entrapment results from
excess powders which traps air in the tablet, deep marking or tablet punches. Warm
or imperfect punches. Too much pressure. Moist and soft granulation or unsuitable
formula.
Picking The removal of the surface material of tablet laid a punch.
Sticking An adhesion of tablet material to a die. Picking and sticking results from or these
problems are caused by excessive moisture or the inclusion of substance with low
melting temperature in the formulation.
Mottling The uneven distribution of colour. Degradation of active ingredients can give rise to
mottling.
Evaluation Tests for tablet (quality control) contain parameter: general appearance, weight variation,
disintegration test, dissolution test, friability, hardness and thickness.
Hardness Measures the degree of force required to break a tablet and also indicates tensile
strength of tablet. Hardness of tablet greatly effects dissolution and disintegration.
Thickness Measured by capillary scale (Vernier calipers)

Friability Ability of the tablet to withstand abrasion in packing, handling and shipping which is
defined as loss in weight of tablet due to chipping or fragmentation in the form of fine
particles. Tumbler method is used for testing friability.
Weight Measuring weight of tablet.
USP methods include Friability, dissolution, disintegration, hardness and weight variation. Thickness is
unofficial test. (Thickness of tablet is inversely proportional to hardness i.e. increase hardness decrease the
thickness.
USP OFFICIAL TESTS USP UN-OFFICIAL TESTS

Weight variation Hardness
Disintegration Friability
Dissolution Thickness
Drug content
Capsules
A solid dosage form in which medicinal
Question Alerts!
or inert substances are put inside a
1) Uses of soft gelatine and hard gelatine capsules?
small gelatin shell.
2) Plasticizer used in capsule shell?
Capsule shell sizes (5 to 000). 000 is
3) You have to fill 500 mg powder in capsules. Choose?
the largest size of capsule, its capacity
is 600 mg. The smallest capsule size is 5 is 30 mg. Manufacturer also makes available number 10, 11, and 12 for
veterinary use. The gelatin shell dissolved in 10 to 20 minutes after ingestion.
CAP # CONTENT
5 30 mg
000 600 mg
Capsule comes in two types. Soft gelatine shell manufactured in one piece with drug usually in liquid form inside
the shell, e.g. fat-soluble vitamins A and E, Procardia (nifedipine), etc. soft-shell capsule are made from gelatine
to which glycerin or some other polyol, such as sorbitol or propylene glycol has been added as plasticizer.
Spherical or ovoid capsules are sometimes called pearl or globules.
Soft gelatin capsules: Made up of gelatin shell, glycerin or polyhydric alcohol are added to make the shell elastic
and plastic-like. It also contains preservatives to prevent microbe’s growth. Advantages of capsule dosage form
are good for drugs with objectionable taste or odour and easy to swallow.
Hard gelatine shell: The hard-shell gelatin capsules are made from the mixture of gelatin, sugar and water, with
without suitable coloring agent. Hard gel caps contain powder and cannot fill liquid. Sulfur dioxide is used as a
preservative. Capsules are made opaque with titanium dioxide. Hard capsule are available in variety of sizes
and designated by numbers 000 to 5. Manufacturer also makes available number 10, 11, and 12 for veterinary
use.
Powders
Particle size Powders generally range from 0.1 to 10 micron (0.1mM to 10 mM) in size. The
screen size indicates the number of openings in the mesh screen per inch. For
example, a # 40 sieve has 40 openings per inch in the screen mesh. Particles that
can sift through that mesh are said to be "40 mesh" size. Very small particles (below
1 mM) posses high surface free energy that results in absolute solubility. Higher the
mesh size, smaller the particle.
Advantages Flexibility in compounding
Good chemical stability
Rapid dispersion of ingredient
Disadvantages Time consuming in preparing powder
The dose is inaccurate
Unsuitable for hygroscopic, deliquescent drugs and unpleasant tasting.
Comminution. The process of reducing the particle size have 3 methods.
Trituration The continuous rubbing or grinding of the powder in a mortar with a pestle. This
method is used when working with hard, fractural powders.
Levigation This method is also used to reduce the particle size of insoluble materials when
compounding ointments and suspensions. Reduces the particle size by triturating it
in a mortar or spatulating it on an ointment slab or pad with a small amount of a
liquid in which the solid is not soluble. The solvent should be somewhat viscous
such as Mineral oil or glycerin.
Pulverization By intervention it is the process of reducing a substance to a fine powder by means

of utilizing solvent, which can evaporate easily. Used with hard crystalline powders
that do not crush or triturate easily, or gummy-type substances.
Mechanical Ball or pebble mills, wiley mill, hammer mill fluid energy mills.
Comminution
Powder mixing methods

Spatulation Small amounts of powder, having the same range of particle sized and densities,
may be conveniently mixed on a sheet or paper or tile with spatula.
Trituration Powders may be mixed in a mortar by gentle trituration with a pestle.

Sifting Where free-flowing, light powders are desired, the ingredients may be brushed
through a sieve. Ordinary household sifters may be used in sifting pharmaceutical
powders.
Tumbling When simple mixing of powders is desired without reduction in particle size.
Geometric Dissolving in small proportions.

Question Watch?
dilution
Geometric dilution?
Special Powders
Hygroscopic A substance that absorbs moisture from the air is termed hygroscopic. (Absorb H 2 O).
Deliquescent Hygroscopic substances, which absorb moisture from the air to the extent that they
liquefy by partially, or wholly forming solution are termed deliquescent. (Absorption
H 2 O).
Efflorescent Crystalline substances, which become powdery and liberate their water of
crystallization are said to be efflorescent. (Liberate H 2 O).
Effervescent Granules or powders consisting of sodium bicarbonate, a suitable organic or inorganic

salts acid, and medicinal ingredients are known as effervescent salts. In the presence of
water, the acid and base react to liberate carbon dioxide, thereby producing
effervescence. (Liberate CO 2 ). Examples of effervescent salts include Alka Seltzer
(ASA with NaHCO 3 ), and Calcitral.
Eutectic A eutectic mixture is defined as that proportion of components, which will give the
mixtures lowest melting point. Example menthol, and camphor. Compound A 50oC and
compound B 80oC after combining mixture 20oC.
Suppositories
Types of Solid or semi solid dosage form intended to be inserted into body orifice.
suppositories The most common method of suppository preparation is fusion Method.
Rectal Bullet-like shape to moves it inward when rectum contracts, 2 g adult, children
smaller than adult.
Tapered shape and rectal suppository can provide systemic medication
Vaginal Ova shape and 5 g. Have local absorption, but systemic absorption may occur.
Variable size, cylindrical shape, often contain poly ethylene glycol (PEG), water
soluble base
Urethral Long and tapered. Has local effect.
Suppository Criteria:
Bases It should have a narrow or sharp melting range.
It should yield a clear melt just below body temperature or it should dissolve or
disintegrate readily in the cavity fluid.
It should be inert and compatible with wide variety of drugs.
It should be non-irritating and non-sensitizing
Question Alerts!
1) Most commercial vaginal suppositories use a base of polyethylene glycol o/w.
2) An excellent choice of diluents for a compressed vaginal tablet would be Lactose.
3) Melting point temperature of suppository base?
Types of Suppository Bases

Lipid Cocoa butter USP (Theobroma oil, cocoa butter). At 34 to 35oC, it melts to produce a thin,
soluble oily liquid. It is a good base for rectal suppositories, but less ideal for vaginal suppositories.
Witepsol bases (Lauric acid): Do not exhibit polymorphism. High melting witepsol can be
mixed low melting witepsol to produce 34 to 44oC.
Contain emulsifiers. Q (surfactants) in suppositories enhance rate of absorption.
Wecobee bases (coconut oil): These bases are derived from coconut oil.
The incorporation of glyceryl monostearate and propylene glycol monosterate them
emulsifiable.
Water Polymer of ethylene oxide and water, molecular weight range 400-6000
soluble Polyethylene glycol polymers e.g. carbowaxes.
Usually anhydrous, water soluble and washable, non-greasy, non-occlusive lipid free.
Glycerin suppositories USP consist of 91% glycerin gelled with 9% sodium stearate. They
are available as adult and infant suppositories to evacuate the lower bowel.
Displacement value.
Displacement Value = number of grams of salt to replace one gram of cocoa butter. Example. ZnO displaces
cocoa butter. Two parts of ZnO displaces one part of cocoa butter.
ZnO ZnO Cocoa butter

1 part 1 part 1part
Preparation of suppositories. To prepare 15 suppositories, each containing 300 mg ASA are required what
amount of cocoa butter? Density factor (displacement value) of ASA is 1.1.
Each, mold is 2 ml.
Solution.
16 x 2 ml = 32 ml
16 x 300 mg = 4.8 g ASA
4.8 g/1.1 g/ml = 4.4 ml
32ml - 4.4 ml = 27.6 ml of cocoa butter
Suppose 12 suppositories, each containing 300 mg ASA, are required. Given the density factor of ASA is 1.1.
What is amount of cocoa butter required for the preparation? Each mold is 2 ml.
a. 18 g B. 20 g C. 20. 73 g C. 20.04 g
Ans. C
Suspension
Suspension is a two-phase system in which the internal or dispersed phase is solid external or continuous phase
is liquid.
Physical and chemical properties of suspension

Colloidal suspension. A suspension containing particles between 1 nm to 0.5 µm in size.
Coarse suspension. The particle size is between 1 to 100 µm, the suspension.
Purpose. Sustaining effect it necessitates drug dissolution prior to absorption.

· Stability. Drug degradation occurs more slowly with suspension compared to solution form.
· It improves the taste.
· Basic solubility, it provides alternative
solvents. Question Alerts!
1) Stoke's law relation of the rate of sedimentation
Ideal Suspensions with particle size, and viscosity.
· A uniform particle size-uniformly distributes 2) Affects of flocculating agents and deflocculation?
· Suspension that have no particle, particle
interaction
· Suspension that have no sedimentation.
Factors for an ideal suspension - SEDIMENTATION LARGE PARTICLE SIZE
· Sedimentation
· Suspending Agent ¯ SEDIMETATION HIGH VEHICLE DENSITY
· Flocculating Agent - VISCOSITY
FLOCULATING AGENTS
Sedimentation: The Stoke’s law can express the relationship of the rate of sedimentation with various
parameters.
V = 2r2 (P1 – P 2 )g
9n
V = velocity of sedimentation in cm/sec
P 1 = density of disperse phase in g/cm3
P 2 = density of dispersion medium in g/cm3
R = radius of the particles in cm
n = viscosity of dispersion medium
g = gravity acceleration 980.7 cm/sec2
The rate of sedimentation is independent of the lipophilic nature of particles.
Summary of Stokes equation. The velocity of sedimentation of particles in a suspension can be determined by
using the Stoke's equation.
Particle size: Larger particles will settle faster at the bottom of the container and too fine particles will easily
form hard cake at the bottom of the container. Larger the particle sizeà increase in sedimentation. In most
good pharmaceutical suspension, the particle diameter is between 1 and 50 mm. Particle size reduction is done
by dry milling method.
Density of particles: The settling decreases as (p 1 –p 2 ) approaches zero.
Density of the vehicle: Adding the following substances either alone or in combination can increase the density
of the vehicle of a suspension polyethylene glycol, polyvinyl pyrolidone, glycerine, sorbitol, and sugar. Increase
vehicle density à decreases sedimentation. However, the density of the dispersion medium cannot be altered
thereby density of particle is changed.
Viscosity of the vehicle: Adding the suspending agents or viscosity enhancers increases the viscosity of a
suspension. Q Increase in viscosity of vehicleà decrease in sedimentation rate.
Suspending agents (viscosity enhancers): Natural hydrocolloids; acacia, tragacanth, alginic acid, locust bean gum,
guar gum, gelatin and cellulose.
Semi synthetic hydrocolloids. Methylcellulose, sodium carboxymethylcellulose, and carbomen.
Synthetic hydrocolloids. Carbopol.
Clays. Bentonite, veegum
Problems in suspension. Sedimentation, and caking
Flocculating Agents: The addition of flocculating agents to enhance particle "dispersability". Flocculating agents
are electrolytes, which carry an electrical charge opposite that of the net zeta potential of the suspended
particles. The addition of the flocculating agent, at some critical concentration, negates the surface charge on
the suspended particles and allows the formation of floccules or clusters as particles are held loosely together by
weak Van der Waals forces. The particles are linked together only loosely. They will not cake and may be easily
re-dispersed by shaking the suspension. Floccules have approximately the same size particles. Examples of
flocculating agents are potassium stearate, potassium laurate, acryl polymers and surfactants.
Addition of viscosity enhancers to reduce sedimentation rate in the flocculated suspension.
Higher volume of sedimentation. NO clear boundary is seen when the particles settle.
COMPARISON BETWEEK DEFLOCCULATED AND FLOCCULATED SYSTEMS

DEFLOCCULATED SYSTEM FLOCCULATED SYSTEM
Clear boundaries No clear boundaries
Small volume of sedimentation Higher dispersion volume of sedimentation
- SEDIMENTATION ¯ SEDMENTATION
¯ DISPERSION - DISPERSION
¯ VISCOSITY
Not ideal suspension Ideal for suspension
The hard cake cannot be redispersed and The sediment is easy to redisperse and Easily
Not easy to disperse dispersible
Pleasant appearance, because of uniform Somewhat unsightly sediment.
dispersion of particles.
Supernatant remains cloudy. Supernatant is clear
Particles exist as separate entities Particles form loose aggregates

Rate of sedimentation is slow, as the size of Rate is high, as flocculation are the collection of
particles are small. smaller particles having a larger size.
The sedimentation is closely packed and Sediment is a loosely packed network and hard cake
form a hard cake. cannot form.
Bioavailability is higher due to large specific Bioavailability is comparatively less due to small
surface area. specific surface area.
Emulsions
Emulsion is a two phase system consisting of at least two immiscible liquids. Internal or discontinuous phase.
The dispersed liquid, external or continuous phase is the dispersion medium.
Emulsion is classified as five different categories:
Water in Oil (W/O): Oil is a continuous phase and water is a disperse phase, i.e., lotions and liniments. Example.
Lotions and liniments.
Oil in Water (O/W): Water is a continuous phase and oil is a dispersed phase, i.e., most of the oral emulsions to
unmask the oily taste of a medication.
Microemulsion. Unlike emulsions, microemulsion is transparent with a small particle size. It is believed to be
thermodynamically unstable. The particle size of microemulsion lies between 10 to 200 nm. It is generally used
for the solubilization of the drug in pharmaceutical dosage form.
Nanoparticles. Micro-emulsion- droplets size range 0.01 to 0.1 mm, the particle size of this kind of emulsion is
limited to nanograms. They are useful for the preparation of globulins and toxoids. Tetanus toxoid and human
immunoglobulin G are examples of nanoparticles emulsion.
* Multiple emulsions: Water in Oil in ware (W/O/W), Oil in Water in Oil (O/W/O). The w/o/w emulsions are
generally more preferable for preparation of various pharmaceutical dosage forms. They are used to prolong
the duration of action of various drugs, to localize drug in the body and to prepare cosmetics
Purpose of emulsion
· Increase drug Question Alerts?
1) Emulsifying agents such as Tween and Span are? Surfactant
solubility
2) HLB is used to classify surfactant
· Increase drug 3) Sodium lauryl sulfate is? Anionic surfactant
stability 4) Creaming in emulsions is due to? Increased in droplet size. (Reversible
· Prolonged drug separation a layer of emulsified particle).
action 5) The process of dispersed oil globule in aqueous vehicle called? Emulsion
· Improve taste 6) Liquid droplets dispersed in another immiscible liquid is called? Emulsion
7) Irreversible phase separation in emulsion may cause? Cracking, or breaking
· Improved
8) What is NOT a problem of emulsion?
appearance A) Cracking B) Creaming C) Aggregation D) Coalescence E) Flocculation
Stability of emulsion: Protect emulsions against the extremes of cold and heat. Emulsions may be adversely
affected by microbial contamination.
Emulsifying agents (surfactants) are categorized as:

· Anionic agent: Sodium lauryl sulphate.
· Cationic agent: Benzalkonium chloride.
· Non-ionic: Tween and Spans. Tween is polysorbate and span is sorbital esters.
Anionic agent surfactants Non-ionic surfactants Cationic surfactants

Sodium lauryl sulphate Tween (POLYSORBATE) Benzalkonium chloride
Span (SORBITAL ESTER)
Problems in emulsion categories. Creaming, breaking (cracking) phase inversion and coalescence.
Creaming: It occurs due to flocculation of globules of the internal phase. It is not a potential cause of instability
of emulsion, however, occurrence of creaming is a potential step towards complete breaking of emulsion. The
rate of creaming can be expressed by Stoke’s law.
V = d2 (Ps – Po) x g
18n
d = diameter of particle in cm
Ps = density of disperse phase
Po = density of dispersion medium
g = gravitational force
n = viscosity of medium
Breaking. Breaking generally results in separation of the internal and external phase. It cannot be reformulated.
Hydrophilic lipophilic balance (HLB) measures the surfactants mixability in water and lipids. Classification of
surfactants based on HLB values and uses.
0-3----------------------- Antifoaming
Question Alert!
4-6-- .................w/o emulsifying
7-9----------------------- wetting 1) TWeen HLB? O/W
8-18------------- - o/w emulsifying 2) Span HLB? W/O
13-15-------------------- detergent
10-18-------------------- solubilizing agent
Combinations of emulsifiers can produce more stable emulsions than using a single emulsifier with the same
HLB number. The HLB value of a combination of emulsifiers can be calculated as follows.
Example. What is the HLB value of a surfactant system composed of 20 g span 20 (HLB = 8.6) and 5 g Tween 21
(HLB = 13.3)?
Creams
Cream (W/O: A semisolid emulsion of oil, e.g. lanolin or petrolatum, and water.
These are either water-miscible or readily washed-off, or oily and not so easily
washed off.
Cold cream Cold Cream (W/O) emulsion and vanishing cream (O/W) emulsion.
Preservatives Chlorocresol and Hydroxybenzoates, both of which may cause skin allergies.
used
Barrier creams Barrier creams often contain water-repellent substances such as dimethicone or
other silicones. They give protection against irritation or repeated hydration and is
useful in the treatment of
napkin rash and bedsores, Question Alerts!
etc. 1) Cold cream is?
2) Vanishing cream?
3) Water washable cream is?
Creams should be stored in cool place and supplied in well closed containers that
prevent evaporation and contamination of the contents.
Cream Eumovate, Elocom, Tridesilon Cream.
examples
Substances such as precipitated sulphur, salicylic acid, menthol and camphor,
hydrocortisone powder, hydroquinone, to mention a few, may be incorporated
into creams and/or ointment bases extemporaneously.
Ointments
Mechanism Ointments are semisolid substances that are greasy, normally anhydrous, and
insoluble in water, and intended for external use.
Therapeutic use The most commonly used ointment bases consist of soft paraffin or a combination
of soft paraffin with liquid paraffin and hard paraffin. Due to their anhydrous
nature ointments do not require any preservatives.
They are typically used as emollient that makes skin more pliable
Protective barriers prevent contact to skin from harmful substances.
Advantages It moisturizes, more occlusive than creams and forming a protective film over the
skin. The occlusive effect tends to prolong and enhance drug penetration.
Disadvantage They are messy to use.
Storage They should be kept in well-closed container that prevents evaporation and
contamination in a temperature not exceeding 25oC. The material making up the
container should be resistant to absorption or diffusion of the contents.
Ointment Levigation to reduce particle size, most commonly used method for
Preparation pharmaceutical compounding.
Levigating agents. Levigating agents used for wet & disperse powder
Main agents: mineral oil, cottonseed oil, and castor oil.
Glycerin: (propylene glycol PEG 400).
Surfactants: polysorbate 80 (Tween 80).
Not all surfactants are compatible
Fusion method: used method if the base contains solid that has higher melting
point.
Some examples ointments are generally used for treatment of hemorrhoids.
Preparations H, Anusol, Anusol HC and Anugesic.
Ointment bases Water and lipid soluble base.
Poly ethylene glycol (PEG) Important Concept!
Lipid soluble base Lanoline 1) Occlusive bases effectively prevent
Occlusive bases: Petrolatum water evaporation from the skin. Tends to
prolong and enhance drug absorption.
1) Hydrophilic Petrolatum, USP

· Contains cholesterol, stearyl alcohol, white wax and white petrolatum
· Forms water-in-oil emulsions
Cholesterol is the emulsifying agent
CREAM OINTMENT GEL

o/w w/o Greasy, insoluble NO WATER
vanishing Cold cream anhydrous
Washable Washable Not washable
Good for dry skin Good for dry skin GOOD FOR OILY SKIN
Pastes
Mechanism Pastes are stiff preparations containing a high proportion of finely powdered solids
such as zinc oxide and starch.
Therapeutic They are less occlusive than ointments and can be used in subacute, lichenified, or
use excoriated skin conditions. Due to the stiff nature, they can be applied accurately to
a particular lesion such as chronic eczema and psoriasis, and are therefore useful for
the local application of irritating drugs.
Examples Anthralin OTC paste 0.025% and 0.2% for seborrhea and psoriasis. Benzoyl peroxide
paste for acne.
Gels
Mechanism Gels are semisolids or solids prepared from high molecular weight polymers in an
aqueous or alcoholic base. They are easy to apply and wash off (example hairy
places).
Therapeutic Gels are useful for promoting wound granulation (example Actovegin Jelly), in
use treatment of acne (example Panoxyl gel) and Scalp psoriasis (example Synalar gel
mix).
Due to their drying effect and especially the alcoholic ones, they may cause irritation
to the skin.
Examples Acne gel preparations. Made of synthetic polymers such as carbo vinyl and
polyoxyethylene laurel ether in hydroalcoholic liquids are used as bases for benzoyl
peroxide in the treatment of acne.
Topical gels. Tretinoin or tretinoin + clindamycin (clindagel), tretinoin + erythromycin
gel should be stored in refrigerator and protect from light.
Panoxyl®, Benazagel®-10, Hormone replacement (Androgel®, Estrogel®).
Diffusimax is a commercially prepared pluronic gel that easily penetrates the skin and
is used as a vehicle to apply such drugs as Diclofenac sodium to ease muscle pains.
Hydrophilic Petrolatum, USP
· Contains cholesterol, stearyl alcohol, white wax and white petrolatum

· Forms water-in-oil emulsions
· Cholesterol is the emulsifying agent
Lotions
Mechanism Lotions are aqueous solutions or suspensions that cool diffusely inflamed unbroken
skin. Finely powdered drugs are suspended in a thin, semi-solid base and applied to
the skin.
Therapeutic Cool skin by evaporation and should be applied frequently.
use Lotions are also used to apply drugs to the skin when only a thin layer of the
preparation is intended to be applied over a large surface area.
Shake lotions (e.g. calamine lotion) that contain insoluble powders are applied to less
acute, scabbed, and dry lesions.
In addition to cooling, they leave a deposit of inert powder on the skin surface.
Examples Benoxyl, valisone and scalp lotion, calamine lotion (Zinc oxide + Ferric oxide).
Counseling Lotions and suspensions require a ‘Shake Well” label and if intended for topical use.
An “External use only” label.
Liquid Dosage Form
Spirits
Spirits or essences are alcoholic or hydroalcoholic solutions of volatile substances prepared usually by simple
solutions or by admixture of the ingredients (contain 50% to 90% alcohol).
Spirits require storage in tight, light-resistant containers to prevent loss by evaporation and to limit oxidative
changes. Some of spirits are medicinal but mostly are used as flavouring agents.
Tinctures: Natural products or herbal extracts taken orally. They are extracted in alcohol.
Tinctures are alcoholic or hydroalcoholic solutions prepared by mixing chemical substances
like iodine. The alcohol content of the official tinctures varies from 10% to 21% with opium
tincture USP; 74% to 80% with benzoin tincture USP. Glycerin may be added to hydroalcoholic
solvent to increase solubility of the active content and reduce precipitation during storage.
Tincture is categorized as protectant. It is used to protect and toughen skin in the treatment of
bedsores, ulcers, cracked nipples, and fissures of lips and anus. Tinctures require storage in
tight, light resistant containers, away from direct sunlight and excessive heat (may undergo
photochemical change).
Topical tinctures: Iodine tincture, compound benzoin tincture and themerosal tincture.
Iodine tincture. The iodine tincture is prepared by dissolving 2% of iodine crystals and 2.4% of
sodium iodide to an amount of alcohol equal to half the volume of tincture to be prepared.
Benzoin tincture Prepared by the maceration in alcohol 10% of benzoin and lesser amounts of
aloe, storax, and tolu balsam totalling about 24% of starting material.
Astringents
Locally applied solutions that precipitate protein. The protein precipitates which
forms serve as a protective coat, allowing new tissue to regenerate underneath. It
causes constriction and reduces secretions therefore they can be used as astringent.
These substances that stop oozing, discharge or bleeding.
Common Zinc oxide used for diaper rash treatment and hemorrhoids. Calamine lotion used for
astringents cold sores or fever blister treatment and poison ivy.
Burrow's solution (Aluminum acetate) used for otitis externa, and dermatitis
treatment.
Calamine Calamine lotion is mixture of zinc carbonate or zinc oxide colored with ferric oxide.
lotion
Collodions
Collodions are liquid preparations consisting of a solution of proxylin in a mixture
of ether and alcohol. When collodions are painted on the skin and allowed to dry
they leave a flexible film over the site of application.
Therapeutic use Collodions may be used to seal minor cuts and wounds or as a mean of holding a
dissolved drug in contact with the skin for a long time.
Counselling Keep away from fire
Emollients
Emollients are derived from animal or vegetable fats or petroleum products, used
to soften or protect internal or external body surfaces.
Emollients are fats or oils in a two-phase system (one liquid is dispersed in the form
of small droplets throughout another liquid).
Emollients soften the skin by forming an occlusive oil film on the stratum corneum,
thus preventing drying from evaporation from the deeper layers of skin.
Therapeutic Emollients are employed as protective and as agents for softening the skin and
use rendering it more pliable in conditions like dry eczema, ichthyosis and psoriasis. They
also serve as vehicles for more active drugs.
Gargles
Gargles are aqueous solutions, usually in concentrated forms intended for use,
after dilution, for treatment of infections of oral cavity and throat.
Therapeutic use A gargle does not, however, act as a protective covering to mucous membranes.
Monitoring In the treatment of mucositis, try to avoid a gargle that contains a high
concentration of alcohol as it may produce irritation.

Examples Examples of gargles are thymol gargle, chlorhexidine gargle and difflam gargle.
Gargles may contain a drug to relieve sore throat such as Tantum (Benzydamine):
commercially prepared mouthwashes or saline solution (0.9% sodium chloride)
may be used for stomatitis.
Chlorhexidine: used for stomatitis, mucositis, and gingivitis. Caution: stains teeth
after excessive use. Use chlorhexidine 30 min before or after use of toothpaste.
Chlorhexidine can interact with fluoride and can stain teeth.
Humectants
Mechanism Humectants promote water retention due to their hygroscopic. They act by being
absorbed into the skin and attract water from atmosphere and serve as a reservoir for
the stratum corneum. Commonly used humectants are propylene glycol and glycerin.
Liniments
Mechanism Liniments are viscous liquid containing substances possessing analgesic, soothing or
stimulating properties when applied on the skin. They are usually made with a base of
oil, alcohol, or soap solutions.
Example. Methyl salicylate liniment.
Liniments should not be applied to broken skin
Syrups (Drug + sugar + water)

Sugar in water is syrup. Generally syrup contain sugars solutions, caution diabetic patients and recommend
syrup containing artificial sweeteners such as aspartame, in place of sugar.
Elixir: Contain alcohol.

Elixir are clear, sweetened, hydroalcoholic solutions intended for oral use and usually flavored to enhance
palatability.
Elixir is prepared for products that are soluble in water and alcohol. Elixir contains less sugar, less viscous than
syrup.
Rubbing alcohol: Rubbing alcohol contains about 70% of ethyl alcohol by volume, the remainder consisting of
water, denaturants with or without color additives and perfume oils and stabilizers. In each 100 mL it must
contain not less than 335 mg of sucrose octa acetate of 1.4 mg of denatonium bentoate, a bitter substances that
discourage accidental or abusive oral ingestion. It is used as rubefacient externally germicide for instruments
and skin cleanser prior to injection. This product is flammable stored in tight container far from fire.
Isopropyl rubbing alcohol: Isopropyl rubbing alcohol contains about 70% of ethyl alcohol by volume, the
remainder consisting of water. Can be used as disinfectant.
Tips
1 Has low accumulation 2 Rate of diffusion 3. Burrow solution
.
4. disintegrating agents 5 Pc=octanol water o/w 6. first pass effect
.
7 Stokes equation 8 stability & solubility 9 all oils except
. mineral oil
1 alcoholic and hydroalcoholic 11 Tocoferol alpha 1 anionic surfactant

0 liquid mixtures 2
1 disintegrating agents 14 sodium lauryl sulfate 1 Sterile Water for
3 5 injection USP
1 small intestine>oral>mucus stratum corneum 1 capsule size 000
6 membrane>stomach 17 8
mixing of 2 subs. Leads to 20 glycerin 2 crystallization
1 lowering in melting point, 1
9 example includes camphor and
menthol
2 o/w emulsion
2
· The definition of tincture is? ( )
· Sodium lauryl sulphate is? ( )
· High HLB values associated with? ( )
· What problem does not occur in suspension? ( )
· Fick's law describes? ( )
· The rate limiting step in ophthalmic drops ? ( )
· Partition coefficient is described as? ( )
· Drug with low volume of distribution? ( )
· The most commonly used humectants is? ( )
· Aluminum acetate is? ( )
· Eutectic mixture is? ( )
· Oils used for parenteral preparations? ( )
· Write the sequence of surface area in GIT ( )
· The largest size of capsule is? ( )
· The rate limiting step for the topical drugs ( )
· Water used in parenteral preparation is? ( )
· What is avoided in transdermal patch? ( )
· What is an example of anionic surfactant( )
· The tablets are disintegrated by? ( )
· Relation of sedimentation and particle size can be explained by? ( )
· What type of tocoferol has the strongest antioxidant properties? ( )
· Complexation can modify which two properties in a drug? ( )
· An example of biphasic include ( )
www.pharmacyprep.com Drug delivery Systems
38
Drug Delivery Systems
Questions Alerts!
· Solvents in parenteral preparations like types water, and sterilization methods
· Asthma devices in children meter dose inhaler + spacer and nebulizers
· Ophthalmic prep preservatives, viscosity enhancers like HPMC
Routes of drug administration

Route Site
Oral (PO) By mouth. Whenever possible, safest and most convenient route
Sublingual (SL) Under the tongue. When rapid effect is desired.
Parenteral Other than the gastrointestinal tract (by injection)
Intravenous Administered directly in vein. Aqueous solutions are used. Single small volume (bolus)
or large volume slow iv drip infusion.
SUSPENSION ARE NOT USED IN IV.
Intraarterial Artery.
IM are given in deep into skeletal muscles, generally Gluteal or lumbar muscles.
IM Drugs that irritate subcutaneous may be administered by IM.
Volume used is 2 to 5 ml. If require more than 5 ml, administered in divided dosages at
two different sites. Faster than subcutaneous. Angle of injection is 90°. Needle gauge is
23 (22-25), and length is 1.5 inch.
Intracardiac Heart
Instraspinal or Spine. CHEMOTHERAPY DRUGS ARE NOT USED AS INTRATHECAL.
intrathecal
Intraosseous Bone
Intraarticular Joint
Inrasynovial Joint-fluid area
Intracutaneous or Beneath the skin loose subcutaneous (hypodermic) tissue.
Intradermal or Subcutaneous Less than <2 ml volume is used. Liquids, or suspension are used. Angle
Subcutaneous of injection is 45°. Needle gauge 23 (22-25) and 5/8 inch.
Intradermal: Injection in to the most superficial skin layer. Deliver only limited drug
volume, it is generally restricted to skin test and some vaccines.
Sites: high fat sites, abdomen, low back thighs, upper back.
Examples: Insulin, heparin, and LMWH.
Epicutaneous Skin surface

(topical)
Transdermal Skin surface
Question Alerts!
1) Intraarticular injections are given in? Joint spaces
2) Avoid suspensions in intravenous preps
3. TPN is solution is given as iv in subclavian vein
4. Epipen is IM inj.
conjunctival Conjunctiva
Intraocular Eye
Aural Ear
Intrarespiratory Lung
Rectal Rectum
Vaginal Vagina
Urethral Urethra
Sublingual Under the tongue à fastest oral absorption
Ranking of various oral dosage (fastest → slowest)

· Solutions (ready for absorption)
· Suspensions (wetted and ready for dissolution)
· Powder [(dispersed + GI fluid → wet) absorbed]
· Capsules (dissolve gelatin cap first → then powder)
· Tablets (disintegration from tab. to smaller granulate then → powder)
· Sustained release tab (barrier of coating materials)
Whenever a drug is more rapidly and more completely absorbed from a solid form, the rate-limiting factor is the
dissolution process.
Parenteral preparations
Parenteral Preparations intended to be administered parenteral should be sterile, pyrogen free and
particulate free.
Sterility testing are two common methods. Immersion (direct inoculation) and Membrane
Filtration.
Methods of removal of pyrogen are double distillation. Limulus amebocyte lysate (LAL) test and
rabbit tests are used to determine pyrogen.
Test for particulate contamination is the light Obscuration Particle Count Test
Parenteral packing integrity test is Package Leak Tests.
IV bags should be tested by compressing to check leakage.
Parenteral should be isosmotic (same number of dissolved particles and same osmotic pressure
as human blood plasma).
OSMOLARITY is a measure of the numbers of milliosmoles of solute per liter of solution
(mOsm/L). Osmolarity refers to the osmotic pressure applied by solution across cell wall.
Osmotic pressure: is the pressure required to maintain equilibrium within the cells.
Requirements Restrictions on buffers, stabilizers, and antimicrobial preservative. Do not use coloring agents.
Sterile and pyrogen free. Must meet compendia standards for particulate matter. Must be
prepared under aseptic conditions. Specific and high-quality packaging.

Vehicles Aqueous: Sterile water for injection USP (<1 liter), water for injection (>1 liter).
Non-aqueous. Glycerin, polyethylene glycol, and alcohol. Must not contain paraffin or Mineral
oil, and methanol.
Fixed oils. Restrictions on fixed oils. Must meet the requirement of iodine number and
saponification number.
Iodine number It represents the number of grams of iodine absorbed, under the prescribed conditions, by 100
g of the substance. Iodine number indicated the presence of number of double bonds.
Saponification It represents the number of mg of potassium hydroxide required to neutralize the free acids
number and saponify the esters contained in 1 g of the substance.
Saponification number indicates the number of ester functional groups.
Solvents Water for injection, pea nut oil, cotton seed oil, sunflower oil, olive oil, corn oil, and canola. Do
not use mineral oils, and theobroma oil.
IV injection must not be a suspension because of the probability of blockage of a blood vessel.
IV. Injection of high concentration of K+ may cause cardiac arrest.
some IV preps can be oleaginous (oily)
Premixed products:
Premixed iv solution contain both diluents and the drug already combined in single unit-of-use iv bag or bottle.
E.g. Minibags metronidazole, gentamycin, ciprofloxacin. LVPs (>100 mL). Heparin, KCl, lidocaine. Gloss bottles.
Nitroglycerin.
Intrapulmonary drugs
Intrapulmonary Metered dose inhalers (MDI), diskus, turbuhaler, handihaler and nebulizers.
drug delivery
devices
Components of Propellants, valves, containers
aerosols
Formulation of Solutions, suspensions, emulsions
aerosols
Inhalation Deposition of particles in the lungs.
Therapy
Metered dose Contain suspension or liquid. Suspension containing metered dose inhaler (MDI)
inhalers (MDI) should shake before use. Safe propellant hydrofluorocarbons (HFA) or HFC.
Aerosol flow rate 30 m/s or 100 km/h. Shake before use.
Do not exceed prescribed dose.
Good for under 5 year old.
Dry powder Dry powder inhalers also known as turbuhaler
inhalers (DPI) or No propellant and no need to shake.
turbuhaler Requires patient’s own inspiratory effort to form aerosol
Powder is delivered only when the patient inhales.
Useful in children above 5 years, teenagers & arthritic patients.
Can be used open mouth and closed mouth technique.
Nebulizers Turns an aqueous solution of drug into fine mist

Drug will be inhaled with normal respiration
Medication reaches lower airways more effectively
Two types. jet & ultrasonic
Jet: Cools during operation, Small aerosol particle size, Less expensive, More
noise
Ultrasonic: Heats up during operation, Larger aerosol particle, More expensive,
Less noise
Choice of inhalation therapy
Infants -----------------Nebulizer
Children
< 4 years----Nebulizer and MDI
4 year or above--------DPI/MDI/Spacer
7 years-------DPI/MDI
Adults-------------------MDI/DPI
Acute episodes-------Nebulizer
Example
compositions
Inhalation Drug…………………………. Albuterol (bronchodilator)
aerosol Surfactant…………………… Oleic acid, and propylene
Propellant…………………… HFC (HFA)
Co-solvent………………….. None
Type of output……………… Dry mist
Topical spray Drug…………………………. Miconazole
Surfactant……………………. Glycol
Propellant……………………..Propane or n-butane
Co-solvent…………………… Isopropyl alcohol
Type of Drug output……Wet mist
Vaginal foam Drug……………………………Nonoxenol-9 (Contraceptive)
Surfactant……………………. Triethanolamine
Propellant…………………….. n-butane, and propane
Co-solvent……………………..None
Type of output……………..… Stable foam
Rectal Dosage forms

Rectal route may be preferred over oral route in order to avoid liver by first pass (less first pass).
· Safe route if patient is vomiting, unconscious or unable to swallow (mainly applies to rectal).
· Often used for local effects e.g. hemorrhoids, local infections.
· Suppositories can provide systemic medication (diffuse through mucosa and transport the veins and
lymph vessels into systemic fluids or tissue. (By-pass liver).
Surfactants in suppositories increase drug absorption.
Rectal ointments: Ointments are generally used for the treatment of hemorrhoids. Some examples are
Preparations H, Anusol, Anusol HC, and Anugesic.
Rectal suppositories. Suppositories are topical dosage forms designed to soften when placed in the rectum.
They may be cylindrical or egg-shaped and are used for local action as laxative.
Suppositories should be protected from heat. Some examples Dulcolax or glycerin, analgesic, Anusol,
Preparation H.
Anti-inflammatory suppositories indomethacin or naproxen. Suppositories are also used for systemic use when
the oral route is either impossible or not desirable. Some examples of drugs available for systemic use rectally
antiemetics such as Gravol, and Stemetil.
Analgesics. Acetaminophen and ASA.
Rectal solutions or rectal suspensions (enemas)

Enema is administered in a syringe or disposable squeeze bottle with an applicator tip.
Some examples: Systemic anti-inflammatory effect: 5-ASA (Salofalk)
Vaginal dosage forms

Vaginal dosage forms include tablets, creams, aerosol foams, jellies, solutions and ovules (suppositories) and the
sponge. The ovule is shaped differently from that of a rectal suppository-the laxative fleet enema are larger,
more oval in shape, and the base is water-soluble.
Vaginal preparations: Most commercial vaginal suppositories use a base of polyethylene glycol o/w. An
excellent choice of diluents for a compressed vaginal tablet would be lactose.
Vaginal products
Vaginal dosage forms for contraception: Delfen Foam, and the sponge Protect Aid.
Some example of anti-infective: Monistat, Canesten, Flagystatin, douches, and Hormone replacements.
Metronidazole (Flagystatin): Partner should be treated same time, it is important to avoid alcohol.
Metronidazole indicated for trichomonas associated vaginitis.
Miconazole: drug of choice in vaginal candidiasis in pregnancy. Cream is preferable over suppositories and
ovules. Cream effective decrease itching associated with vaginitis.
Topical Dosage forms

Four bases are used: Hydrocarbons, Important concept!
which are greasy to the touch 1) Some products may be used in both the ear and eye like Sofracort.
(petroleum jelly). While otic preps have a glycerin or PEG base cannot be used in eye.
Absorption bases, which are also 2) What type of topical preps requires sterilized preps? Ophthalmic
greasy but allow the addition of 3) Ophthalmic ointments have high contact time so high absorption
liquid usually water or dissolved than drops.
chemicals in aqueous solution. 4) Percentage of bioavailability from ophthalmic preps is? 5%
Water removable bases, which are
oil-in-water mixtures, easily
removed form the skin with water (Glaxal Base) and water-soluble bases, which can be mixed with substances
that will dissolve in water. (Polyethylene glycol bases).
Ophthalmic Ointments/Solutions/Suspensions:
Cornea as a barrier to ophthalmic drug absorption.

Formulation: Isotonic, sterile and pH additive (should be formulated at a pH equivalent to tear fluid value of 7.4.
Ophthalmic ointments are sterile ointments containing antibiotics or substances to relieve dry eyes. Only sterile
products are used in the eye. The advantage of using an ointment rather than a solution is that the ointment
allows increased contact time in the eye.
Ophthalmic ointments are packaged in 3 or 3.5 g tubes.

Examples Cetamide, Tobra-Dex, Garamycin. Sterile solutions and suspensions are used in the eye (ophthalmic
preparations) to treat infections, allergies, and inflammation and dry eyes in the ears (otic operations) to treat
infection. Examples of ophthalmic preparations used in the eye are Sulamyd, Opticrom, Inflamase, prednisolone,
and Isopto Tears.
Ophthalmic drops
· Voltaren. Cause stinging and burning, and blurred vision.
· Ketorolac. Cause stinging and burning
· Trifluridine. Store in refrigerator
· Pilocarpine. cause miosis
· Latanoprost (Xalatan). Causes pigmentation, and enlargement of eyelashes.
· Latanoprost + Timolol (Xalacom).
· Timolol
· Some products may be used in both the eye and the ear, such as Sofracort, Cortisporin while otic
preparations have a glycerine or propylene glycol base and cannot be used in the eye.
· Examples of otic preparations: Cortisporin Otic, Garamycin Otic, Garasone Otic, Locacorten Vioform, and
Otic Drops.
Modified drug delivery system:
Modified release drug delivery system
Sustain release dosage forms Controlled dosage forms

Provides medication over extended period of time Maintain constant drug levels in blood or tissue
Do NOT attain zero order release kinetics Release the drug in zero order pattern
SR for 12 hrs, XL for 24 hrs CR, MR, CD, continuous
Bupropion SR Q12hr
Bupropion XL Q24hr
Ritalin 3-4 hr
Ritalin SR 6-8 hr
Ritalin LA 8-10 hr
Concerta 12 hrs
Controlled/targeted delivery:
An ideal controlled release mechanism for a device is the one, which exhibits a zero order drug release. i.e. the
release of drug is independent of time.
Delayed release or sustain release (SR) --> repetitive intermittent dosing of IR. (e.g. Bupropion SR).
Extended release (XL)--> maintain therapeutic levels prolong time (e.g. Bupropion XL)
Site specific target-->target to one organ location (enteric coated)
Receptor targeting--> target a drug receptor.
Conventional dosage forms, drug concentration raises rapidly, peaks, and then falls until the next dose is taken.
Controlled delivery systems

Advantages of controlled delivery systems. Maintenance of optimum therapeutic drug concentration in the
blood or in a cell predictable and reproducible release rates for extended periods of time enhancement of
activity duration for short half-life drugs the elimination of side effects, frequent dosing, waste of drug,
optimized therapy better patient compliance.
Drug may be coated on small inert beads of sugar & starch. Some beads can then be coated with lipids to delay
release. Beads with different coating thickness can then be combined in a capsule to achieve sustained release,
e.g., the Spansule technology (Contac, Dexedrine).
Technological methods
Drug can be embedded in slowly eroding matrix, e.g., SLOW-K (KCl in a wax matrix), SLOW-Fe etc.
Two-layered or press-coated tablets for sustained release.
Drug embedded in inert plastic matrix, e.g. Gradumet
Drug complexes with ion exchange resins, e.g. Pennkinetic systems
Floating capsules or tablets, e.g. slow release diazepam (Valrelease), a hydrodynamically balanced (HBS) drug
delivery system.
Coating or sustained release tablets should not be crushed or chewed.
Osmotic release: Nifedipine (Adalat), and Concerta (Methylphenidate).
Liposomes for drug delivery systems

Liposomes are lyotropic liquid crystals composed mainly of amphiphilic bilayers.
Liposomes have the advantage of primarily consisting of lecithin and cholesterol, which are materials that occur
naturally in the human body. Lecithin and cholesterol are also present in the body in large amounts, and thus
demand good bioacceptability.
This liposome’s can entrap drugs and may be used for drug targeting, sustained release, or reduced drug
toxicity. Phospholipid can spontaneously form concentric, bilayer lipid vesicles when dispersed in water. Can be
processed into various types & sizes.
PEGylating
Transdermal delivery involves diffusion of the drug through the skin. The drug properties that are suitable for
transdermal preps are drugs with short half life, and lipid soluble drugs.
Nicotine patch. Volatile (may evaporate), Androderm, Estraderm, Habitrol, Nicoderm, Nitro-Dur, and Estalis.
(Moisture and photosensitive)
Nitroglycerin patch: Use nitrate free period to reduce tolerance (apply 12 hours and 12 hours without patch).
Can be applied on chest. Avoid applying on lower extremities.
Fentanyl patch. Effective for 72 hours.
Estrogen patch. Do not apply on the chest. If it falls frequently apply new patch.
Scopolamine patch: Apply behind the ear, effective for 3 days.
Oxybutynin Patch: Anticholinergic drug for the treatment of urinary incontinence
Tolterodine Patch: Anticholinergic drug.
Clonidine Patch: Centrally acting antihypertensive drugs.
Implants for drug delivery

Implantable drug delivery systems are being developed to take the place of traditional drug delivery systems,
such as pills and hypodermic injection.
Implantable systems that are currently available include Norplant and various pumps, such as insulin pumps. The
systems are designed to deliver drugs directly into the bloodstream at a controlled rate of transmission.
Tips
1. it is rapid onset & no 2. 8 to 12 hrs 3. drugs that act directly on the bronchi
first pass metabolism & inhalation
anesthetics
4. for drugs that cause GI 5. no shaking but 6. it is the most convenient to both the
irritation and N, and uncooperative or prime patient
unconscious patient and physician
7. hydrofluoroalkane hfa 8. iv 9. the physical and
chemical characteristics of the drug
10. the tissue mass, extent 11. it is the fastest 12. they provide continuous drug
of ionization acting method administration
and no first pass
metabolism
13. im 14. ophthalmic and 15. injection in joints
parenteral
16. salbutamol, fluticasone, budesonide, 17. the taste and or 18. into the spinal column
salmeterol smell and possible
first pass
metabolism and
slow
· What are the advantages of oral administration? ( )

· What dosage forms require sterile? ( )
· Intra articular injections ( )
· What propellant used in meter dose inhaler? ( )
· Nitroglycerin patch require nitrate free period for? ( )
· Meter dose inhalers that require shaking ( )
· Nitroglycerin spray require ( )
· What are the disadvantages of oral administration? ( )
· What is the advantage of IV drug administration? ( )
· What are the advantages of sublingual administration of a drug? ( )
· What is meant by the intrathecal administration of a drug? ( )
· Drug distribution into different tissues depends on which factors? ( )
· What is the most direct route of drug administration? ( )
· What factors must be considered in choosing a specific route of administration? ( )
· Which provides a more rapid absorption, IM or SC administration? ( )
· What type of drugs can be given by inhalation? ( )
· What are the advantages of rectal administration of drugs? ( )
www.Pharmacyprep.com Pharmaceutical Analysis
39
Pharmaceutical Analysis
Questions Alerts!
· Chromatography methods like HPLC, GC, TLC
· Spectroscopic methods like mass spectroscopy, or NMR.
· Bioassays like ELISA, gel electrophoresis, western blot, eastern blot and Polymer chain reaction (PCR)
and real time PCR (RtPCR).
Chemical separation or purification techniques include, distillation, chromatography, extractions and centrifuge.
Chromatography
Chromatography is a method of separation of mixture of chemicals that relies on differences in partitioning
behaviour between a flowing mobile phase and a stationary phase to separate the components in a mixture. The
commonly used chromatographic methods of analysis include: Gas chromatography, HPLC, TLC, and paper
chromatography.
Chromatography instrumental procedures
Liquid
Gas
Column Planar
GLC GSC
HPLC
TLC Paper
Normal phase (NR-HPLC) Reversed phase (RP-HPLC)
Liquid Chromatography
Liquid chromatography (LC) is an analytical chromatographic technique that is useful for separating ions or
molecules that are dissolved in a solvent.
High Performance Liquid Chromatography (HPLC) or High-Pressure Liquid Chromatography:

Used for non-volatile and thermally stable compounds to separates macromolecules, ionic species, labile natural
products, polymeric materials and high-molecular weight compounds.
Diagram.
Columns Records
Solvent Injector Detector
and Pump chromatogram
Mobile phase. Solvent such as methanol, water, ethanol and CCl 4 .

Stationary phase. Silica gel column.
Column. 4 to 5 mm heavy wall, glass-lined metal tubing or 10 to 30 cm.
Detectors
Question Alerts!
· UV-VIS photometers (diode array detector) Mobile phase are solvents; these are two
· Fluoviometric detector types
· Electrochemical 1) Organic (methanol, ethanol,
· Refractometers (RI) acetonitrile, CCl4) are normal phase
· Conductivity for ion chromatography 2) Aqueous solvents (water) are reversed
· Radiodetector phase HPLC
3) Silica gel is? Stationary phase.
Parameter that affects resolution.
· Mobile phase. Nature of solvent should be compatible
with substance.
· Solubility’s of mixture in mobile phase.
· Concentration of mixture substance.
· Stationary phase, thickness of silica gel, column size and pressure in HPLC.
· Temperature (gas and column chromatography).
· pH of solvent and flow rate.
· Detectors does NOT enhance resolution of separation of mixtures.
Gas Chromatography (GC): The gAS CHROMATOGRAPHY IS A CHROMATOGRAPHIC TECHNIQUE THAT CAN BE
USED TO SEPARATE VOLATILE ORGANIC COMPOUNDS. EXAMPLE VOLATILE LIQUIDS, OILS AND ALCOHOLS ETC.
Mechanism. The organic compounds are separated due to differences in their partitioning behaviour between
the mobile gas phase and the stationary phase in the column.
GLC (Gas Liquid Chromatography)

· Mobile phase is gas for example, helium, argon, or nitrogen
· Stationary phase is liquid surface on solid
GSC (gas solid chromatography)

· Mobile phase: gas for example helium, argon, or nitrogen
· Stationary Phase (solid)

· Used: For volatile and thermally stable compounds
Components of gas chromatography; Gas chromatography columns known as capillary columns, Oven, Detector,
and Recorders
Types of detectors in GC.

· TCDàThermal conductivity Detectors
· FIDàFlame ion detectors
· ECDàElectron conductivity detectors.
Thin Layer Chromatography (TLC)

· A simple and rapid method to monitor the extent of a reaction or to check the purity of organic compounds.
The mobile phase is a solvent and the stationary phase is a solid adsorbent on a flat support.
· Mechanism: Relies on capillary action
TLC Spray Reagent

· Ninhydrin is used for detection of amino acids, amines, and aminosugars.
· Ehrlich's reagent is dimethyl aminobenzaldehyde/hydrochloric acid reagent for detection of amines, indole
derivatives.
Paper Chromatography
· Stationary phase. The stationary phase is cellulose paper (paper is made from cotton fibres and highly
purified about 90% alpha cellulose).
· Properties of stationary phase: Highly hydroxylated polysaccharide, this has great affinity for water and
other polar solvents.
· The tightly bound water is actual stationary phase and as mobile phase passes over the surface of paper.
· Mobile phase: The solvents used for paper chromatography analysis are similar to those employed in other
forms of chromatography.
Spectroscopic Methods of Analysis

Spectroscopic methods: Instrumental methods that are used to identify chemical structure and analysis of drugs.
The following instrumental techniques are commonly used in drug analysis and structure determination of new
and unknown chemical structures.
Spectroscopic Methods
Mass spectroscopy Ultraviolet light Nuclear Magnetic Other spectroscopy

(MS) spectroscopy Resonance Infrared (IR)
(UV/Vis) (NMR) Atomic Absorption (AA)
Mass Spectroscopy (MS):

Mechanism. The basics mass spectrometry is that a charged particle passing through a magnetic field is
deflected along a circular path on a radius that is proportional to the mass to charge ratio, and m/e. (Electronic
ionization method).
General Diagram of a mass spectrometer

Collection &
recorder
electron beam
Radius of curvative
Neutral ionized mixed ion beam

Gas Molecules molecules
separated
magnetic field ion beam
Sample Vaporized
Inlet Inlet Mass Ion

System Source Analyze Collection
System
Vacuum Data
System Handling
System
Used in structural determination of unknown chemical structures. Detect molecular weight of substance.
Advantage. This can detect trace amount of substances.
· Blood sample analysis (drugs or alcohol in blood) à GC-MS
· Pharmacokinetics analysis of drug samples.
· Detection of environmental samplesàGC-MS
· Probably the most useful information you should be able to obtain from a MS spectrum is the molecular
weight of the sample.
· Used in detection and analysis of unknown chemical structures molecular weight of substances or drugs.
Type of detectors in mass spectroscopy

· CI-MS; Chemical Ionization mass spectroscopy
· FAB-MS. Fast atomic bombardment mass spectroscopy
Question Alerts!
1) What is used to determine molecular weight?
2) What spectrometer is used to determine number of hydrogen carbons and functional groups by
resonating nucleus or spinning technique?
3) What spectroscopic method shows pharmacophores?
4) What spectroscopic method is used to identify enantiomers?
5) What spectroscopic methods breakdown chemical structure?
· EI-MS. Electron impact mass spectroscopy.
Ultra Violet/Visible light spectrophotometer: Question Alerts!

· Wavelengths (l) 190 and 800 nm Bathochromic shift is?
· Ultraviolet radiation <400 nm
· Visible light 400 to 700 nm
· Chromophore any group of atoms that absorbs light whether or not a color is thereby produced.
· Auxochrome: A group, which extends the conjugation of a chromophore by sharing of nonbonding
electrons.
· Bathochromic shift (Red shift): The shift of absorption to a longer wavelength.
· Hypsochromic shift. The shift of absorption to a shorter wavelength.
· Hyperchromic effect. An increase in absorption intensity.
· Hypochromic effect. A decrease in absorption intensity.
Processes or equipment radiation

· Welding arcs àUV, visible, and IR
· Lasersà UV, visible, and IR
· Bactericidal lamps in ultra pure water systemàUV
· Radiant heat sources; boilers, IR lampsàIR
Infrared spectrophotometer
· Infrared à >700 nm
· Infrared light lies between the visible and microwave portions of the electromagnetic spectrum.
· Infrared light has a range of wavelengths, just like visible light has wavelengths that range from red light to
violet.
Atomic-absorption spectroscopy
Atomic-absorption (AA) spectroscopy uses the absorption of light to measure the concentration of gas-phase
atoms. The analyte concentration is determined from the amount of absorption.
The Beer-Lambert law

· The Beer-Lambert law (or Beer's law) is the linear relationship between absorbance and
concentration of an absorbing species.
· A = a (l) * b * c
Where
· A is the measured absorbance
· a (l) is a wavelength-dependent absorptive coefficient
· b is the path length
· c is the analyte concentration.
Nuclear Magnetic Resonance Spectroscopy (NMR): NMR techniques are used to identify unknown chemical
structure.
Functional groups and isomers of structure can be determined by NMR.
Magnetic Resonance Imaging (MRI): MRI is used to scan tumours, minor blood clots etc.
CAT scan (computer assisted tomography).
Bio and Immunoassay Methods

Gel electrophoresis, ELISA, Western blot, and PCR.
Immunoassay are an assay (test) that detects antigens (Ag) or antibodies (Ab). Immunoassays described into
various types based on their different techniques such as radioimmunoassay, enzyme immunoassays etc. Radio
immunoassay are more sensitive assay (0.0001 to 0.001 µg/ml, 0.1 to 1 ng/ml). This makes it suitable for
measuring hapten size drugs and hormones in the blood, things you can't get in large concentrations needed for
precipitation or agglutination.
Enzyme Immunoassay (EIA) is a laboratory test that detects specific antigens or antibodies utilizing enzyme
tagged antigens or antibodies, and in the presence of a specific substrate, it produces a colour change that
indicates a positive reaction.
ELISA: The name stands for Enzyme- Linked Immunosorbent Assay (ELISA): It is a useful and powerful method in
estimating ng/ml to pg/ml antigens (Ag) or antibodies (Ab) in the solution, such as serum, urine and culture
supernatant. Used for diagnosing HIV viral infections.
Gel electrophoresis: It is a method that separates macromolecules either nucleic acids or proteins on the basis
of size, electric charge, and other physical properties.
1. Restriction enzyme cleave the DNA into smaller segments of various sizes.
2. DNA segments are loaded in to gel. This gel floats in buffer.
3. When apply electric current DNA fragments move toward the positive charge cathode.
4. Small segments move faster and farther than larger DNA segments.
Western blot Easter blot Northern blot Southern blot

Using antibodies For analysis of post For detection of RNA For detection DNA
separate mixture of translational proteins,
proteins. Lipids.
Blot consisting of a Blot consisting of a Blot consisting of a Blot consisting of a cellulose
cellulose derivative cellulose derivative that cellulose derivative that derivative that contains
that contains spots of contains spots of proteins contains spots of RNAs spots of DNAs for
antibodies for for identification by for identification by identification by suitable
identification by suitable molecular probe. suitable molecular probe. molecular probe.
suitable molecular
probe.
PAGE: Polyacrylamide gel electrophoresis system is used for protein and protein mixture separations.
PCR is Polymer chain reaction is used for magnifying DNA.
Question Alerts!
1) ELISA stands for? Enzyme Linked Immunosorbent Assay
2) Purpose for ELISA is? Diagnosis of HIV
3) Western blot is used for? Using antibodies detects proteins and nucleic acids
4) Eastern blot is used for? Analyze protein post translational modifications like lipids, phosphates, and
glycoconjugates.
5) PCR is? Polymerase chain reaction magnifies DNA utilizes. Taq polymerase and this produced by Thermos
aquaticas.
· Polymerase chain reaction (PCR) is utilizes heat stable DNA polymerase such Q Taq polymerase (this enzyme
is isolated from bacteria Q Thermus aquaticus).
· The Taq polymerase enzymatically assembles a new DNA building blocks using single stranded DNA
nucleotides as a template. It is also known as DNA primers.
· Polymerase chain reaction includes 3 major steps?
1) Denaturation at 94-96◦C
2) Annealing at -68 ◦C
3) Elongation at 72 ◦C
Bioassay use
PCR
Gel electrophoresis
Western blot
ELISA
Titration’s
Non-aqueous solvents. Acid base titration in non-aqueous solvents. Three types of solvents: Amphiprotic, non-
ionisable, and aprotic or inert.
Amphiprotic: Autoprotolysis produce both an acid and base species, or solvent dissociates such that it produces
cation and anion species. Example: H 2 O, methanol, ethanol and acetic acid
H 2 O à H+ + OH-
CH 3 OH à CH 3 O- + H+
Non-ionisable-with basic properties: No autoprotolysis, but solvent has a group that can react with acids. No
reaction bases. Only act to transport on pairs. E.g. pyridine, ethers, benzene, esters, ketenes, and aldehyde
Protic Upon reaction provides H+ ion. Example: Methanol, Acetic acid. Water etc.
Aprotic or inert There is no reaction with acids or bases, they simply provide medium in which the sample
species or titrant are soluble (only contribute solubility).
Example: CCl 4 (Carbon tetrachloride)
Levelling effect Regardless of the type of acid and basis, the actual acid strength is actually determined by the
strength of H 3 O+.
Equilibrium reactions
· At equilibrium hydrolytic reaction
· The rate of forward reaction is equal to backward reaction
· Example. In aproteolytic reaction of acetic acid with water, the rate of forward reaction increased as the
hydronium ions are depleted or when acetate ions are depleted
Gravimetric Analysis
The quantitative determination of a substance by precipitation followed by isolation and weighing of the
precipitate.
The basic method of gravimetric analysis

A weighed sample is dissolved after which an excess of a precipitating agent is added.
The precipitate which forms is filtered dried or ignited and weighed.
From the mass and known composition of the precipitate, the amount of the original ion can be determined.
Criteria for successful determinations

The desired substance must be completely precipitated. In most determinations the precipitate is of such low
solubility that losses from dissolution are negligible. An additional factor is the common ion effect; this further
reduces the solubility of the precipitate.
Example:
When Ag+ is precipitated out by addition of Cl- the (low) solubility of AgCl is reduced still further by the excess of
Cl-, which is added, pushing the equilibrium to the right.
Ag+ + Cl- =<-> AgCl (s)
Extraction Methods
Liquid/liquid
· Examples of liquid/liquid extraction methods are fractional distillation, which functions based on boiling
points of solvents
· Mixture of two volatile liquids can be separated using fractional distillation techniques
· Example: Ethanol in water, Hexanes in Chloroform
· Immiscible liquids: this mixture can be separated by using separating funnel.
· Example: Hexanes in water (Organic solvents in water)
Solid phase extraction (SPE)

· A solid sorbent material, typically an alkyl bonded silica, is packed into a cartridge or imbedded in a disk and
performs essentially the same function as the organic solvent in liquid-liquid extraction.
· Example,
· Reverse-phase SPE employed to extract non-polar compounds, pesticides for instance, from polar samples
such as water generally utilize a solid sorbent containing non-polar functional groups such as octadecyl (C 18 )
or octyl (C 8 ) bonded silicas.
Tips
1. to dry wet powders, 2. Electronic ionization (EI) results 3. purification and analysis of
which are heat in well-established pharmaceuticals
sensitive drugs fragmentation pattern that are
useful in identification of
unknown
4. Analysis and detection 5. protein separation 6. protein isolation
of volatile chemical in
samples
7. Enzyme linked 8. HPLC 9. UV, DAD, Fluorescent & RI
immunosorbent assay
10. Gas Chromatography 11. capillary action 12. amine, amino sugars and
proteins
13. Increase in solubility by 14. Decrease in solubility by addition 15. Detectors, printers
addition of salt of salt
16. Detection of HIV 17. Mass Spectroscopy
infection
· Pump is present in what type of chromatography? ( )
· Types of detectors used in HPLC? ( )
· Drugs present in blood samples can be detected by? ( )
· Salting in is? ( )
· Salting out is? ( )
· Mechanism of TLC is based on? ( )
· Ninhydrin is used to detect? ( )
· What are the factors that does not affect resolution in HPLC? ( )
· GC-MS is? ( )
· Lyophilization (freezing) is used for? ( )
· Electron impact (EI) ionization mass spectroscopy is? ( )
· HPLC is used for? ( )
· ELISA is? ( )
· ELISA is used for? ( )
· Western blot test for? ( )
· Gel electrophoresis separates? ( )
www.Pharmacyprep.com Canadian Healthcare System
40
The Canadian HealthCare
System
Questions Alerts!
· Role of governments in healthcare (Health Care system components)
· Canadian Health Act (CHA) five principles: Comprehensiveness, Universality, Portability, Public
administration and Accessibility.
· Drug Benefit Programs. Federal drug benefit programs and provincial drug benefit programs.
· Federal drug benefit programs covers natives, veterans, inmates, refugees and RCMP.
· Provincial drug benefit programs covers seniors over 65 yo, and social welfare recipients.
· Financial support for healthcare in Canada. Federal, and provincial taxes.
This chapter provides information about Canadian healthcare system; explore key concepts around health care
delivery system and health care professionals. This chapter is focus on Canadian health act (CHA), the role of
federal, provincial, & territorial government in health care.
FEDERAL PROVINCIAL MUNICIPALITIES

Making federal law (e.g. CDSA, office of Provincial HealthCare Police/Fire/
control substance) F&DA, marijuana for Administration (Medicare) Roads/Parks/ Libraries etc
medical purpose use) and bill. Education District health officer
International affairs Flu vaccination BY-LAWS
Canadian safety. Physician salaries
Decentralized
Federal Health Portfolio. administration healthcare
1.Health Canada (Drug Approvals in system
Canada DIN; NPN; DIN-HN; PIN)
2.Public health Agency (PHA)
3. Canadian Institute of Health
Information. (CIHI).
4. Patented Medicine Price Review Board
(PMPRB)
5. Canadian Food safety agency
Royal Canadian Mounted Police (RCMP) Provincial police City/regional
Drug trafficking & CDSA

Health Canada determines the DIDFA: Drug
manufacturing conditions of drugs.(GMP) Interchangeability
Dispensing Fee Act.
Primary care: This is first contact a person makes a with the system when a person feels the necessity of health
care. This usually occurs through the family physician, pharmacist, or nurse at medical centers.
Secondary care. This is specialized service from a specialist. This requires referral from primary health care
levels.
Tertiary care. This is specialized in diagnosing and highly technical care and treating complicated or unusual
health problems. This generally takes place in hospital setting where generally diagnostic and complicated
therapies can take place.
Health care system components:

Health care team members: Physician, pharmacist, nurses, dentist, physiotherapist etc.
Physician agencies: CMA, Royal College,

Pharmacy agencies: NAPRA, provincial college of pharmacy, Canadian Hospital Pharmacy Society, Canadian
Pharmacy Association.
Primary Care; Family health care; Community Health Centres; Hospitals; Public Health Care Systems.
Health Canada is a federal agency: it is responsible for drug quality, safety and efficacy
The Health Protection Branch (HPB) or The Health protection Food Branch Inspectorate (HPFBI) of Health
Canada regulates drugs imported into and manufactured for sale in Canada.
The Canadian health care system

The Canadian health care system is universal health care (Medicare: Essential healthcare services are insured by
the government to all Canadian), this mean that all citizens and immigrants will have access to health care
regardless of their ability to pay. All Canadian are insured on equality basis and offered health in all ten
provinces and three territories.
Canadian health act (CHA): Canada health act (1984) unanimously passed in parliament, with adherence to the 5
principles, enforced by threat of withholding funds. Extra billing is banned as a restriction on access.
Canadian health act five principles Question Alerts!

· Universality Five principles of the CHA!
· Public administration
· Portability
· Accessibility
· Comprehensiveness
Universalityà All insured parties are entitled to equal access to essential services.
Public administrationà Healthcare insurance is to be administered on a non-profit basis by a public authority

responsible to the province and subject to audit. The Canadian healthcare delivery is decentralized and offered
for provincial delivery of care.
Comprehensiveness à The insurance must cover all insured services supplied by hospitals, medical practitioners
and “essential services” dentists. Each province determines which services are insured. Funded health care
services are NOT provided equally across the Country. (Decentralized healthcare system).
Portability à A series of obligations on provinces which essentially guarantee any Canadian resident (after a
maximum wait of three months upon first becoming a resident) access anywhere in Canada on the same basis as
local residents.
Accessibility à Charges or other obstacles must not impede access to insured services.
The CHA covers

· Medically necessary hospital services.
· Medically required physician’s services.
· Medically or dentally required surgical-dental services requiring a hospital for proper performance.
· The coverage reflects the two-stage evolution of public health care insurance in Canada. The 1959. Hospital
Insurance and Diagnostic Services Act and the 1966 Medicare Act respectively brought hospital and medical
insurance to the federal level.
CHA does not cover

The following services are not covered under the CHA. Services delivered by health-care professionals other
than doctors, particularly outside of hospitals (some provinces do cover some of these services, but are not
obligated to do so under the CHA). Services in sectors outside the hospital. These include long-term care
facilities and home care. Pharmaceuticals, rehabilitation services and dental care are also not covered
when provided outside of hospitals.
Drug benefit program: Provincial drug benefit programs and Federal drug benefit programs.
Provincial Drug Benefit Programs covers: People age over 65-year-old and Social Assistance (welfare),
disabilities and long-term illness.
Federal Drug Benefit Programs covers

· Natives or aboriginals (covered by NIHB)
· Inmates
· Refugees
· Veterans
· Royal Canadian Mounted Police (RCMP)
Canadian are likely to hold private health insurance.
Non-insured health benefit (NIHB) programs:
The role of federal government in health care. The federal government sets and administers national principles
of healthcare system through Canada health act. Federal government gives funds to provincial and territorial
health care services through fiscal transfers.
Delivers health care services to specific groups e.g. first nations (aboriginal), Inuit’s. Canadian forces and
veterans, refugee claimants and penitentiary inmates, and RCMP. Provides other health related functions such
as public health/health promotion programs and health research.
Role of provincial and territorial health care as CHA principle is public administration this means the
administration and delivery of health care services is the responsibility of each province and territory. Provinces
and territories fund health services with assistance from the federal government in the form of transfer
payments and some times equalization payments.
Some examples of essential services that offered by provinces and territories are Physicians, diagnosis, and
other health care services in primary clinics and emergency services in hospitals.
Drugs coverage plans for specific groups, such as seniors, and social assistance. Some provinces have
supplementary health benefits.
Federal Health Portfolio

The Minister of Health is responsible for maintaining and improving the health of Canadians. This is supported
by the Health Portfolio which comprises;
· Health Canada
· Public health agency of Canada
· Canadian Institute of health research
· The Patented Medicine Prices Review Board
· Canadian Food Inspection Agency
Public health Agency of Canada

Health promotion and disease prevention. Health promotion is the process of enabling people to increase
control over and improve their health. Disease prevention focuses on efforts to avoid disease and injury.
CIHI: gather and provide health information to the federal and provincial agencies.
PMPRB: Determines the prices of brand or patented medicines in Canada.
Canadian Food Inspection Agency (CFIA): monitored food safety across Canada.
Provincial plans
Some examples of the disease prevention include smoking cessation programs, breast cancer screening
(mammogram), Pap smear screening, prostate specific antigens (PSA) colonoscopy and colorectal cancer
screening.
Cost of Health Care system:

Health care financing: Provincial, Federal, health premium and charities.
Distribution of health Expenditure in Canada %

Hospital 29.9%
Other institutions 9.9%
Physician salaries 12.8%
Other professionals 10.7%
Drugs (Rx and OTC) 17.5%
Other health spending 6.1%
Public health 5.5%

Capital 4.2%
Administration 4.1%
Canadian health human resources 2010

Total physicians in Canada ~80,000 The third highest public sector expenditure
Total registered nurses in Canada ~240,000
Dentist/dental hygienist 45,554 The highest private section expenditure
Pharmacist 42,000
Optometrists 4,841
Source National Health Expenditure Database, Canadian Institute for Health Information
Tips
1. Pharmaceuticals 2. Non essential services 3. Federal
4. Provincial or territories 5. Comprehensiveness 6. Universality
7. Portability 8. Public administration 9. Accessibility
10 Natives or aboriginals 11 Inmates 12 Refugees
13 Veterans 14 RCMP
· What are the five Canadian health act principles? ( )

· Federal Drug Benefit Program covers ( )
· What is not covered in CHA? ( )
· Funding for healthcare system is paid by? ( )
www.pharmacyprep.com Canadian Pharmacy Regulations
41
Pharmacy Regulations
Questions Alerts!
· National Drug Model or Harmonized Drug Model. NAPRA categorized drugs into Schedule I, II,
III and unscheduled drug.
· Food and Drug Act (F&DA) and Control Drug Substance Act (CDSA) regulates narcotics,
benzodiazepine & targeted substance, and control substances.
· Narcotics are categorized as straight narcotics (single opioids), narcotic preps (1+1+1)-
(verbal), and exempted narcotics (1+1+1).
· Benzodiazepine and targeted substances like all benzodiazepine
· Control substances have 3 parts. The part 1. CNS stimulants part 2. Barbiturates part 3:
anabolic steroids.
Canadian Federal Regulations
Control Drugs Food and Drug Act National Association of Tips

and Substance (F&DA) pharmacy regulatory
Act (CDSA) authority (NAPRA)
Narcotics, BZDs, Manufacturing Pharmacy professional
Control drugs, conditions and standards sales. Set
sales, Rx and prescription drug standards of professional
disposing. advertising. qualifications and
competencies.
Schedule I Schedule A
Schedule II Schedule B
Schedule III Schedule C
Schedule IV Schedule D
Schedule V Schedule E
Schedule VI Schedule F part 1 Schedule 1 (require Schedule F part1.
prescription) Prescription drug
Schedule F Part 2 advertisement standards
FDA part 2. Veterinary drug
Schedule VII Schedule G
Schedule VIII Schedule H

Schedule 2 (behind the Behind the counter (BTC),
counter) dispensed by under the counter. INSIDE
pharmacist without PHARMACY AREA.
prescription
Schedule 3: OTC Over the counter (OTC) or
self-selection area or 10-
meter rule
Unscheduled Corner store
Federal regulations
Three federal regulations are F&DA, CDSA, and NAPRA applies to pharmaceuticals in Canada.
Food and Drug Act (F&DA). This federal legislation controls the manufacture of all drugs in Canada. Also, the act
controls manufacturing conditions, packaging, advertising standards and the sale of foods, drugs, cosmetics and
therapeutic devices. As with all the laws in Canada, the law exists to protect the consumer or the public. Drugs
regulated by the F&DA are grouped into A to H schedules.
· Schedule A. Disease which treatment may not permit to public.
· Schedule B. Describe official standard.
· Schedule C. Radiopharmaceuticals. Drugs other than radionuclides for use in preparation of
radiopharmaceuticals.
· Schedule D. Allergic substances, vaccine, blood and blood derivatives.
· Schedule F: Food and
prescription drugs. Question Alerts!
Advertisement standards. Schedule F have all prescription drugs that are present in
NAPRA schedule 1
· Schedule G. Controlled drugs
Schedule F have prescription drug advertisement
· Schedule H. Restricted drugs
standards.
The Controlled Drugs and
Substances Act (CDSA): The Controlled Drugs and Substances Act, 1997, is an act sets standards for the control
of narcotics, controlled drugs and targeted substances (benzodiazepines). It is a federal act and the strictest of
all the acts that govern the pharmacy industry. The CDSA is administered by office of control substance.
Drugs regulated by the CDSA are grouped into 8 schedules.

· Schedule I. Narcotics, opium poppy, cocaine, phenylpiperidine (pthedine)
· Schedule II. Cannabis and cannabis preparations
· Schedule III. Amphetamines, methylphenidate, LSD plus other listed psychoactive substances.
· Schedule IV. Barbiturates, specific anorexiants, benzodiazepines, and anabolic steroids.
· Schedule V. Phenylpropanolamine and others
· Schedule VI. Ephedrine, ergotamine, pseudoephedrine and others.
· Schedule VII. Cannabis that serves enforcement purposes regarding possession and trafficking.
· Schedule VIII. Cannabis that serves enforcement purposes regarding possession and trafficking
Narcotics regulations have categorized as straight narcotics, narcotic prep, and exempted narcotics.
Straight narcotics: Opioids like morphine, codeine, hydromorphone, oxycodone, methadone, fentanyl,
Suboxone, OxyNeo, meperidine, buprenorphine, Tylenol # 4 (acetaminophen 300 mg + codeine 60 mg),
ketamine, pentazocine, nabilone etc.
· Given by written Rx only.
· No repeats
· No Rx transfers
· Sales report require
· Rx hard copies for stored 2 yrs (digital for minimum 7 yr)
Narcotic preparations or verbal narcotics (1+1+1): opioid + 2 non-opioid. Tylenol # 2, (acetaminophen 300 mg+
codeine 15 mg + caffeine 15 mg). Tylenol # 3 (acetaminophen 300 mg + codeine 30 mg + caffeine 15 mg),
Fiorinal c 1/4 (butalbital + ASA+ codeine 15 mg) Fiorinal C1/2 (butalbital + ASA+ codeine 30 mg)
· Given by verbal or phone
· No Repeats or NO refills
· No Rx transfers
· Rx hard copies store for 2 yrs
Exempted narcotics or OTC narcotics: (1+1+1): Opioid (<8 mg) + non-opioid + non opioid
Tylenol # 1 (acetaminophen 300 mg + codeine 8 mg + caffeine 15 mg) (codeine 19.6 mg/30 mL).
No Rx needed
Dispensed by pharmacist only
Benzodiazepines and Targeted substance: All

benzodiazepines are included. Can be Question Alerts!
unlimited refills. One transfer is allowed. 1) Benzodiazepine prescription expires in 1 year.
Prescription expires in one year. 2) Benzodiazepine early refills what to do?
Can be verbal or phone

Can be Rx. transferred once only
Can have unlimited refills
Rx expires in a year.
Control drugs: The drugs are categorized as control drug part 1 to 3.

· Part 1: CNS stimulants like amphetamines, dexamphetamine, and methylphenidate require sales report.
· Can be given verbally
· Repeats are allowed (Refills are allowed with specified intervals).
· No Rx transfers
· Need to keep sales report
· Part 2. Barbiturates (Phenobarbital, thiopental, primedone), Fiorinal (butalbital+ ASA+ caffeine)

· Repeats are allowed
· No Rx transfers
· Part 3. Androgens (anabolic steroids performance enhancing drugs), Androgel

· Repeats are allowed
· No Rx transfers
Rx REPEATS TRANSFERS SALES Tips

REPORTS
Straight Written only No NO Yes 2 yrs
Narcotics
Narcotics preps Written or verbal No NO No
(verbal)
Exempted None None NO No Schedule 2
Benzodiazepine Written or verbal unlimited 1 time only NO Rx expired in 1 yrs
Control drug 1 Written or verbal Yes (need NO YES
interval
timing)
Control drug 2 Written or verbal Yes No No
Control drug 3 Written or verbal Yes NO NO
STRAIGT NARCOTICS RX
Dr. Name Dr. Name
Drs. CPSO Drs. CPSO
PATIENT NAME: PATIENT NAME:
PATIENT ID: PATIENT ID:
DRUG NAME
SIG HYDROMORPHONE 20 MG Q6H PRN
DRUG QUANTITIY MITTE: 40 TAB
MITTE:
REPEATS: 0 REPEATS: 0
DR. INITIALS
CONTROL DRUG PART 1

Dr. Name
PATIENT NAME:
METHYLPHENIDATE 20 MG
DRUG NAME GIVE DAILY ONE TAB IN THE MORNING
SIG MITTE: 30 TAB
DRUG QUANTITIY
MITTE: REPEATS: 3 EVERY 30 DAYS
REPEATS:
DR. INITIALS
National Association of Pharmacy Regulatory Authorities (NAPRA) or the Harmonized

National Drug Model: The National Association of Pharmacy Regulatory Authorities (NAPRA) is an association
comprised of mainly the provincial regulatory authorities (the registrars of each province that has a college of
pharmacy that licenses and regulates its member pharmacists). NAPRA is incorporated under the Canada
corporation act as a voluntary, not for profit associations.
Mission of NAPRA is to evaluate the activities of the Question Alerts!
pharmacy regulatory activities by representing the NAPRA regulates pharmacy profession
common interests of the member of organizations. in Canada
Serving as a national resource centre and promoting the
national implementation of progressive regulatory programs and standards.
All provinces have similar conditions of sale.
· Schedule Ià Require prescription.
· Schedule IIà Pharmacist intervention à behind the counter or under the counter (recommended by
pharmacist).
· Schedule III à Pharmacist intervention à over the counter, self-selection or 5 to 10 m rule. Lock and
leave.
· Schedule U à Unscheduled Drugs à can be sold from any corner store.
Schedule I
The Highest risk, these drugs require a prescription for sale and are provided to the public by a pharmacist in a
pharmacy. Most drugs in schedule F (FDA) and some drugs that were listed under Schedule E. Some drugs are
listed in Schedule I of the NAPRA schedules, but are not listed under Schedule F, The Food and Drugs Act
Regulations.
Schedule II
Prescription is NOT required. Requires professional intervention from the pharmacist and possible referral to a
physician. Need direct pharmacist supervision. The decision to sell a schedule II product must be made by the
pharmacist. (e.g., injectable epinephrine for anaphylactic reactions).
The drugs are retained in a non-patient access area (behind the counter) no opportunity for patient self-
selection and have no public access to the public.
Example of schedule II drugs:

· Tylenol # 1 (Codeine 8 mg + Acetaminophen 300 mg + caffeine 15mg)
· Nitroglycerin SL
· Regular Insulin
· Epipen
· All Vaccines
· Iron supplement (>30 mg)
· Lactulose
· Vitamin D 3 drops
· Vitamin B 12 inj.
Schedule III: Over the counter

· The lowest risk however, may present risks to certain populations.
· Prescription is not required. Need direct pharmacist supervision.
· These drugs may be stored in a self-selection area of the pharmacy
· The pharmacist should be accessible, and approachable to assist the patient in making an appropriate self-
medication selection or to refer physician.
· Example. Plan B. Emergency contraception, bacitracin and its salts for ophthalmic
Unscheduled Drugs
· May be sold from any corner store.
· Labelling is considered sufficient to ensure safety of drug.
· No pharmacy knowledge required.
Example: Bacitracin and its salts for topical use
Pharmacy related professional associations in Canada

· Canadian Pharmacist Association (CPhA) (www.pharmacists.ca)
· Voluntary national association.
· Identify, respond to emerging issues of importance to the profession, assisting and acquiring new
technologies and using information.
· Create educational and professional development tools.
· CPhA publications include:

· Canadian Pharmacy Journal (CPJ)
· Compendium of Pharmaceutical Specialties (CPS)
· Therapeutic choices (TC)
· Patient selfcare (PSC) or Therapeutic Choice for Minor Ailments.
· Compendium of patient self-care products (CPSP)
· E-therapeutics
Canadian Society of Hospital Pharmacist (CSHP)

· Voluntary national association.
· Develop continuing education programs, residency training programs.
Tips
Find answers from the table.
1 Institute of Safe Medication 2 NAPRA 3 CPhA
Practices Canada (ISMP)
4 Narcotics 5 Benzodiazepine & Targeted 6 Control Substances
Substance
· National Association of Pharmacy Regulatory Authority ( )

· Examples of pharmacy associations, where pharmacist can be a member? ( )
· Examples of medication incident reporting systems in Canada? ( )
· Who regulates pharmacy profession in Canada? à
· Who regulates pharmacist and its members in Canada? à
· Morphine, codeine, meperidine are regulated under ( )
· Lorazepam, and Diazepam are regulated under ( )
· Methylphenidate and amphetamine are regulated under ( )
www.Pharmacyprep.com Social, Behavioral and Administrative Sciences
42
Social, Behavioral, Economics
Aspects of Pharmacy Profession
Questions Alerts!
· Professional Misconducts
· Pharmacist should always think as professionals
· What factors that effects on patient compliance on medication therapy? Patient
behavior on medication compliance
While pharmacists are still responsible for managing the overall pharmacy environment and overseeing
dispensing, they now focus more on reviewing prescriptions for therapeutic appropriateness, performing
medication reconciliation and medication reviews, developing care plans and monitoring patients. The care plan
is often focused on taking steps to resolve or prevent drug-related or health-related problems. Depending on
the province or territory, the pharmacist may accomplish this by performing expanded scope activities such as
adaptation of prescriptions, prescribing for minor ailments, ordering and/or interpreting laboratory tests and
administering drugs, including injections for immunization or other purposes.
Although the scope of practice can be slightly different in different provinces and territories, pharmacists must
always assume responsibility for their own actions, be accountable to the public and manage the overall
functioning of the pharmacy to ensure a safe and healthy environment.
Pharmacy technicians recently became a regulated profession in some Canadian provinces. The other provinces
and territories are also moving towards the regulation of pharmacy technicians.
Along with regulation, pharmacy technicians have been given an expanded scope of practice that allows them to
more effectively assist pharmacists so that the pharmacist can take on more clinical, patient-focused services.
The scope of practice of pharmacy technicians can be slightly different in different provinces.
The pharmacy technician may gather patient information for the pharmacist to review; order, receive and
manage inventory, perform computer order entry and prepare products including compounding, counting,
measuring and labelling. Depending on the province or territory, they may also perform expanded scope
activities such as medical device demonstrations, transcribing verbal orders, transferring prescriptions, checking
the technical aspects of a prescription and releasing the final product.
Regulated pharmacy technicians assume responsibility for their own actions, are accountable to the public and
contribute to the overall functioning of the pharmacy to ensure a safe and healthy environment.
Pharmacy technicians do not currently exist in Québec.
Pharmacy assistants are other members of the pharmacy team who help support pharmacy technicians and
pharmacists.
They can perform certain tasks assigned to them by the pharmacy technician or pharmacist, but always do so
under the direct supervision of the pharmacy technician or pharmacist. These may include tasks such as filing of
pharmacy records, replenishing supplies and putting away drug orders. This may also include more advanced
tasks such as computer order entry, counting, packaging, labelling and sometimes compounding of products if
the pharmacist or pharmacy technician supervising them assigns them these tasks and verifies their work.
Pharmacy assistants cannot transfer prescriptions, take verbal orders, check prescriptions or release products.
Professionalism is described as the competence and skill expected and required of a professional. Professions
have a formal knowledge base that is continually upgraded and practitioners usually require a long period of
preparation and hands on training before they become independent practitioners. To become professional a
candidate must meet certain educational standards, usually these set by regulatory bodies.
Professions are committed to the public through their code of ethics: Healthcare professions are constantly
changed with latest developmental technologies, identification of new diseases & treatments consequently
there is emphasis on adopt to change and meet the rising expectations.
· Personal attributes of professionals

· Practice ethics and high moral standards
· Reflection and self-awareness.
· Responsibility and accountability of actions.
· Cooperative attributes of professionals

· Respect for patients.
· Working as team.
· Taking social responsibility.
A report on professionalism in medicine, the CMA (2001) states that, professionalism is:
· A strong commitment to the well being of others.
· High moral, ethical, integrity standards.
· Mastery of body of knowledge and skills and continue education, or lifelong learning.
· A high degree of autonomy.
LAW ETHICS OR CONDUCT

BREAKING LAW CAUSE ILLEGAL AND HAS BREAKING ETHICS CAUSE MISCONDUCT.
CONSEQUENCE.
TAKEN CARE BY LAW ENFORCEMENT REGULATED AGENCY DISCIPLINE MISCONDUCT
Scope of pharmacist and pharmacy technician

Pharmacist (R.Ph) Regulated Pharmacy technician (R.PhT) ASSISTANT
Patient care and therapeutic drug Solving technical problems (Rx receiving, Same as tech
related problem data entry, preparing, labelling, packaging
and dispensing, insurance codes for
billing).
Counseling No
Recommending therapies No
Resolving DTPs (Drug interactions, side No
effects, therapy monitoring)
Assessing and recommending therapies No
for minor ailments
Liability insurance Liability insurance NO LIABILITY
Narcotics ordering NO, pharmacist can delegate for inventory
count.
Receiving verbal narcotic (CDSA) Rx NO
Receiving verbal Rx orders Yes NO
Independent compounding of sterile Yes
and non-sterile products.
Schedule II recommendations NO NO
Demonstrating medical devices Yes only for OTC devices (blood glucose NO
monitor, blood pressure monitor, inhaler,
aero chambers, peak flow meter, Epipen,
thermometers, and pregnancy test kit.
Immunization NO NO
EXPANDED SCOPE (PROVINCIAL)
ADAPTATION NO
IMMUNIZATIONS NO
ORDERING LAB TEST NO
PHARMACEUTICAL OPINION NO
ADVANCING NO
Professional boundaries:
Professional boundaries are the defining lines that separate the professional relationship from any other
behavior. The professional relationship is a purposeful relationship in which the client’s healthcare needs are
priority. There are warning signs, which can prompt professional. It is health professional responsibility identifies
and deals with boundary of violations if they arise.
Patient and pharmacist relation is COVENENT. (Trust worthy, privacy, confidential and integrity).
· Some warning signs that professional boundaries are being crossed are:
· Noticing sexual content in interactions with the client.
· Favouring one client’s care at the expense of another’s.
· Giving/receiving gifts or continued or continued contact after discharge.
· Acting and or feeling possessive about the client. Giving special attention, treatment to this client, which
differs from that given to other clients.
· Denying the fact that you have crossed the boundaries from professional relationship to non-professional
relationship.
Reporting requirements. Reporting wrong behavior of healthcare professional protect public and reputation of
healthcare system. Each regulatory body have set different requirement for reporting by the members of the
profession.
Professional expectations: Public expect professional to offer activities with responsibilities and the best care.
Here are some situations you may be expected to report:

· Sexual abuse of patients
· Misconduct, incapacity, incompetence
· Unsafe practice
Reporting requirement about abused patients: Sexually abused adult patient, pharmacist should report or give
contact number of support groups or support agencies to patient.
Reporting requirement about sexually abused child. Contact child associate society (CAS).
Patients centred care values:

· Respect. Respecting patients, wishes, concerns and strength
· Human dignity. Caring for patients as whole or unique
· Experts. Patient are experts of their own lives
· Timelines. Needs deserve a prompt response Prescription scope of practice of some healthcare
professions
Regulated health professions in Canada · Pharmacist
· Pharmacist · Physicians
· Physician · Veterinarians
· Physiotherapist · Dentists
· Chiropractor (spine) · Nurse practitioners (NOT registered nurse, or
· Respiratory therapist registered practical nurse)
· Podiatrist (Chiropodist) or Foot doctor · Midwife
· Registered Massage Therapist (RMT) · Optometrist
· Optometrist Question Alerts!
· Midwife · Who can prescribe narcotics?
· Veterinarian · Doctor, Dentist, veterinarians, midwife, podiatrist,
· Dentist and nurse practitioner.
Pharmaceutical care delivery system

· The major pharmaceutical care activities take place in the following systems
· Community pharmacy
· Hospital pharmacy
· Long term care facilities
· Specialty hospital units
Community Pharmacies
· Community pharmacies are considered one of the important components of the pharmaceutical care
delivery system. However, health related services are primarily limited to dispensing medications and
patient counselling.
· They can be subdivided into three categories:

1. Chain-retail pharmacy services,
2. Individually owned pharmacy
3. Internet pharmacies (mail order pharmacies)
· Retail pharmacy and individually owned pharmacies work in a similar fashion. However, mail order
pharmacy service is a little bit different in aspect of retail pharmacy. The latter lacks face-to-face patient
counselling and OTC services.
Health Belief Model (HBM)

· It was first proposed by Rodenstock and later modified by Becker. According to this model, the authors have
hypothesized that people generally do not engage in preventive healthcare practices or participate in health
detection and screening programs unless they view themselves vulnerable and/or have certain kinds of
health relevant problems.
· There are three categories of behavior related to healthcare, these include:
1. Health behavior
2. Illness behavior
3. Sick-role behavior
Health behavior: It is defined as any activity undertaken by an individual who believes himself or herself to be
healthy, for the purpose of preventing illness.
· Weight reduction screening program
· Exercise program
· Stress reduction
· Regular self-examination for breast or testicular cancer
· Change in diet to reduce fat or cholesterol consumption
Illness behavior: It is defining as any activity undertaken by an individual who believes he/she may be ill.
· Discussing health problems with a family member, friend or pharmacist
· Making an appointment to see physician
· Self testing to determine blood pressure or blood sugar level
· Experimenting with OTC products
Sick-role behavior: It is defined as an activity undertaken by an individual who considers them to be ill or who
have been diagnosed by a health professional as being ill.
· Following medical advice
· Taking medication as prescribed
· Selecting an appropriate OTC product
· Staying home from work or school
Tips____________________________________________________________________________
· The transtheoretical model of behavior change is starts with precontemplation & ends up with termination.
· Health behavior is defined as any activity undertaken by an individual who believes himself or herself to be
healthy, for the purpose of preventing illness.
· Professionalism is described as the competence and skill expected and required of a professional.
PharmacyPrep.Com Pharmacy Management
43
Pharmacy Management
Questions Alerts!
· Types of pharmacy ownership and formats of pharmacy
· Financial statements like income statement and balance sheet
· Human resources management and delegation
· Inventory management (calculating turnover rate)
Pharmacy management in the community pharmacy

Pharmacy management in retail stores comprises several business issues, those discussed include: terminology
commonly used in pharmacy business. Starting and managing pharmacy business, financial management,
human resource management, and merchandise & inventory management.
Starting and managing a pharmacy business

Starting any business requires clear understanding and knowledge of the business. However, it is clear that lay
people start pharmacy business. Like any other business, starting pharmacy business requires; business plan,
organizing, staffing, and budgeting.
Business plan:
Business plan comprises: Business structure, Market area analysis, Business products and services, Competitive
strategy, Positioning, Financing, Human resources, Operation and monitoring of performance.
Types of business ownership

Sole proprietorship
· Advantage. Sole owner, low start up cost
· Disadvantage. Unlimited liabilities
Partnership
· Advantage. Skills and knowledge can be shared Question Alerts!
· Disadvantage. Rate of conflicts is high. What type of pharmacy business structure is easy
to start?
Corporations and Limited Liability Companies (Inc). The
most common business form, business name often ends with “Inc”.
· Advantage: Legal entity, several directors (several owners), and limited liabilities.
· Disadvantage: Higher government involvement.
FORMATS OF PHARMACY
CARPORATE FRANCHISE BANNER INDEPENDENT
LABLAW (DRUG SHOPPERS DRUG IDA, PHARMASAVE, MY PHARMACY
STORE), Rexall MART (associates) GUARDIAN, Remedy
Rx,
WAL-MART London Drugs, Gives ownership
No initial capital No initial investment Yes, need initial capital Yes, need initial
investment investment capital investment
Fixed salaries for Fixed salaries + No fixed salaries No fixed salaries,
Manager bonus (PROFIT You pay royalties to and no royalties
SHARING) banners
Franchises: Associate franchises

Associate have fixed term and payment plan from franchise corporations.
· Owner of specific franchise location
· Fixed and secure salary
· Additional bonus or commission on performance.
· No capital investment (do not own physical assets)
· Central distribution
Banner: own locations and pay franchises fee or commission to corporations.

· Capital investment require because you own physical assets.
· No fixed salary.
· Franchising company provide name and marketing.
· No central purchase require.
Associate franchise Banner

No capital investment Capital investment
Central distribution No central distribution
Example: Shopper drug mart Example: IDA
TYPES OF PHARMACY OWNERSHIP STRUCTURES INCLUDE Retail pharmacy, Banner pharmacy, Chain pharmacy,
Franchise pharmacy, Food store pharmacy, Mass merchandise, Specialty pharmacy, mail order pharmacy and
central fill facilities (in hospital).
BUSINESS LOCATION ANALYSIS.

Methods applied in locating community pharmacy decision Question Alerts!
focused on. What is the most important in business
Region: Broad geographical area example country, and location analysis? Market area analysis
provinces.
Market area analysis: Basic information about market like population, sites consideration, and trading areas.
Population. Trading area, business area, and market area analysis. Population is of interest to business and
professional practice.
Trading area: Once location decisions are made regarding regional and market area, it is necessary to select
particular trading area, type of retail operation desired. Example outlets, supermarkets, discount stores, national
departmental stores (already established stores).
Site considerations: There are scientific methods (techniques) to assess the site location.
Site considerations: Important consideration in site selection is the relationship of cost to productivity. Physical
characteristics of space in a building under consideration should be scrutinized. The shape of the space, its
width and depth, exposed pipe and ductwork. Parking is a key concern. Techniques in assessing site locations.
The use of ratios as rule of thumb is fairly common. Another rule of thumb deals with convenience and distance.
Example sales per square feet.
Financial Statements: There are three basic financial statements. A balance sheet, an income statement and a
statement of retained earnings.
Income Statement or profit and loss statements:

Income statement is an indicator of sales, total sales, cost of the good sold, gross margin, expenses, total
expenses, profit (net income), and profit and loss statements.
· Unit price x unit volume = Sales % gross profit =
· Unit volume x unit cost = Cost of goods sold
· Sales – cost of goods sold = gross margin or gross profit Sales – Cost x 100
· Gross margin – expenses = Net profit Sales
Balance sheet: Balance sheet is an important indicator of assets and liabilities. Balance sheet is an indicator of
current assets (cash, current inventory, prepaid expenses), total current assets (fixture, furniture), liabilities
(account payable), and long-term liabilities (over one year).
Total liabilities.
Net worth = assets – liabilities.
· Cash + Account receivable + Inventory + Prepaid expenses = Total Current Assets
· Total current assets + Fixed assets = Total Assets
· Accounts payable + Notes payable + Accrued expenses = Total current liabilities
· Total Current liabilities + Long term liabilities = Total liabilities
· Total liabilities + net worth (owner equity) = Total liability and net worth
Retained Earnings Statement.

Retained earnings statement indicates business retained earning that includes dividend payments (share profit
to share holders) that will reduce retained earnings, and net income that will increase retained earnings.
Basic Management Principles

Basic Management Functions includes
· Recruiting/Staffing/Human Resource Management
· Accounting
· Strategic Planning/Organizing
· Purchasing/ Negotiating
· Inventory/Merchandising
· Marketing
· Dealing with regulatory officials
Recruiting/Staffing/ Human Resource Management

Described three commonly used steps in human resources. Job analysis, position description and job
description.
Job Analysis
Job analysis is a concise and factual study of pharmacy’s staffing need. The scope of each job must be
delineated, anticipated problems outlined, and hierarchy of position established.
A thorough job analysis will possess all areas of the work to be done, and alert the pharmacy owner on
duplication of functions. On long run, it will determine the responsibility of each employee and help prevent
conflict.
Position Description (Job advertisement). The position description outlines the main components of each
position. A good position description should be relatively short (no more than two pages).
General description of the job includes. Nature and the scope of the position, the main areas of responsibility,
required qualification, experience, and other job related skills.
Job description: The detailed job description should list, the entire task to be accomplished, in order of
importance and described in detail.
Pharmacists manager are responsible for the supervision of the activities of pharmacy and non-pharmacist staff
in their activities of pharmaceutical services. This is useful in establishing the priorities of job functions within
each position.
Job analysis Position advertisement Job description

Determine how many staff Advertise and interview Describe list of activities of staff.
need?
A pharmacist manager maintains appropriate job description. Ensure adequate staff coverage for pharmacy
activity levels.
Delegation: Authorizing job to others. The principle of delegation consists of Question Alerts!
three components responsibility, authority, and accountability. Delegation
· Responsibility. Assigning a task or a project.
· Authority. Given certain authority to operate a business. Like hiring
personnel’s.
· Accountability. Manager or staff pharmacist is accountable for completion of task or project.
What can or cannot delegated to tech?

Scope of pharmacy technician Regulated Pharm Assistant
Technician (NOT regulated)
Counseling no NO
Verbal Rx order from prescriber Yes NO
Verbal narcotics on phone NO NO
Counseling on natural products NO NO
Witness to dispose narcotics or BZD Yes NO
OTC devices demonstration Yes NO
Independent sterile preparation and non-sterile Yes NO
compounders.
Rx transfer Yes NO
Data entry Yes YES
Monitor storage conditions Yes YES
Package (blister packs) and labelling Yes YES
Can they recommend sugar free vs sugar cough syrup yes NO
Employee motivation: The manager who supervises, controls, and motivates a management team.
Basic principles of employee relation and motivations aspects are described by Maslow’s hierarchy.
Maslow’s theory describes that every person has five basic levels of needs. Physiological needs, Safety and
Security, Social needs, Esteem Needs, Self-actualization needs.
Physiological needsàthe most basic level
Safety and SecurityàPerformance report
Social needsà every employee wants to become part of the group.

An employer may ask the following questions: What degree of sharing of information about the business and it
goals will be?
Esteem Needsà If the three levels are satisfied, employees will become interested in addressing higher levels,
through recognition of groups as leader or experts in a particular area.
Self-actualization needsàthis is the highest level of needs, wherein employees will strive toward greater
accomplishment and responsibility, because it gives them personal satisfaction.
Workplace safety
Workplace safety and Insurance board (WSIB)
Workplace Hazardous Materials Information Systems (WHMIS)
Material Safety Data Sheet (MSDS)
Spill kits
Risk Management; Strategic Planning

SWOT Analysis (Strength, Weaknesses, Opportunities, Threat) analysis.
STRENGTH WEAKNESS
How can you maximize, How can you minimize, THEFT, POOR
SERVICES, LANGUAGE.. SPECIALTIES.. MANAGEMENT, NOT UPTODATE.. POOR
DRIVE THROUGH… FREE BP CHECK, CUSTOMERS SERVICES…
FREE DELIVERY.. INTERNET
REFILL..FOLLOW UP…
24 HRS… WEEKENDS…WEIGHING
SCALE…DIABETIC CLINIC..
DIETICIAN…SMOKING,
VACCINE..TRAVEL CLINIC.. BLOOD
SAMPLE COLLECTION… OFFER
DISCOUNT..
OPPORTUNITIES THREAT
How can you maximize, SPECIALTIES.. SERVICES.. How can you minimize, competition,
IF ANY SERVICES NOT AVAILABLE IN THE AREA.. regulations change,
Project Management: Project management functions, risk management, human resource management, and
communication management.
Quality Management: Four principles of quality management "P-D-C-A" Plan, Do, Check and Act.
Merchandising: Visual selling or visual display merchandise using floor plan (Planogram).
Question Alerts!
What is merchandising? Visual display of item in store
Inventory and merchandise management

· SKUs: Stock keeping unit of each size, strength, format of stock items in one unit. Individual items of
inventory are referred to SKU.
· UPC: universal Product Code.
ABC analysis (Pareto’s law): (20:80 LAW)

· Category A. 20% of products stocked represent 80% of the inventory cost.
· Category B. 15% of the products represent 15% of
Question Alerts!
the inventory cost.
Pareto's law. 20% of products stocked
· Category C. 65% of the products stocked
represent 80% of the inventory cost.
represent 5% of the inventory cost.
· By closely monitoring the 20% of the items in
category A, control is gained over 80% of the inventory costs. Identify your top 20% SKUs and maximize
inventory control efforts on these. Some of the items in the 80% category of SKU should be probably not be
stocked or sold on a special order basis.
Third Party Insurance. The payment system can be classified into two different categories. Retrospective
payment and Prospective payment.
Retrospective payment (reimbursement) System. In this type of payment service, payment is generally made
after the service has been provided by the hospital. The payment depends on the service actually provided by
the hospital. The payment depends on the service actually provided by the hospital during the patient’s stay.
There is little incentive for a hospital to keep a patient in the hospital for long because payment increases as
more costs are incurred. It is not preferred by third party insurances.
Prospective payment (reimbursement) system (PPS). This was introduced in 1982. A form of payment
(reimbursement) system usually pays the hospital on the basis of DRG (Diagnostic Related Group) services. DRG
includes lists of different kinds of illnesses and a fair amount of cost is required to treat such illnesses. Under
this payment service, the hospital will reimburse a predetermined amount specific to the DRG in which the
patient is classified. This single payment will cover the entire episode of care regardless of the patient’s stay in
the hospital, the number of tests performed, or the number of drugs that are used.
Commercial third party insurances:

They offer a variety of services with the condition that an initial certain amount of money should be spent by the
consumer which is known as “deductible”. Also, most of them do not cover charges for certain types of services.
They also collect the prepaid fixed monthly fees from the enrolled customers.
Maximum allowable cost (MAC): The maximum amount that will be paid by a third party to a pharmacy when
the drug is available from more than one source.
Estimated acquisition cost (EAC): the third party estimate of the prices paid by a pharmacy for a particular drug
product.
Actual acquisition cost (AAC): The actual price paid by the pharmacy after all trade, volume and cash discounts.
Average wholesale price (AWP): The published list price of a particular product.
Cash flow: a summary of cash receipts and disbursements of a business, for a defined period of time.
Cash management: freeing up funds for operating purposes by minimizing assets and maximizing liabilities and
specifically accounts payable.
Coinsurance: It is one type of cost sharing plan in which patient pay a specific percent of all expenses.
Co-payment: It is one type of cost sharing plan in which patient has to pay fixed amount each time a service is
provided. OR patient pays fixed amount for each prescription.
Deductible: It is one type of cost sharing plan in which patient has to pay a specified amount during a specific
period of time. Before benefits are paid by third party.
DEDUCTIBLE CO-PAYMENT CO-INSURANCE

Pay onetime in the beginning of Pay each time fixed amount for Each time you share the
every year. every prescription expenses with insurance
A 65yo patient of your A 65yo patient of your A 50 yo women presents
pharmacy presents with 4 pharmacy presents with 4 prescription with 4 medications.
prescriptions. Total cost of Rx is prescriptions. Total cost of Rx is The total cost of Rx is $156. Her
$156. The senior’s insurance $156. Patient insurance pays coinsurance plan covers 50%.
deductible for the year is $100. total Rx cost. Your pharmacy For this transaction. Patient
For this transaction. Patient bills $2 for each prescription. pays?
pays? $100 Patient pays? $8 $78
Business Indicators and Financial analysis

Functions of ratios that indicates overall financial position of pharmacy:
Ratios indicating profitability
Ratio indicating efficiency
Ratio indicating liquidity and solvency
Ratio indicating financial position
Ratios indicating profitability:

· Net profit to net sales (NP:NS): The normal ratio lies between 3 to 7%.
· Net profit to total assets (NP:TA): The normal acceptable ratio lies between 10 to 15%.
· New profit to inventory (NP:IN): The normal acceptable ratio lies between $0.21 to $0.27.
· Net profit to net worth (NP:NW): The ratio lies between 20 to 25%, and 15% is acceptable for older
pharmacies and 40% is attainable for newer pharmacies.
Ratio indicating efficiency

Question Alerts!
Inventory turnover rate (IN: TOR): It is
1) Turnover rate indicates? Inventory efficiency
normally calculated by dividing the cost of
4) TOR is days, inventory in hand. Examples TOR 4 is, in a
goods sold by an average beginning and
year 4 times inventory bought and sold (365/4).
ending inventory. The inventory turnover
rate should be 4 as a minimum, with a
target of 6 or higher. Theoretical number of times during a special period, usually one year, that inventory is
bought and completely sold.
· Average turnover rate is for retail pharmacy 4 min and 6 max or more. For hospitals turnover rate is 8 to 10.
· Inventory turnover rate = Cost of goods sold/average inventory capital.
or
Inventory turnover rate = Cost of goods sold
Beginning inventory (opening stock) + End of inventory (closing stock)
2
Example if inventory purchased two times a year, one at beginning of inventory and end of inventory.
TURNOVER RATE RATIOS

TOR <3 TOR 4 TO 6 TOR >6
excessive stock or over stock Recommended average frequent shortage
Net sales to networking capital (NS:NWC); The normal ratio range is 4 to 8. Ratios greater than 8 are considered
inadequate capitalization or overtrading. A value below 4 indicates under trading or too much capitalization.
Net sales to inventory (NS:IN). The ratio normally ranges from 6 to 9.
Net sales to net worth (NS: NW): The normal ration range is from 3 to 8. Greater than 8 is considered under
capitalization and overtrading while below 3 indicates under trading.
Net Sales to net worth = Net sales/ Net worth
Account receivable collection time (A/R CT): This ratio is a direct measure of efficient credit management.
Normally, a 30-day collection period is a reasonable target.
A/R = Year end account receivable/ Mean credit sales per day
Account payable remittance time (A/P RT): This is normally calculated by dividing year end accounts payable
divided by mean credit purchase per day.
A/P = Year end account payable

Mean credit purchase per day
RATIO INDICATING LIQUIDITY AND SOLVENCY:
Liquidity normally measure’s a pharmacy’s ability to meet its current liabilities with little or no interruption in
the regular conduct of business.
Solvency measures a pharmacy’s ability to meet current liabilities with moderate change in the composition of
current assets.
Acid test ratio: It is also known as quick ratio.

Question Alerts!
The normal ratio is 1:1.
Definition of liquidity and solvency (bankruptcy)
Current ratio: The minimum standard value is
2:1.
Inventory to networking capital (IN: NWC). Mean inventory is the average of the beginning and ending
inventory for the accounting period. This ratio is an indirect measure of liquidity and solvency. A high ratio
indicates low liquidity and too much inventory. A ratio if 80% is a reasonable target.
Ratio indicating financial position

Total liabilities to net worth (TL: NW). It is the most direct measure of the financial position of the pharmacy. A
ratio of 50% or lower is acceptable.
Founded debt to networking capital FD: NWC). It is also expressed as a percentage. Long term liabilities are
defined as liabilities extending longer than one year. The normal acceptable value of a ratio is 20 to 25.
Fixed assets to net worth (FA:NW). This helps to identify over investment in fixed assets. A high value indicates
over investment in fixed assets while a low value indicates there is a need for remodelling. The target value
would be a 20% or less.
Business Math:
Calculating markup% = [(sales price-cost)/cost] x 100
Calculating sales price = Cost+ (Cost x %markup)
Calculating cost = Sales price/(1+%markup)
% Gross margin = [(Total SALES- COST)/SALES] x 100
Cost Mark up (gross profit) Sales

Sales price/(1+%markup) [(sales price-cost)/cost]x100 Cost+(Cost x %markup)
Marketing in pharmacy “4 Ps “of marketing management. These activities, which are under the direct control of
the business, were known as the “4 Ps” of marketing product, place, price, and promotion.
Promotion: The methods of promotions are door-to-door flyers, local radio, TV, posters and news papers.
Management use of Structure-Process-Outcome component (SPO)

Measure of SPO
· Structure component. Examples. Facilities, equipment, staffing, and personal qualification
· Process component. Examples. Provider, healthcare system etc.
· Outcome component. Examples. Mortality, morbidity, and consumer satisfaction
Tips
1. POS 2. salaries 3. income statement

4. Balance sheet 5. Turnover rate 6. 4 to 6
7. Nature and scope of 8. Market area analysis 9. Corporation
position
10 Sole proprietor 11 Partnership 12 Franchise
13 Cash 14 Account receivable 15 Furniture
16 Building
· What are the forms of business structure in Canada? ( )
· What is banner pharmacy ownership? ( )
· What is the most important in business location analysis? ( )
· What financial statement includes sales of prescription drugs? ( )
· What financial statements include assets and liabilities? ( )
· Examples of current assets include? ( )
· Examples of fixed assets include? ( )
· What is the most expensive in pharmacy business? ( )
· Cost of goods sold/average inventory capital ( )
· The average turnover rate for a pharmacy ( )
· Staffing need is described as? ( )
· Position description includes ( )
· Point of sale system is ( )
Select True or False Statements

Backorder is (If an order is received, and an item has 'BO' means that item is out of stock at the supplier. The
'BO' signifies that the supplier will ship when the item becomes available or it may need to be re-order).
A pharmacy has a net income of $90,000.00, what would be best purchasing offer if you want to have return
on investment of 15%
www.PharmacyPrep.com Pharmacoeconomics
44
Pharmacoeconomics
Questions Alerts!
· Definition. A study of affordability of drugs or therapy COST to SOCEITY.
· Pharmacoeconomic methodologies like cost effective analysis (CEA), cost minimization
analysis (CMA), cost utility analysis (CUA), and cost of illness analysis (COA).
Pharmacoeconomics is “the description and analysis of the costs of drug therapy to healthcare systems and
society.” Pharmacoeconomics research, identifies, measures, and compares the costs and consequences of
pharmaceutical products and services.
PE has been defined as the description and analysis of cost of drug therapy the health care system and society.
It is process of identifying, measuring, and comparing the cost, risks/consequences and benefit of program,
services, or therapies and determining which health alternative products the best health outcome for resource
invested.
Pharmacoeconomic Methodologies: There are some scientific methods are used to evaluate
pharmacoeconomics.
· Cost-benefit analysis (CBA)
· Cost-effectiveness analysis (CEA)
· Cost-minimization analysis (CMA)
· Cost-utility analysis (CUA)
· Cost-illness analysis (CIA)
Methodology Cost (spend) Outcome unit

Cost-benefit analysis Dollar Dollar
Cost-effectiveness Dollar Units such as blood pressure mm Hg, blood glucose or units of
analysis. clinical effects (example costs per year of life saved). The most
commonly used in PE calculations. Example the selection of drugs
in hospital formularies. Also used to determine the first line
therapy of clinical practice guidelines.
Cost-minimization Dollar Assumed to be equivalent in comparative groups. Only cost is
analysis compared, so cheap intervention will be chosen.
Cost-utility analysis Dollar Quality-Adjusted Life Year (QALY). This is used when the impact a
health-related quality of life is important outcome to treat a
condition.
Cost of illness No comparison is made. Choose the best one.
analysis
Quality-Adjusted Life Year (QALY): The results of CUA analysis are normally expressed in terms of quality
adjusted life year gained. QALY includes both improvements in quantity of life and quality of life, QALY is used
when, and quality of life is the only outcome. Quality and quantity of life are health outcomes. When
intervention affects both mortality and morbidity and combined unit of outcome is desired.
Cost-benefit analysis (CBA): It is a basic tool that helps to improve the decision-making process in the healthcare
program.
Cost and consequences: The outcome is measured in dollars. This study calculates all of the possible benefits
that may occur from the program. All the benefits must be expressed in dollar value.
Disadvantage: (require the economic evaluation of a human life.)
It is very difficult to assign dollar values to non-financial benefits, e.g. benefits of the program that may improve
a patient’s life.
Cost-effective analysis (CEA) (dollars à clinical effects

· This technique is used to make a decision in order to select the most cost effective intervention from the
available alternative.
· Cost and consequences
· The output measure of this type of study is a health related measure rather than a financial, exampleà
blood pressure, mm Hg, or blood glucose.
Cost-minimization analysis (CMA) (dollars à equal in both groups

· It is defined as: when two or more interventions are examined and assumed to be equivalent in terms of
a given outcome. Cost associated with each intervention may be examined and compared.
Example. The comparison of cost of two ca-channel blockers, which may successfully produce similar
blood pressure reduction, patterns in a selected group of patients.
Cost-utility analysis (CUA) (dollars à QALY)

· It is an economic tool that measures the consequences in terms of outcome of the program in terms of
quality and quantity of life QALY.
· Cost and consequences
· The outcome measured in CUA is cost per QALY (Quality Adjusted Life Year).
· When the objective is to compare a gold standard intervention that already has the cost per QALY.
QALY is calculated by multiplying the utility value obtained for the specific health condition with
quantity of life year spent in that specific health condition. Comparison can be made for program and
intervention.
Cost of illness analysis (COI or CIA) à does not address both cost and consequences.
· It is very important for evaluating new therapies.
· No cost and consequences
Healthcare Outcome Research

· Outcome research (OR): The study of health care interventions (treatments, such drug therapy, surgery,
palliative therapy etc) and healthcare quality that are evaluated to measure the extent to which optimum
desirable outcome can be reached.
· The purpose of OR is to assess the value of a program or therapy under study:
· ECHO model: Provides framework for comprehensive evaluation of outcome.
· Economic outcome: Acquisition cost associated with care, labor cost associated with care, treat side effect
reactions, cost of treatment failure, hospital readmission, cost of emergency room, clinic visits.
· Clinical outcomes: length of hospital stay, side effect reactions, hospital readmission and death.
· Humanistic Outcome: Patient satisfaction, functional status of validated instruments, quality of life
assessment.
Health Related Quality of Life (HRQOL):

· QALY focuses on all aspects of life. However, HRQOL only focuses on patient non- clinical information such
as functional status, well being, perception of health, return to work from illness and other outcome that are
effected by illness
· Health Related Quality of Life (HRQOL): According to the WHO (world health organization), health is
defined as complete physical, mental and social well-being.
· HRQOL normally focuses on non-clinical components of healthcare such as functional status, well-being,
and other important health- related outcomes.
· HRQOL has a very large database. This database is prepared either by personal interviews, by telephone
interviews, or by postal survey.
· Personal interviews, telephone interviews and postal surveys are defined standardized questionnaires or
instruments of HRQOL.
Question Alerts!
Techniques of pharmacoeconomic assessment What is SF 36?
Short Form 36 (SF 36): The SF 36 was designed for use in clinical practice and research, health policy evaluation,
and general population survey.
Budget impact analysis (BIA)
Multi-attribute Utility Theory (MAUT)

· Used in assessing utilities. This include, clinical, financial effects as well as quality of life. Example. A hospital
administrator may view clinical outcome 20%, financial outcome 70% and the quality of life 10%. The
individual perspective will have a major impact on the final decision made, based on varying levels of priority
chosen for evaluation.
Willingness To Pay (WTP)

· This technique is used to assess the perceived value or benefit of a product and service.
Pharmacoeconomic Resources
Methods for Economic Evaluation of Health Care Programmes, 3rd ed. Michael F. Drummond, Mark J. Sculpher,
George W. Torrance, Bernie J. O'Brien, and Greg L. Stoddart. Oxford University Press.
Review example of Cost Benefit Analysis (CBA)
Drug A Drug B
Cost drug $1000 $1100
Administration $100 $10
Monitoring $50 $0
Side effects $75 $0
Total cost $1225 $1110
Benefit Days at work ($)
Extra months of life ($) 750 1200
C/B = <1 is beneficial

C/B = 1 no benefit or no loss
C/B = >1 is loss
Review example of Cost effective analysis (CEA): A marginal cost effectiveness ratio is calculated by determining
the added cost divided the added benefit.
Drug A Drug B
Cost dose $300 $300
Hospitalization $300 $300
Stay require $600 $600
Outcome Extra years of life 2 6
Cost effectiveness ratio 600/2 600/6
$300 $100
Review example Cost Minimization analysis (CMA): Assume the outcome to be equivalent in comparable groups.
Drug A Drug B
Cost Drug $250 $430
Monitoring $100 $10
Side effects $100 $15
Sub total cost $525 $455
Outcome
Antibiotic effectiveness 80% 80%
Result = Cost Drug A>Cost of Drug B

Cost utility analysis: A CUA takes patient preferences, also referred to as utilities, into account when measuring
health consequences. The most common unit used in conducting CUA is QALYs, which incorporates both quality
and quantity of life.
Drug A Drug B
Cost
Drug $250 $430
Monitoring $100 $10
Side effects $100 $15
Utilities Extra years of life 2 3
Quality of life 0.33 0.25
QALY 0.5 0.40
Cost utility ratio $525/0.5 $455/0.4
$1050 $1137
QALY = Quality Adjusted Life Years
Tips
1. Units 2. Society 3. Short Form 36

4 Cost Minimization 5. Quality Adjusted Life 6. Dollars
Analysis Years
7 cost utility analysis
· What is QALY ( )?
· Pharmacoeconomics is the study that determine affordability of drugs to ? ( )
· Cost minimization analysis outcome is measured in? ( )
· Cost effectiveness analysis outcome is measured in? ( )
· QALY is outcome of? ( )
· What is SF 36? ( )
· To compare cheaper intervention, what methodology is used? ( )
www.Pharmacyprep.com Drug Development Process
45
New Drug Development Process
Questions Alerts!
· Role of Health Canada. Drug market authorization in Canada is approved by Health Canada
after review based on “safety, effectiveness, and manufacturing quality”
· Drug approval process Clinical trials phase 1 to phase 4
· Adverse drug Reaction Reporting
Drugs are approved by the therapeutic directorate of Health Canada.

Pre market ……………………………………………………………………….. … Post-market
Physician Physician Physician
Prescribing prescribing
prescribing
Clinical Regulatory
Pre-clinical
trials product Market CADTH Public access
studies
(phase I, submission authorization Common Drug
II, and III By health Review Prescribing practices
Canada (CDR)
Clinical trial Submission Public and private Real-world use studies
applications
review Notice of drug (phase IV) by ADR
Compliance plans/policies Pharmacovigilance.
(NOC). listing and Therapeutic cost-
New drug submission (NDS) or abbreviated Drug Product reimbursement effectiveness.
NDS (generic products) or supplemental Database decisions
DRUG UTILIZATION
NDS (changes in existing products) Labelling and REVIEW
product Surveillance, inspection,
monograph and investigation for
safety and regulatory
compliance.
STEPS INVOLVED IN DRUG APPROVAL PROCESS

Preclinical trials
Clinical trial application
Phase 1 to 3 clinical trials
New drug submission review
Notice of compliance (NOC); DIN, drug product database; drug monograph
Patented Medicine Price Review Board (PMPRB)
Post marketing surveillance (phase IV, Canadavigilance ADR)
Common Drug Review (CDR) by the CADTH
Drug included in provincial and private formularies
Drug utilization review (DUR)
CADTH: Canadian Agency of Drug and Technologies in Health. Conducts common drug review (CDR) after drug
approved by health Canada.
Notification issued indicating that manufacturer has complied with FDA regulations. Notice of compliance (NOC)
is issued following satisfactory review of submission.
Pre-clinical research (in animals)

¯
Phase I trials (small healthy human population, PK, Safety)
¯
Phase II trials (small disease human population, safety, effectiveness)
¯
Phase III trials (safety, dosage info, decisive phase)
¯
Trial review and approval
¯
Phase IV trials (post marketing surveillance), adverse drug reaction (ADR) monitored
NO phase I trials for chemo preps.
Drug identification number (DIN)
A DIN is made up of exactly 8 digits. Only numbers allowed (0-9). Unlike other drug classes no meaning can be
derived from the number itself. (Similar drugs are NOT clustered together at similar numbers). DIN is printed on
the label.
Preclinical Research
Stage # of patients Duration Purpose
Pre-clinical research None 18 months - 3 years Laboratory investigation for
efficacy and toxicity
Phase I trials
Phase I 20-100 Up to 2 years Safety and dosage
· Human Healthy volunteers
· Small or limited population
· Designed to establish the effects of new drugs in humans, specifically determine a pharmacokinetic studies,
drug toxicity, absorption, distribution and metabolism.
Phase II trials
Phase II 100-300 Several months-2yrs Some shows term
safety but mainly
effective
· Test on disease patients
· Slightly larger but limited population
· Tested safety and efficacy in slightly larger populations who afflicted with the disease or conditions, which
the drug is developed.
Phase III Trials

Phase III 100-3,000 2-3 years Safety, relative
effectiveness dosage
· Tested on Disease patient
· Larger population than phase II
· Last pre-approval round of testing. Test the new drug with comparison of standard drug. The results of new
trials usually provide the information that included in the package insert labelling.
· After approval drug from phase III, this can be sold in market.
Trail Review and Approval
Review and None 1-2 years Safety, effectiveness,
Approval dosage
Phase IV Study
Phase IV 100- several thousand No limit Safety, effectiveness dosage
After drug has been approved. Studies are conducted to compare the drug to a competitor. Explore addition
side effects.
Tips
1. Notice of Compliance 2 Phase III 3. Disease patient, large number of
patient, it is decisive phase
4. Animals 5. Post marketing, inspection 6. Health Canada

of safety and regulatory
compliance
7. Patented Medicine 8. Pharmacy Manager/Owner 9. Healthy volunteers,
Price Review Board pharmacokinetics & safety
PMPRB
10 Disease patient and 11 NPN 12 Natural Product
smaller number Directorate
· Who approves and authorizes the sale of medications in Canada? ( )

· Who sets the prices of prescription drugs in Canada? ( )
· Who sets the prices of over the counter drugs in Canada? ( )
· Pre-clinical studies is done in? ( )
· Phase I clinical studies is done in? ( )
· Phase II clinical studies is done in? ( )
· Phase III clinical studies is done in? ( )
· Phase IV clinical studies is done in? ( )
· What is notice of compliance (NOC)? ( )
· Decisive Phase in clinical trials is ( )
· Approves the prescription & OTC medications ( )
· Natural Products Number is ( )
Terminology:
· Medline or Pubmed: Online source of indexes and abstracts.
· Red book: Pharmaceutical prices are described in this book.
· SOP = Standard Operating Procedures used in preparation and formulation of pharmaceuticals
· GMP = Good Manufacturing Practices or Procedure, the guidelines that determined by FDA for
pharmaceutical preparations.
· GLP = Good Laboratory Practice
www.PharmacyPrep.com Epidemiology
46
Epidemiology
Questions Alerts!
· Cross sectional, case control and cohort studies
· Clinical study designs like parallel and cross over designs
· Types of bias and confounders
· Types of blinding
· The credible clinical studies are randomized double blind
General Design Elements: These are the several important tools that researchers use to improve the validity of a
clinical trial, its ability to achieve the clinical endpoints, and its ability to provide the highest possible level of
evidence.
Clinical Studies
Descriptive studies Explanatory Studies Experimental (clinical trials)
Case reports Case series Meta analysis Observational
Cross sectional (or) Case control or retrospective or past. Cohort or follow up

Prevalence (now) Good for rare disease, initial etiology. Future or prospective
Collect the data after both No incidence and prevalence. Get incidence and estimate.
disease and exposure. Outcome is measured by odds ratio Calculate the risk
Determine prevalence rate method.(relative risk) Example post marketing
No incidence rates Example. Antibiotic resistance pattern surveillance (ADR monitoring)
for the past 10 yrs.
CROSS SECTIONAL CASE CONTROL COHORT

Present: Disease and exposure Present: Disease Present: Exposure
Past: Exposure Future: Disease
Prevalance only No prevalence and NO incidence. Incidence only
Measured by odd ratio
Asses the prevalence of an Compares histories of people with a Follows a group of people to track risk
outcome in a broad population at condition to a group without factors and outcomes over time.
one point in time. condition
Important concepts
Epidemiological study designs to study drug use and outcomes in large populations.
Prevalence: Collect data after both disease and exposure. or the number of cases of disease that are
present in population at given time.
Measured by cross sectional study.
Incidence: Collecting data from exposed. The number of new cases that develop in given period of
time. Measured by cohort studies.
Prevalence Incidence
Measures existing cases of diseases and Measures NEW cases of disease and is expressed
expressed as proportion in person, time, and units.
Measures all side effects of a drug Measure a NEW side effect of drug.
Total all number of cases Only new cases
Cross sectional examples

· Determines or identifies the risk factors and etiological agents
or disease or conditions.
· To evaluate receiver characteristics of diagnostic procedure.
· To evaluate a new laboratory tests.
· Advantage: results appears at the time of study
Fig 55.1
Fig 55.1
Case control study

A case control study compares a population of patients with a specific pre-existing condition to a similar
population without – to establish the influence of a disease or other event (e.g. Intervention, hospitalization,
death). Data collection is usually done using medical records and patient interviews.
Example. Studies of antibacterial resistant for the treatment of pneumonia. This study often the best way to
study rare diseases that develops over a long period of time. It can be less reliable than randomized controlled
trials or cohort studies because the difference that can be made about the influencing factors is limited by bias.
Pros and Cons

· (+) Requires fewer subjects than cross-sectional trials
· (+) Only way to study long-term, rare disorders
· (+) Fast and inexpensive
· (-) Difficult to select control
· (-) Potential bias form patient selection and recall
· (-) Exposure status relies on records and recall
Odds analysis: Probability that an event occurring vs the probability that will not occur.
Odds ratio: measures association with exposed and outcome.

Odd Ratio (OR): The odds represent the number of patients in a given group with an event divided by number of
patient in the same group without it.
The 2 x 2 table OR = (A/C)/(B/D) OUTCOME
OR = AD/BC Exposure Yes No
A= number of exposed cases
B=Number of exposed NON cases Yes A B
C=Number of unexposed cases NO C D
D= Number of unexposed non case
Tips. Always divide experiment by control (goes down in table)
Sample of 100 people received flu vaccine 10 people has flu and sample of 100 people NOT received flu
vaccine 40 people had flu during the same period. What is odd ratio?
A. <1 B. > 1 C. 10 D. 40 E. 100
OUTCOME
Exposure Yes No
For disease
The odd of people taken flu vaccine 10 to 90 or 1:9 while Yes A B
The odd of people NOT taken flu vaccine 40 to 60 or 4:6 NO C D
OR = odds of exposure among cases
Odds of exposure among control
10/90
40/60
0.1/0.9 = 0.1 x 0.6 OUTCOME
0.4/0.6 0.9 x 0.4 Exposur No Yes
= 0.16 e
IF OR > 1 those who were exposed have an increased risk of the Yes B A
outcome NO D C
IF OR < 1 those who were NOT exposed have an increased risk of
the outcome
OR>1 those who were exposed have an
For treatment
increased risk of the outcome?
Cohort Studies
An observational study that allows a large population of patients with a specific pre-existing condition or
treatment for a period of time, comparing them with another group unaffected by the affliction or the
treatment.
Cohort studies are employed when it would be unethical to test the effects of a condition or treatment on
otherwise healthy patients (e.g. obesity in children), often in the etiology or prognosis of a disease.
Pros and Cons
· (+) Lower cost, easy administration (compared to RCTs).
· (+)Can establish time and direction of events Question Alert!
· (+) Ethical 1) Methods for continually monitoring
· (-) Not randomized, difficult to blind side effects and safety of medication
· (-) Control difficult to identify use in large populations.
· (-) Differences can take a long time to develop.
· (-) Participants can withdraw, develop other conditions,
or die.
CLINICAL TRIALS (EXPERIMENTAL TRIALS)

Randomized Controlled Trials (RCTs):
A clinical trial that answers questions about the effectiveness of different therapies by studying the effect of an
intervention on randomized patients. This can be achieved by using 2 possible methodologies designed to
reduce bias and promote comparison between the intervention group and 1 or more control groups (also known
as ‘arms’) treated with a placebo and/or the current standard of care. RCTs are the standard trial design for
answering clinical questions about therapy effectiveness.
Example: A clinical trial of ACEi to determine the blood pressure lowering effect!
Independent variable Dependant variable

ACEi, lifestyle, SALT ETC. Blood pressure
Predictor variable Outcome variables
Randomization: Participants are selected by computer codes, randomization improves the validity of a trial’s
results.
Stratification: In some trial designs, patients may have important differences that researchers know will affect
the outcome of the intervention, such as different stages in disease state or concurrent conditions. In such a
case, patients may first be intentionally divided into 2 or more groups, example “smokers and non-smokers” or
diabetics and non-diabetics”.
Stratification enables researchers to evaluate how an intervention affects both groups by studying whether or
not there is a difference in the subgroup.
Population. Population, from which trial subjects will be selected.
Sample size. The total number of participants included in a clinical trial is determined by the change the
researchers want to observe in the chosen primary outcome.
Placebo. A placebo is a device that imitates the active intervention but has no therapeutic value. The placebo
effect is important when discussing adverse events (AEs) with a healthcare practitioner. AEs from the group
taking the placebo can be compared with those from the group taking the intervention to determine to what
degree adverse events are really attributed to the active agent.
Multi-Centre Trials
Multi-centre trials are conducted at more than one location, often by more than one investigator, but using one
central protocol. When conducted at multiple centres in more than one country they are referred to as multi-
centre, multi-national trials.
Systematic Reviews
Are critical assessment and evaluations of primary research trials that use rigorous methods to combine the
current best evidence to answer a specific question on a clinical topic.
· A comprehensive literature survey of the topic is conducted
· Primary trials of sound methodology and the highest level of evidence are identified (eg. Randomized
controlled trials)
· The results of each trial are appraised
· All results are summarized using predetermined, explicit, reproducible methodology.
A systemic review shares many common characteristics with the first 4 steps of the evidence-based medicine
process: phasing a clinical question (endpoint); researching the answer; evaluating the evidence; integrating and
applying the evidence (conclusion).
Meta-analysis Systematic review

Analysis of several clinical trials to answer clinical Review all relevant studies to answer a clinical
question or result of trial (endpoint) question (endpoint).
More credible
Preferred for primary endpoint (most important). Surrogate endpoint
Example: a clinical trial of migraine with triptan Example: Death from heart disease, is the
gives direct outcome of how many patient endpoint of interest, but cholesterol is the
migraines is relieved. surrogate marker. A clinical trial may show that a
particular drug example statin is effective in
reducing cholesterol without showing directly
that statins prevent the death.
Primary endpoint: most important reference for study.

Secondary endpoint: data analyzed indirectly from the study
Surrogate (marker) endpoint: correlate with real endpoint
Study designs
Parallel group design: The more common of the 2RCT designs, the parallel group design, is often used for
confirmatory trials. Participants are randomized into 2 or intervention, the other treated with placebo or current
standard of care.
Pros and Cons

· (+) Randomized improves statistical analyses
· (+) Unbiased distribution
· (+) Can be blinded
· (-) Requires extensive resources
· (-) Can present ethical challenges
· (-) Nature of volunteers can bias trial
Question Alerts!
Parallel design studies often used for confirmatory trials
Crossover Design: Participants are randomized into 2 or more groups. However, each group receives all the
treatment (e.g. Intervention, standard, placebo) in a random order with a “washout” period in between, a
period of time between two active treatments when the patient receives a placebo in order to remove the
residual effect of the previous treatment before initiating the next active treatment. The basic crossover design
is 2 x 2, in which 2 groups receive 2 consecutive treatments.
Pros and Cons

· (+) Reduced error variance, reduced sample size
· (+) All participants serve as own control
· (+) All participants treated
· (+) Can be blinded
· (+) Comparative studies
· (-) All participants receive intervention, standard,
and placebo
· (-) Cannot be used for intervention with permanent
outcome (like irreversible side effects)
· (-) Length washout period QAlerts!
· (-) Long duration Cross over design all participants get treatment
and placebo in crossover design. Reduce error
variance
Meta Analysis:
It thoroughly examines data from a number of valid trials that are similar enough to permit them to be
combined and analyzed as one large trial. The evaluation of quantitative evidence from 2 or more trials involves
combining the raw data or the summary of statistical results using a
special statistical methodology. Question Alerts!
Meta analysis is the top ranking
The meta analysis trial design provides the highest level of evidence of clinical evidence
any trial design because part of its methodology includes the analysis,
critical appraisal, and summary of the results of many selected
randomized controlled trials.
Pros and Cons
· (+) Top ranking in the levels of evidence
· (-) Trials demonstrating a positive effect are published more often than those that don’t exposing a meta-
analysis to a publication bias.
· (-) Results from different trials do not always agree.
· (-) Authors of a meta analysis could unconsciously or intentionally omit trials that may or may not support
the clinical question.
· (-) “Grouping” results from trials with different designs, statistical analyses, and patient populations may be
problematic.
Bias
Bias is systemic error or distortion of a test measurement.
Interview bias. Because of blinding of interviewer’s response may be influenced, known as interview bias.
Recall bias: Differentials in the memory capabilities. Example case control studies.
Lead time bias. The selection of cases from both of these groups introduces a form of non-random error known
as lead-time bias.
Berksons bias (admission rate bias): Distortion in risk ratios occurs as result of different hospital admissions.
Confirmation bias: Linking directly to results.
Selection bias: The selection of subjects into your sample or Question Alerts!
their allocation to treatment group produces a sample that is Confirmation bias!
not representative of the population, or treatment groups Look alike drugs, Look alike labels, Look
that are systematically different. alike shape drugs can result in
confirmation bias.
Publication bias: Not publishing negative results.
Confounder. A factor that is prognostically linked to the outcome of interest and is unevenly distributed
between the study groups. Example. If study is examining the effect of age on ulcer relapse rate and several
ulcer also smokers (smoking could be confounder).
Example: A promising drug for the gastrointestinal protection is being developed. The study misses primary end
point of GI bleeding symptom severity, but there does seem to be some effect at the higher doses.
Blinding: It helps limit or eliminate factors that could unconsciously influence results. Blinding minimizes bias in
several ways.
Single blind. One if the most basic forms of blinding in which trial participants have no knowledge of
intervention (example patients cannot distinguish
between the intervention, placebo, or active product used Important Concept!
to compare different treatment regimens. Who is NOT blinded? Biostatistician
Double blind. Neither the trial participants nor the investigators have knowledge of the assignment to the
various trial groups of the interventions, placebo, or active product used to compare different treatment
regimens.
Triple blind. Neither the participants, the investigators, those monitoring the safety, nor any of the personnel
involved in the selection of participants or evaluation of the outcomes have knowledge of the assignment of the
interventions and placebo to the various trial groups.
Tips format 002: Epidemiology

1. case-control 2. cross-sectional 3. prospective
4. Cohort 5. Single-blind studies 6. Double-blind
7. Randomization of the 8. Parallel Studies 9. crossover studies
sample
10 Dependent variable 11 Meta analysis 12 Prevalence
13 Case report 14 15
16 17 18
· Factors reduces best bias ( )
· The odds ratio associated with ( )
· A study designed to determine the relationship between emotional stress and ulcers used the records of
patients diagnosed with peptic ulcer disease versus controls over the period from May 2009-May 2010. This
is an example of what kind of study? ( )
· Twelve patients are given a drug or a placebo to determine the effect of medication on blood pressure.
The dependent variable in this study is ( )
· A study was undertaken to determine if prenatal exposure to marijuana is a cause of low-birth weight.
Mothers of 50 infants weighing less than 5 lbs (low-birth weight) and 50 infants weighing more than 7 lbs
(high-birth weight) were questioned about their use of marijuana during pregnancy. The study found that
20 mothers of low-birth weight infants and only 2 mothers of high-birth weight infants used the drug during
pregnancy. This is an example of what kind of study? ( )
· In this study, the odds ratio associated with smoking marijuana during pregnancy is (16)
· The odds ratio is 16 and is calculated as follows
· Mother smoked marijuana Mother did not smoke marijuana
· Low-birth weight babies A = 20 B = 30
· High-birth weight babies (normal) C = 2 D = 48
· Odds ratio = (A)(D) or (20)(48) = 960/60 = 16
· (B)(C) or (30)(2)
· Combining data from several studies (often via a literature search) to achieve greater statistical power. (
)
· is the number of people who have an illness at a specific point of time ( )
www.Pharmacyprep.com Biostatistics
47
Biostatistics
Questions Alerts!
· Statistical significance: Probability of error (P) or level of significance (LOS) and confidence
intervals (CI).
· Hypothesis testing: Types of error like Type 1 (alpha) and Type 2 (beta) errors.
· Calculating risk reductions like absolute and relative risk reductions
· Calculating number needed to treat (NNT) or number needed harm (NNH).
Characteristic of data: Descriptive statistical measurements are often used in medical literature to summarize
data statistical distribution. Frequently used in clinical medicine are symmetrical distribution, measuring central
tendency and measures of dispersion.
Normal distribution: representation of normal phenomenon.

Symmetrical distribution: The symmetrical distribution is also known as normal (Gaussian) distribution or bell
shape curve. The dispersion or spread form the mean is represented by the standard deviation 68% (two thirds)
of the value falls within one standard deviation of the mean. 95% of the values are found within two standard
deviations of the mean. 99% of the values are found within three standard deviations of the mean.
99%
SD1 is 68%; SD2 is 95%; SD3 is 99%

95%
Bimodal = Two lumps

68%
Positive skew = Mean>median> mode: Tail on right handed side

Negative skew = Mean < median <mode): Tail on left handed side
Measures Of Central Tendency (middle of distribution):

A measure that describes a typical value in a set of data is referred to as a -3 -2 -1 0 +1 +2 +3
measure of central tendency. Three measures of central tendency describe
Number of standard deviations from the mean value
such values when they are found in a normally distributed sample mean,
median and mode.
Mean: The sum of the scores divided by the number of scores that is, the average score.
Mean. Sum of the score/number of scores = 3 + 5 + 5 + 8 + 9 = 30/5 = 6
Median: Midpoint of the sequence = 5 (if there is an even number of values, the mean of the middle two
numbers becomes the median), 4, 3, 8, 5, 5
3, 4, 5, 5, 8 (arranged in increasing order)
9, 4, 3, 2, 1, 5
1, 2, 3, 4, 5, 9 (arranged in increasing order)
3+4/2 = 3.5
Mode: The score that occurs most frequently or repeats is referred as mode. Note. All measures of the central
tendency may be altered by the addition of very high or very low values is distribution, the mode is usually
unaffected by such values, and the mean is susceptible to the greatest degree of change.
3, 4, 5, 6, 6, 7------Mode is 6
4, 4, 8, 5, 5-----Mode is 4 and 5, this is referred as bimodal
1, 2, 3, 4, 5, 9 à No mode
Examples. In a follow up study of five patients admitted to the coronary care unit with diagnosis of acute
myocardial infarction, the length of stay was found to be 5, 3, 8, 5 and 9 days. Calculate the mean, median, and
mode for these sample patients. First arrange the data in ascending or descending order; 3, 5, 5, 8, 9
Mean = 3, 5, 5, 8, 9 = 30/5 = 6
Median = 5
Mode: The score that occurs most frequently = 5
Measures Of Dispersion
A measure that described the spread or variation of the observations is referred to as a measure of dispersion.
Four measures of dispersion that are used in clinical epidemiology and medicine are range, standard deviations,
variance, and standard error of mean.
Range: The difference between the highest and lowest observation

Example. 99, 105, 115, 125, and 130.
Range: (130-99) = 31
Standard deviation: The standard deviation is another way to calculate dispersion. This is the most common and
useful measure because it is the average distance of each score from the mean. The formula for sample
standard deviation is as follows.
For sample data 5, 6, 8 and 9, what is the standard deviation?
N = total number of data

X bar = mean of data
Calculator: SHARP EL-510R
SD = 1.8
Calculated standard deviation for the data 6, 7, 8 and 9

6+7+8+9 = 30/4 =7.5
√(6-7.5)2 + (7-7.5)2+(8-7.5)2+ (9-7.5)2

3
SD = 1.28
Variance: The third method of measuring dispersion. Compare the two-variance formula with their
corresponding standard deviation formula. Variance is the square of the standard deviation.
Coefficient of variance SD
Coefficient of variance = x 100
Given (x bar) and standard deviation (SD), calculate of % of variance
X
coefficient.
Standard error of the mean (SEM). The standard error of the mean plays an important role in many of the
statistical procedures used in epidemiology and clinical medicine. It is used for confidence limit determination
and becomes and estimates of standard deviation of population through. As the standard error of the mean
decreases as the size of the sample increases.
S
S = Standard deviation, N = Sample size SEM =
n
Statistical tests analysis: Statistical test can be divided into three categories that are parametric and non-
parametric tests and meta analysis.
Statistical tests
Parametric tests Non-parametric tests

Mean and standard deviation and student Chi Square, median, and mode
t-test, ANOVA Test statistic is arbitrary
Test statistics based on distribution. Apply to variable and attributes
Applicable for only variables Not so powerful
More powerful
Parametric statistical tests: The parametric statistics are the most popular data analysis procedures that assume
that data are from populations that are normally and independently distributed. The population of parametric
tests must have the same variances. Examples of parametric statistic are t-tests, mean, and standard deviation.
Student t tests: The t tests is used for comparing the means of 2 treatment, even if they have different number
of replicates. The student’s t tests used to compare the means of small (n <30) independent samples for the
purpose of determining the statistical significance (p value) of the observed findings.
· T-test checks difference between the means of 2 groups.
· The degree of freedom (DF) in paired t test can calculated by (n-1)
· The degree of freedom in two independent sample t-test would be (n 1 -1) + (n 2 -1)
· Example. A drug is used to treat 50 placebo and 50 patients. Find out the degree of freedom.
Analysis of variance (ANOVA): It is also known as F test and is used to compare means of three or more samples
or groups for the purpose of determining the statistical significance of the observed findings. Degree of freedom
can be calculated by (n-2). Consist of positive value.
t-test F-test (ANOVA)

2 SAMPLES: t-TEST is used to find out if the means 3 OR MORE SAMPLES
between two populations is significant. Similar to chi-square test.
N <30. Ratio of variance of two samples.
UN PAIRED T-TEST: (INDEPENDENT TEST); TWO
UNRELATED MEANS.
PAIRED T-TEST: TWO RELATED MEANS
Non-parametric statistical tests:

The non-parametric statistics are also known as “distribution free” statistics. They do not require assumption of
same variances. Their observations are independent. Examples of non-parametric statistics are mode, median
and chi square tests.
Chi Square test: The chi square test is used for comparing two or more dependent variable proportions within
two or more groups making it useful for multi group comparisons. Compares percentage (%) or proportions.
(Not mean values). The degree of freedom is defined as (R-1) x (C-1). Here, R = row and C= column. Example
find out the degree of freedom in chi-square tests in 2 x 2 contingency table.
(R-1) x (C-1) = (2-1) (2-1) = 1.
Used to test differences of two proportions from two independent samples can calculate by
Chi-square can be calculated by:

X2 = e (observed frequency-expected frequency)2
Expected frequency
The Wilcoxon signed-rank test. Non-parametric statistical hypothesis test used when comparing two related
samples or repeated measurements on a single sample to assess whether their population means differ.
Statistical approach to compare 2 groups like new drug vs placebo using p value or Level of significance (LOS),
hypothesis and confidence intervals.
1. Calculates main effect
2. Calculates variance in main effect
Statistical difference: measures the probability of outcome due to chance.
statistical significance tells us the difference is real or not just due to chance.
Statistical Significance: It’s important to determine whether a treatment effect is really caused by the study
intervention or whether it is merely due to chance. A result is said to be statistically significant when it is
reasonably unlikely to be due to chance alone.
There are two main measurements that can help us i.e. p-value (probability of error or margin of error) and 95%
confidence interval.
The statistically significance (level of significance) results is one in which the observed p is less than 5%, which is
formally written as p<0.05.
p-value (probability of error or level of significance)
if p is 0.05 or 5% means, 1 in 20 results are by chance.

if p is 0.01 or 1% means. 1 in 100 results are by chance.
Null hypothesis (Ho). State that there is no difference between. Example smokers and non-smokers with respect
to the risk of developing lung cancer.
Alternate hypothesis (HA) (relationship hypothesis). The alternate hypothesis states that there is difference
between smokers and non-smokers with respect to the risk of developing lung cancer.
Types of error
Types of error
Type I (a-error) Type II (b-error)

False + ve False -ve
Chance Sample size
P or LOS
Type I (a-error): False positive error. Stating that there is a difference when NO difference exists. Or mistakenly
accept the experimental hypothesis and reject null hypothesis. Rejecting null hypothesis when Ho is true.
Investigator can error in concluding that there is difference between treatment group and control group when,
in fact, no such difference exists. In statistical terminology, it is called a type I error and the probability of making
such an error is referred to as alpha level.
· P = Probability of making type I error, also

referred level significance. Question Alert!
· The level significance is set at a 5% level or Type I error is false positive. Stating there is
0.05 levels. The alpha error is set in difference (placebo and drug) when NO difference.
advance.
· The a error is commonly chosen as 5%, however, sometime it may set up to 1%.
· P = 1/20 = 5/100 = 0.05 = not significant
· P <0.05 significant
· P = 0.0005 = Highly significant
Confidence interval = 1- a
Type II (b-error) or False -ve. Stating that there is NO difference when different exists. Accepting null hypothesis
when it is false. Beta is probability of making type II error. The b-error is the probability of declaring no
difference between the observed value and the hypothesized value of an experiment. Parameter, a difference of
error delta exists. Accepting null hypothesis when null hypothesis (Ho) is false.
Type II error is due to small sample size.
Power = 1-b
Example. A study sample of 50 patient for hypertension drugs shows 100% response. If the same study is done
for 10,000 patients, and only 98% response.
Probability that test will reject null hypothesis when null hypothesis is false (probability to avoid error).
Higher power = more confident that null hypothesis is correctly rejected
Confidence interval
Confidence interval (CIs) are inversely proportional to p-value, therefore p-value 0.05 is expressed as a
confidence interval 95%. Confidence intervals are provides range within which the true treatment effect is most
likely to occur across trial population.
Confidence level Probability of error

(1-alpha)
0.90 0.10
0.95 0.05
0.99 0.01
Measure of Risk: Probability of an individual who have not developed the event will develop the event.
Risk Reduction
Absolute Risk Relative Risk Attributable Risk
Measure of risk: Factors that are likely to increase incidence, prevalence or mortality of disease are called risk
factors.
MEASURING THE SIZE OF THE MEASURING THE SIZE OF AN ADVERSE
TREATMENT EFFECT EVENT
Absolute risk is the difference in treatment and Absolute risk increases due to the treatment vs
control. placebo
ARR = EER-CER ARI = CER- EER
Relative risk is the risk in the treatment group
relative to the control group.
RR = EER
CER
Relative risk reduction = (EER-CER) Relative risk increase = (CER-EER)
EER CER
NNT = 1/ARR NNH = 1/ARI
Absolute Risk (AR): The difference in risk between exposed and unexposed groups that is also percent of disease
occurrences that are result of the exposure (example smoking causes 1/3 cases of pneumonia). Allows to
separately calculating the incidence of a particular disease in both populations of a risk factor study for the
purpose of making individual risk comparisons for each population.
The absolute risk = A/(A+B) i.e. A = Drug, B = Placebo
Absolute risk reduction (ARR): The difference between treatment group and control group.
· The difference in the absolute risk between the intervention and control groups.
· ARR = EER -CER or CER– EER

EER = Experimental event rate (treatment event), CER = control event rate (placebo events)
NNT: The number needed to treat is the number of patient you need to treat to prevent one event (one bad
outcome, death, and stroke). If a drug has an NNT of 40, it means you have to treat 40 people with drug to
prevent one additional bad outcome.
NNT = Number needed to treat = 1/ARR
NNT = Number of patient needed to be treated to prevent one bad outcome
NNT are always rounded up to the nearest whole number.
A study experiment event rate or treatment reduced 10% risk and control reduced 7.5% risk. What is
absolute risk reduction?
A. 7.5% B. 2.5% C. 10% D. 15%
Ans. B
ARR = EER-CER or 10-7.5 = 2.5%
Relative Risk (RR): Relative probability of getting a disease in the exposed group. Calculated as percent with
disease exposed group divided by percent with disease unexposed.
· Relative risk = a (a+b)/c(c+d)
· Relative risk gives risk as a ratio of incidence among subjects exposed to a particular risk factor divided by
the incidence among subjects who were not exposed to the risk factor.
Relative risk reduction (RRR): Reduction in adverse outcomes in the treatment group relative to those in the
control (placebo) group.
· RRR = [EER-CER]/EER
· RRR= ARR ¸ EER
RRR = [1x CER]/NNT
· RRR = Relative Risk Reduction
Relative risk reduction measures how much risk is reduced in treatment vs control.
When experimental treatment reduces risk of When experimental treatment increases
bad event probability of good event
RRR (CER-EER)/CER (EER-CER)/EER
ARR CER-EER EER-CER
NNT 1/ ARR 1/ARR
Tips
· When will be the results on the same point in symmetrical curve-->
· P = Probability of making type I error, also referred level significance.
· Chi square test: The degree of freedom is defined as (R-1) x (C-1)
· The absolute risk = A/(A+B); A = drug, B = placebo
· ARR = (placebo events) – (treatment events) or (treatment event) - (placebo event)
· RRR = [EER-CER]/EER
· RRR=ARR ¸ placebo events.
· RRR = 1 x CER)
NNT
· Example: A statistical data mean is 100, median is 100, and mode 100, the statistical distribution is?
Indicates symmetrical distribution
· A statistical data mean is 200, median is 150, and mode 100, the statistical distribution is?
· What are the examples of parametric tests are à
· What are the examples of non-parametric tests are à
· False +ve test is à
· Type I error can occur by à
· Type II error can occur by à
· Probability of error is presented as à
· What is precision à
· What is specificity à
· What is accuracyà
· What is validityà
· The Wilcoxon signed-rank test is a? à
48
Hospital Pharmacy
Questions Alerts!
· Managing Drug Distribution and Workflow (Electronic medication records (EMR), medication
administration records (MAR).
· Unit dose system, Ward Stock.
· Formulary systems: Hospital committees (P&T committee prepares formularies, medical
advisory committee or MAC).
· Inventory management (Perpetual inventory is used for narcotics), POS.
· Medication Reconciliation (gathering patient medication history)
· Quality Assurance: Accreditation of hospital are done federally for narcotics and dispensing
by provincial college of pharmacies. Drug utilization review (DUR)s. Reporting medical
incidence to Canadian Institute of Health Information (CIHI). ISMP. Institute of safe
medication practices) Canadian Medication Incident Reporting Services (CMIRS). IV
admixture and sterile preparations. FMEA and RCA
· Failure Mode and Effect Analysis (FMEA). Before error occurs analysis
· Root cause analysis (RCA). After error occurs analysis.
Hospital organization structure
Board of Trustees
(board of director)
CEO
CFO COO CMO
VPs
Director of
Pharmacy
Pharmacy
manager
Activities and services of hospital pharmacy can categorized into:

· Clinical Pharmacy Services (Dispensing, Rx reviews, ward rounds, monitoring ADR, DRPs)
· Drug Distribution Services (Dispensing PO, IV, TPN, distribute MAR)
· Drug and poisoning information services
· Hospital Committees
Clinical Pharmacy Services

· Participating medical rounds (review of patient cases) by the healthcare team
· Ensuring patient receiving correct dose of correct medication at correct time.
· Evaluating patient medication list before, during stay and after the hospital stay to ensure accuracy and
appropriateness (medication reconciliation). Institute of safe medication practices (ISMP) have developed
best possible medication history (BPMH).
· Making sure what medication has been
prescribed and they understand the Questions Alerts!
correct way to use and expected effects. What is incorrect in Role of clinical pharmacist?
· Working with healthcare team to A) Medication order review
determine whether medication having B) Administering medications to patients
desired outcomes, and if not evaluating C) Eternal tube feeding nutrition calculations
to find if medication therapy need to D) Participates in cardiopulmonary emergencies rounds
change. E) Calculating flow rates for IV infusions
Drug Distribution Services

· The delivery of medication in hospital is multi step process.
· After physician orders a prescription, it is sent to pharmacy department, where 3 things happen.
· A pharmacist assesses the order appropriateness, according to patient diagnosis and treatment plan.
· A pharmacy technician fills the order for the medication, which may be oral, topical, and parenteral.
· The pharmacy technician labels the medication. Medication name, dose, how to administer and patient
information Pharmacist oversees the process of medication delivery from central pharmacy. Pharmacy
technicians have important role to play in filling medication and checking each other’s works.
· A variety of programs, equipments and procedures are necessary to make sure medication are delivered
accurately, minimizing the chance of errors and medication waste.
· Automatic machines for packaging labels.
· Unit dose system that package each
dose of medication for each patient in Question Alerts!
ready to use form. 1) Unit dose system medication is dispensed 24 hr period.
· Narcotic legal liabilities. System for 2) Unit dose label have drug name, strength, lot numbers
controlling narcotics for legal and exp. date.
accountability of these medications. 3) In patient label contains patient name, Lot #, Exp. date,
· Destroying of narcotics, mail a list of room #, Date, Doctors name, drug name and drug strength.
narcotics to be destroyed to office of 4) All iv preps must be sterile, particle free, and pyrogen
control substance. free, should be reconstituted in laminar airflow hood.
Unit Dose System Ward Stock System (Floor Stock)

Delivered in unit dose for 24 hr for a Stocking commonly used medication in nursing floor.
specific patient. Emergence carts (Crash cart)
Expensive but effective Short shelf life cannot be stored in ward stock and no
narcotics in emergence cart.
MAR (Medication Administration Record) is
used for administration.
Technician fills unit dose or robots
(automation) fills unit dose
Nurses retrieve and check medication
against MAR before administration.
The technical responsibilities of preparing patient specific unit dose and floor stocks medication are done by the
pharm. technician.
Unit dose dispensing

· In unit dose dispensing, medication is dispensed in a unit of use package that is ready administer to patient.
· The unit dose system is part of the hospital’s system of drug distribution in which medications are dispensed
for a 24-hour period.
· CIVA (centralized intravenous admixture). This utilized prepackage iv drug admixture.
Drug and Poison Information

· Pharmacist represents good source of information about medications and their toxic effects.
· Pharmacist working in drug information centres provide information either verbally or written.
Drug Information Centres

• Healthcare professional or public may have some questions urgently or some of questions require detail
literature search using electronic search programs, and journals to find out up-to-date information on
variety of topics.
· Availability and uses of different medications
· Side effects of medications
· Drug interactions
· Mixing intravenous medications
· Current approaches to therapy
· Controversial topics on medical use
Poison information centres

· Pharmacist working in poison information centres answer questions from other healthcare professional and
public about poisons, toxicities and overdoses of drugs.
· Management of accidental ingestion of medications by children
· Antidote to medications
· Management of overdoses
· Contents of household products
· Identification of unknown medication ingestions
· Poison prevention tips
Hospital Committees
Patient care committees with pharmacist involvement in many hospitals
Patient safety and Quality
Human investigation review board Question Alerts!
Infection control P&T committee is responsible for medications related issues, and
Cancer care develops and operate formulary.
Pharmacy therapeutic committee (P&T)

· Formulary committee
· Drug and therapeutic committee
· Paramedical committee
· Pharmacy therapeutics and nutritional support committee
MEDICATION ADVISORY COMMITTEE (MAC)

¯
PHARMACY & THERAPEUTIC COMMITTEE
¯
MEDICATION INCIDENCE OR PATIENT SAFETY COMMITTEE
Quality Assurance
Drug Utilization Review (DUR). Examine the following quality and efficiency of;
· Quality and efficiency of a unit dose drug distribution system
· Quality and efficiency of clinical pharmacy services
· Quality and efficiency of antibiotic drug use in a hospital
· Quality and efficiency of a centralized IV admixture program
DUR are conducted both perspective and retrospective. The perspective DUR involves setting up parameters
such as dosing too high or drug-drug interactions that sent to dispensing pharmacist at the time and point of
service to alert the potential problems.
Retrospective DUR. Performed by the clinical pharmacist reviewing claims of patient several weeks or months
following dispensing of medication to track clinical problems and excess use of high cost medications.
Formulary systems
Formulary contain list of drugs, which reflects the clinical judgement of the medical staff.
This list of drugs generic name will be arranged alphabetically and or by therapeutic class (AHFS classification)
and usually contain information on the dosage form, strength, names, and ingredient combination products.
Means to manage the medication inventory and provide high quality, effective, and safe medication.
P&T committee develops formulary effective, safe, economical drugs in hospital formulary.
Advantages. Eliminates duplication of drugs.
The selection of drug for hospital formulary Cost effective analysis (CEA) is used, this means drug that are
selected are cost effective.
Automatic Stop Order: Antibiotic 3days,
Hospital dosage system include:

Unit dose (cap, tab, susp, powder)
Floor stock
IV dose
TPN dose
Special Access Program (SAP): Emergence drugs or investigational drugs: Drugs that are NOT approved,
investigational drugs, withdrawn drugs can be obtained by special access program (SAP) from health Canada.
Hospital Financing: Health care in Canada is public administration. It is owned and managed by provincial
governments. However provincial, federal, offers hospital funding from health premiums, and charities.
Medication reconciliation: Gathering patient medication information at the time of hospital admission, transfer
ICU and discharge. ISMP recommend to use Best possible medication history (BPMH) chart to gather
information.
Medication reconciliation is performed by pharmacy technician.
Medication safety procedure. QA, QC and risk management:

ADR reporting: Pharmacovigilence of MedEffect. Health Canada.
Incident reporting: Canadian Institute of Health Information (CIHI) or Institute of safe medication practices
(ISMP).
Poison management: Poison control centres.
Pharmacy technician Role

· Med. reconciliation
· Sterile preparation can be prepared independently
· Preparing unit dose system
· Final check before delivering to wards
Tips
· Pharmacist functions in hospital pharmacy à
· Pharmacist role in P&T committee à
· Therapeutic equivalent drugs in hospital à
· What is least likely pharmacist functions in hospital pharmacy à
· Who is the last person to check medications in hospital ward à
· A patient in hospital is using different brand of drug, then hospital formulary. Patient wants same drug? à
· Hospital funding -->
· Medication Reconciliation: gathering medication information from patient at the point of hospital
admittance and discharge.
Can doctor determine price of drug from drug formularies? yes
www.pharmacyprep.com Pharmaceutical sciences
Part 4
Pharmacy Practice
PharmacyPREP.com
BASIC & CONVERSIONS PHARMACOKINETIC
POUNDS = 2.2 KG DISTRIBUTION: Vd = D/Cp
D = M/V M =D x V V = M/D Cp = D/Vd D = Vd x Cp
BSA (FOR CHILDREN): BSA in m2 = (H0.3964) (W0.5378) (0.024265) Clt = Amount absorbed/AUC
Clt = FD/AUC
BSA (FOR CHEMOTHERAPY) C = R o /KV d (1-e-kt)
BMI = = weight in Kg/height m2 Half life T 1/2 = 0.693/k t 1/2 = C o /2k
For DILUTIONS Elimination Constant k = 0.693/t 1/2
C 1 V 1 =C 2 V 2 OR Q 1 V 1 =Q 2 V 2
FOR CONCENTRATIONS STEADY STATE
%C= SOLUTE X 100 C ss = R/K x V d
SOLUTE+SOLVENT Rate of Infusion (R) = C ss x k x V d
ELECTROLYTES 1st order:
mEq = (mg × valence) C = C o x 10 –kt/2.303
MW Log C = log C o –kt/2.303
Mg = (mEq x MW)
Valence C = C o x e-kt
mmol = Dose in mg/ Molecular weight ln C = ln C o –kt
mOsmol/L = Wt. Of substance in g/L x number of species x 1000 F= AUC po /AUC iv
Molecular weight in g
Relative bioavailability = AUC generic/AUC of reference
AUC = [F x Dose]/V d x K
SENSITIVITY REQUIREMENT = WEIGHT X ERROR V= W X e =111.1
ARR = EER-CER Partition Coefficient (P)= (Drug) lipid /(Drug) aqueous
NNT = 1/ARR
n= number of data; x = data number RRR = [EER-CER]/EER
IV INFUSION CALCULATIONS Pharmacy Prep Chapter Management:

IV flow rate (gtt/min) = volume (mL) x drop factor (gtt/ml) TOR = total sales/average inventory
Time (min) Calculating markup% = [(sales price-cost)/cost]x100
Infusion rate (ml/min) = total volume (ml) Calculating sales price = Cost+(Cost x %markup)
Total time (min) Calculating cost of drug = Sales price/(1+%markup)
Infusion rate (ml/hr) = total volume (ml) % gross margin = [(Total sales- COGS)/total sales]x100
Total time (hr) Net profit = Gross margin – expenses
Drip factor = 20 drips/min (macrodrip) 60 drips/min (microdrip)
% net profit = net profit x 100
Total sales
Estimated GFR MDRD (Modification of Diet in Renal Disease) depends on factors CrCl, gender, age, and race
GFR (mL/min/1.73 m2)=186x(SCr)-1.154x(age)-0.203X(0.742 if female)x (1.210 if African American)
COCKGRAFT-GAULT ClCr (mL/min) = 1.2 (140−age) (weight in kg)
Serum creatinine (µmol/L)
For females, multiply the result by 0.85.
49
Basic Pharmacy Calculations
Question Alerts!
· Conversions
· Ratios and Proportions and Concentration
· Active drug quantity
· Conversion of dosage forms
· Dose Tapering
· IV Rate of infusion
Units
Volume
In Metric System 1 pint = 473 ml = 16 fluid ounces
1 fluid ounce = 29.6 ml = approximately 2
Weight
tablespoonfuls
1 Kilogram = 1000 grams 1 fluidram = 3.75 ml scientifically
1 teaspoonful = 5 ml
1 Gram = 1000 milligrams 1 tablespoonful = 15 ml
1 Milligram = 1000 micrograms One wine glassful = 60 ml
1 Microgram = 0.001 milligrams One tea cupful = 120 ml
1 Milligrams = 0.001 grams One full glass = 240 ml
4 cups = 1 pint
1 Microgram = 10 -6 grams
8 pints = 1 gallon
1 Nanogram = 10 -9 grams 1 gallon = 3.8 L
1 Grain (1 gr) = 65 milligrams An "official" dropper contains 20 drops/ml (of water)
1 kg = 2.2 lbs
Pounds and Kilograms or Kilograms (Kg) and Pounds (lbs)

· To convert lbs into Kg = divide by 2.2
· To convert Kg to lbs = multiply by 2.2
Example.
1) A newborn child weighs 10 lbs. What is weight in kg? 4.5 kg
A child weighs 22 lbs, and doctor wants to give a drug

1 mg/kg/day bid, how much you should give per day?
a. 10 mg/day B. 5 mg/day C. 15 mg/day D. 20 mg/day
Ans. A
22/2.2 = 10 kg= 10 mg
10 mg/day
A child weighs 22 lbs, and doctor wants to give 1 mg/kg/day bid drug, how much you should give per dose?
a. 10 mg/dose B. 5 mg/dose C. 15 mg/dose D. 20 mg/dose
Ans. B
each dose is 5 mg
Per day Per dose divide (Bid, tid, qid)
A patient weight 180 lbs has admitted to emergence for congestive heart failure and severe edema. Patient was
give furosemide iv infusion for the past 24 hours. After discharge the patient weight was 173 lbs. How many kg
patient weight is lost?
A. 7 kg B.3.2 kg C. 2.2kg D. 172 kg
Ans.
180 lbs-173 lbs = 7 lbs
7/2.2 = 3.2 kg
Body Surface Area (BSA):

The "BSA" stands for "body surface area." units are m2. BSA is used for chemotherapy dosing, children and adult
dosing etc.
MEMORIZE: Height conversions:
BSA in m2 = (H0.3964) (W0.5378) (0.024265) 1Foot = 12 inch
Where height is in centimetres and weight in 1meter = 100 cm
kilograms. 1 inch = 2.54 cm
BSA in m2 1 meter = 3.28 ft
Example: Height of a patient is 5ft.2 inch? 1.57 meters
How to use calculator (SHARP EL 510RN)?
Height is in centimeters and weight in kg
Press 2ndF
A patient weight 75 kg and height 162 cm. What is Press square root
BSA (m2)? What is the dose of cisplatin?
Dose of cisplatin is 1.6 mg/ m2 x 1.84 m2 = 2.94 mg
Rx. Cisplatin 1.6 mg/m2
BSA = 1.84 m2
Cisplatin dose 1.6 mg/m2 x 1.84 m2 = 2.9 mg
A client Calculate BSA (m2) or dose

Weight 68 kg and height 1. 8 meter 1.84 m2
Weight 90 kg and height 2 meter 2.23 m2
Weight 10 kg and height 0.6 meter 0.40 m2
Methotrexate 75 mg/m2 dose for patient with body 2.35 m2 x 75 mg/m m2 = 176.2 mg
weight 110 kg and height 180 cm
Cyclophosphamide 2.5 mg/m2 for pt with BSA 2.1 2.5 mg/m2 x 2.1 m2= 5.25 mg
m2
Ø A prescription order of cisplatin 750 mg/m2/day, IV tid. The patient weighs 75 kg and is 162 cm tall. Calculate
the dosage to administer?
BSA in m2 = √ (162 cm x 75 kg)/3600 How to use Calculator
= √ (12,150)/3600 SHARP EL-510R
= √3.37 2ndF
= 1.84 m2 press square root.
BSA (m2) = 1.84 m2 3.37
= 750 mg/m2 x 1.84 m2 = 1380 mg per day
1380/3 = 460 mg TID
Ø Patient age 60 yo, weight 78 kg and height 184 cm. Doctor prescribed 5-flurouracil 300 mg/m2 x 1 dose.
Calculate the dose for a day using body surface area?
BSA = √ (184 cm x 78 kg)/3600
1.99 mg/m2
1.99 x 300 mg = 597 mg per day
A chemotherapy protocol for a pt. body weight 68 kg and height 1.7 m. Chemo drug leucovorin 400 mg/m2 is
recommended what is daily dose?
√ (170 cm x 68 kg)/3600
= 1.79 m2
= 1.79 x 400 mg
= 716 mg per day
For leucovorin, in day 2 cycle each dose of medication is reduced by 50%?
716/2
= 358 mg
Body Mass Index (BMI) MEMORIZE: Height 1 meter = 3.28 ft; 12

2 conversions:
BMI = weight in Kg/height m inch = 1 ft
OR 1Foot = 12 inch 1 m = 3.3ft (3.28 ft)
Weight in Kg/height m x height m
1 Foot = 30.48 cm i.e. the conversion
1meter = 100 cm factor from meters to
· BMI = normal 18.9 to 24.9 (healthy weight) 1 inch = 2.54 cm feet is 3.28
· BMI = overweight >26 to 30 1 meter = 3.28 ft or
· BMI = obese >30 3.3 ft = 1 m
· BMI = morbid obese >35 1 ft = 12 inch
1 m = 39.37 inches
Example.
1) A person body weight is 180 lbs and height is 4 ft 6 in? What is right BMI?
A) normal 4ft = 120 cm
B) overweight 6 inch = 15 cm
C) Obese 120+15 = 135 cm
D) Morbid obese 135
Ans. 100
Height = 1.35 m
Weight = 180/2.2 = 81 kg
BMI = 81 kg
1.35 x 1.35
81/ (1.35x1.35) = 44 so BMI = 44 kg/m2
2. A doctor likes to prescribe Orlistat for a patient, weighing 150 lbs and height 4 ft 6 inch. Clinical practice
guidelines recommends, Orlistat is used only for patient BMI >30. What is correct?
A. Patient is not eligible for orlistat because BMI<30
BMI = weight in Kg/height m2
B. Patient is eligible for orlistat because BMI >30
C. Orlistat is not related to BMI
or Weight in Kg/height m x height m
D. Orlistat is not used for weight loss
Ans. B
4 ft x 30.5 cm = 122 cm
Weight = 150/2.2 = 68 kg
6 inch x 2.54 cm = 15.4 cm
Height= 137.4 cm/100 = 1.37
Total height in cm = 137 cm = 1.37
BMI = 68 kg/1.37 x 1.37
OR
BMI = 36.2 kg/m2
4.5 ft /3.28 = 1.37
Tips. Orlistat is only suitable if BMI is 28 kg/m2 or greater and other conditions related to weight like blood
pressure. or BMI >30 or treatment without any conditions and must be combined with low fat diet.
A client BMI = weight in Kg/height m2 Calculate BMI?

Body weight 90 kg and height 160 cm
Pt. body weight 190 lbs and height 5.2 ft
Pt. body weight 150 lbs and height 5 ft
Pt. body weight 78 kg and height 5ft.4in
Density (specific gravity):

· Density = Weight/volume (D = W/V)
· Volume = Weight/Density
· Weight = Volume x Density

· Unit of density is g/ml
· Water density 1 g/ml
D = W/V V = W/D W=VXD
Example:
1. If there is 1000 ml water. What is weight?
A. 10 g B. 100 g C.1kg D. 10,000 g
Ans. C
2. Glycerine 1000 ml, and its density is 1.2. How many grams?
A.1000 g
B. 1200 g Weight in g = volume x density
C. 2000 g = 1000 ml x 1.2
D. 2500 g = 1200 g
Ans. B
3.An oil 1000 ml, and its density is 0.9 g/ml. How many grams?
A.1000 g
B. 1200 g Weight = volume x density
C. 900 g Weight = 1000 ml x 0.9 g/ml = 900 g
D. 9000 g
Ans. C
3. A prescription order for glycerine 1200 ml, to prepare suppository in base. Glycerine density is 1.1. What is
weight of glycerine in suppository?
A. 1200 g
B. 1000 g Weight = volume x density = 1200 ml x 1.1 g/ml = 1320 g
C. 1320 g
D.1500 g
Ans. C
Practice examples
Given Want?
Theobroma oil 2.2 g and density is 0.9 g/ml How many mls?
Glycerine 1500 ml and density is 1.2 g/ml How many grams
Winter green oil 900 ml and density is 0.89 g/ml How many grams?
Teaspoons (tsp) and Tablespoons (Tbsp)

The physician has prescribed 1 Tbsp of Riopan. The unit dose container available contains 30 ml of this
medication.
The correct dose is 15 ML
The client has been taking 25 ml of a medication in the hospital. In preparing him to administer this medication
in the home setting, you would teach him to take _5_ tsp of this drug.
Milligrams and Grains

You are to administer phenobarbital gr ¾ . There are scored 60 mg tablets available in floor stock.
You would administer __mg or _____ tablet(s).
65mg x 3/4 = 48 mg
60 mg/4= 15 mg per piece

3 x 15 mg = 45 mg dose
45 mg
Morphine sulfate gr 1/8 IM is to be prepared from a solution containing 10 mg/1 ml. The volume to be given is
_____ ml.
Ans:
1
65 x 8 = 8 mg
10 mg.....................1 ml
8 mg...................?
= 0.8 ml
Millilitres and Ounces

The physician has ordered ss ounce of a laxative. The correct dose is _____ tbsp
ss = one half
ounce = 30 ml
tbsp = 15 ml
Ans. 1 tbsp
You are to administer 5 ml of ferrous gluconate that must be “diluted in” water to protect the client’s teeth and
gastrointestinal track. The directions in your drug reference state that each ml of this medication must be
diluted in 20 ml of water. Once diluted, the total volume to be administered is
A. 100 ml
B.105 ml Diluted in, added to, “added in” may increase total volume or weight.
C. 125 ml Dilute up to, quantity sufficient or qs, mark up to the volume should not increase
D. 120 ml volume.
Ans. B
CCALCULATIONS INVOLVING PERCENTAGE, RATIOS, PROPORTIONS
Percentage: To convert percent to fractions

25% = 25/100 = ¼
0.25 . 100% = 25%
50% = 50/100 = ½
200% = 200/100 = 2
To convert fraction to percentage: multiply by 100
3/4 . 100 = 75%
RATIOS AND RATIO PERCENT: Relation between two quantities.
A/B or A:B
W/W 1 gram in 100 grams = 1g:100 g

W/V 1 gram in 100 ml = 1g:100 ml
V/W 1 ml in 100 grams = 1mL:100 g
V/V 1 ml in 100 ml = 1mL:100 mL
Express Eatio to Ratio percent Express ratio percent strength to ratio
5:100 = 5% 0.1% = 1:1000

10:100 = 10% 0.2% = 1:500 What is ratio?
5:1000 = 0.5% 0.02% = 1:5000 0.1………….100
3:7000 = 0.04% 0.5% =1:200 1…………….x
0.05% = 1:2000 100 x 1 = 1:1000
0.1
What is the ratio percent? 100 = 1000
0.1
(5/100) x 100 = 5% 100 = 500
0.2
100 = 5000
0.02
5% ratio percent to ratio?
1:100 = (1/100) x 100 = 1% A. 5:500
1:200 = 0.5% B. 5:1000
3:500 = 0.6% C. 5:5
1:2500 = 0.04% D. 5:20
1:10,000 = 0.01% E. 1:20
Ans.
5% = 5:100
5:100 = 1:20
Express 0.02% as ratio strength
Solution: 0.02à100 ml
2à10 000 than 1à5000
Ø Add 5 g of sugar in 100 mL to prepare a syrup? What is the ratio?

A. 5:100 w/v
B. 5:100 w/w
C.5:100 v/w
D.5:100 v/v
ans. A
Ø Dissolving 4.8 g of NaCl in water can make how many millilitres of a 1:1500 solution?
Solution:
We have 1 gram for every 1500 ml of solution
So for 4.8 we will give x ml of solution
X ml = 4.8 * 1500 /1=7200 ml
PRODUCT PREPARATIONS
An order calls for How much each ingredient needed?
Cream A and Cream B 1:1 mitte 10 g 1+1 = 2PARTS so 10 g/2 = 5 g
1X 5 g = 5 g
1X5 g = 5 g
Cream A and cream B 2:1 mitte 10 g 6.6g : 3.3g
200 mg of 1:1:3 topical ointment 40 mg; 40 mg; 120 mg
150 mg of custom 2:3:5 topical cream 30 mg; 45 mg; 75 mg
Cream A+ cream B + Cream C 1:2:1 mitte 12 3 mg; 6 mg; 3 mg
mg
PHARMACY PREP: RATIO STRENGTH PRACTICE EXERCISE

For solids in semi solids; For solids in liquids For liquids in liquids (v/v) For liquid in solid (V/W)
weight/weight (w/w) weight/volume (w/v)
Weight in grams (g/g) Weight in gram and
volume in milliliter
(g/mL)
EXAMPLES
2 g of hydrocortisone in 2 g of amoxicillin 5 ml of glucose in 50 mL
100 g of base powder. powder in 100 ml water. Express percent
Express ratio strength water. Express ratio strength? 10% v/v
2:100 w/w OR strength?
1:50 W/W 2:100 w/v OR
1:50 W/V
Express percent strength? Express percent
2% w/w strength? 2% w/v
Ratio percent: W/W%

· Example: 5 g of glucose in 50 mL water, what is ratio percentà 10% W/V
(5/50)x 100 = 10%W/V
· Examples: 50 g of glucose in a 1 kg glycerine, what is ratio percentà 5% W/W
· Example: If 2% of glucose in water, what is ratio? 2 g/100 ml = 1/50 = 1:50 W/V
· 12.5 g glucose in 100 ml Water, what is ratio percent?= 12.5% w/v
· Example: 2.5% glucose in 80 ml of water? Glucose?
2.5g -------------- 100 ml

?--------------------80 ml
= (80 ml x 2.5 g)/100 ml = 2 g of glucose is present in 80 ml
Example: if 10% of dextrose in water, what is ratio? 1g :10ml W/V

Example: if 50g/L glucose, what is ratio percent? 5%W/V

Example: 100g/1L water, what is ratio percent? 10%
= 5g/50 mL = 5:50 or 1:10
Example: 50 grams of glucose in 1 L?
= 50g/1L =50:1000 = 5:100 = 1:20
Example: Convert 5 grams of glucose in 100 mL into percent?

· 5g/100mL. 100 = 5 W/V%
· 5 grams of glucose in 1L water, what is ratio percent?
· 5/1000 . 100 = 0.5 W/V%
· 50 gram of glucose in 500 ml of water, what is ratio percent?
· 50/500 .100 = 10 W/V%
5 grams of glucose in 500 mL water, what is ratio percent? 5/500 .100 = 1 W/V%
Convert 10 grams of glucose in 10 ml into percent? 10 g/10 mL = 100/1 = 100 w/v%

A drug x is 1 mg/10 ml present. What %W/V? 0.01% W/V
Two ratios with the same value are equivalent.

1/3 x 2/2 = 2/6 = 1/3
If two ratios are equal, then their reciprocal are equal:
If 1/3 = 2/6 then 3/1 = 6/2
PROPORTIONS: (TWO RATIOS) RELATION OF TWO RATIOS IS THE PROPORTION

or two equal ratios forms proportion.
A:B = C:D
A/B = C/D
or
AD = BC
From the four term one is unknown? Find the unknown

Units for each term need to be correct
Cross multiplying is used to solve X
X/D = A/B
? = (D xA)/B
Example: How many mg (?) of glucose in 500 mL water if this is equal to 1 g /L of water.
Unknown Known
X mg 1000 mg
500 ml 1000 ml
X mg = 500 ml x 1000 mg
1000 ml
X = 500 mg
Ampicillin 1 g drug vial. Add 6.8 ml sterile water to provide final concentration volume 8 mL. What is
concentration of the reconstituted solution in the vial in mg/mL?
A. 8 mg/mL
Unknown Known
B. 125 mg/mL
x mg/mL 1000 mg/8mL
C. 100 mg/mL
125 mg/mL
D. 150 mg/mL
What is the volume of ampicillin powder in vial?

A. 8 mL
B. 1.2 mL
8 mL – 6.8 mL = 1.2 mL
C. 6.8 mL
D. 100 mL
E. 2 mL
Given ampicillin 1 g vial. If the final concentration has been calculated to 125 mg/mL. What is the volume taken
if dose of the ampicillin is 500 mg?
A. 8 mL
125 mg...........1 mL
B. 4 mL 500 mg.............?
C. 2 mL or
D.1 mL (unknown) (Known)
Ans. B X ml/500 mg 1 ml/125 mg
= 4mL
A sterile methylprednisone powder vial contain 125 mg drug. Reconstituted by adding 1.8 mL of sterile water to
final volume 2 mL. What is final concentration of reconstituted solution in the per mg/mL?
A. 125 mg/mL
B. 62.5 mg/mL 2 mL ..................125 mg (known)
C. 31.5 mg/mL 1 mL .................? (Unknown)
D.16.5 mg/mL OR
Ans. B Unknown known
x mg/1mL 125 mg/2mL
An order for product preparation to maintain x mg = (1 mL x 125 mg)/2 mL alkaline
urine. = 62.5 mg/mL
Final concentration.
Sodium citrate 1% W/V
Citric acid 6% w/w
Sterile water for irrigation added up final volume 1000 mL.
How many grams of sodium citrate and citric acid powder needed?
A. 100 g and 10 g
B. 10 g and 60 g
C. 60 g and 10 g
D. 50 g and 10 g
E. 10 g and 10 g
Ans. B
Xg/1000 mL 1g/100 mL
Xg = (1000 mL x 1g)/100 mL
= 10 g
OR
1 g ……… 100 ml
? g…….......1000 ml
A 15 g of cream contains 1.45 g of Zinc oxide and 0.4 g of bismuth oxide.

i). How much Zinc oxide will there be in a 180 g tube?
ii). How much bismuth oxide will there be in a 180 g tube?
A. 17.4 g of ZnO and 4.8 g of bismuth oxide
B. 4.8 g of ZnO and 17.4 g of bismuth oxide
C. 15 g of ZnO and 0.4 g of bismuth oxide
D. 0.4 g of ZnO and 15 g of bismuth oxide
Ans. A
x g/180 g = 1.45 g/15 g
1.45 g x 180 g
15 g
= 17.4 g of ZnO
Bismuth oxide
0.4g x 180 g
15 g
=4.8 g of bismuth oxide
Product order to prepare 100 ml of hydrocortisone oral suspension with final concentration 1 mg/mL. Available
hydrocortisone 20 mg tablets. How many tablets needed to prepare 100 mL?
A. 20 tablets
B. 10 tablets
C. 5 tablets
D. 1 tablet
Ans. C
Proportion and Percent Calculations
Weight / weight Weight / Volume Volume / Volume

W/W% W/V% V / V%
Number of grams of substance Number of grams of Number of milliliters of a
in 100 grams of solvent or constituent per 100 ml of substance in 100 ml of the
mixture. solvent. solvent
1. How much drug should be added to 30 ml of water to make 10% w/w solution?
Solution: The mass of the final solution in this case in unknown, we only have the mass of solvent (water) as 30
ml will weight 30 grams.
So know we need a solution which contains 10 grams (10%) of drug in 100 grams of the solution (solvent + drug).
In this case the solvent will represent 100 –10 = 90%
So if 90% à30 grams, how much is 10 %?
The weight of the drug is = 10* 30/90 = 3.33 g
10 g + 100 g (w/w)
110 g/30 g = 3.6 g
90 ml/30 g = 3 g
2-What is the percentage strength of an injection that contains 50 mg of pentobarbital sodium in each millilitre
of solution?
Solution: [(50 mg / 1 mL) x 1 g /1,000 mg] x 100 = 5 % w/v
3-If an injection contains 0.5% w/v of diltiazem hydrochloride; calculate the number of milligrams of the drug in
25 mL of injection.
Solution: [(0.5 g / 100 mL) x ( 1,000 mg/ 1 g)] x 25 mL = 125 mg
4-How many grams of potassium permanganate should be used in compounding the following prescription?
Rx
Potassium permanganate 0.02% w/v
Purified water ad 250 mL
Solution: (0.02 g / 100 mL) x 250 mL = 0.05g = 50 mg = 50, 000 mg
Parts Per Million (ppm)

Occasionally, you will see a number followed by the term "ppm." This stands for "parts per million" and is most
often used to indicate the amount of trace substances in water. The standard dilution for fluoride added to a
municipal water source, for example, is 1ppm. In every 1,000,000 ml of water, therefore, there is 1 g of fluoride.
1) Express 5 ppm of iron in water as ratio strength and in percentage strength

Solution: 5 ppm = 5 parts in 1,000,000 parts
Ratio strength: 5:1,000,000 = 1:200,000
Percent strength: (5 /1,000,000) x 100 = 0.0005%
2) Express 10 ppm, in percent strength? 0.001%

10:1,000,000 = 0.001%
3) Express 0.0001% in how many ppm? 1ppm
4) Express 0.0005% of iron in water as parts per million (ppm)?

(0.0005 x 1000000)/ 100 = 5:1000, 000 = 5 ppm
5) Express 0.023% of iron in water as ppm? [0.023 x 1,000,000]/100 = 230 ppm

____________________________________________________________________
1-A parenteral solutions used in TIPS pharmacy. If 100 g of parenteral solution dissolved in 900 mL of petrolatum
(Density of petrolatum is 0.9 g/mL), the concentration of parenteral solution is: D = W/V
900 mL x 0.9 g/mL = 810 g
810g+100g = 910g
100g/910g .100 = 10.9% w/w
% concentration = solute x 100

Solute+ solvent
100 g x 100
100 g + 810 g
= 10.9% w/w
____________________________________________________________________
2) If 500 mL of a 15% v/v solution is diluted to 1,500 mL, what is the resultant percentage strength?
Q 1 (quantity) x C 1 (concentration) = Q 2 (quantity) x C 2 (concentration)
500 (mL) x 15 (%) = 1,500 (mL) x? (%)
1,500 x = 7,500
x = 7,500 / 1,500
x = 5% v/v
___________________________________________________________________
3. If syrup containing 65% w/v of sucrose is evaporated to 85% of its volume, what percent of sucrose will it
contain?
Note any convenient volume of syrup may be selected, say 100 mL. Then, 85% x 100 mL = 85 mL (V 2 )
C1 = 65
V1 = 100
C2 = ?
V2=85
C2 = ( C1V1)/V2
C2= 76.47% w/v
_____________________________________________________________________________
If 1 gallon of a 30% w/v solution is evaporated so that the solution has strength of 50% w/v, what is its volume
in milliliters?
C 1 = 30
V1 = 3800 mL
C2 = 50
V2=?
V2 = (C1V1)/C2
= (30 x 3800 mL)/50
= 2280 mL
5) A pharmacist mixed 100 mL of 37% w/w concentrated hydrochloric acid (specific gravity, 1.20) with enough
purified water to make 360 mL of diluted acid. Calculate the percentage strength (w/v) of the diluted acid.
100 mL x 1.20 (specific gravity) = 120 g of concentrated acid
120 g x 37% w/w = 44.4 g HCI
(44.4 g / 360 mL) x 100 = 12.33% w/v

________________________________________________________________________
Drug Strength Expressions. Units (International units) or IU. Insulin, Penicillin G, Vitamin K, Vitamin E, Vitamin A,
Vitamin D, Heparin, LMWH (Fragmin), interferon alpha, Nystatin, Polymixin, and Bacitracin.
Example. U-100 insulin contains 100 units/mL

Rx
Insulin 40units
For 60 days and bid.
How many ml of insulin you dispense?
Solution: (1 mL/100 units) x 40 units = 0.4 mL
For 60 days and two times a day = 48 mL
Q.If U-500 insulin (Humulin R U-500) is ordered for patient, a 1 ml syringe should be used. Dr prescribed 40 U of
Humulin R U-500 insulin. How many ml of insulin is drawn in syringe?
500 .............. 1 mL
40.................?
= 0.08 mL
_______________________________________________________________________
2.How many millilitres of a heparin sodium injection containing 200,000 heparin units in 10 mL should be used
to obtain 5,000 heparin units?
Solution:
200,000..........10 ml
5000............?
(10 mL/200,000 units) x 5,000 units = 0.25 mL
Practice calculations
1. In dosing the drug gentamicin in pediatric patients, for every 1 mg/kg of gentamicin administered, serum drug
concentrations are expected to increase by 2.5 µg/ml. What would be the expected serum drug concentration
following an administration of a 2.5 mg/kg dose of gentamicin?
A) 5 µg/ml B) 6.25 µg/ml C) 10 µg/ml D) 2.5 µg/ml
2) An elixir is to contain 250 mg of an alkaloid in each teaspoonful dose. How many grams of the alkaloid will be
required to prepare 5 liters of the elixir?
A) 0.25g B) 5g C) 250 g D) 2.5 g
3-A pediatric product contains 100 mg of erythromycin ethylsuccinate in each dropperful (2.5ml) of the product.
How many kilograms of erythromycin ethylsuccinate would be required to prepare 5000 pint-size bottles?
A-74.6 kg B-84.6 kg C-99.5 kg D-94.6 kg
4-A physician places a patient on a daily dose of 48 units of U 80 insulin (80units/mL). How many ml should the
patient inject each day?
A-0.4 mL B-0.5 mL C-0.6 mL D-0.25 mL
5-A 20-ml vial of biologic solution is labeled “2.0 megaunits.” How many units of drug are present in every ml of
solution?
A) 2000 B) 1000 C) 100,000 D) 10,000
6-A prescription calls for 10 units of a drug to be taken 3 times a day. How much will the patient have taken
after 7 days?
A-21.0 units B-0.21 units C-2.10 units D-210 units
7-A physician orders Meprobamate 0.2 g. How much is to be administered if the dose on hand is 400 mg. in
each tablet?
A-do not dispense B-give 2 tablets C-give 1 tablet D-give ½ tablet
8-The usual initial dose of chlorambucil is 150 µg per kg of body weight once a day. How many milligrams
should be administered to a person weighing 154 lbs.?
A-10.5 mg B-18 mg C-15 mg D-8 mg
9-An initial heparin dose of not less than 150 units/kg of body weight has been recommended of open heart
surgery. How many ml of an injection containing 5000 heparin units per milliliter should be administered to a
300 pound patient?
A-5.1 µl B-4.1 µl C-5.1 ml D4-.1 ml
10-The pediatric dose of cefadroxil is 30 mg/kg/day. If a child is given a daily dose of 2 teaspoonful of a
suspension containing 125 mg of cefadroxil per 5 ml, what is the weight in lb. of the child?
A-19.5 lbs. B-18.8 lbs. C-18.3 lbs. D-18.1 lbs.
11-If the loading dose of Kanamycin is 7 mg/kg of body weight, how many grams should be administered to a
patient weighing 130 lbs.?
A-0.492 g B-0.414 g C-414 g D-0.485 g
12-The adult dose of a liquid medication is 0.1 ml/kg of body weight as single dose. How many teaspoonfuls
should be given to a patient weighing 220 lbs.?
A-2 tsp. B-2.5 tsp. C-2 tbsp. D-2.5 tbsp.
13-If a prescription order requires 25 g of concentrated HCI (Density 1.18g/ml), what volume should the
pharmacist measure?
A-29.50 ml B-0.0212 ml C-23.0 ml D-21.2 ml
14-If the dose of a drug is 0.5mg/kg body weight/day, how many mg will a 35lb infant receive per 24hours?
A-7.9 mg B-7.1 mg C-7.2 mg D-7.4 mg
15-What is the weight of 60 ml of oil whose density is 0.9624 g/ml?

A-5.770 g B-57.7 g C-6.0 g D-0.577 g
16-A prescription calls for 0.3 g of phosphoric acid with a specific gravity of 1.71. How many milliliters should be
used in compounding the prescription?
A-0.5 B-0.7 C-0.18 D-0.3
17-How many ml of 0.9% (w/v) NaCl solution should be prepared from 250 ml of 25% (w/v) solution?
A-3750 B-2500 C-6944.4 D-9
18-A patient is determined to have 0.8 mg of glucose in each milliliter of blood. Express the concentration of
glucose in the blood as mg%.
A-800 mg% B-0.8 mg% C-8 mg% D-80 mg%
19-How many mL of a 1:400 (w/v) stock solution should be used to make 4 liters of a 1:2000 (w/v) solution?
A-1000mL B-200 mL C-800 mL D-1600mL
20-If a patient is determined to have 100 mg % of blood glucose, what is the equivalent concentration in terms
of mg/dL?
A-1 B-10 C-40 D-100
21-Strong Iodine Solution USP contains 5% w/v iodine. How many mg of iodine are consumed daily if the usual
dose is 0.3 mL t.i.d.?
A-15 B-90 C-22.5 D-45
22-Express in percentage the fluoride concentration in drinking given in 0.6 ppm.

A-0.06% B-0.00006% C-0.0006%
23-How many grams of dextrose are required to prepare 4 liters of a 5% solution?
A-0.2g B-200g C-2g D-20g
24-Change to percent the number 1/300.

A-3% B-33% C-3.3% D-1/3%
25-A Pharmacy tech adds 75 mL of strong iodine solution USP (5.0% w/v) to 1 liter of sterile water for irrigation.
What is the % w/v of iodine present?
A-0.35% B-0.375% C-0.53% D-0.60%
26-How many grams of potassium citrate are needed to prepare 1 liter of 10%?
A-1000 g B-50 g C-100 g D-10 g
27-How many grams of a drug are required to make 120 mL of a 25% solution?
A-30 g B-10 g C-12.0 g D-12 g
28-Calcium Hydroxide Topical Solution contains 170 mg of calcium hydroxide per 100 mL at 15º C. Express this
concentration as a ratio strength.
A-1: 688 B-1: 888 C-1: 588 D-1: 788
29-How many mg of isofluorophate are contained in 15 g of a 1: 10,000 ophthalmic solution of isoflurophate in

peanut oil?
A-1.7 mg B-1.9 mg C-1.8 mg D-1.5 mg
30-Express 0.2 % in a ratio strength.

A-1: 5000 B-1:50 C-1: 500 D-1:5
31-How much of a substance is needed to prepare 1L of a 1: 10,000 solution?

A-0.1 g B-10 g C-0.01 g D-1.0 g
32-A cupric chloride injection (0.4 mg Cu/mL) is used as an additive to IV solution for TPN. What is the final
ration strength of copper in the TPN solution if 2.5 mL of the injection is added to enough of the IV solution to
prepare 500 mL?
A-1: 500 B-1:5000 C-1: 500,000 D-1: 50,000
33-How many milliliters of a 23.5% (w/v) concentrate of Sodium Chloride solution should be used in preparing
650 mL of a stock solution such that 30 mL diluted to liter will yield a 1: 5000 solution?
A-0.2 mL B-4.33 mL C-18.44 mL D-11.75 mL
34-You have a stock solution of 50% Sodium citrate and you were asked to prepare 300 mL of a 10% solution.
How many mL is needed?
A-20 B-15 C-30 D-60
35-How many milliliters of 1:16 solution of sodium hypochlorite should be used in preparing 5,000 mL of a 5%
solution of sodium hypochlorite for irrigation?
A-800 ml B-2500 ml C-4000 ml D-300 ml
36) Prepare 1000 ml of KMnO 4 1:12,000 compresses out of KMnO 4 1: 8,000.

A-Add 333.3 mL water to 1000 mL KMnO 4 1: 8,000
B-Add 666.6 mL water to 333.3 mL KMnO 4 1: 8,000
C-Add 333.3 mL KMnO 4 1: 8,000 and enough water to make final volume 1000 mL
D-Add 333.3 mL water to 666.6 mL KMnO 4 1: 8,000
37-How many milliliters of 24% (w/v) concentrate of saline solution should be used in preparing 600 mL of a
solution such that 10 mL diluted to a liter will yield a 0.09% solution?
A-300 ml B-150 ml C-50.0 ml D-225 ml
38-The only source of Sodium Chloride is in the form of tablets, each containing 5.0 g. How many tablets should
be used in preparing 3000 litres of a solution of such strength that 20 mL diluted to 100 mL with water will yield
a 0.9% (w/v) solution?
A) 60,000 tablets B) 27,000 tablets C) 12,000 tablets D) 9,000 tablets
39-How many grams of 10% (w/w) ammonia solution can be made from 1800 g of 28% (w/w) strong ammonia
solution?
A) 6428.57 g B) 5040 g C) 50,400 g D) 642.86 g
40. Griseofulvin HCl 50 g was added to 20ml of Glycerine to form a paste. Density of Glycerine is 1.25.
The final concentration of Griseofulvin in the paste dosage is:
A) 80% w/w
20ml x 1.25 = 25gm of Glycerine
B) 40% w/w
50% w/w = wt of solute / (wt of solute + wt of solvent)
C) 66.7% w/w
=[ 50 / (50 + 25)] x 100% = 5000 / 75= 66.7% w/w
D) 33.3% w/w
Ans. (C )
50
Dosage Calculations
Questions Alerts!
· Tapering dosage for prednisone, SSRI, BZD, Methadone, stimulants.
· Number of tablets for prophylaxis therapies
· Calculating dosages of loading dose of antibiotics
· Calculating dosages for contraceptives pills
One of the most common calculations in pharmacy practice is that of dosages. The available supply is usually
labeled as a ratio of an active ingredient to a solution:
Active ingredient (available)/solution (available)
The prescription gives the amount of the active ingredient to be administered. The unknown quantity to be
calculated is the amount of solution needed in order to achieve the desired dosage of the active ingredient. This
yields another ratio:
active ingredient (to be administered) / solution (needed)
The amount of solution needed can be determined by setting the two ratios equal:
[active drug/Solution available] = [active drug (to be administered)/ solution (needed)]
When solving medication-dosing problems, use ratios to describe the amount of drug in a dosage form (tablet,
capsule, or volume of solution). It is important to remember that the numerators and denominators of both
fractions must be in the same units – for example, mg/ml, 5 mg/ml or mg/tablets = mg/tablets.
CHILDREN DOSES:
1. Young’s Rule: Child dose = Age/Age + 12 x Adult’s dose
2. Cowlings Rule: Infant dose = [Age (at next birthday) x Adult’s dose]/ 24
3. Frieds Rule: Infant dose = [Age (in months) x Adult’s dose]/ 150
4. Clarks Rule: Child dose = [weight (in pounds) x Adult’s dose)]/150
Tips: Rarely applied now, generally dose for children is depending on weight of pt. & the technician should ask
the agent or caregiver about the weight of pt. so that the pharmacist can check the dose.
Example
If the adult dose of X, is 5 mg. What is the dose for child of 8 years?
Since we know according to
Young’s rule: Child dose = AgexAdult’s dose
Infusion rates:
Flow rate (ml/hr) = total solution/number hrs to run
Drops per minute = (volume x drops factor)/time in minute
Q&A
1. A prescription calls for 10 units of a drug to be taken 3 times a day. How much will the patient have
taken after 7 days?
A-21.0 units B-0.21 units C-2.10 units D-210 units
Ans: D
10 units x 3 x 7 = 210 units
2. A physician orders Meprobamate 0.2 g. How much is to be administered if the dose on hand is 400
mg. in each tablet?
A-do not dispense B-give 2 tablets C-give 1 tablet D-give ½ tablet
Ans: D
Tips: 200 mg/400 mg = 1/2 tab
3) Prednisolone each tablet containing 5 mg. Start 35 mg and then taper by 5 mg every 1 day. How
many tablets are needed?
A) 20 tab B) 56 tab C) 14 tab D) 28 tab E) 8 tab
Ans: D
Tips: 7 + 6 + 5 + 4 + 3 + 2 + 1 = 28 tablets for 7 days
4) Prednisolone each tablet containing 5 mg. Start 35 mg and then taper by 5 mg every 2 day. How
many tablets are needed?
A) 20 tab B) 56 tab C) 14 tab D) 28 tab E) 8 tab
Ans: B
Tips: 7+7+6+6+5+5+4+4+3+3+2+2+1+1 = 56 tablets
5) Doctor prescribed a dose of 180 mg TID of Amoxicillin suspension for 10 days. Best Amoxicillin
suspension size to pick up and reconstitute is
(180 x 5 ml)/ 250 =3.6 ml
A) Amoxicillin 250 mg/5 ml, 100 ml size
3.6 ml x 3 doses= 10.8 ml
B) Amoxicillin 250 mg/5 ml, 150 ml size
10.8 x 10= 108 ml
C) Amoxicillin 125 mg/5 ml, 100 ml size
So it is better to pick out 250 ml/5 ml, 150 ml size.
D) Amoxicillin 125 mg/5 ml, 150 ml size
Ans.(B)
6) Using a vial containing 200,000 units of penicillin G potassium how many mL of solvent should be
added to the dry powder to prepare a solution having a concentration of 25,000 units per mL.
a) 8 b) 10 c) 15 d) 25
Ans: A
Working:
i. vial contains 200,000 units of penicillin G
ii. Each mL of reconstituted solution will contain 25,000 units. Therefore, you will need (1/25,000)
200,000 = 8mL to produce a solution containing 25,000 units / mL
7) A patient who is 3 year old experiencing sore throat. His Dr. prescribed for him:
Rx
Zithromax 200 mg
1 QD for 5/7 days
Best bottle of Azithromycin suspension to choose for reconstitution is:
A) Azithromycin 300 mg which is 100mg/5ml
B) Azithromycin 600 mg which is 200mg/5ml
C) Azithromycin 900 mg which is 200mg/5ml
D) None of the above
Ans. (B)
Tips: Since give for 5 days will constitute 1000mg so 2 bottles of Azithromycin 600mg is ok.
8) A 3-year-old boy with otitis media. Doctor prescribed Amoxicillin suspension in a dose of 90 mg/kg
for 5 days. Child weight is 56 lbs. If the product in the pharmacy is 250 mg/ 5ml and the Doctor wants to
give it in 3 divided doses. How much is the total volume required?
A) 100 ml of 250 mg/5ml
56 lbs /2.2 lbs = 25 kg
B) 150 ml of 250 mg/5ml
90 x 25 = 2,250
C) 200 ml of 250 mg/5ml
250 mg________5 ml
D) 200 ml of 125 mg/5ml
2,250________X
E) 225 ml of 250 mg/5ml
X= 2250 x 5 / 250= 45 ml per day
Ans. (E)
45 ml x 5 = 225
9) 3 parts per million of CO 2 in water is equal to

A) 0.3 mg b) 3 mg C) 3 g d) none of the above
Ans. (A)
3 parts g-------------1000 000
X-----------------100
X= 300/1000 000 = 3 x 10-4 g = 0.3 mg
10) 0.05 mg of glucose in 1L of water equal to:

0.05mg-------------------1000ml
A) 50 parts per million
x----------------------------1000000
B) 5 parts per million
hence, 50 parts per million
C) 0.5 parts per million
D) 10 parts per million
Ans. (A )
11) A patient who is 3-year-old experiencing sore throat. His Dr. prescribed for him:
Rx
Zithromax 200 mg
QD for 5/7 days
Best bottle of Azithromycin suspension to choose for reconstitution is:
E) Azithromycin 300mg which is 100mg/5ml
F) Azithromycin 600mg which is 200mg/5ml
G) Azithromycin 900mg which is 200mg/5ml
H) None of the above
Ans. (B )
Since give for 5 days will constitute 1000mg so 2 bottles of Azithromycin 600mg is ok.
12) 20 mg of Gentamycin Sulfate inj. In 2 ml of water was added to 500ml glucose water. The
concentration of Gentamycin is going to be:
A) 0.08mg b) 0.16mg c) 0.09mg d) none of the above
Ans. (A)
(20mg) x (2ml) = (500ml) x (X)
X= 40/500 =0.08 mg of Gentamycin Sulfate in 500 ml of glucose water.
13) Rx
40mg M.S contin I BID for 10days
Available MS contin 20mg.
The number of M.S contain given
A) 20 B) 40 C) 10 D) None of the above
Ans. (B )
40 x 2 = 80 x 10 = 800 mg
800 ÷20 mg= 40 tab
14) Rx
Ratio-prednisolone 1% ophthalmic drops
Mitt: 5ml
Sig. Gtt ii.o.s
On the label the instruction should be:
A) Instill 2 drops on the right eye
B) Instill 2 drops on both eye
C) Instill as directed
D) Instill 2 drops on the left eye
Ans. (D)
16. Syrup is an 85% w/v solution of sucrose in water. It has a density of 1.313 g/ml. How many grams of water
should be used to make 125 ml of syrup? (D = W/V)
A. 85 g B. 106 g C. 125 g D. 164 g E. 58 g
Ans. E
125 ml x 1.313 g/ml = 164 g
100 ........... 85
125.............?
125 x 85
100
= 106 g
164g -106g = 58 g of water
51
Dilution, Concentrations
Questions Alerts!
· Dilution from Stock C1 x V1 = C2 x V2 or Q1 x C1 = Q2 x C 2
· Concentration = [quantity of solute/quantity of solution] x 100
· Using Allegation methods to prepare ointments mixture.
· Electrolytes: Converting from milliequivalent to milligram mEq = [mg x valence/M. wt (mg)]
· Converting from milligram to milliequivalent mg = [mEq x M. wt/Valence]
· Isotonicity: MilliOsmole, isotonic preparation.
· Sensitive requirement of balance.
Stock solution: Solutions of known concentration that are prepared in the most concentrated form. Sometimes
a stock solution will be pure drug in powder or crystalline form. At other times it will be a liquid or a solid paste
or cream.
Stock solutions and additives. Here are some common IV stock solutions. A pharmacist or pharmacy technician
will withdraw a calculated number of milliliters from the vial and place it into a bag of fluid, thereby diluting the
original concentration of the stock solution. These stock solutions are also called "additives" because they are
added to another IV solution.
Most commonly dilution and concentration can be solved by inverse proportion method and by determination
of percentage or ratio strength. The following formula can be used to calculate dilutions and concentrations:
Q1 (quantity) X C1 (concentration) = Q2 (quantity) X C2 (concentration)
Or We can use the equation = C 1 x V 1 = C 2 x V 2

C1x V1= C2 x V2
C1 = (C2 V2)/V1
C 1 = stock concentration V2 = (C1V1)/C2
V 1 = stock volume V1 = (C2 V2)/C1
C 2 = final concentration
V 2 = final volume
Examples:
1) A prescription for hydrocortisone cream 0.1%. Pharmacy has 0.25% available in 30 g tube. How many grams
diluents base (vanishing cream) should be added?
A) 30 g B) 45 g C) 50 g D) 75 g E) 25 g
V 2 = (C1 x V1)/C2
V 2 = (0.25% x 30 g)/0.1%
V 2 = 75 g
but the added tube contains 30 g

so the used base = 75 g - 30 g = 45 g
Dexamethasone is available as 4 mg/mL preparation. in infant is to receive 0.35 mg. Prepare a dilution so that
the final concentration is 1 mg/mL. How much diluents will you need if the original product is in a 1mL vial and
you use the full vial?
A) 4 ml
Step1: determine the volume of final product. Since dexamethasone is 4mg/mL, a 1 ml vial
B) 3ml
have 4mg of drug. X ml/ 4 mg = 1 ml/1 mg = 4 mL
C) 1ml
Step2: subtract the volume of concentrate from the total volume to determine the amount of
D) 0.35ml
diluents needed. 4 ml-1ml = 3 mL
Ans: B
If a 600 ml (v 1 ) of a 15% (v/v) (c 1 ) solution of methyl salicylates in alcohol are diluted to 1500 ml (v 2 ) what will be
the percentage strength.
A. 6% v/v C2 = (C1xV1)/V2
B. 12% v/v C2 = (15% x 600 ml)
C. 6% w/v 1500 ml
D. 6% v/w = 6% v/v
E. 6% w/w
A physician has prescribed 60 g (v 1 ) of 0.01% (c 1 ) fluocinolone acetonide cream. You have available the
commercially prepared cream containing 0.2% (c 2 )fluocinolone acetonine (Synalar cream) and cream base
(Dermabase ) for dilution. To prepare the Rx you would require:
a) 1.2 g Synalar and 58.8 g Dermabase
b) 3 g Synalar and 60 g Dermabase C1x V1= C2 x V2
c) 0.3 g Synalar and 59.7 g Dermabase 0.01% x 60 g = 0.2% . Q2
d) 3 g Synalar and 57 g Dermabase X = (60 g x 0.01)/ 0.2 = 3 g Synalar
Order is for 60 g - 3 g = 57 g dermabase
If 50 ml (v1) of 1:20 w/v (c1) solution are diluted to 1000 ml (v2), what is the ratio strength (w/v)?
A. 1:20 1:20 = (1/20) x 100 = 5%
B. 1:30
C. 1:40 C2 = 5% x 50
1000 ml
D. 1:400
= 0.25% or = 25/10,000
E. 1:500
Ans. D = 1:400
If a potassium chloride elixir contained 20 mEq of potassium ion in each 15 mL of elixir, how many milliliters will
provide 25 mEq of potassium ion to the patient?
Solution/Answer:
20 mEq = 25 mEq
15 mL x mL
x = 15 x 25 x = 18.75 mL
20
How many grams of dextrose are required to prepare 4,000 mL of a 5% w/v solution? Equivalent factor: a 5%
w/v solution = 5 g in 100 mL of solution.
Solution/Answer
(5 g / 100 mL) x 4,000 mL = 200 g
Calculations involving dilution and concentration of Stock solutions

A solution of known concentration that is prepared in the most concentrated form is referred as stock solutions.
Sometimes a stock solution will be pure drug in powder or crystalline form. At other times it will be a liquid or a
solid paste or cream.
How many mL of a 1:500 (w/v) stock solution should be used to make 4 liters of 1:2000 (w/v) solution?
Solution/Answer: 1:500 = 0.2%

4 liters = 4000 mL
1:2000 = 0.05%
0.2%/0.05% = 4000 mL / x mL = 1000 mL
Concentrations:
2) A parenteral solution used in hospital pharmacy. If 250 g of parenteral solution dissolved in 1000 mL of
glycerin (density of glycerin is 1.25 g/mL), the concentration of parenteral solution is?
A) 8% w/w %concentration = solute x 100
B) 20% w/w Solute+ solvent D = M/V or W = D x V
C) 24% w/w Solvent (glycerine)=
D) 16% w/w 250g x 100 W = 1.25 x 1000 mL = 1250 g
E) 32% w/w 250 g + 1250ml
= 16% W/W
Allegation Method
Allegation medial: A method for calculating the average concentration of a mixture of two or more substances.
1) What is the final percentage of ZnO ointment made by mixing ZnO ointment of the following strengths?
200 g of 10% + 50 g of 20 % +100 g of 5%
Solution:
+200 * 10% = 20 +
+50 * 20% =10 +
+100 * 5% = 5+
Therefore, we have 350 g of the ointment which contain 35 g of ZnO

Therefore, the percentage is 35/350=10%
Ointment mixture of 15 g of 70%, 5 g of 90%, 10 g of 40%, 5 g of 10%, what is final concentration of this mixture?
A. 15%
15 g + 5 g + 10 g + 5 g = 35 g
B. 5%
C. 55% (15x70)/100 + (5x 90)/100 + (10 x 40)/100 + (5x10)/100 =
D. 70%
E. 40% 10.5 + 4.5 + 4 + 0.5 = 19.5
Ans. C (19.5 /35 g) x 100 = 55%
ALLEGATION ALTERNATE: A method of calculation of the number of parts of two or more components of
known concentration to be mixed when the final desired concentration is known.
Which proportion of 95% alcohol and 50% alcohol should be used to make a solution of 500 mL of 70% alcohol?
Solution:
.................................. 20 parts of 95 % ............223 ml

95%
70%
(desired)
50%
5 .............................. 25 parts of 50%..............277 ml
The final proportion is 20+25 = total 45 parts

Take 95%: (20/45) x 500 ml = 223 ml
Take 50%: (25/45) x 500 ml = 277 ml
Prescriber orders to prepare 1% hydrocortisone 60 g. Your pharmacy has stock of 0.5% hydrocortisone and 2.5%
hydrocortisone. How many each grams is mixed?
A. 15 g of 2.5% and 45 g of 0.5% HC 1.5 parts (1.5/2)60
0.5%
B. 45 g of 2.5% and 15 g of 0.5% HC
C. 15 g of 2.5% and 15 g of 0.5% HC 1%
D. 45 g of 2.5% and 45 g of 0.5% HC 2,5% 0.5
E. 2.5 g of 2.5% and 0.5 g of 0.5% HC
0.5 1.5
1
2.5 0.5
2.5% of HC ..........( 0.5/2)x60 = 15 g

0.5% of HC...........(1.5/2)x60 = 45 g
Rx
A prescription for Hydrocortisone 1% 60 g. Your pharmacy has 2.5% hydrocortisone and petrolatum base (0%).
What fraction of each hydrocortisone needed use to prepare above prescription
A. Petrolatum 36 g & 2.5% HC 24 g
B. Petrolatum 24 g & 2.5% HC 36 g 2.5% 1 part
C. Petrolatum 60 g & 2.5% HC 24 g 1%
D. Petrolatum 36 g & 2.5% HC 36 g 0% 1.5 part
E. Petrolatum 24 g & 2.5% HC 24 g 2.5% HC = (1/2.5) x 60 g = 24 g
Petrolatum base = (1.5/2.5)x60 g = 36 g
Rx
A prescription for Hydrocortisone 1% 60 g. Your pharmacy has 0.5% hydrocortisone and hydrocortisone powder
(100%). What fraction of each hydrocortisone needed to use to prepare above prescription
A. HC powder 0.3g and 0.5% HC 59.7 g
B. HC powder 59.7 g and 0.5% HC 0.3 g 0.5% 99
C. HC powder 0.3 g and 0.5% HC 0.3 g
D. HC powder 59.7 g and 0.5% HC 59.7 g 1%
E. HC powder 59.7 g and 0.5% HC 0 g
Ans. A 100% 0.5
0.5% of HC = 59.7 g
HC powder = 0.3 g
Calculation involving electrolyte solutions
Electrolyte solutions. These preparations used in treating electrolytes imbalance in body. The concentration of
electrolytes is almost exclusively expressed in milliequivalents which reflect a unit of chemical activity.
Mole: molecular weight in grams

Reference atomic weights: Na = 23, C = 12, O = 16, K = 39, One mole of NaCl = 58.5 g
Cl = 35, Ca = 40 One mole of KCl = 74.5 g
One mole of HCl = 36 g
Eq. wt = Molecular Weight/Valence One mole of Na2CO3 = 106 g
One mole of CaCl2 = 111 g
Converting between milligrams (mg) and milli equivalent
(mEq)
Number of mEq = Weight of substance in mg/mEq weight
Molarity
Molarity is the expression of the number of moles of solute is dissolved in litre of solution. Molarity can be
calculated by diving the moles of solute by the volume of solution in litres.
One mole dissolved in 1liter solution is 1M.
1M HCl = 36.5g of HCl dissolved in 1L

1M NaCl = 58.5g of NaCl dissolved in 1L
One mole of substance dissolved in a liter solution
Molarity = molecular weight in grams/ Litres
1molar NaCl = 58 grams in litre
To prepare 100 mL of 1M NaCl, how many grams of NaCl (Mol. wt of NaCl = 58.5g) needed?
Solution: 58.5 / 1000x 100 = 5.85g

________________________________________________________________
To prepare 28 mL of 0.5M NaCl, how many grams of NaCl needed? (M. Wt of Na = 58.5)
Solution: 58.5/2 = 29 g
29/1000 x 28 mL = 0.8 g
Millimole
Millimole (mmol)/L = Molecular Wt in milligrams/Litres
1 mmol of NaCl solution contain how many milligram of sodium chloride? 58.5 mg /L
1 mmol of 100 mL NaCl contain how many milligram of NaCl? 5. 8 mg
0.5 mmol of NaCl contain how many milligram of NaCl? 29 mg
Magnesium has an atomic weight of 24, what is weight of 1 mmol? 1mM = 24 g/1000 = 0.024 g = 24 mg.
Normality
A method of dealing with acids, bases, and electrolytes which involves the use of equivalents. One equivalent of
acid is the quantity of that acid that supplies or donates of mole of H+ ions. One equivalent of base is quantity
that gives off one mole of OH- ions.
One equivalent of acid (H+) reacts with one equivalent of base (OH-). Equivalent can be calculated for atoms or
molecules.
Equivalent wt dissolved in 1L
Equivalent Wt = M. wt in g/Valence
1N HCl = 36 g of HCl dissolved in 1L

The salts with valence 1 have the same molarity and normality. The valence in salts is referring to metal ions.
The salts with valence 1: NaCl, HCl, KCl, Li 2 CO 3 , Na 2 CO 3 , NaHCO 3
The salts with valence 2: CaCO 3 , CaCl 2 , MgCl 2 , Mg (OH) 2 , ZnCl 2
The salts with valence 3: Al, citrate
One mole of NaCl contain one equivalent of Na+ (Na mol. weight 23 g)
One mole of NaCl contain one equivalent of Cl- (Cl mol. weight 35 g)
0.9 % NaCl contain 0.9 g of NaCl in every 100 mL
0.9% NaCl contain 9 g of NaCl in every 1liter
MilliEquivalent: The amount in mg, of a solute equal to 1/1000 of its gram equivalent weight per unit volume.
Converting milliequivalents per unit volume to weight per unit volume.
Valence: Na, K, Li = 1; Ca, Mg = 2 and Al = 3
mEq = [mg x valence]/(Mol.Wt) mg = [mEq x (mol.wt)]/valence
1. How many milliequivalents of sodium ion is in 92 mg/ml of NaCl salt? M.wt of Na = 23

A. 1 mEq
B. 2 mEq mEq = 92 mg/ml x 1
C. 3 mEq 23
mEq = 4 mEq
D. 4 mEq
E. 5 mEq
How many mEq of magnesium sulphate are represented in 1 g anhydrous magnesium sulfate? (M. wt of MgSO 4
=120)
A) 120 mEq
B) 32 mEq mEq = 1000 mg x 2
C) 16.6 mEq 120
D) 33.2 mEq mEq = 16.6 mEq
E) 66.6 mEq
Ans: C
A solution contain 10 mg% of Ca2+, describe this concentration in mEq/L. (Atomic weight = 40 and valence = 2
A. 5mEq/L
B. 10 mEq/L
C. 40 mEq/L 10 mg% is = 10 mg/100 ml
D. 2 mEq/L 10 mg% for 1L is 100 mg/L
E. 50 mEq/L mEq/L = [(mg/L) (valence)]/atomic weight
Ans. A [(100 mg/L) (2)] / 40 mg = 5 mEq/L
What is the concentration in g per ml of a solution containing 4mEq of calcium chloride (CaCl 2 x 2H 2 O) M. wt =
147
A. 294 mg
Mg/L = (mEq x Mwt)
B. 0.294 g/L
Valence
C. 0.0002 g/ml
Mg/L = [(4 x 147)]/ 2
D. 147 mg
= 294 mg/L = 0.294 g /L = 0.0002 g/mL
E. 147 g
Ans. C
mEq? Mg/ml?
mEq = [mg x valence]/(Mol.Wt) Mg = [mEq x (mol.wt)]/valence
If valence is 1 (Na, K, Li) If valence is 1 (Na, K, Li)
mEq = mg/Mol.wt Mg = mEq x mol.wt.
How many mEq of sodium salt if 196 mg NaCl in A 100 mL bag contain 40 mEq of potassium chloride. What is
10 mL solution? (Na=23, Cl 35.5) the weight potassium is contained in IV bag? (K = 39, Cl=35.5)
196/58.5= =74.5
3.35 mEq of Sodium ion present in 10 mL. 40 mEqx 75 mg
3000 mg of K is present in 100 mL of IV bag.
What is concentration in mg/ml of a solution containing 2 mEq
of KCl per mL? 149 mg/ml
What is the concentration in mg/ml of solution containing 4
mEq/ml of CaCl 2 .2H 2 0?
Mol.weight = 147
(4x147)/2 = 294 mg/mL
Potassium chloride 75 mg = 1mEq of KCl. (KCl MW: 75)
Potassium citrate 108 mg = 1mEq of K.citrate (K.citrate MW
108)
Potassium chloride 75 mg = 1mEq of KCl. (KCl MW: 75)—K+ is 39 mg

Potassium citrate 108 mg = 1mEq of K.citrate (K.citrate MW 108) K+ is 39 mg
Rx
Give K+ 39 mg. (atomic weight of K+ 39)
Your pharmacy has potassium citrate salt (K+citrate MW = 108 mg). How many mg of potassium citrate is used
to prepare this prescription?
A.108 mg
Rx
Give K+ 39 mg.
Your pharmacy has potassium chloride salt (KCl MW= 75 g). How many mg of potassium chloride is used to
prepare this prescription? 75 mg
Rx
Give Ca2+ 40 mg
Your pharmacy has calcium chloride salt. How many mg of calcium chloride (MW:111) is used to prepare this
prescription? 111/2 = 55.5 mg
Rx
To prepare potassium ion 20 mEq and how many mg of potassium chloride needed (KCL MW = 75)?
A.1500 mg
B. 200 mg 20 x 75 = 1500 mg of KCl salt gives 20 mEq of K+
C. 750 mg
D. 75 mg
E. 7500 mg
To prepare potassium ion 20 mEq and how many mg of potassium citrate needed (KCitrate MW = 108)?
A.2160 mg
B. 200 mg 20 x 108 = 2160 mg of KCitrate salt gives 20 mEq of K+
C. 750 mg
D. 75 mg
E. 7500 mg
or potassium citrate?
A. KCl = 75 mg x 20 = 1500 mg OR K.citrate = 108 mg x 20 = 2160 mg
What is the concentration in mg/ml of a solution containing 2 mEq of KCl per millilitres (KCl M.Wt = 74.5)?
A. 74.5 mg/mL
B. 149 mg/mL 2 mEq. Of KCl= 74.5 mg × 2 = 149 mg/ml
C. 39 mg/mL
D. 75 mg/mL
E. 58 mg/mL
Ans. B
OR
mg/ml = 2 (mEq/ml) × 74.5 = 149 mg/ml

What is the concentration, in grams per milliliter of a solution containing 4 mEq. Of CaCl 2 .2H 2 O per milliliter?
(M. weight of CaCl 2 .2H 2 O = 147)
Eq. wt. Of CaCl 2 .2H 2 O = 147/2 = 73.5

1 mEq. CaCl 2 .2H 2 O = (1/1000) × 73.5 g = .0735 g
4 mEq. Of CaCl 2 .2H 2 O = 0.0735 g × 4 = 0.294 g/ml
OR
by mg/ml = [4 x 147]/ 2 = 294 mg/ml = 0.294 g/ml
Converting Milligram % to mEq/L

1-A solution contains 10 mg% of K+ ions. Express the conc. In terms of mEq/L?
Solution:
Atomic weight of K+ = 39
Equivalent weight of K+ = 39
1 mEq. Of K = (1/1000)x39 g = 0.039 g = 39 mg
10 mg% of K + = 10 mg K + per 100 ml
= 100 mg per liter
100 mg x 39 = 2.56 mEq/L
Or
MEq/L = [100 mg/L × 1] / 39 = 2.56 mEq/L
2-A solution contains 10 mg % of Ca ++ ions. Express this concentration in terms of mEq/Liter
mEq/Liter = [100 mg /L ×2 ] / 40 (atomic weight of Ca ++)
Converting weight to milliequivalents
1-How many mEq. Of KCL are represented in a 15 ml dose of 10 % w/v KCL elixir ? Mol. Weight KCl = 74.5 g
Solution:
Equivalent weight = 74.5 g
1 mEq of KCL = 0.0745 grams =74.5 mg
15 ml dose of 10 % w/v elixir = 1.5 g or 1500mg KCL
74.5 mg --à 1 mEq
1500 mg --àx x = 20.1mEq
Milliosmole: The unit of osmotic activity. It is the unit of measuring the osmotic concentration. Osmotic
pressure is directly proportional to the number of particles in the solution.
Osmotic pressure µ Number of Particles in solution
Milliosmole is a way of expressing number of particle in solution.

i.e. if there is one particle then millimole = 1 milliosmole
if there is two particle then millimole = 2 milliosmole
Solute which dissociate (i.e. electrolytes) exert osmotic activity based on the number of particles present in
solution after they have dissociated.
1 millimole of NaCl = 2 milliosmole
1 millimole of CaCl 2 = 3 milliosmole

1 millimole of NaH 2 PO 4 = 2 milliosmole
Solutes which do not dissociates in solution, such as dextrose exerts 1 mOsm for each millimole.
Osmol/L = wt. Of substance in g/L X number of species

mOsmol/L = Wt. Of substance in g/L x number of species x 1000

CALCULATING mOsmol FOR ELECTROLYTE SOLUTIONS
Solutes, which dissociate exert osmotic pressure based on the number of particles present in the solution after
they have dissociated.
Some Example salts:

For NaCl, the number of species = 2
NaCl à Na+ + Cl-
For CaCl 2 , the number of species = 3
CaCl 2 à Ca2+ + 2Cl-
For Li 2 CO 3 the number of species = 3

Li 2 CO 3 à 2Li + + CO 3 2-
For MgSO 4 the number of species = 2

MgSO 4 à Mg + SO 4
For Solutes which do not dissociate, the milliosmole = millimole
NON-IONIC SOLUTES (SPECIES IS ALWAYS 1)

Dextrose, gluconate are examples of substances that do not dissociates. However salts dissociates into ions.
________________________________________________________________
1) Solution contains 5% anhydrous dextrose in water injection. How many milliOsmoles per litre are present in
this concentration? (M. wt = 180 g).
A. 278 mOsmol/L
B. 180 mOsmol/L mOsmol/L = 50 g x 1 x 1000 = 278 mOsmol/L
C. 50 mOsmol/L 180
D. 920 mOsmol/L
IONIC SOLUTS (SPECIES FOR NaCl = 2, CaCl 2 = 3; KCl = 2)

________________________________________________________________
2) How many milliosmoles per litre are present in 0.9% NaCl solution (MW NaCl= 58.5 g?
A. 278 mOsmol/L
B. 307 mOsmol/L 0.9% NaCl is 0.9g in 100ml, however, solution in one litres,
C. 58 mOsmol/L thereby NaCl concentration is 9 g
D. 45 mOsmol/L (9 x 2 x1000) = 307 mOsmol/L
58.5
ISOTONIC SOLUTION PREPARATIONS

Isotonic à "Normal saline" and is 0.9% NaCl concentration
Hypotonicà Less than 0.9% NaCl concentration
Hypertonic à More than 0.9% NaCl concentration
Tonicity is affected by number of particles in solution. Substances that dissociate have greater tonic effect than
non-dissociated substances. Greater the dissociation greater the osmotic pressure and greater the tonic effect.
Q. How much NaCl required to prepare?

Rx (1/500) x 100 = 0.2%
Silver nitrate 1:500 (0.2%); NaCl equivalent = 100 ml………..0.2g
0.34 60 ml……..?
Isotonic solution 60 ml = 0.12 g of Silver nitrate
A. 0.9 g NaCl 0.12 g x 0.34 = 0.0408 g silver nitrate
NaCl =
B. 0.6 g NaCl
100 ml……….0.9
C. 0.49 g NaCl
60 ml............?
D. 0.2 g NaCl 0.9/100 = X/60
E. 0.34 g NaCl X = 0.54 g NaCl is isotonic
Required NaCl = 0.54 - 0.04g = 0.50 g of NaCl should be added to make
isotonic
Rx
ZnSO4 ----------1/4 %
Phenylephrine--1/8 %
NaCl----------------Q.S.
Aq. Distilled ad to 30 mL
How much NaCl must be added to the following Rx to make it isotonic? NaCl equivalent of ZnSO 4 =0.16, NaCl
Equivalent of phenylephrine=0.29.
A. 247 mg NaCl
B. 16 mg NaCl
C. 290 mg NaCl
D. 900 mg NaCl
E. 40 mg NaCl
First step:
Calculate the amount of each ingredient in the prescription
so if we look at the prescription you will find that the final volume is 30 ml .
so for ZnSO 4 , we need 0.25 for each 100 ml so for 30 ml we need 30 * 0.25/100=0.075
grams. now for phenylephrine do the same so we will need 30 * 0.125/100 = 0.0375 grams.
Second step:
By using the NaCl equivalent of each of them calculate the contribution of these salts to the isotonicity of the
solution .
now for ZnSo 4 : 1 gram of ZnSo 4 is equivalent to 0.16 grams of NaCl , but in our prescription we have only 0.075
so this makes the solution as if it contains
1 gram ------> 0.16 NaCl
0.075 gram -------> x NaCl
x = 0.075 * 0.16 / 1= 0.012 NaCl
Applying the same for phenylephrine: 0.0375 *0.29 / 1 = 0.0108 NaCl
Therefore total contribution of the salts = 0.012 + 0.0108 = 0.022875 NaCl
Third step:
Find the amount of NaCl needed to make 30 ml - which is the volume of the final solution - isotonic.
so we need 0.9 grams NaCl for every 100 ml ...so for 30 ml we need :
0.9 g --------100 ml
x g ---------30 ml x= 30 * 0.9/100 = 0.27g NaCl
Therefore the amount of NaCl needed = 0.27 - 0.022875 =0.247 grams = 247 mg NaCl
You are given ZnCl 2 0.7%, phenylephrine 0.1% and boric acid 1.1% with E values 0.16, 0.32 and 0.5 respectively.
This solution will be:
A) Hypotonic [(0.7 x0.16] + [(0.1 x 0.32] + [(1.1 x 0.5)]
B) Hypertonic = 0.112 + 0.032 + 0.55 = 0.69 g
C) Isotonic = 0.9>0.69 = Hypotonic
D) Non-isotonic
Ans. A
0.9 - 0.69 = 0.21g
How much NaCl required to make above solution to isotonic solution?

A. 0.21 g
B. 0.69 g
C. 0.9 g
D. 2 g
E. 9 g
Ans. A
Dissociation factors: The dissociation factor is the measure of the number of particles resulted in when a
substance is placed in aqueous solution.
Non-electrolyte substances have low dissociation factor. Dissociation factor for non-electrolytes substances are
assigned a value of 1.
Substance dissociate into two ions dissociation factor (i) = 1.8
For three ions (i) = 2.6
For four ions (i) = 3.4
For five ions (i) = 4.2
Salts that dissociate into two ions: NaCl, KCl, LiCl, NaHCO 3
Salts that dissociate into three ions: Li 2 CO 3 , Na 2 CO 3 , ZnCl 2 CaCl 2 , Mg(OH) 2
Sodium chloride equivalent

1-Calculate the sodium chloride equivalent for fluorescein sodium, which dissociates into three ions and has a
molecular weight of 376.
i factor for sodium chloride = 1.8
i factor for fluorescein sodium = 2.6
Mol. wt of sodium chloride x i factor of substance = sodium chloride equivalent
i factor of sodium chloride Mol. wt of substance
58.5 x 2.6 = 0.22

1.8 376
NaCl equivalent (E) = 0.22
1) Zinc sulfate is a two-ion electrolyte, dissociating 80% in weak solutions. Calculate its dissociation factor.
A. 1.8
B. 1.7
ZnSO4 à Zn + SO4 +
C. 2 ZnSO4
D. 2.5 100 à 70 + 70 +
E. 1
EXPLAINED:
On the basis of 70% dissociation, 100 particles of zinc sulphate (ZnSO 4 ) yield:
70 zinc ions
70 sulphate ions
30 undissociated particles
170 total particles
Because 170 particles represent 1.7 times as many particles as were present before dissociation, the dissociation
factor is 1.7.
CALCULATIONS INVOLVING BALANCE SENSITIVITY
A prescription balance class III, balance has a sensitivity requirement of 6 mg, it means?
A. Maximum weighing capacity of balance is 6 mg
B. Minimum weighing capacity of balance is 6 mg
C. As much as 6 mg could be added to or removed from pan before the balance marker move 1 division
D. Have maximum capacity weight of balance 120 g

Ans. C
Pharmacy electronic balances typically have a less 10 mg sensitivity

What is the minimum quantity that can be weight on a balance with sensitivity requirements of 10 mg of a 5%
error is permissible?
A. 6 mg
B. 15 mg Sensitivity Requirement = Weight x Error
C. 300 mg 10 = weight x 5/100
D. 600 mg Weight = (10/5) x100 = 200 mg
E. 200 mg
Ans. E
2) What is the sensitivity of a balance that can weight 120 mg of a substance and has a permissible error of 5%?
A. 15 mg
SR = Weight x Error
B. 6 mg
C. 5 mg SR = 120 mg x 5 /100 = 6 mg
D. 120 mg
E. 12 mg
Ans. B
SR = W x E E = SR/W W = SR/E
W = 150 mg SR = 10 mg SR = 10
E = 5% W = 300 mg E = 5%
7.5 mg 3.3% 200 mg
Error = sensitivity requirement/weight
Weight = sensitivity requirement/error
The balance SR is 6 mg. A pharmacist makes an attempt to calculate 120 mg of codeine sulfate, calculate the
percentage error?
Error = sensitivity requirement/weight
Practice Calculations
1) How many ml of 0.9% (w/v) NaCl solution should be prepared from 250 ml of 25% (w/v) solution?
A-3750 ml B-2500 ml C-6944.4 ml D-9 ml
Ans: C
C 1 V1 = C 2V 2
(X)(0.9)= 250(25)
X = 6944.4 ml
2) A Pharmacy tech adds 75 mL of strong iodine solution USP (5.0% w/v) to 1 litre of sterile water for irrigation.
What is the % w/v of iodine present?
A) 0.35% B) 0.475% C) 0.53% D) 0.60%
Ans: A
C 1V1 = C 2V2
75 (5) = (1075) X
X = 0.35%
3) Determine the specific gravity of a mixture of 900 mL of syrup with a sp. Gr. of 1.1898, 700 mL of elixir with a
sp. Gr. of 0.975 and 1150 mL of glycerin with a sp. Gr. of 1.240.
a) 1.1349 b) 1.1486 c) 1.1486 d) 1.1561
Ans: d
900 ml x 1.1898 = 1070.82
700 ml x 0.975 = 682.5
(1150 ml/3179 ) x 1.240 = 1426
3179./ 2750= 1.1561
4)What is the percentage alcohol in a mixture of 2000 mL of 50% (v/v) alcohol, 500 mL of 70% (v/v) alcohol and
2.5 L of 95% (v/v) alcohol?
a) 71.67% b) 73.25% c) 72.50% d) 74.5%
Ans:
2000 ml x 0.5 = 1000
500 ml x 0.7 = 350
(2500 ml /5000 ml) x (0.95 / 3725) = 2375
(3725 /5000) = (X/100)
X = 74.5
5) If 800 g of 5% coal tar ointment is mixed with 1200 g of a 10% coal tar ointment. What is the concentration of
coal tar in the finished product?
a) 8.5 % b) 9.5% c) 8% d) 9%
Ans: C
800 x 0.005 = 40
1200 x 0.001 = 120
160/ 2000 = X/100 X = 8%
www.PharmacyPrep.com Generic and Brand Names
52
Generic and Brand Names
Antiemetics: to treat vomiting
Generic Name Brand Name Generic Name Brand Name
Dimenhydrinate Gravol (generics) Metoclopramide Generics
Meclizine Bonamine Scopolamine Generics
Ondansetron Zofran Domperidone
Prochlorperazine Stemetil (generics) Diclectin (vitamin B6 + doxylamine)
Promethazine Phenergan
Cardiovascular Drugs
Antiarrhythmics: To treat irregular heart rhythms
Amiodarone Cordarone (generics) procainamide PronestylSR, Procan (generics)
Disopyramide Rhythmodan (generics) Quinidine Biquin (generics)
Lidocaine Xylocaine Propafenone Rythmol (generics)
Antihypertensive: to treat high blood pressure
Diuretics (water pills): There are five types of diuretics i.e. Thiazides, Loop diuretics, potassium sparing, osmotic and
carbonic ahnydrase diuretics
Hydrochlorothiazide Generics Furosemide Lasix (generics)
Metolazone Zaroxolyn
Potassium Sparing Diuretics

amiloride + Moduret (generics) Triamterene + generics
hydrochlorothiazide hydrochlorothiazide
spironolactone + Adactazide (generics)
hydrochlorothiazide
βeta Blockers (suffix "lol")

Acebutolol Monitan, Sectral (generics) Nadolol Corgard (generics)
Atenolol Tenormin (generics) Pindolol Visken (generics)
Bisoprolol Mococor Propanolol Inderal (generics)
Carvedilol Coreg Sotalol Sotacor (generics)
Labetalol Trandate (generics) Timolol generics
Metoprolol Lopresor, Betaloc (generics)
Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) (suffix "pril")

Benazepril Lotensin Lisinopril Zestril, Prinivil (generics)
Captopril Capoten (generics) Perindropril Coversyl
Cilazapril Inhibace Quinapril Accupril
Enalapril Vasotec Ramipril Altace
Fosinopril Monopril Trandolapril Mavik
Angiotensin II, AT 1 Receptor Blockers (ARBs) (Suffix "sartan")

Candesartan Atacand Losartan Cozaar
Eprosartan Teveten Telmisartan Micardis
Irbesartan Avopro Valsartan Diovan
Calcium-Channel Blockers (CCBs) (suffix "dipine, except verapamil and diltiazem)

Amlodipine Norvasc Non-Dihydropyridines
Nifedipine Adalat XL Diltiazem Cardizem CD (generics)
Felodipine Plendil, Renedil ER Verapamil Isoptin SR (generics)
Vasodilating Agents
Hydralazine Apresoline (generics) Nitroglycerin SL spray Nitrolingual Spray
(generics)
Isosorbide dinitrate Cedocard SR Minoxidil Loniten
(generics)
Isosorbide mononitrate Imdure
Nitroglycerin SL tablet Nitrostat
Centrally Acting Antihypertensive Agents

Methyldopa Aldomet (generics) Clonidine Catapres (generics)
Alpha-Adrenergic Blockers (alpha1 receptor blockers) (Suffix "zosin")

Alfuzosin Xatral Prazosin Minipress (generics)
Doxazosin Cardura (generics) Tamsulosin Flomax
Terazosin Hytrin (generics)
Antihyperlipidemic Agents (HMGCoA reductase inhibitors suffix "statin"): To treat high cholesterol, there are 4 categories
of drugs i.e. statins, fibrates, niacin and resins
Atorvastatin Lipitor Fluvastatin Lescol
Bezafibrate Bezalip Gemfibrozil Lopid (generics)
Cholestyramine Questran (generics) Lovastatin Mevacor (generics)
resin
Fenofibrate Lipidil (generics), Pravastatin Pravachol (generics)
Lipidil Supra
Rosuvastatin Crestor
Simvastatin Zocor (generics)
CNS drugs
Opiates & Other Narcotics
Codeine generics Meperidine Demerol
Dextropropoxyphene Darvon N, 642, Morphine MS Contin and generics,
(generics) M.O.S.
Hydrocodone and Hycodan, Hycomine Oxycodone preps Percocet (generics)
preps Novahistex DH,
Novahistine DH,
Tussionex
Hydromorphone Dilaudid (generics) Pentazocine Talwin
Fentanyl Duragesic Oxycodone Oxycontin
Anticonvulsants (antiepileptics or antiseizure drugs)

Carbamazepine Tegretol (generics) clobazam Frisium (generics)
Phenytoin Dilantin clonazepam Rivotril (generics)
Gabapentin Neurontin (generics) diazepam Valium (generics)
vigabatrin Sabril lorazepam Ativan (generics)
phenobarbital Generics primidone Mysoline (generics)
divalproex Epival (generics) lamotrigine Lamictal (generics)
valproic acid Depakene (generics)
Antiparkinson Drugs: To treat Parkinson's disease

levodopa/carbidopa Sinemet (generics) Amantadine Symmetrel (generics)
levodopa/benserazide Prolopa pergolide Permax
bromocriptine Parlodel (generics) pramipexole Mirapex
trihexyphenidyl generics ropinerole ReQuip
benztropine Cogentin (generics) selegiline Eldepryl (generics)
Antidepressants: SSRIs, TCAs, SNRIs and MAOIs

Monoamine Oxidase Inhibitors (MAOIs)
phenelzine Nardil
tranylcypromine Parnate
Tricyclic Antidepressants
Amitriptyline generics maprotiline Generics
clomipramine Anafranil (generics) nortriptyline Aventyl (generics)
desipramine Norpramin (generics) trazodone Desyrel (generics)
doxepin Sinequan (generics) trimipramine Surmontil (generics)
imipramine Tofranil (generics)
Selective Serotonin Re-uptake Inhibitors (SSRIs)

Citalopram Celexa fluvoxamine Luvox (generics)
Fluoxetine Prozac (generics) paroxetine Paxil
sertraline Zoloft (generics)
Serotonin norepinephrine reuptake inhibitors (SNRI) and Dual action antidepressants

Venlafaxine Effexor Bupropion Wellbutrin SR, Zyban
Mirtazapine Remeron Buspirone BuSpar (generics)
Reversible Inhibitors of Monoamine Oxidase (RIMAs)
Moclobemide Manerix and generics
Psychotropic (neuroleptic) agents (Antipsychotic drugs, antischizophrenia drugs)

Chlorpromazine Novo-Chlorpromazine Hydroxyzine Atarax (generics)
Fluphenazine Moditen (generics) Lithium Lithane, Duralith (generics)
Haloperidol generics pericyazine Neuleptil
loxapine generics perphenazine Trilafon (generics)
pimozide Orap prochlorperazine Stemetil (generics)
thioridazine generics trifluoperazine generics
thiothixene Navane
Second generation antipsychotics
quetiapine Seroquel risperidone Risperdal
olanzapine Zyprexa, Zyprexa
Zydis OD
Benzodiazepines (suffix "am") sleeping pill

Alprazolam Xanax (generics) Temazepam Restoril (generics)
Chlordiazepoxide generics Triazolam Halcion (generics)
Diazepam Valium (generics) Clonazepam
Flurazepam Dalmane (generics) Bromazepam
Lorazepam Ativan (generics)
Oxazepam Generics
Barbiturates (suffix "tal")

Phenobarbital Thiopental
Stimulants
dextroamphetamine Dexedrine methylphenidate Ritalin (generics), Ritalin SR
Gastrointestinal Drugs
Antacids
Aluminum hydroxide Amphogel Magnesium hydroxide Milk of Magnesia
Aluminum and magnesium Maalox, Mylanta, Sodium/potassium Alka seltzer
hydroxide Gelusil bicarbonate
Calcium carbonate Tums® Alginic acid/aluminum Gaviscon
hydroxide
Dihydroxy-aluminum Rolaids®
sodium carbonate
H 2 -Receptor antagonists (Suffix "tidine")

Cimetidine generics Nizatidine Axid (generics)
Famotidine Pepcid (generics) Ranitidine Zantac (generics)
Proton pump inhibitors (suffix "azole"): To treat ulcers

esomeprazole Nexium omeprazole Losec
lansoprazole Prevacid pantoprazole Pantoloc
rabeprazole Pariet
Gastroduodenal Cytoprotective Agents

sucralfate Sulcrate misoprostol Cytotec
Prokinetic Agents (antiemetics)

metoclopramide generics domperidone generics
Hormones
Thyroid Hormones
Levothyroxine Synthroid, Eltroxin Levothyroxine sod Cytomel
sodium
Thyroid Thyroid
Sex hormones
Androgens
Danazol Cyclomen Testosterone Andriol, Androgel, Androderm
Depo-Testosterone, Delatestryl
Estrogen
estradiol-17β Estraderm®, conjugated estrogens Premarin, C.E.S.
Estrace®, Estalis®,
Estrogel®
estradiol-17β Climera hormone replacement Fem-HRT® Premplus®
micronized
estradiol Estring, Vaginal Ring
Progesterone
levonorgestrel Mirena megastrol acetate Megace® (generics)
medroxyprogesterone Provera (generics), norethindrone Norlutate® Micronor®
acetate Depo-Provera
progesterone Prometrium
Combined Oral Contraceptives

Ethinyl estradiol and Alesse Demulen®
Levonorgestrel
Brevicon® Marvelon®
cyproterone acetate Diane-35 Ortho-Cept®
and ethinyl estradioL
Ortho7/7/7 Min-Ovral®
Triphasil® Synphasic®
Diabetes: Insulin
Iletin® Humulin R,N,U Humalog® Humalog Mix25
Novolin® Mixtures of 30/70; NPH (intermediate)
20/80; 50/50; 40/60
Glargine (long Lantus
acting)
Oral Hypoglycemic Agents

acarbose Prandase pioglitazone Actos
metformin Glucophage (generics) rosiglitazone Avandia
repaglinide GlucoNorm chlorpropamide Generics
gliclazide Diamicron® Diamicron MR® glimepiride Amaryl®
(generics)
glyburide Euglucon®, Diaβeta® (generics)
Neuromuscular Blocking Agents

pancuronium Pavulon succinylcholine Quelicin
bromide
Anticholinergic Drugs
Atropine generics Ipratropium Atrovent
benztropine Cogentin (generics) Oxybutinin Ditropan
dicyclomine Bentylol Tiotropium Spiriva
Adrenergic Drugs (Decongestants)

norepinephrine Levophed pseudoephedrine Sudafed
bitartrate
(levarterenol)
oxymetazoline Claritin Eye drops phenylephrine Prefrin, Mydfrin
xylometazoline Otrivin
Anti-infective agents: Penicillin's

amoxicillin generics bacampicillin Penglobe
ampicillin generics cloxacilin Generics
penicillin V generics pivampicillin Pondocillin®
Anti-infective agents: Cephalosporin's

cefaclor Ceclor (generics) cefuroxime Ceftin (generics)
cefazolin Kefzol cephalexin generics
cefixime Suprax cefprozil Cefzil
cephradine Velosef
Anti-infective agents: Macrolides

azithromycin Zithromax clarithromycin Biaxin
erythromycin Eryc (generics)
Anti-infective agents: Amino glycosides

gentamicin Garamycin (generics) tobramycin Nebcin®
amikacin Amikin
Anti-infective agents: Tetracycline

minocycline Minocin (generics) tetracycline generics
doxycycline Vibra-Tabs (generics)
Anti-infective agents: fluroquinolones

Ciprofloxacin Gatifloxacin
Norfloxacin Ofloxacin
Moxifloxacin
Anti-infective agents: Others

clindamycin Dalacin (generics) vancomycin Vancocin
metronidazole Flagyl (generics)
Anti-infective agents: sulfa drugs

co-trimoxazole Septra (generics)
Antifungals
Amphotericin B Fungizone® griseofulvin Fulvicin® U/F
clotrimazole Canesten® (generics), otraconazole Sporanox
Lotrimin- OTC
fluconazole Diflucan (generics) ketoconazole Nizoral (generics)
Single dose
Miconazole Monistat, Micatin® terbinafine Lamisil (generics)
OTC
Nystatin Nilstat, Myocostatin tolnaftate Tinactin OTC
(generics)
undecylanate Desemex OTC
Anti-Viral Agents
abacavir Ziagsen® lamivudine Heptovir®
amprenavir Agenerase® nelfinavir Viracept®
amantadine Symmetrel® nevirapine Viramune®
(generics)
acyclovir Zovirax (generics) oseltamivir Tamiflu
delavirdine Rescriptor® ribavirin Rebetron®

didanosine Videx® ritonavir/ lopinavir Kaletra®
efavirenz Sustiva® saquinavir Invirase®
famciclovir Famvir stavudine Zerit®
ganciclovir Cytovene® valacyclovir Valtrex®
indinavir Crixivan® zalcitabine Hivid®
zidovudine Retrovir® zanamivir Relenza®
Anti-neoplastic Drugs
bleomycin sulfate Blenoxane® ifosfamide Ifex®
busulfan Myleran® methotrexate generics
carboplatin Paraplatin mitomycin Mutamycin®
chlorambucil Leukeran® mitoxantrone Novantrone®
cisplatin Cisplatin® paclitaxel Taxol®
cyclophosphamide Cytoxan®, Procytox® tamoxifen Nalvodex® (generics)
cytarabine Cytosar®, ARA-C® vinblastine sulfate Vinblastine®
dacarbazine DTIC® vincristine sulfate Vincristine®
daunorubicin Cerubidine® idarubicin Idamycin®
doxorubicin Adriamycin® 5-fluororoucil Adrucil®, Efudex®, 5-FU
fludaribine phosphate Fludara®
Antihistamine/Decongestant Products
cetirizine Reactine (generics) fexofenadine Allegra
chlorpheniramine Chlor-Tripolon® hydroxyzine Atarax (generics)
desloratadine Aerius®* loratadine Claritin
dimenhydrinate Gravol® (generics) meclizine Bonamine®
diphenhydramine Benadryl®, Allerdryl®
Coughs and Colds Drugs

Neo Citran® Actifed® Drisdan® Tylenol Cold and Sinus®
Drixoral® Contac®
Anti-emetics
droperidol Droperidol® prochlorperazine Stemetil® (generics)
metoclopramide generics promethazine Phenergan®
ondansetron Zofran®
Antipyretics, Analgesics; Non-steroidal Anti-inflammatory Drugs

acetylsalicylic acid, Aspirin® ibuprofen Motrin®, Advil® (generics)
enteric coated ASA Entrophen®, indomethacin Indocid® (generics)
Novasen®
celecoxib Celebrex® ketoprofen Orudis® (generics)
diclofenac Voltaren® (generics) ketorolac Toradol®
diflunisal generics meloxicam Mobicox®
floctafenine Idarac® (generics) naproxen Anaprox®, Naprosyn® (generics)
flurbiprofen Ansaid® (generics) piroxicam Feldene® (generics)
tolmetin Tolectin® sulindac generics
tiaprofenic acid Surgam® (generics)
Antidiarrheal
diphenoxylate/atropine Lomotil® psyllium mucilloid Metamucil®, Prodiem®,
Mucillium®
attapulgite Kaopectate® bismuth subsalicylate Pepto-Bismol®
loperamide Imodium® (generics)
Laxatives
bisacodyl Dulcolax® magnesium citrate Citro-Mag®
cascara sagrada magnesium hydroxide Milk of Magnesia®
castor oil magnesium sulphate Epsom Salts®
docusate sodium mineral oil (heavy)
docusate calcium polyethylene glycol GoLytely®, Colyte®
products
lactulose Acilac® psyllium Metamucil®, Prodiem®,
(generics) Mucillium®
senna Senokot®
www.pharmacyprep.com Prescription Processing
53
Prescription Processing
Questions Alerts!
· Definition of prescription
· Essentials in prescription. Prescriber name and address, patient name, date and medication and
directions, repeats (regulations). Prescriber signature.
· Directions of ophthalmic and ear drop
· Directions that often causes errors
Receiving prescription. (implied consent)
Entering prescription in computer (KROLL, HEALTHWATCH, DELTA, NEXYSS)
Preparing a prescription
Labeling
Dispensing (checked by the pharmacist)
The prescription: Written direction from a registered medical practitioner to a pharmacist for
preparing and dispensing a drug.
1230 yonge street, Toronto
Dr. Michael Chang MD.

416 233 4545
HealthCare
TIPS Medical Centre DIN 12345678
4789 Yonge St., Toronto. 416-227-7737 Rx: 1002345 00/00/00
Date: 00/00/00 Herzberg, Laura Refills:
Name: Laura Herzberg 4
Age: 55 Gender: Female Synthroid 112 mcg
Levothyroxine 112 mcg
Rx 90 Tab Abbt Dr. Chang Michael.
Synthroid 0.112 mg TAKE 1 TABLET TWICE DAIL
1 tablet qd.
Mitte: 90
Repeat 4 times
Sign: Dr. Michael Chang

PRESCRIPTION LABEL
Rx Meaning Latin Phrase Abbreviation Meaning Latin Phrase

Abbreviation
a Before Ante OD Right eye
ac Before meals Ante cibum OS Left eye
Ad lib As desired Ad libitum OU Both eyes
AD Right ear pc After meal Post cibum
AS Left ear p.o. By mouth Per os
AU Both ear pr Per rectum
bid Twice a day bis in die p.r.n. As needed Pro re nata
bx Biopsy pt Pint
c with cum Every quaque
cc With food qam. Every morning
dr Dram qd Everyday Quaque die
dx Diagnosis qod Every other day
dx Fracture qid Four times a day Quarter in die
g Gram Q2h, q3h, etc Every two
hours… etc
gr Grain qt Quart
gtt Drop rx, Rx Prescription
h Hour s Without sine
hr Hour ss One half
h.s. At bed time Hora somni stat Immediately
hx History supp Suppository
ID Intradermal sx Symptoms
IM Intramuscular T, Tbsp or tbs Tablespoon
IU International t, tsp Teaspoon
unit
IV Intravenous t.i.d. 3 times a day ter in die
IVPB IV piggyback T.O. Telephone order
kg Kilogram tr Tincture
L Litre tx Treatment
lb Pound ung Ointment
mcg Microgram VO Verbal order
mEq Milliequivalent Ex. aqua In water
mg Milligram
ml Milliliter
oz Ounce Fl.oz Fluid ounce
p post post
ISMP. The Institute of Safe Medication Practices dangerous abbreviations.
Interpreting Directions (SIG) of prescriptions

· caps ii tid pcà Take two capsules three times a day after meals (after food).
· suppos I pr q6h prn à Unwrap and insert 1 suppository into the rectum every 6 hours as needed.
· tabs ss stat. tabs I q6h ccà Take one half tablets now (at once), then take 1 tablet every 6 hours with food.
· fl.oz I tid cc àTake two tablespoonful three times a day with food
· gtts ii ou qid for 7 daysàInstil 2 drops into both eyes 4 times a day for 7 days
· For a child. 10 mL stat, then 5 mL tid for 10 daysàgive 2 teaspoonful at start then 1 teaspoonful three times
a day for 10 days.
· gtts IV au qid for 7 daysà Instil 4 drops in both ears, 4 times a day for 7 days
· tabs ii qam ss at noon & tabs ii qhsàTake 2 tablets every morning, half tablet at noon and two tablets at
bed time.
· fl.oz IV stat; fl.oz II q4h udàTake teacupful (120 mL) at start: four tablespoonful every 4 hours as directed.
· app ung sp aa tidà Apply ointment sparingly to affected area three times a day.
· 10 gtts x po q12h udàGive 10 drops orally every 12 hours as directed
Direction of administration of prescription order

· For adults:
· For eye drops, and nasal drops useà instil or place
· For tabs and capsulesà take
· For liquidà take
· Suppositoriesà unwrap and insert 1 suppository into the rectum or into vagina
· Ointment and cream, topicalà apply
· Aerosolsàinhale
· Sublingual tabletsà place or dissolve one tablet under the tongue
· Effervescentàdissolve one tablet in water and take
For children:
Oral liquid, tablets, or capsules use "give"
Chewable tablets use "chew"
Quantities in prescriptions: Rx
1/7 to denote days Prednisone 5 mg
10/7 = 10 days supply 3/12
1/52 = 1 week’s supply Sig. Take 1 tab daily
3/52 = 3 weeks supply How many 5 mg tablet is dispensed?
1/12 = 1 month supply
A. 3 tablets
3/12 = 3 month supply
B. 12 tablets
1/24 = 1 hour
C. 90 tablets
D. 36 tablets
Ans.
Prescription should consist of:

Prescriber
Prescriber name and title (number)
Prescriber office address
Prescriber phone number
Prescriber signature
Patient
Patient name and address
Patient age
Date on which prescription was written

Rx
Drug name, strength
Quantity to be dispensed
Signa: direction to patient
Refill instructions
Date of prescription
Dispensing direction to pharmacist or subscription
Direction for patient or signa (to be placed on label)
Refill, special labeling or other instructions
Prescriber signature and license or CPSO #
Clarify with patient

· The following information should be added to the prescription if missing or clarified.
· Patient demographic information
· The correct spelling of the patient’s full name (last and first)
· The patient addresses
· The patient home phone number
· Payment
· The age and date of birth (DOB)
The physician full name (last and first)
The physician address and telephone number
Clarify with doctor

· Drug interactions, contraindication or DRPs or DTPs.
· Potential side effects to patient medical conditions.
· Interchangeable. (except generic and brand)
· To verify dose, missing information of prescription drug (dosage form, strength, duration) and route
administration.
· Doctor signature is illegible.
Suspicious prescription of forged narcotic prescription.
What if doctor signature is not legible?
Expanded scope of practice include

· Dispensing emergence medication (advancing)
· Extending Prescription (Rx fee can be charged).
· Pharmaceutical opinion
· Ordering, Monitoring and interpreting Lab Test to optimize medication management.
· Adaptations (changing dosage form, strength, therapeutic equivalent drug)
What is prescription adaptation (expanded scope of practice)?

Prescribed dosage form does not exist.
Prescribed dosage release form is not available?
The following Information added to the prescription at the time of dispensing:

The prescription numbers. Retail price (cost + professional fee = total)
Label. The information, which must be on the prescription label include:

· Patient full name (first and last)
· Prescription number Question Alerts!
· Instruction for the patient use of the What is NOT present on label of
medication prescription drug container?
· Name of drug
· Manufacturer (if drug was ordered by generic name).
· The quantity
· The strength
· Filling date
· Physician name/initial
· Drug Identification Number
· Pharmacist name/initials
NOT on label. Expiry dates
Package insert
The package insert is a document that is included in the medication's surrounding box or wrapper.
Tips
1. OD 2. pc 3. OS
4. ac 5. prescription 6. expiry dates
7. ex aqua 8. OU 9. AD
· What is prescription? à
· Written direction from a registered medical practitioner to a pharmacist for preparing and dispensing a drug
( )
· The information which must be on the prescription label includes: (patients full name, prescription number,
instruction for the patient use of medication, name of drug, manufacturer, quantity, strength, date,
physician name or initial, drug identification number, pharmacist name/initial (optional)
· This should not be on the label ( )
· Prepared in water ( )
· before meals ( ); after meal ( ); right eye ( ), left eye ( ), both eyes ( ), right ear ( )
Select True or False Statement

· Abbreviation "AU" is mistaken for? "OU".
· Abbreviation "o.d" or "OD" is mistaken for "right eye" use daily
· Abbreviation "per os" intended meaning is? orally or by mouth
· Abbreviation "mg" when handwritten is misinterpreted as? microgram "mcg"
www.pharmacyprep.com Safety of Medications in Special Populations
54
Safety of Medications in Special
Populations
Pregnant, breast feeding, Infants, and Seniors (geriatrics)
Geriatric Population
Pharmacokinetic factors
Increase with age

Gastric pH (basic) or achlorhydric
Body fat or lean body mass ratio Questions Alerts!
Decrease with age What pharmacokinetic factors
Lean body mass increase with age? Catabolism
Acid secretion (breakdown)
GI motility
Renal function (CrCl)
Serum albumin
Total body water
Cytochrome P450 enzyme
First pass metabolism
Serum creatinine
Decrease cardiac out
Note. Serum creatinine is not a good predictor because creatinine production decreases with age.
Pharmacokinetic changes related to aging (absorption, distribution, metabolism, elimination)

Heart - Decrease Cardiac out put ¯
Renal-Decreased blood flow ¯ ¯ renal elimination (half-life -)
Liver-Reduced enzyme production ¯ ¯ CYP metabolism or phase I metabolism, hepatic
blood flow
GI - pH increased (alkaline) -
Total body water ¯ 15%
Body fat - 50% women and 100% man

Drug excretion ¯
Absorption (drugs, nutrients, vitamins, ¯ ¯ gastric emptying time, ¯absorption surface
supplements).
The Modified Cockcroft and Gault equation is a commonly used formula to estimate creatinine
clearance (ClCr) using a stable serum creatinine level and patient demographics (e.g., age, gender, weight).
1.2 (140−age) (weight in kg)

ClCr (mL/min) =
Serum creatinine (µmol/L)
For females, multiply the result by 0.85.

Modification of creatinine clearance estimates may be required in some patients. The accuracy of using the
serum creatinine value to predict creatinine clearance is influenced by diseases (e.g., cirrhosis), clinical
conditions (e.g., malnutrition, obesity, spinal cord injuries) and dietary intake (e.g., high consumption of meat).
Drug absorption
· Rate of absorptionà may be altered in some patient
· Extent of absorptionà No effect
Calcium supplements:
· Calcium supplements: 1500 mg/day and vitamin D 800 IU
· Calcium carbonate is required acidic medium, thus it is not preferable in seniors.
· Calcium citrate is recommended
· Calcium carbonate takes in divided doses
Distribution
· Decrease in total body water. Decreases water distribution of water-soluble drugs. (e. g.
acetaminophen).
· Lipid soluble drugs (diazepam, propranolol) distribution increases.
· Albumin levels are decreased with age therefore albumin bound drugs have greater free concentration.
· Renal function (renal excretion) decreases with age, 50% decrease of renal function by age of 70.
· Geriatric patients have sensitive reaction drugs cause anticholinergic effects and should be avoided.
Vitamins in seniors
Vitamin B 12 supplements is recommended
Medications to use lower dosages (¯ clearance) Decreased hepatic clearance in the older adults
due to decreased renal clearance in the elderly
· Aminoglycosides · Benzodiazepines
· Vancomycin · Calcium Channel Blockers
· Fluoroquinolones · Lidocaine
· Penicillins · Phenytoin
· Imipenem · Celecoxib
· Digoxin · Theophylline
· ACE Inhibitors · Imipramine or desipramine, and trazodone
· Beta Blockers (Atenolol, Nadolol) · Isoniazid
· Sotalol · Procainamide
· Glyburide
· Ranitidine, Cimetidine, Famotidine
· Lithium
Beers criteria: Describes the list potential inappropriate medications to elderly (drug to avoid in seniors).
Anticholinergic drugs (antihistamines, TCA are not included) - BPH due to urinary retention.
Benzodiazepine (- side effects due to low therapeutic index in elderly)
Beta blocker (¯ drug effect due to ¯ beta receptors)
Glyburide (- hypoglycemic effect)
Antiarrhythmic drugs
Alpha blockers
Alpha2 agonist
Digoxin >125 mcg/day
· Ticlopidine
· Methyldopa
· Reserpine
· Disopyramide (Norpace)
· Meperidine (Demerol)
· Propoxyphene (Darvon)
· Barbiturates (e.g. Fiorinal, Nembutal, Seconal)
· Benzodiazepine (e.g. Librium, Valium, Dalmane, Halcion)
· Meprobamate
· Sedating Antidepressants (Elavil, Doxepin, Imipramine)
· Methylphenidate (Ritalin)
· Antiemetics (Phenergan, Tigan)
· GI antispasmodics (e.g. Donnatal, Bentyl, Levsin)
· Antidiarrheals (Lomotil)
· Urinary antispasmodics (Ditropan)
· NSAIDs (especially indocin, toradol, ponstel, feldene)
Drugs in Pregnancy and Lactation
PREGNANCY (Approximately 40 WKs. There are 3 trimesters i.e. each 13 wks.)
Biogenesis The first 15-21 days after fertilization. Cleavage, and germ layer formation.
Organogenesis 2-8 wks. The major organ starts developing. (Congenital defects or hereditary birth
defects). e.g. down syndrome, cleft palate, septal defects.
Fetal period at 9th wk, the embryo referred to as fetus.
PREGNANCY TRIMESTERS
1st trimester 2nd trimester 3rd trimester Most critical period week 2 to 8 wks
EMBRYO (2-8 WKS) FETUS (>9WKS) least critical period week 1 to 2 wks
HIGH RISK WITH DRUG
EXPOSURE.
Embryotoxic. Most critical period in pregnancy for drugs therapy 14 to 56 days (2 to 8 weeks).
FETOTOXIC: Most critical period of fetotoxic drugs Ninth week to birth. (Effect on fetal growth or formed
organs or functional maturation organs thus affects. On function of organ rather than gross structural damage.
Example
Behavioral teratogenicity due to phenytoin, antidepressants, or alcohol.
Embryo toxic Drugs

Embryo toxicity (Embryonic period from 18 to 60 d after conception) results in termination of pregnancy. Basic
steps of organogenesis affected and damage irreparable. Can cause structural abnormality.
Examples. Hormones (estrogen, progestin, androgen), oral contraceptives, plan B, ACEi, ARBs, statins,
misoprostol, clomiphene, and antidiabetic drugs.
Teratogenic Drugs
Risk is highest in 1st trimester. Teratogenicity causes mental and physical deformation to the developing fetus.
Examples. Isotretinoin, tretinoin, warfarin, tetracycline, finasteride, dutasteride, and quinolones.
Drug Factors that affect on teratogenicity.

Teratogens must reach the developing conceptus.
Large molecules with Mol. Weight >1000 (e.g. heparin) do not cross placenta.
PLACENTAL EXCHANGE: (SIZE, ELECTRICAL CHARGE, PROTEIN BINDING, AND LIPID SOLUBILITY)
Factors related to drugs affects rate and extent of placental transfer include polarity, lipid solubility, and
existence of specific carrier protein (P-glycoprotein) binding, Molecular weight, pH, and drug distribution.
The transfer of drugs, nutrients and oxygen through placenta occurs via passive diffusion.
Absorption -
Gastric emptying time Delayed
Distribution -
Plasma albumin ¯ (protein binding and more free drug
- body fat
PK changes in pregnancy cause

- progestin levels ¯ GI motility (-constipation) & ¯ esophageal sphincter pressure
(-heartburn)
Placenta - hCG - N&V
- lung perfusion & alveoli drug transfer - absorption of pulmonary drugs
¯blood albumin - fraction of free drug molecule
-plasma volume - V d , - renal blood flow, - GFR, - cardiac output
Alter liver function Alter metabolism
FDA classification
Category A à Safe. Adequate clinical controlled trials, has not evidence of harm.
Category B à Animal studies showed safe. Can be safe in human?

Category C à Animal studies shows risk, but human data not available?
Category D à Demonstrate risk to fetus
Category X à Positive evidence of risk to fetus in clinical well controlled trials.
Category X The positive evidence of risk to fetus. Contraindicated in woman who are pregnant or who may
become pregnant.
· Vitamin A derivative (isotretinoin, and tretinoin)
· ACE inhibitors, ARBs, and statins
· Warfarin causes Fetal Warfarin Syndrome (first trimester)
· Estrogen and androgen, can cause genital tract mal formation.
· Methimazole and carbimazole.
· Leflunomide
· Finasteride and dutasteride
· Methotrexate and chemotherapeutic drug
· Alcohol in large quantities can cause abnormalities in growth, cardiac, skeletal development. Fetal alcohol
syndrome (FAS).
· Misoprostol
· Drugs not used in pregnancy Tetracyclineà Mottling of teeth (taken by mother after 18 week of
pregnancy).
· MetronidazoleàUse in first trimester must be evaluated carefully. Completely contraindicated for
Trichomoniasis in 1st trimester.
· QuinolonesàNot recommended in pregnancyàcauses arthropathies (cartilage erosion)
· Lithium àcardiovascular malformations
Anticonvulsants contraindicated in first trimester. Phenytoin, Valproic acid; Sodium valproate (neural tubule
defect). Phenytoin à cleft-palate, spina-bifida
· Anticancer or antineoplastics are contraindicated in pregnancy (potential
risk for toxicity).
· Finasteride cause abnormalities in male genital, should avoid contact with men who are on this medication.
The most teratogenic antibiotic

· Nalidixic acid derivative as quinolone
· Fluroquinolones
· Amantadine
· Tetracycline
Can be used in Pregnancy

· Erythromycin
· Cephalexin
· Ampicillin
· Amoxicillin
Alteration of organ function in pregnancy
Increases Decreases
Heart-increase CO and blood volume
Renal-increased blood flow

Liver-placenta and fetal liver contribute to
metabolism
GI-Increased HCL production and N&V.
Decreased peristalsis
DRUG OF CHOICE IN PREGNANCY

· Nausea and vomiting (morning sickness) à Diclectin (vitamin B 6 +doxylamine)
· Anti-hypertension (pre-eclampsia) à Methyldopa, hydralazine, and labetalol
· Diabetic Type I and II à Insulin
· Epilepsy à Carbamazepine
· Hyperlipidemia à Cholestyramine
· Hyperthyroidism à Propylthiouracil (PTU)
· Ulcerative colitis à 5ASA or sulphasalazine
· Constipation à Psyllium (bulk laxative), and stool softener
· Stomach ulcers à Antacids, H 2 blockers, and PPI.
· Vulvovaginitis candida à Clotrimazole (except 1st trimester), miconazole or nystatin.
· Migraine, fever and pain à Acetaminophen, NSAID’s (avoid full anti-inflammatory dose in 3rd trimester.
· Depression à Fluoxetine or SSRIs
· Urinary tract infections à Cephalosporin's (cephalexin), Nitrofurantoin, cotrimoxazole (Possible increase in
the risk of neural tubule and cardiovascular, oral cleft in 1st trimester exposure, this can be minimized by
folic acid supplements).
· Drug of choice to treat Syphilis Penicillin G
· Drug of choice to teat herpes? Acyclovir
· Drug of choice to treat Chlamydia? Azithromycin
· Drug of choice to treat gonorrhea? Cefixime, doxycycline
Drugs in lactation
Factors that effect on drug secretion into breast milk
Lipid solubility
Membrane permeation
Low Molecular weight
Base drugs have high excretion into breast milk because breast milk is weak acidic. This cause ionization increase
excretion.
Protein binding affinity
Pediatric population
Neonates (1st 4 postnatal weeks)
Infants (weeks 5 to 52 postnatal)
Children (1 to 12 years)
Adolescents (12 to 16 years)
Tips
1) Eat in small & frequent 2) Urinary tract infection 3) Diclectin
meals, avoid fat, oily and
spicy food, avoid heavy meals
4) decreased renal clearance, 5) Dimenhydrinate 6) body fat/lean muscle mass ratio
7) fiber diet 8) stool softeners 9) lactulose
10)Calcium citrate 11) Vitamin B 12 12)Drugs must be able to diffuse
across lipid barriers to enter the
fetus
13)ginger root 14) There is decreased 15) Neurotubular defect
rate of absorption as well
as change in drug
distribution
16)Category X 17) Folic acid & 18) morning sickness
multivitamins
· Pharmacokinetics factors that increase with age? ( )

· Calcium supplements that are preferably given to seniors? ( )
· What vitamin supplements are recommended to seniors? ( )
· What therapy recommended for constipation in seniors? ( )
· Drugs that should be discontinued in pregnancy? ( )
· Supplements that should be recommended in pregnancy? ( )
· Folic acid supplements in pregnancy prevents? ( )
· Nausea and vomiting in pregnancy also referred as? ( )
· Drug of choice therapy against nausea and vomiting in pregnancy is? ( )
· OTC drug therapy against nausea and vomiting in pregnancy include? ( )
· Self care that is recommended for nausea and vomiting in pregnancy? ( )
· Cranberry juice is used against? ( )
· How do pharmacokinetic characteristics in the very young differ from that of an adult? ( )
· What pharmacokinetic characteristics change in elderly? ( )
· What is the significance of the placental barrier? ( )
· Herbal products that is recommended for nausea & vomiting in pregnancy? ( )
www.Pharmacyprep.com Prevention and Intervention in Medication Overdose
55
Promoting Medication
Adherence
Medication works only when patient takes them as prescribed.
Non-adherent definition
Primary medication nonadherence is failing to fill or take a new prescription
Steps to improve medication adherence.
A patient is considered adherent if they take 80% of their prescribed medications. If patient takes less
than 80% of their prescribed medications they are considered non-adherent.
Eight steps to improve medication adherence.

1. Consider medication nonadherence first as the reason a patient's condition is not under control
and especially when considering increasing therapy or adding another medication. Increasing or
adding additional therapy when non-adherence is hidden can be dangerous.
Case: A patient who is hospitalized and has started all medication according to their
medication list. The hospital nurse is not aware that patient is NOT taking all of prescribed
medications.
2. Develop a process for routinely asking about medication adherence. Gathering patient medication
information and medication review. Potential medication non-adherence alerts the physician to
discuss the potential issues.
Case:
3. Create a blame-free environment to discuss medications with the patient.
Asking patients non-judgemental way, “Why aren't you taking the medications I prescribed?”
is confrontational and suggests that you think the patient's nonadherence is because they are
defying your recommendations. Instead, try saying, “Many people have trouble taking their
medications on a regular basis. Do you find this is the case for any of your medications?” This
removes blame from the patient to allow them to open up about their particular situation.
www.Pharmacyprep.com Prevention and Intervention in Medication Overdose
4. Identify why the patient is not taking their medicine

Most non-adherence is intentional, patient make conscious decision not to take their medication
based on their knowledge, experience, and belief, here are some common reason for non-
adherence.
FEAR: Patient may be frightened for potential side effects, they had with same or similar
medications or they might have witnessed side effects experienced by family member or friends.
COST: Cost of medicine can be a barrier and may not fill in first place.
TOO MANY MEDICATIONS: Greater the number and higher the frequency, will likely cause more
non-adherence.
LACK OF SYMPTOMS: Patient may not see any difference, in taking their medications.
WORRY: Concern of depending on medication can cause non-adherence
MISTRUST: Patient may not have trust on doctor motive to prescribe medication, believe that this
pharmaceutical companies marketing efforts.
DEPRESSION: Patient who are depressed less likely to take their medication.
MISUNDERSTANDING: Patient may not understand the need for the medicine or expected time it
takes to medication response. For chronic therapies, patient taking medication, do not see any
significant changes and thinks medication do nothing. Failure to see immediate improvement may
lead to premature discontinuation.
5. Respond positively and thank the patient for sharing their behavior. Good communication by
physician and pharmacist improve patient medication adherence. inadequate physician
communication with patients may account for 55% of medication nonadherence.
6. Tailor the adherence solution to the individual patient. Identifying and discussing their reasons for
not taking medication may help to personalize their therapy.
Case: Changing to less sedative.

Changing to long acting medications to avoid withdrawal effect of medicaitons.
7. Involve the patient in developing their treatment plan
8. Set patients up for success
www.Pharmacyprep.com Pharmacy Practice and Management
56
Professional Communication
Skills
Questions Alerts!
· The best communications skills are verbal and writing
· Barriers in communications are environmental barriers, personal barriers, and financial and
administrative barrier.
· Cultural competence or cultural diversity.
· Communication with other healthcare professionals.
Type of communication methods.

· Verbal communication methods
· Non-verbal communication methods
Verbal communication
· Verbal communication comprises speaking and listening
· The sender. One who transmits a message to another person
· The message. It is an element that is transmitted from one person to another
· The receiver. One who receive message from sender
· Feedback. It is the process of replying to sender.
Barriers in communications. The interference that affects the receiving, sending transmitting of message.
· Environmental barriers (noise, loud music, counter heights, poor lighting etc).
· Personal barriers ( cultural diversity (language), no confidence, shy, incompetence)
· Patient barriers (knowledge)
· Administrative and financial barriers
Environmental barriers:
Distractions in environment often can result into environmental barriers like height of prescription counter
separating the patient from the pharmacist.
· Crowded and noisy prescription areas inhibit one to one communications.
· Presence of support workers like technician who stands between pharmacist and patient.
· Distraction or loud noise, telephone rings, music, and traffic.
The following potential factors that are associated with environmental barriers:
· Is pharmacist visible?
· Is counter top or stuff on counter tops blocking pharmacist visible?
· Does it easy to get pharmacist attention?
· Is it private counseling area available to conduct private interview?
· Is that lost background noise or distractions?
· Is it easy to get pharmacist attention?
Recommendation to minimize environmental barriers
· Place computers terminal near the patient counseling area to minimize distractions.
· Create a quite private counseling area.
· Make countertops wider to accommodate
computers, printers etc. Question Alerts!
Personal barriers 1) Your pharmacy is located in multicultural area. What
· Low self confidence. is appropriate to do offer good customer service?
· Cultural differences (cultural competent). a) have multicultural language signs in pharmacy
· Discomfort to sensitive situations b) hire multicultural staff, or staff speaks many
· Conflicting values of therapy languages
c) Print information in different language.
· Shyness
d) Find a translator
e) Sign language
Patient barriers
The following are the examples of patient
2) What is cultural competence? For language barrier?
barrier.
A. Find a translator or sign language
· Patient perceive being as knowledgeable?
B. Translate in internet
· Patient perception about pharmacist
C. Print in English language
knowledge?
D. Ask someone to translate
· The perception of impersonal atmosphere
· Patient perceptions about their medical
conditions as minor?
· Patient may be anxious about their conditions.
Administrative and Financial barriers
There are several factors of administrative and financial aspects effects pharmacy practice. Like bureaucracy can
be administrative barrier.
· Pharmacist are not paid directly for educating or communicating with patients, therefore many managers
perceive the task of talking with pharmacist is expensive service and not a high priority.
· Pharmacy policies that encourage minimum number of pharmacist.
· Excessive tasks to pharmacist by typing label, count medications, talk on phone, and completing other tasks
while communicating with patients.
Time barriers
· Setting inappropriate timing of appointment.
· Large number of prescription needs to be filled in short time.
Non-Verbal Communication
· Communication does NOT require verbal language.
· The elements of non-verbal communication kinesis and proxemics.
Kinesics or body language
The manner in which one uses her/his eye contact, arms, legs, hands head to convey a message to receiver.
Example: Relaxed posture, slight lean toward the other person, eye contact, and smile.
Proxemics
The distance between two interactive people put more emphasis on content of communication, and it is defined
as proxemics.
Written. It is powerful nonverbal communication tool.
Tips
1. Low self-confidence 2. Distractions 3. language
4. Promotion sales 5. Telephone 6. Noise
7. Verbal 8. Written 9. Cultural differences
10. Discomfort to 11. Conflicting values to 12. Shyness
sensitive situations therapy
· The best communication skills are? ( )

· Examples of communication barriers includes? ( )
· Examples of communication distractions includes? ( )
· Examples of personal barriers includes? ( )
www.Pharmacyprep.Com Pharmacy practice and management
57
Bioethics/Professional Ethics
This chapter provides basic understanding of ethical principles, code of ethics, professional responsibility and
liability. You will learn how to make ethical decisions. Lecture presentation includes scenarios of ethical
decisions and professional liability and legal issues.
Questions Alerts!
· Beneficence = doing good or doing the very best to patient
· Nonmaleficence = preventing harm
· Autonomy = patient right to choose (paternalism breaks autonomy)
· Veracity = honesty or telling the truth without deception.
· Justice = equality or first come first service (fairly).
Difference in ethics and regulations

LAW and RULE (REGULATIONS) ETHICS (conducts/moral/character) uphold or followed or break?
Described in constitution Professional judgement in the best of interest patient in the
ethical principles
Must be followed Followed or uphold/broken
Cannot advance narcotics, benzodiazepine, Breaking ethics is misconduct
and control drugs.
Beneficence
Beneficence: to do good or doing well or doing the very best to patient.
The health professional should act in the best interest of the patient. Decisions made with perception are based
on what patient needed.
In other words:
· Acting in the patient’s best interest. Current thinking is to involve patient letting the patient
determine what is in their best interest.
· Pharmacists demonstrate beneficence whenever they provide critically needed prescription drugs to their
patients in emergency situations without regard to possible legal consequences.
Nonmaleficence
Nonmaleficence is do no harm or prevent harm. Pharmacists who refuse to fill a prescription order
because of their concern for patient safety or well being observed the principle of nonmaleficence.
Professional interventions on drug related problem OR DRUG THERAPY PROBLEM that can prevent harm is
action of nonmaleficence.
Harm reduction services such dispensing syringes to drug addicts. Receiving narcotics to destroy from
customers.
Autonomy: Whether like to take or not like to take?

Letting the patient have the final decision, even if it is not in their best interest i.e. refusing treatment, surgery,
etc. In other words. Patient’s right to self-determination. To choose what will be done to them.
Respect for life and autonomy of patient: Contraception, emergence contraception, abortion.
Palliative care (care before 24 hr of death), pain management, and end-of-life care.
Euthanasia = Assisted suicide or planned death or physician assisted suicide.
Mental capacity to assess patient's capacity to make decision (advance directive).

Terminology
Consent (Mental Capacity)
Substitute decision making
Palliative care (end-of-life care)
Living will (advanced directive)
Last will
Disclosure The action of telling new or secrete information known.
Empathy
Autonomy opposite is Paternalism.

Paternalism: When one fails to respect another’s autonomy, and acts with disregard to the individual rights.
Substitute their own beliefs, opinions and judgment to that of another. Claim they acted in the person’s best
interest.
Honesty and Veracity: Act with honesty without deception.

The patient has the right to the truth medical condition, course of the disease and treatments.
Code of ethics states that a pharmacist, “has the duty to tell the truth and to act with conviction of conscience”
Rapport is built on trust, which is based on honesty.
Rx
Obecalp
Fidelity (loyal)
In other words, fidelity is the right of a patient to have health professionals provide services that promote
patient interests rather than their own. The right of patients to have practitioners provide services that are in
the patient’s best interest.
Infidelity from a prescriber could be recommending vitamins that patients don’t need. Failing to confront a
doctor with an inappropriate prescription out of fear that the doctor will direct his/her patients elsewhere.
Justice or Fairness
First come first serve. It means providing services equally.
Professional Ethics
Informed Consent (permission) and decision making
Three types of consents implied, express, and informed.
Requires honesty and autonomy to exist. Patients have the right to full information of all relevant facts and must
give explicit consent before treatment.
Informed consent exists when.
· All relevant information has been provided
· The patient understands the information
· Consent is freely given and there is no coercion
· The patient is capable of understanding the information
· Note. Often, practitioners rely only on the disclosure part of the list!
Confidentiality
Federal regulations of confidentiality is personal information protection and electronic documentation act
(PIPEDA).
Provincial regulations are personal health information protection act. (PHIPA).
From the patient’s perspective, this is “self-disclosure” and they should be the ones making this decision.
In other words, the principle of confidentiality serves to assure the patient that information about their health,
medical condition, treatment will not be given to individuals without their permission.
Confidentiality of patient Information. The pharmacist preserves the confidentiality of information about
individual patient acquired in the course of his or her professional practice, and does not divulge this
information except where authorized by the patient or required by law.
Spouses: If someone is asking a copy of his or her spouse’s prescription information, get permission from the
patient whose information is being released.
Exceptions of confidentiality based on your reasoning? Cognitive impairment (advance directives require or care
giver)?
Patient decision making capacity should be assessed by health care professionals
Unconscious patients (circle of care)? Mental illness (alert family) ? HIV patients (imply information) or
contagious disease?
Tips
1. Violating autonomy 2. Tell the truth 3. Right of determination
4. Beneficence 5. Ethics 6. Equality with everyone
7. preventing harm 8. Best interest of patient 9. honesty without deception
· Doing good ( )
· Non maleficence ( )
· Autonomy ( )
· Honesty ( )
· Veracity ( )
· Justice ( )
· Fidelity ( )
· Paternalism ( )
· Code of conducts or morals ( )
www.Pharmacyprep.com Drug Information Resources
58
Drug Information Resources
Questions Alerts!
Types of literature primary, secondary and tertiary.
· Canadian drug references like compendium of pharmaceutical specialties (CPS).
· Compendium of Therapeutic choices (CTC) and Compendium of Therapeutic for Minor Ailments
(CTMA).
· USP DI vol.1 drug information for health care professionals.
· Motherisk program. Safety of drugs in pregnancy.
· References like Cochrane data base (Cochrane Collaborative Library) an evidence base medicine
database.
· Medline is used for new drugs and therapies and off label use.
· Martindale. Foreign drugs.
Response to drug information request? What reference is appropriate for minor ailment treatment? CTMA
selection of suitable references for foreign drug and information sources?
Peer review: Assessment of a clinical trial by experts for scientific merit, participant safety, and ethical
considerations.
Literature: It is defined as an extensive, heterogeneous collection of resources, which provide information about
drugs. Drug information sources can be categorized into primary literature, secondary literature and tertiary
literature.
Primary Sources: Consist of original information about clinical trials or research. Examples Scientific Journals
containing clinical trial information.
· Peer reviewed articles are published in scientific journals. The primary source literature provides latest and
current information.
· Examples. Canadian Medical Association Journal (CMAJ), Canadian Pharmacy Journal (CPJ), Journal of
American Medical Association (JAMA). Pharmacy connection, Clinical research data, Journal of Informed
Pharmacotherapy, Canadian Family Physician, Canadian Journal of Clinical Pharmacology, Etc.
· Benefits: Gives most current information and keeps up latest development and research in pharmacy. It is
good resource of continuing education.
· Limitation: Does not guarantee that the article is accurate, however respected journal enhances the
credibility of information contained in the article.
Secondary Sources: Examples Indexes, bibliography and abstracts.

· Information published in secondary sources obtained from various primary sources and compiled as
abstracts and indexed into publications.
· Example. Internet search, Medline.
· Current Content (Abstracts), Index Medicus (Index); Monthly Biomedical research- results.
· Clin-Alert (Index). Abstracting service as a newsletter edition semimonthly (bi weekly) adverse reaction.
· Current content: Weekly-Clinical practice
· International pharmaceutical abstracts, monthly and quarterly pharmacy practice
· Online sources: MedLine or Pubmed (recent drug information, and off label use)
· Benefits: It is an important resource for quick and selective screening of primary literature for specific
information, or article.
· Limitations. Each indexing service provider may provide specific list of journals, so this can limit and
thoroughness of literature search.
Tertiary Sources: Examples text books and compendia
· Information published in tertiary sources such reference book and textbooks are obtained from primary
and/or secondary sources.
· Example: Compendium of pharmaceutical specialties (CPS). United States pharmacopeia (USP-DI),
Martindale, Remington, Compendium of Therapeutics choice, all text books and reviews.
· Benefits: Provide easy and comprehensive topics in one textbook.
· Limitation: No recent information.
PRIMARY LITERATURE SECONDARY LITERATURE TERTIARY LITERATUR

ORIGINAL INFORMATION INDEXES AS GROUP COMPENDIUM, TEXT
BOOKS
CLINICAL TRIALS, NEW SEARCH RESULTS IN INTERNET BOOKS PUBLICATIONS
INVENTIONS DATA MEDLINE, PUBMED
Compendium of Pharmaceuticals Specialties or CPS

· Compendium of Therapeutic Choices (CTC)
· Compendium of Therapeutic Minor Ailments (CTMA)
· RxTx (CPS, CTC CTMA & CPMA)
· RxFiles.ca
· United States Pharmacopeia DI-Vol.1 (USP-DI Vol.1)
· Martindale
· Cochrane data base or reviews
· Health Canada Drug Product database (DPD)
· Drugs in pregnancy and lactation or Motherisk program
REFERENCES A prescriber requesting drug information. What drug information request, would
you select?
Compendium of pharmaceutical Drug monographs, side effects, clinical use, drug interactions, contraindications.
speciality (CPS or RxTx) Pharmacology. Dosing, storage conditions.
CTC Treatment options (1st line therapy or alternates)
CTMA Self care and over the counter drugs
USP-DI Vol.1 FDA approved drugs in USA
Cochrane data base Evidence base medicine systematic review
Health Canada DPD New drugs approved
Medline (Pubmed) Off label drugs
Professional product monograph Consumer product monograph

Health care professional use Public use/patient information
CPS Package inserts
Pharmacy Practice Reference Resources
Compendium of pharmaceuticals specialties

· Discontinued products
· Brand and generic name index (green pages)
· Therapeutic guide (pink pages)
· Product identification (pages containing photographs of the medicines)
· Directory (Yellow pages)
· Clini-info (Lilac pages)
· Monographs (white pages)
· Appendices (white pages at the end of the CPS)
· Drugs that have peanut and soya proteins, lecithin’s preps, and ethanol.
· Drugs that can be crushed and chewed.
EVIDENCE BASED MEDICINE INFORMATION SOURCES:

Cochrane reviews, database
Drugs manufactured in United States

· USP-DI volume I
· The American Drug Index (updated annually)
· Drug Facts and Comparison (updated monthly and bound annually)
· Drug Topics Red Book (released monthly and bound annually)
· Physician desk reference (PDR) (updated annually)
· AHFS Drug Information. American Hospital Formulary Society (supplemented quarterly and updated
annually).
Drug Manufactured in foreign countries

· Martindale. The complete drug references
· Index Nominum
· USP Dictionary
· USAN
For Investigational Drugs

· Medline or Pubmed and Health Canada website
· Martindale. The complete drug reference
· Drug facts and comparison
· Unlisted drugs
· FDA website. The new drug application (NDA) pipeline
· Health Canada
For unknown drugs. Try to identify them by physical characteristics such as special marks, color, shape etc. and
or recommend chemical analysis.
· USP DI volume I
· The PDR
· Drug facts and comparison
· Manufacture
· Laboratory
Side Effects
· Compendium of pharmaceutical specialties
· USP DI Vol. I: Drug Information for the Health Care Professional
· Clin-Alert
· Meyler's Side Effects of Drugs
· AHFS Drug Information
Drug-Drug Interactions
· Drug Interaction Facts (Tatro)
· Drug Interactions. Compendium of Pharmaceuticals and Specialties
· Clin-Alert (Generali)
· Hansten and Horn's Drug Interactions Analysis and Management
· Drug-Drug Interactions. Handbook of Clinical Drug Data (Anderson)
· Handbook of Adverse Drug Interactions
· Drug Interactions: A Source Book of Adverse Interactions, Their Mechanisms, Clinical Importance and
th
Management (Stockley: 6 ed. 2003)
· EDI: Evaluations of Drug Interactions
· Concise Guide to Cytochrome P450 System: Drug Interaction Principles for Medical Practice
Drug-Lab Test Interactions

· American Hospital Formulary Society (AHFS) Drug Information
· Effects of Drugs on Clinical Laboratory Tests (Young: 5th ed. - 2000)
· Drug-Laboratory Test Interferences. In: Handbook of Clinical Drug Data (Anderson)
Drug-Food Interactions
· Drug Interaction Facts (Tatro)
· USP-DI volume I
· Reference Guide to Drug and Nutrient Interactions
· Food Medications Interactions Handbook (Pronsky)
· HIV Medication-Food Interactions Handbook (Pronsky)
Drug-Herb Interactions
· Database of Natural product
· Herbs: Everyday Reference for Health Professionals (CphA)
· Herb Contraindications and Drug Interactions (Brinker)
· Herb-Drug Interactions Handbook (Herr)
· Drug Interaction Facts: Herbal Supplements and Food
· Interactions between Drugs & Natural Medicines: What the Physician and Pharmacist Must Know About
Vitamins, Minerals, Foods and Herbs (Meletis)
Compounding or Extemporaneous prep

· Remington: The Science and Practice of Pharmacy
· Merck index
· A Practical Guide To Contemporary Pharmacy Practice
· Pharmaceutical Dosage Forms and Drug Delivery Systems
· Pharmaceutical Practice
· The Art, Science, and Technology of Pharmaceutical Compounding
· The Pharmaceutical Codex
Formulas For Compounding
· United States Pharmacopea-National Formulary (USP-NF)
· Merck index
· British Pharmacopoeia Vol. 2
· Contemporary Compounding Compendium
Extemporaneous Oral Liquid Dosage Preparations (CSHP)

· The Ghen and Rains Physicians Guide to Pharmaceutical Compounding
· Extemporaneous Formulations (Children's hospital of Philadelphia)
· Pediatric Drug Formulations
· Pocket Book of Extemporaneous Formulations
· Allen's Compounded Formulations: The US Pharmacist Collection
· The Art, Science, and Technology of Pharmaceutical Compounding
· Trissel's Stability of Compounded Formulations (Recommended for parenteral solution stabilities)
· Minutes from manufacturer
Characteristic Of Specific Chemicals/Drugs

· The Merck Index
· Martindale. The Complete Drug Reference
· Remington. The Science and Practice of Pharmacy
· Handbook of Pharmaceutical Excipient
· The Pharmaceutical Codex
· The United States Pharmacopeia/The National Formulary
· Trissel's Stability of Compounded Formulations Compounding
· Extemporaneous Ophthalmic Preparations
· Guidelines for Preparation of Sterile Products in Pharmacies (CSHP)
· Handbook on Injectable Drugs (Trissel)
· Principles of Sterile Product Preparation (ASHP)
· Sterile Dosage Forms (Turco) Question Alerts!
Compatibility IV mixture can be found in?
Compatibility and Stability Of Parenteral Drugs
· Handbook on Injectable Drugs (Trissel)
· Parenteral Drug Therapy Manual (Ottawa General Hospital)
· Trissel's Tables of Physical Compatibility
· Pocket Guide to Injectable Drugs (Trissel)
· IV Index System (Micromedex) subscription required.
Pharmacokinetic Monographs
· Compendium of pharmaceutical specialties
· USP-DI Volume I. Information for the Health Care Professional
· Handbook of Clinical Drug Data
Patient Counseling
· Compendium of Therapeutic Minor Ailments CTMA (CPhA) for over the counter products
· USP DI: Volume II: Advice for the patient in lay language
· Communication skills in pharmacy practice: a practical guide for students and practitioners (Tindall: 4th ed.
2002).
· Communication skills for pharmacists: building relationships, improving patient care (Berger)
Pregnancy and Lactation

· Drugs in Pregnancy and Lactation (Briggs)
· Mother Risk Program (Sickkids hospital, Ontario)
· Clinical Therapy in Breastfeeding Patients (Hale)
· Nausea and Vomiting of Pregnancy: State of the Art 2000
th
· Teratogenicity and Drugs, in Breast Milk. In Applied Therapeutics: The Clinical Use of Drugs (7 ed. 2001)
· USP DI - Volume I. Information for the Health Care Professional
· Breast-Feeding Precaution Listing. USP DI-Vol. II (22nd ed.)
nd
· Pregnancy Precaution Listing. USP DI-Vol.II (22 ed. 2002)
Pediatrics
· Manual of Clinical Problems in Pediatrics (Roberts)
· Manual of Pediatric Therapeutics (Graef)
· Martindale: The Complete Drug Reference
· Nelson Essentials of Pediatrics
· Nelson's Textbook of Pediatrics
· Neofax
· Pediatric Dosage Handbook
· Pediatric Pharmacology
· Problems in Pediatric Drug Therapy
· Red Book 2000: Report of the Committee on Infectious Diseases
· Rudolph's Pediatrics
· The Harriet Lane Handbook
· The Pediatric Drug Handbook (Benitz)
Poisoning and Toxicology

· Refer to poison control centers: Addresses are found in Yellow pages CPS.
Casarett and Doull's Toxicology: The Basic Science of Poisons (6th edition - 1996)
· Clinical Management of Poisoning and Drug Overdose (3rd edition - 1998)
· Comprehensive Review in Toxicology for Emergency Clinicians (3rd edition - 1998)
· Drug Toxic kinetics
· Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning (2nd edition - 1997)
· Poisoning and Toxicology Handbook (APhA - 1997)

· Principles and Methods of Toxicology (4th edition - 2000)
Veterinary Medicine
Compendium of Veterinary Products
Current Therapy in Equine Medicine (Robinson)
Current Veterinary Therapy 4: Food Animal Practice (Howard)
Development and Formulation of Veterinary Dosage Forms (Hardee)
The Exotic Animal Drug Compendium: An International Formulary
Handbook of Comparative Veterinary Pharmacokinetics and Residues of Pesticides and Environmental
Contaminants
The Veterinary Formulary: Handbook of Medicines Used in Veterinary Medicine
Veterinary Drug Handbook (Plumb)
Doses And Drug Administration

Physician desk reference (PDR)
Drug facts and comparison
Martindale: The extra pharmacopia
Intravenous and Intramuscularly Compatibilities

Handbook of injectables drug (Tresel)
Martindale: The extra pharmacopia
Teratogenicity
Physician desk reference (PDR)
Drugs in Pregnancy and Lactation (Briggs)
Indexes
Drug Interaction Index
FDA/Manufacturer Alert Index
First Report Index
Legal Action Index
Newly Marketed Drugs: 1997-2000
Drug Index
Summaries of some important reference sources

Martindale. The complete reference. Reference books contained with complete source of information about
foreign drugs and approved and off labeled drugs.
Martindale’s Extra Pharmacopoeia is probably one of the most comprehensive, international, single volume
references on drugs and drug products. Martindale’s is divided into three parts:
The first part consists of monographs on drugs and ancillary substances. (Although drugs that are manufactured
in the England are stressed, generic and propriety products from many other countries are included). The
monographs include chemical data, storage, incompatibilities, uses, doses, and toxic effects.
The second part contains a supplementary discussion of new drugs, obsolete drugs, and miscellaneous
substances.
The third party lists formulas of OTC products sold in the England. There is also a directory of worldwide
pharmaceutical manufacturers.
Merck Index: Contained information about chemical properties and compounding.
Merck Manual: Basic information about anatomy, physiology and pathophysiological conditions.
USP DI
Available USP DI® Drug Reference Guides include:
Volume I: Drug Information for the Health Care Professional
Volume II: Advice for the Patient in lay language
Volume III: Approved Drug Products and Legal Requirements
USP DI Volume I
USP DI® Volume I. Drug Information for the Health Care Professional contains
· In-depth monographs cover dosing
· Indications
· Interactions
· Pharmacology/pharmacokinetics
· Side/adverse effects
· Patient counselling guidelines
· Labelled and off-label uses are discussed to facilitate third-party reimbursement.
USP DI Volume II
USP DI® Volume II: Advice for the Patient - Drug Information in Lay Language. Provides patient-oriented drug
information to help patients understand and successfully follow their drug regimens. These include brand
names, descriptions, proper use, and precautions, Side effects. Instructions for how to handle missed doses are
included, as are guidelines for when to seek medical assistance or supervision.
USP DI® Volume III
USP DI® Volume III: Approved Drug Products and Legal Requirements. Staying apprised of federal guidelines and
legislations related to prescribing and dispensing drugs are time consuming. This is a single, easy-to-use
reference containing all the information you need including the complete FDA "Orange Book." USP DI Volume III
helps you quickly identify a drug's chemical properties, determine if a drug has been discontinued, or select an
appropriate generic substitute for a more expensive brand name drug. Excerpts from USP-NF offer data on
quality, packaging, storage, and labeling requirements. Contains guidelines and laws governing the safe
handling and distribution of drugs.
USP Dictionary
USP Dictionary Content Overview

United States and international drug names
The USP Dictionary is the authoritative source for generic drug names established by the United States Adopted
Names (USAN) Council. The dictionary also provides other types of drug names used worldwide: Brand names.
Chemical names. International Nonproprietary Names (INNs). British Approved Names (BANs). Japanese
Accepted Names (JANs). Official USP-NF names. FDA-established names.
The Medical Letter
Its newsletters, The Medical Letter on Drugs and Therapeutics and Treatment Guidelines from The Medical
Letter, publish critical appraisals of new drugs and comparative reviews of older drugs.
Clin-Alert
The adverse drug reaction events reported by Clin-Alert during the year 2000 have been compiled, organized,
re-formatted, indexed, and published in a convenient one-volume reference book
Drug Interaction Facts

Drug Interaction Facts loose-leaf edition provides drug-drug and drug-food interaction information in a quick
reference format.
Drug Interaction Facts covers more than 20,000 brand and generic drugs and more than 70 therapeutic classes.
Drug significance ratings are also included.
Drug Interaction Facts includes: Herbal Supplements and Food. Which covers over 100 monographs and
discusses the interactions' significance, onset, severity, documentation, mechanism, and more.
Updated quarterly.
Remington. The Science and Practice Of Pharmacy

This textbook has been the definitive reference for all aspects of the science and practice of pharmacy, and is
used for pharmaceutics, therapeutics and pharmacy practice courses in primary curricula. Remington covers
many education and practice issues, from the history of pharmacy and ethics, to industrial pharmacy and
pharmacy practice.
Tips
1 Second use of drug or 2. CPS 3. Compendium of Therapeutic

unapproved use of drug Choices
4 Drug monographs. 5. Immunization 6. Compendium of Therapeutic
Guide of Health Minor Ailments
Canada
7 Clinical practice guidelines. 8 Remington. The 9 Antibiotic recommendations
science and practice of or clinical practice trial
pharmacy recommendations
· Children immunization schedule is found in? ( )

· Dental prophylaxis clinical practice guidelines can be found in? ( )
· Initial treatment can be recommended by using? ( )
· Off label indication is? ( )
· Compendium of pharmaceuticals specialties ( )
· What is found in compendium of pharmaceuticals specialties? ( )
· What is NOT found in CPS? OTC drugs and selfcare. (but vitamins, iron, folic acid present in CPS).
· What is found in compendium of therapeutic minor ailments? (Recommendation of OTC drugs therapy)
· What is not present in compendium of therapeutic minor ailment? ( )
· Compounding reference ( )
· Remington reference is used for? Buffer, compounding, excipients
· What is present in CTC? Treatment options (1st line, & alternate therapies).
www.Pharmacyprep.com Medication Errors
59
Medication Errors
Questions Alerts!
· Institute of Safe Medication Practices (ISMP). The ISMP is a non-profit independent agency established
for the collection and analysis of medication error reports and development of recommendation of
enhancement of patient safety.
· Dangerous abbreviations and High alert drugs
· Near missed errors
THE CANADIAN ORGANIZATIONS INVOLVE IN MEDICATION SAFETY

Organization Functions
Health Canada's MedEffect Advisories, withdrawal, recall
Health Canada's pharmacovigilance ADR in post marketing surveillance
Canadian Institute of Health Information (CIHI)- Medication incidence in hospital.
Institute of safe medication practices (ISMP-Canada) medication incidence in community pharmacy
Canadian patient safety institute (CPSI) Promotes innovative solutions and facilitate collaboration among
government and stakeholders to enhance patient safety.
Drug recalls:
Class I (Type I) Class II (Type II) Class III (Type III)
Strong likelihood that product will May cause temporary but reversible Product is not likelihood to cause
cause serious adverse effect or adverse effects or in which little adverse effect.
death. likelihood of serious adverse
effects.
Example of recall.
0.9% Sodium Chloride Injection, 1000 mL (2017-05-10)
Recall
Starting date: May 10, 2017
Posting date: May 19, 2017
Type of communication: Drug Recall
Subcategory: Drugs
Hazard classification: Type I
Source of recall: Health Canada
Issue: Product Safety
Audience: General Public, Healthcare Professionals, Hospitals
Identification number: RA-63340
Affected products
Cefazolin for Injection
DIN, NPN, DIN-HIM
DIN 02237140
Dosage form
Powder for solution
Strength
Cefazolin Sodium 10 g/vial
Lot or serial number
303723
Companies
Recalling Firm
Adverse drug reaction (ADR) Unintended effects, Side effects, new side effects
Adverse drug reaction (ADR) reporting;

ADR form is reported to Canada Vigilance Program, of Therapeutic Directorate, Health Canada.
Or can report to HealthCanada/MEDEFFECT
Consumers/patients and health professionals can report adverse reactions (also known as side effects) to health
products, including prescription and non-prescription medications, biologics, (includes biotechnology products,
vaccines, fractionated blood products, human blood and blood components, as well as human cells, tissues and
organs), natural health products and radiopharmaceuticals, to the Canada Vigilance Program.
Health Product InfoWatch (old name was CARN)
The Health Product InfoWatch is a monthly publication intended primarily for healthcare professionals. It
provides clinically relevant safety information on pharmaceuticals, biologics, medical devices and natural health
products.
This chapter focuses on errors that occur during the medication use process that includes the prescribing,
dispensing, and administration phases of medication use. Monitoring the patient for expected and unexpected
drug related problems and patient compliance. It reviews common causes of medication errors and suggest
measures to safe and effective use of medications/strategies to prevent dispensing errors.
Types of medication errors: According ASHP guidelines on preventing medication errors in hospitals, medication
errors can be categorized into 11 types.
· Prescribing errors
· Omission errors
· Wrong time errors
· Unauthorized drug errors
· Improper dose errors
· Wrong dosage form errors
· Wrong drug preparation errors
· Wrong administration errors
· Deteriorated errors
· Monitoring errors
· Compliance errors
· Other errors
Prescribing errors
A prescribing error occurs at the time a prescriber orders a medication for specific patient. These errors may
include the selection of incorrect drug, dose, dosage form, route of administration, length of therapy, or number
of doses.
Omission errors
Failure to administer an ordered dose to a patient in hospital, nursing home, or other facility before the next
scheduled dose is considered an omission error.
Wrong Time
Timing of administration is critical to effectiveness of some medications. Maintaining an adequate blood level of
some drugs such as antibiotics, frequently depends on evenly spaced, around the clock dosing.
Unauthorized drug error
Administration of a medication to a patient without proper authorization by a prescriber is categorized as an
authorized drug error
Improper dose
Improper dose error occur when a patient is given a dose that is greater or less than prescribed dose
Wrong dosage form errors
Doses administered or dispensed in a different form from the ordered by the prescribed are classified as wrong
dosage form error
Wrong drug preparation errors
Drugs requiring reconstitution (adding liquid to dissolve a powdered drug), dilution or special preparation prior
to dispensing or administration are subject to wrong drug preparation.
Wrong Administration Technique Errors
Doses that are administered using an inappropriate procedures or incorrect technique are categorized as wrong
administration technique error.
Preventing dispensing errors: In order to prevent dispensing errors, pharmacy should have policy and
procedures in place.
College of Pharmacists and professional regulatory agencies provide guidelines to prevent dispensing error. All
pharmacy staff should obey and discuss those guidelines.
Before you dispense any medication, check the followingà (7 point check)
Name of patient
Name of medication
Name of doctor
Pharmacist and technician initials (check expiration date)
Check DIN
Quantity of medication
Number of refills
3 point check during preparation
Read label when taking drug from shelf
Read label before preparing label
Read label when placing back on the shelf
Incidents (errors) Medication errors, dispensing errors.

Near missed incidents Error did not reach to patient
Related agencies of medication incidences are ISMP and CIHI.
Strategies in reducing dispensing errors

· Procedures and policies must be developed to deal with these errors, keeping in mind that the patient
safety is paramount.
· Discuss commonly dispensing error drug with staff.
· Bringing the common drugs that may have dispensing problems to others attention, that means everyone is
extra careful as they are dispensing them.
· Drugs that look similar separate and label them.
Dispensing error occurred.

Question Alerts!
· When dispensing errors occur, rapid resolution of
1) In community pharmacy If dispensing error occur
the problem is essential, including the recall of
who should be informed first?
the product.
· Inform the pharmacist manager immediately for
any misfills or other serious problems. Do not try to handle the situation yourself.
· Inform patient
· Inform manager
· Inform doctor if patient have taken wrong medication.
· Documenting all errors and discussing them with all staff helps keep everyone aware of mistakes that are
easily made.
Resolving dispensing errors. Pharmacy should have policies and protocol about resolving dispensing error.
Follow the guidelines provided by the provincial college of pharmacists. However, this is a general discussion to
help you get started understanding resolving dispensing errors.
In case an error has occurred, the patient needs to be informed of the error that has occurred that the
medication she is taking is not the correct medication as the pharmacy has made an error in dispensing the
medication she was supposed be taking Diclectin as the doctor has prescribed but the pharmacy dispensed
dicetel 7 by mistake. Tell her to stop taking the medication, Ask her how many dicetel 7 she has taken,
apologize for the mistake that has happened, take reasonability for the mistake, Call the doctor and report the
mistake, replace the medication with the right medication, speak to the staff about the error that has occurred.
Examples of medication error that could occur if auxiliary labels are not used or used inappropriately:
1) Codeine containing medication auxiliary label: dizziness may occur be careful when operating machinery, A
car accident may occur if the patient is not aware that this medication may cause dizziness.
2) Fosamax auxiliary labels: drink with plenty of water, remain upright for about ½ hour after taking the dose,
take on an empty stomach, If the patient is to take the medication and lie down right after taking it then the
patient may experience oesophageal adverse experiences
3) Ventolin auxiliary labels: shake well; don’t take too much of the medication
If the patient is to take too much of the medication then the patient may experience adverse drug reactions
such as palpitations, tachycardia, tremors, nervousness, hypokalemia.
4) Flovent auxiliary labels: shake well, rinse mouth after using this inhaler. If you don’t wash your month a
pharyngeal candidiasis fungal infection in the mouth may occur in the mouth.
5) Lipitor auxiliary label: avoid grapefruit juice. Grapefruit juice may have the potential to increase plasma levels
of HMG CoA reductase inhibitors metabolized by this isoenzyme causing increased potential for adverse effects
such as muscle weakness and pain.
Medications that should be taken with plenty of water:

Sulphonamides: Recommended for sulphonamides to decrease likelihood of crystalluria.
Expectorants: Expectorants to enhance viscosity reduction of bronchial secretions
Bulk laxatives: Bulk laxatives to increase stool bulk and decrease the likelihood of compaction
Irritating drugs: Such as potassium supplements, Chloral hydrate, theophylline
and some antibiotics.
Take with food or milk: Recommended for the drugs that cause stomach upset when this effect may be
decreased by taking medication with food.
Medication examples include:
· NSAIDs, and ASA
· Erythromycin
· Nitrofurantoin
· Valproic acid
Take Medication on an empty stomach, 1 hour before or 2 to 3 hours after 3 hours after meals unless or
otherwise directed physician.
Recommended for drugs that have decreased absorption or increased destruction in stomach when taken with
food.
Examples of drugs that should be taken empty stomach like ampicillin and tetracycline.
Actions that should be taken o resolve dispensing errors;

· Discuss with all staff to keep everyone aware of mistake
· Discuss and identify drugs that have similar names such as:
· Biaxin à one tablet twice a day (500 mg)
· Biaxin à 2 tablets once a day (500 mg)
· Lasix (furosemide)
· Losec (omeprazole)
· Procedure and policies must be developed to deal with these problems.
· Check DIN (Drug Identification Number)
· Cautionàsame DIN for different quantity packaging
· Expiry date
· Check patient name and date of birth
· Check allergy
· Paediatric dose child weight
Handling Returned Products
· It is against the law to replace returned medication as stock bottle once it has been dispensed and given to
the patient. Exceptions are hospital pharmacies.
· Prescription drugs may not be returned by a customer and placed back in stock.
· Sometimes, the manager’s attention needs to be drawn to a complaint. In other cases, policies will need to
be developed e.g. for product recalls and dispensing errors.
Expired drugs. Do not sell expired drugs.
Medical incidents
Institute of Safe Medication Practices (ISMP) is a non-profit independent agency established for the collection
and analysis of medication error reports and development of recommendation of enhancement of patient
safety.
Reference. American Society of Hospital Pharmacists. ASHP guidelines on preventing medication errors in
hospitals, Am. J Hosp Pharm. 1993; 50: 305 to 14.
ISMPs dangerous drug abbreviations.

· Use units instead "U" or "IU"
· Use "daily" instead of "o.d"
· Use mcg instead of "mg"
· Use "0.5" instead of ".5"
· Use "5" instead of "5.0"
· Use "qd" instead of "q.d"
· "D/C" is used for discharge but confused with discontinue
· "CC" is intended for "cubic centimeter" mistaken for units
· "@" is intended for "at", mistaken for 2 or 5
· ">" is intended for greater than mistaken for 7
Dangerous abbreviation Mistaken as Recommended

IU IV or 10 Units
OD Right eye Daily
"mg" mg mcg
".5" 5 0.5
"5.0" 50 5
@ 2 at
D/C Discontinue discharge
> 7 Greater
CC Units Cubic centimeters
High alert drug: The drug errors that can cause serious harm to patient.
Opioids, warfarin, digoxin, insulin, epinephrine, KCl solution, TCA, pregnancy x category drug, pediatric liquid
formulation that require measurements. Anticancer drugs and Lithium.
Home work:
To avoid error. Label as “HIGH ALERT” Vincristine and vinblastine
prednisone and prednisolone
Sound alike names, look alike drugs: lisinopril and fosinopril
Tallman letters are used for sound alike name drugs to avoid medication errors.
DAUNOrubicin and DOXOrubicin
BuPROPIon and BuSPIROne
ALPRAZOLam and LORAZEPam
ClomiPHENE and ClomiPRAMINE
INFLIximab and RITUximab
HydrALAzine and HydrOXYzine
diPHENhydramine and diMENhydrinate
www.pharmacyprep.com Health promotion
60
Health Promotion and Disease
Prevention
Questions Alerts!
A role of public health agency.
Levels of health care prevention: It can be categorized as primary, secondary and tertiary preventions.
Primary prevention Secondary prevention Tertiary prevention

Immunizations, smoking Cancer screening. Drug prophylaxis or treatment to
cessation. Lifestyle ASA 81 mg therapy or anticoagulants for prevent
patient with atrial fibrillations.
Activity are designed to Early detection and management of To manage clinical diseases in order
completely prevent the disease to prevent them from progressing to
disease. avoid complications of disease.
The drug of choice for secondary
prevention of stroke associated with
atrial fibrillation? warfarin
The drug of choice for the prevention
stroke in patient with transient ischemic
attack (ASA)? ASA 81 mg
Public Health units of public health agencies (PHA) offer health promotion and disease prevention programs to
help Canadian of all ages learn more about health, including healthy lifestyles, communicable disease control
and immunization.
The role of public health agencies is to promote health;

· Prevent and control chronic diseases and injuries.
· Prevent and control infectious diseases.
· Prepare for and respond to public health emergencies.
· Serve as a central point for sharing Canada’s expertise with the rest of the world.
· Apply international research and development to Canada’s public health programs and Strengthen
intergovernmental collaboration on public health and facilitate national approaches to public health policy
and planning.
Health promotion (Wellness): a process enabling people to increase control over and to improve their health. In
health promotion, pharmacists provide information and skills to individuals so that they can prevent specific
diseases and participate in services for early detection and treatment of disease. The process involves a
behavioural change approach such as in advising individuals on the importance of preventing and managing
obesity.
Health promotion activities from community pharmacies include the organizing of workshops, clinics where
patients are advised on a specific topic, and written and other visual aids are available in the pharmacy for
further information and for shop window dressing.
Topics for health promotion or primary prevention in community pharmacy includes;
· Smoking cessation
· Diet, exercise, body weight (Eating well with Canada Food Guide)
· Cardiovascular risk factors and prevention (Compendium of Therapeutic Choices)
· Sun exposure or sunscreen
· Travel Medicine (Specific countries travel.gc.ca)
· Patient compliance for treatment
· Immunization or vaccination programs (public health agency of Canada)
· Screening Programs or Tests (Pap smear test, mammography, PSA, DRE), colorectal cancer screening.
· Alcohol, drug abuse prevention
Screening test For detection of

Pap smear Cervical cancer associated with papilloma virus
PSA BPH and prostate cancer
DRE Colon cancer, prostate cancer
mammogram Breast cancer
Fecal occult blood test Colon cancer, colorectal cancer, peptic ulcers, ulcerative colitis, Crohn’s
(FOBT) disease
Sunscreen
UVA UVB UVC
AGING, WRINKLES, SKIN CANCER BURN OR SUNBURN, Q, SAFE
& EYE DAMAGE PRIMARY CAUSE OF SKIN STOPPED BY OZONE LAYER
CANCER, AGING, EYE DAMAGE
PREVALENT YEAR AROUND AT STRONG SPRING TO FALL SHARTEST WAVES
ALL TIMES ALL DAY AND BETWEEN 10.00 AM TO 4PM
PENETRATED UNTREATED GLASS STILL ALL-DAY YEAR-ROUND
RISK.
ZnO, Titanium dioxide,
Avobenzone blocks UVA.
Sun protection factor (SPF): The average light-skinned person can stay in the sun with no sun protection for 10
min before start to burn. If person applied sunscreen with SPF 15. Person can stay in sun for multiple of 15 x 10
min = 150 min can stay in sun with screen without burn.
SPF 15 x 10 min = 150 min
Higher SPF also filters more UVB. i.e.

SPF 15 blocks 93% of UVB
Folic acid in pregnancy

Primary prevention of neurotubule defect, it recommended to use 0.4 mg of folic acid daily. Starting from 3
months before conception and continue to the first trimester.
Avoid vitamin A retinol in pregnancy. However, vitamin A with beta-carotene are safe.
Immunization
Flu vaccine
Hepatitis A & B
Pneumococcal
Dukoral
Zoster vaccine
Factors influencing health promotion (wellness) activities in community pharmacy

Positive factors Negative Factors
Accessibility of pharmacy Lack or resource material, Lack of space
Communication skills of pharmacist. Lack of confidentiality
Strong pharmacist and patient relation Improper time management of pharmacy personal
Environment within pharmacy conducive to
health promotion
61
Collaboration and Teamwork
Questions Alerts!
Teamwork and collaboration components includes communication, scope of practice, conflict
management and management of patient care.
Academic detailing goal is to enhance prescription practices.
A collaborative care involves a number of health professionals working to treat a patient. The team
generally comprises a physician, pharmacist, nurse practitioners, physiotherapist etc. To address this
issue there were several collaboration models have been studied.
Examples of collaborative traditional patient care models include biomedical model, bio-psycho-social
model.
Biomedical model: In this model, disease is defined as biophysical malfunction and goal of treatment is
to correct the malfunction in order to cure the disease. The biomedical model includes pathophysiology
of disease, objective tests and therapeutic interventions at centre of patient care. However biomedical
model offers one dimensional approach to patient care that excludes the patient experience of illness
and how this affects the other facets of life such as work disability, finances, and social networks
because they are believed to lie outside of medicines responsibility and authority.
Bio-psycho-social model (BPS): The bio-psycho-social model (body and mind) includes bio, psychological
and social dimension of patient into the care plan. The biological component of this model examines the
cause of the illness and how it affects the functioning of body. The psychological component of the
model explores any potential psychological causes for the illness (example lack of self-control, emotional
stressors, negative-thinking). The social component considers how different social factors (e.g.,
socioeconomic status, religion, culture) impact illness. In order to address all aspects of this three-
dimensional model, an integrated team approach involving allied healthcare professionals, such as
physicians, nurses, psychologists, pharmacists, social workers and rehabilitation specialists, are critical
for ensuring that more comprehensive patient care is provided.
Recovery Model: In this model the patient is involved in a lifelong recovery process that involves a
number of incremental steps across various facets of his or her life. The primary illness is seen as only
one dimension in the patient’s recovery process. Other key aspects of this model include negotiating
treatment approaches between patients and practitioners such that the patient feels empowered.
PharmacyPrep.
Patient-centred cared model (PCC): In this model the patient individuality is central. The patient has
right to have his or her needs, desires, beliefs, values, and goals respected and placed at centre of the
care plan. Respect for patient individuality is part of the team commitment to understand the patient
perspective of his or her own health status and continued care.
Model for Collaborative working relationship (CWR)

There are five stages in CWR
Stage 0: Professional awareness
Stage 1: Professional Recognition
Stage 2: Exploration and Trial
Stage 3: Professional Relationship Expansion
Stage 4: Commitment to the collaborative working relationship
Stage 0: exchange is minimal. Example pharmacist calling for refill request or alerting physician for
possible side effects, drug interactions.
Stage 1: The efforts are mostly from pharmacist. Example as pharmacist develop new services,
pharmacist may be visiting physician to ask for referral of patients.
Stage 2: Pharmacist still continues to be initiator. Recommend high quality and priority
recommendations to physician. Value added services like Med check, screening.
Stage 3: Continue developing relationship to offer patient care.
Stage 4: Relatively high input, lengthy duration and great consistency.
Pharmaceutical Care Delivery System

· The major pharmaceutical care activities takes place in the following systems
· Community pharmacy
· Hospital pharmacy
· Long term care facilities
· Specialty hospital units
Community Pharmacies:
· Community pharmacies are considered one of the important components of the pharmaceutical
care delivery system. However, health related services are primarily limited to dispensing
medications and patient counselling.
Pharmacist collaboration: Pharmacists needs to work in collaborative relationship with physician and
other healthcare providers.
Academic detailing (AD) defined as process of outreach in which a knowledgeable heath professional
(pharmacist) visit physicians to discuss issues of drug use and (often) overuse. AD is also known as
counter detailing. The goal of academic detailing is to enhance appropriate prescribing practices.
Soumerai and Avorn described eight components that contribute the success of academic detailing.
· Establish credibility of agency developing the intervention
· Conduct interviews with physicians to establish baseline knowledge
· Focus the intervention on educational outreach, university-based educational detailing, and public
interest detailing specific physicians.
· Define clear objectives for intervention
PharmacyPrep.
· Stimulate physician interaction during the detailing visit
· Use concise graphic educational material during the presentation
· Highlight and reinforce the essential messages during presentation
· Provide positive reinforcement with a follow up visit to the physician
Pharmaceutical opinion: Pharmacist identify a potential drug related problem for patient and then
provide the prescriber with a clinical recommendation to resolve the therapeutic problem.
Pharmaceutical opinion or documentation is prepared in SOAP formats.
S= subject; patient info
O= Objective: lab results
A= assessment: risk factors, symptoms
P = therapeutic plan
PharmacyPrep.
www.Pharmacyprep.com Sterile Preparations
62
Sterile Preparations
Questions Alerts!
· The most common source contaminants in laminar airflow hood is personals.
· Types of needles, syringes, vials and ampoules. The “gauge” measures the size of needle. The higher the
gauge tinier the needle.
· Cytotoxic preparations precautions.
· Cytotoxic products sterile preparations use vertical laminar airflow hood and clean rooms.
Sterilization methods
Dry heat Steam Filtration Gaseous Radiation
Dry heat sterilization

· Equipment. Oven
· Method. Dry heat sterilization is carried out at 240 °C to 250 °C for 2 to 4 hrs.
· Application. Glassware, fixed oils, glycerine, petrolatum, liquid petroleum (mineral oil), paraffin, and various
heat stable powders, glassware and surgical instruments.
· Dry heat method of choice when dry apparatus or dry containers are required, as in the handling of
packaging of dry chemicals or non-aqueous solutions.
· Advantages & disadvantages. Sterilization by means of heat requires higher temperatures and longer
exposures than sterilization by steam. Heat transfer is slow, small volume of oil and thin layers of powder
should be used.
Steam (wet) sterilization

· Equipment. Autoclave
· Temp. 121oC 15 min, pressure 15 to 20 lbs
· Method. In the presence of moisture, microorganisms are destroyed at a lower temperature than in dry
heat. This is the method of choice when product can withstand such treatment.
· Application. Solutions sealed in containers. Ampoule, vials, bulk solutions, glassware, surgical dressing, and
instruments.
· Advantages. Rapid, inexpensive, effective, large volumes can be sterilized.

· Disadvantages. Cannot use for oily preparation (oil base ointment), cannot use for moisture sensitive
preparations.
Filtration sterilization
Physical removal of microorganisms by adsorption on the filter medium. Used for heat sensitive materials.
· Equipment. Porcelain filters, siliceous earth filter, sintered glass filters, asbestos filters membrane filters.
· Bacterial filtration: Microbial filter used in water filtrations 0.22 microns.
Application. Thermo labile solutions of low viscosity.

Advantages & Disadvantages. Depend on filter media, thermo labile solutions can be sterilized such as
hormones, proteins.
Gaseous sterilization
· Equipment. Special oven, for admission of gas and humidity & hermetic.
· Method. ethylene oxide
· Ethylene oxide gas require 4 to 16 hours
· Humidity of less than 20% RH
· Ethylene oxide-carbon dioxide, pressure 30 psi, temperature 20 to 55 °C.
· Application: Thermo labile powder, plastic/polymers, ophthalmic preparations, subcutaneous, vaginal
inserts, plastic syringes, and tubing sets.
Advantages & Disadvantages: Explosive hazard, toxic, not appropriate for solutions
Radiation sterilization
· Equipment: Ultraviolet lamp (laminar airflow hood), ionization (beta rays, gamma rays-from nucleus, X-rays)
· Application: Thermo labile drugs (powdered)
· Disadvantages: Highly specialized equipment required, effect of irradiation on products and their containers.
Sterile Preparations
To make sterile preparations aseptic Question Alerts!
techniques are procedure conducted 1) Doxorubicin preps are done in? Vertical or BSC
under controlled condition to minimize 2) The most common contaminant? Personals, hand wash.
the chance of contamination. 3) The gold standard reference for sterile prep is? USP Chapter 797
4) The work area in LAF from the edge should be in? 6 in (15 cm)
Sterility is the freedom from bacteria
and other microorganisms. Formulations must be sterile, which is not a relative term an item is either sterile or
not sterile. The word “sterile” refers to as free of living microorganism.
If the sterile formulation is a solution, it must be free of all visible particulate material.
Pyrogen free à Pyrogen is a chemical substance that is produced by microbial cell wall.
Heating to high temperatures and double distillation can eliminate pyrogen.
Aseptic preparation area: A limited access room of area in which laminar airflow hood is situated, usually
separated from other pharmacy high traffic areas. Special measures should be taken to reduce airborne
particles.
Laminar Flows Hoods (Biological Safety Cabinets) that used for sterile preparations categorized as two types
based on direction of airflow. Horizontal laminar airflow hood and vertical laminar airflow hood.
Vertical laminar airflow (biological safety cabinet) hood is recommended for cytotoxic, anticancer antibiotics
like doxorubicin and microbial preparations.
Horizontal Flow Hood Vertical Flow Hood
HEPA filter: A HEPA filter is described as a high efficiency particulate air filter. It is employed with laminar flow
for preparation of aseptic parenteral products. It has an efficiency of removing 99.97% particles of 0.33 microns
or diameter larger.
Class 100 clean room: A class 100 clean room is defined as an environment that contains no more than 100
particles per cu. Ft. of 0.5 microns or larger diameter size.
Hypodermic Needle
· HUB. Extension of needle that fits onto the syringe.
· Bevel. portion of the needle that is ground
· Heal. the back portion of the bevel
· Cannula. shaft portion of the needle (made of steel)
· Lumen. The needle holes.
· The gauge is thickness or the "inner diameter" of the bore of needle and ranges from 27 to 13. The smaller
the number the greater the diameter.
· Needles discarded in sharp container.
· Insulin needle gauge 31-32 is the thinnest needle available. The 30G is thinner than 28G.
Types of Glass
Type І glass is made of borosilicate the material, more resistant to water attacks.
Type II glass Is specially treated soda-lime glass
Type III glass Is the typical soda-lime glass
NP glass Non-parenteral i.e. not suitable for injection
Type II glass is prepared by dealkalinizing the surface of type III glass by sulfur dioxide which will improve its
resistance to breakdown and migration of alkali parenteral product. This internal coating will be weakened by
repeated sterilization or exposure to alkaline detergents.
Tips
1. filtration and 2. Dry heat 3. Vertical laminar
radiation air flow hood
4. ethylene oxide 5. dealkalinizing by sulfur dioxide 6. For microbial filtration
0.22mm in sterile H 2 O
7. Distillation 8. microorganism, 9. absolute form
pyrogen & particulate
10. free from bacteria 11 Autoclave, 121oC ,At least 15 min. 12 heat sensitive products
13 Rabbit test and 14 pyrogen free, sterile, particulate free, 15 0.22mm
LAL test and isotonic
16. needle
· How do you prepare type II glass, from type III glass? ( )

· Filtration sterilizations ( )
· Steam (wet) sterilization autoclave temperatures ( )
· Gas sterilization ( )
· Radiation methods ( )
· Pyrogen test ( )
· Hormones sterilized by ( )
· Tubing’s sterilization method ( )
· Proteins sterilization methods ( )
· Petrolatum, waxes are sterilization methods ( )
· Parenteral solutions should be: ( )
· Sterility is? ( )
· Cytotoxic drug preparations should be done in? ( )
· Doxorubicin is an anticancer antibiotic prepared in? ( )
· The size of HEPA filter that is used in laminar airflow hood? ( )
· Parenteral preparations should be free from? ( )
· Pyrogen are eliminated by? ( )
· What part of the syringe that should not be touched? ( )
www.PharmacyPrep.com Drug Storage and Handling
63
Drug Storage Conditions
Proper storage is very important key component of Quality Assurance to maintain medicines efficacy, stability.
The drug is affected by the factors such as temperature, light sensitivity, chemical reactions.
· Drug storage areas must maintain proper temperature and humidity conditions to ensure stability of all
medications as recommended by manufacturer.
· Temperature in refrigerators and freezers should be monitored and documented daily.
· Before preparing any medication, each drug, ingredient and container should be visually inspected for
damage defects and expiry date.
· All the drugs and supplies use in the sterile room should be unpack before brining into the sterile room.
· All the medications and supplies should be stored on shelves, cabinets, and cart, not on the floor. That way,
the floors can be clean properly.
· Chemo/toxins should be stored on an eye level or on lower shelves in order to avoid breakage.
· All the drugs, supplies and equipment should be storage as the manufacturer indicated on the label.
· All high-alert medications are safeguarded and that known safety requirements for storage, availability and
labeling are followed.
Stability: Refers to the extent that a pharmaceutical preparation retains specified properties and characteristics
within specified limits that it possessed at the time of compounding or preparation.
Cold Temperature: Temperature that does not exceed 8º C
Refrigerated Temperature: Temperature that is between 2º C to 8º C
Cool Temperature: Temperature that is between 8º C to 15º C
Room Temperature: Temperature that is between 15º C to 30º C
Temperature
Four ways to convert Celsius Four ways to convert

to Fahrenheit Fahrenheit to Celsius · Deep freeze -10 to -72 oC
· Frozen 0 oC
°F = [(°C) (9)/5] + 32 °C = [(°F - 32) / 9] (5) · Refrigerator or cold 2 to 8 oC
°F = °C x (9/5) + 32 °C = [(°F - 32) (5)] / 9 · Cool 8 to 15 oC
°F = (°C x1.8) + 32 °C = (°F - 32) (0.56) · Room temp 15 to 25 oC
°F = (9°C+160) / 5 °C = (5°F - 160) / 9 · Warm 30 oC
· F = 9C/5 + 32
Cold chain Management: Temp 2 to 8 oC (optimal temp 5 oC)

63-1
Drug Recommended Storage Stability at room temperature

Insulin Refrigerate at 2° to 8° C 28 days
Triflurdine (Viroptic) Refrigerate at 2° to 8° C
Idoxuridine Room temperature
Xalaton (Latanoprost) Prior to dispensing or unopened After first use, store at a room
refrigerate at 2° to 8° C temperature not to exceed 25°C
for up to 6 weeks
Xalacom (Latanoprost + timolol) Prior to dispensing or unopened After first use, store at a room
refrigerate at 2° to 8° C temperature not to exceed 25°C
for up to 10 weeks
Etonogestrel/ethinyl estradiol Refrigerate at 2° to 8° C After dispensing, store at 25°C
vaginal ring (Nuvaring) for up to four month
Infliximab Refrigerate at 2° to 8° C
Vaccine Recommended Storage Stability at room temperature

Dukoral Refrigerate at 2° to 8° C Can be stored at RT for up to 2
wks one occasion only. After
mixing buffer solution, should be
consumed within 2 hrs.
Influenza virus Refrigerate at 2° to 8° C
Influenza live vaccine Refrigerate at 2° to 8° C
(FluMist)
MMR Refrigerate at 2° to 8° C Diluent may be stored in fridge
or room temperature. Do not
freeze.
Hepatitis a Refrigerate at 2° to 8° C
Hepatitis B Refrigerate at 2° to 8° C
Hepatitis A and B Refrigerate at 2° to 8° C
Zostavax II Refrigerate at 2° to 8° C
All Biologicals Refrigerate at 2° to 8° C
Prolia Refrigerate at 2° to 8° C
Powdered antibiotics require reconstitution with distilled water, added at the time of dispensing.
While many of these medications are stored in the refrigerator, some are not.
Reconstituted products Recommended Storage Stability at room
temperature
Azithromycin suspension Room temperature for 10 days
Amoxicillin suspension Refrigerate at 2° to 8° C for 14 days
Amoxicillin/clavulin 400 mg Refrigerate at 2° to 8° C for 7 days
Amoxicillin/clavulin 250 mg Refrigerate at 2° to 8° C for 10 days
Clarithromycin suspension Room temperature for 14 days
Erythromycin suspension Refrigerate at 2° to 8° C
Clindamycin suspension Room temperature for 14 days
Phenytoin suspension Room temperature Protect from freezing and
light
Metronidazole suspension Refrigerate at 2° to 8° C Room temperature stable
63-2
for 1 month
Chloramphenicol suspension Room temperature for 2 weeks
Ciprofloxacin suspension Room temperature for 2 weeks
Furosemide solutions
Cefuroxime axetil suspension Room temperature for 2 weeks
Cotrimoxazole suspension Room temperature until expiry
Norfloxacillin Room temperature for 2 weeks
Cloxacillin Room temperature for 2 weeks
For cold chain follow National Guidelines for Vaccine Storage and Transportation.
Short dated products are those which will expire before the patient will finish using them.
Tips
1. Streptomycin 2. Xalatan 3. Amoxicillin

4. Insulin 5. Ampicillin 6. Clarithromycin
7 Combination + Amoxicillin + 8 Azithromycin 9. Clindamycin
clavulanate
10 Cotrimoxazole 11 15 to 25 oC 12. 8 to 15 oC
13 2 to 8 oC also known as cold) 14 0 to 4oC 15. Erythromycin
· What temperature is fridge? ( )
· What is room temperature in Canada? ( )
· What is cool temperature? ( )
· What is freezer temperature? ( )
· Suspensions, store in refrigerator. Discard after 14 days. ( )
· Reconstituted solution does not shake. Use immediately. Discard after 8 hours. ( )
· Store in refrigerator, do not freeze and can be stored at room temperature for a month( )
· Store unopened bottles in refrigerator. Opened bottles may be stored at room temperature up to 25 oC for
up to 6 weeks ( )
· What drug 200 and 400 mg is used within 7 days. 125 to 250 mg use within 10 days ( )
· Refrigerate, if unused for 14 days discard it. ( )
· Shake well before use and do not store in refrigerator. Discard unused portion after 14 days. ( )
· Suspensions stored at room temperature ( )
· Extemporaneous azithromycin suspension à
· Extemporaneous clarithromycin suspension à
· Extemporaneous clindamycin suspension à
· Cotrimoxazole suspension à
· Insulin stored at à
63-3
PharmacyPrep.Com Pharmaceutical Care
64
Patient Care
Patient care describes specific activities (job description) and services which an individual pharmacist offer
services to patients that include dispensing, collaborating, implementing, developing and monitoring
therapeutic plan that will produce specific therapeutic outcome for the patient.
Patient care process includes Medication Assessment (gathering medication information) --> Care Plan -->
Follow up evaluation, documentation
The pharmaceutical or patient care is the services rendered by the pharmacist to improve patient quality of life
within reasonable economic expenditure. Pharmaceutical care requires the pharmacist to incorporate some
essential skills in practice that include.
· Prescription processing and dispensing.
· Making sure that the patient understands how to use the product, to ensuring that use of a medication will
have the outcome desired.
· Skills in assessment of patient health status.
· Identification of potential and actual drug related problems or drug therapy problem (DRP or DTPs).
· Identification of drug related problem and therapeutic choices
· Developing and implementing therapeutic care plan.
· Monitoring and evaluating patient progress with therapy
· Documentation of finding and follow ups
Drug-related problems (DRPs) or Drug therapy problem (DTP): The pharmacist’s focus is on the patient’s use of a
product, to the patient’s situation as a whole including his or her need for the medication, the appropriateness
of the product as prescribed, factors that could affect the patient’s use of the medication as prescribed, and
whether the desired outcome will be achieved (from both the patient’s and physician’s points of view). An
important part of this focus for the pharmacist involves the identification of current or potential drug related
problems and their subsequent resolutions.
DRPs RELATED TO Examples

No valid indication (unnecessary INDICATIONS
use)
Drug NOT receiving or Need
additional drug
NOT taking/receiving appropriate EFFECTIVENESS
drug OR INEFECTIVE DRUG
Dosage is too low
Dosage is too high SAFETY
Adverse drug reactions

Drug interactions
Non-compliance NON-COMPLIANCE
Drug-related problems (DRPs). That are described in the concept of pharmaceutical care include:
1. The patient is taking/receiving a drug for which there is no valid indication or unnecessary drug therapy.
2. The patient requires drug therapy for an indication and is not receiving it (includes symptoms of disease and
of side effects).
3) The patient is not taking/receiving the appropriate drug (includes allergies, contraindications, or a drug that is
not cost-effective, not working or not the drug of choice).
4) The patient is taking/receiving too little of a drug (includes insufficient dose, frequency and drug disease
interactions, and drug food interactions).
5) The patient is taking/receiving too much of a drug (includes excessive dose, inappropriate frequency and
drug-disease interactions).
6) The patient is not taking/receiving the prescribed drug appropriately (economic constraints, dispensing or
administration error, non-compliance).
7) The patient is experiencing an adverse drug reaction (non-dose-related).
8) The patient is experiencing a drug-drug, drug-food or drug-laboratory test interaction.
Developing therapeutic plan: A pharmacist must develop therapeutic plans, recommending therapeutic options,
doses, scheduling/administration, required drug devices and compliance aids.
Documentation of pharmaceutical care. Formulate a SOAP progress notes to describe and document the
interventions intended or provided by the pharmacist.
S = Subjective
O = Objective
A = Assessment Question Alerts!
P = Plan 1) Patient age is categorized in?
SOAP stands for Subjective data (S) separated

from objective data (O), A = assessment P = Plan
SUBJECT S = Subjective (summary of case). MP is a 55-year-old man, receiving treatment of
hypertension. MPs doctor prescribed hydrochlorothiazide 50 mg daily.
OBJECTIVE Current BP 150/90, SrCr (80), FBG 6.5 mmol.
(Findings)
ASSESSMENT MP using HCTZ 50 mg and have still high BP and require additional antihypertensive
drug.
PLAN MP Doctor adds Ramipril 10 mg.
Tips
1. ARBs 2 Refer to doctor 3 Pharmaceutical care
4. FARM 5 SOAP 6 improving patient quality of life
· What is defined as the services offered by the pharmacist to improve patient quality of life within
reasonable economic expenditure ( )?
· Finding, Assessment, Resolution, Monitoring ( )
· Subjective data, Objective data, Assessment, Plan ( )

· Pharmaceutical care should be focus to? ( )
· A 50-year-old patient currently using enalapril for hypertension. Experiencing dry cough. What alternative
therapy should you recommend? ( )
· A customer searching for OTC antidiarrheal medications. If you realized diarrhea is associated with
clindamycin, what is appropriate action? ( )
· Pharmaceutical care should be focus to à
· Write examples of drug related problem (DRP) à
· A 50-year-old patient currently using enalapril for hypertension. Experiencing dry cough. What is alternative
preferably therapy is recommended?à
· A customer searching for OTC antidiarrheal medications. If you realized diarrhea is associated with
clindamycin, what is appropriate action? à
Examples of DRPs:
No indication
Indication
Wrong drug
Low dose
High dose
Not administered properly
ADR
Drug Interactions
Write the most common DRPs of the following drugs and patient presentations:
· Alendronate -->
· Statins -->
· Metformin -->
· Insulin -->
· Salbutamol -->
· Steroid inhalers -->
· Anticholinergic drugs (ipratropium) -->
· Contraceptive pills -->
· Methotrexate -->
· Minocycline -->
· Metronidazole -->
· NSAIDS -->
· Warfarin -->
· Accutane -->
www.Pharmacyprep.com Adverse Drug Reactions
65
Adverse Drug Reactions
Questions Alerts!
Clinical significant adverse drug reactions like most common and serious side effects
ADRs affecting the cardiovascular system

Cardiovascular Causative drug Tips/Comments
disorder
Hypertension Venlafaxine dose dependant >225 mg act on 5HT and NE
hypertension, sympathomimetics
(pseudoephedrine) and mineral
corticoids. Licorice.
Postural hypotension Alpha-blockers, ACEi, diuretics, · Caution on standing
(syncope) antipsychotic (a1 blockade), vasodilator · Take first dose of alpha-blockers
(hydralazine, nitrates) and opioids. and ACEi on at bedtime
Myocardial ischemia Levothyroxine, adenosine, · In patients with hypothyroidism
amphetamines, beta agonist, beta- and cardiovascular disease, the
blockers (withdrawal), caffeine, initial dose of levothyroxine
ergotamine, nifedipine (short-acting), should be low and increased every
theophylline, verapamil. Oral 4 wks.
contraceptive pills.
Peripheral Beta-blockers · Choose a more cardio selective
vasoconstriction (DVT, agent such as atenolol, which has
Raynaud's less affinity for beta 2-
phenomenon) adrenoceptors
· Choose a beta-blockers with
vasodilators actions, e.g.
carvedilol and labetalol
Hemorrhagic stroke Anticoagulants, thrombolytic and · These drugs should be avoided
antiplatelet drugs
Arrhythmias; Antiarrhythmic: amiodarone, · Risk of torsade de pointes (QT

prolonged QT interval disopyramide, procainamide, interval prolongation) or sudden
(Ventricular propafenone, quinidine, sotalol. death due to ventricular
tachycardia) fibrillation
Normal QTc Interval Antihistamines (Terfenadine, astemizole), · Recommended doses for
<440 ms antibacterial (clarithromycin, Terfenadine should not be
erythromycin, cotrimoxazole), exceeded. Terfenadine should be
fluroquinolones (moxifloxacin and avoided in hepatic impairment,
levofloxacin) antifungals (ketoconazole, hypokalemia and pre-existing QT
itraconazole), antimalarial (chloroquine, interval prolongation or with
quinine), antipsychotics (chlorpromazine, grapefruit juice in addition to the
haloperidol, pimozide, thioridazine), risk factors listed above.
antidepressants, Tricyclic, (amitriptyline · Hypokalemia and hypo magnesia
and imipramine and Ziprasidone), increase QT prolongation (interact
cisapride, pentamidine, tacrolimus, with diuretics)
terodiline.
Atrial fibrillation Antidepressant (trazodone, fluoxetine), · Drug causes are rare. Other
(Lab test is. absence of and alcohol. includes hypertension,
P wave). hyperthyroidism, rheumatic heart
disease, infection and pneumonia.
Bradycardia Beta blockers (including eye drops), H 2 · Serious interaction between beta-
receptor antagonists, carbamazepine, blockers and verapamil leading to
A = AMIODARONE clonidine, digoxin, diltiazem, and a systole. Risk of bradycardia with
B = BETA BLOCKER verapamil. beta-blockers and diltiazem
C = VERAPAMIL & (carefully monitoring required).
DILTIAZEM · Adjust dose of digoxin to keep the
D = DIGOXIN heart rate above 60 beats/min.
· Watch HR for Amiodarone, BB,
CCB (verapamil, diltiazem)
Digoxin.
AV node arrhythmias TCAs Amitriptyline toxicity · Amitriptyline is proarrhythmic
ADRs involving hematological system

Hematological Causative drugs Comments
disorder
Aplastic anemia Antidiabetic (chlorpropamide, tolbutamide), Reduced red blood cell (anemia), white
(total or partial Antiepileptics (carbamazepine, phenytoin, cell (leucopenia), and platelets
failure of the bone lamotrigine), anti-inflammatory (diclofenac, (thrombocytopenia) counts.
marrow). gold, indomethacin, penicillamine, Often irreversible despite drug
phenylbutazone, piroxicam, sulindac, withdrawal.
sulfasalazine), Antimicrobials
(chloramphenicol, co-trimoxazole,
sulphonamides), antiplatelets (ticlopidine),
antipsychotics (chlorpromazine), antithyroid
agents (methimazole, propylthiouracil)
Agranulocytosis Antibiotics (penicillin's, cephalosporin's, Recovery usually 2 to 3 weeks after

(profound reduction cotrimoxazole, chloramphenicol, drug is withdrawn; repeat exposure to
of granulocytes with sulphonamides), antidepressants (imipramine, causative drug not recommended due
neutrophil count clomipramine, desipramine), antiepileptics to sensitization.
less than 0.5 x 109/L (carbamazepine, phenytoin), anti-
inflammatory (gold, penicillamine, What is monitored for
leflunomide, sulfasalazine, NSAIDs), agranulocytosis? WBC
antipsychotics (chlorpromazine, thioridazine,
clozapine), antithyroid drugs (methimazole,
propylthiouracil), captopril, procainamide, and
Q ticlopidine.
Thrombocytopenia Antimicrobials (chloramphenicol, co- May present as easy bleeding, bruising
(reduced platelets to trimoxazole, trimethoprim, penicillin's, or purpura; prolong bleeding time but
less than 150 x sulphonamides, rifampicin), antiepileptics INR remains normal. Usually occurs 7 to
109/L). (sodium valproate), anti-inflammatory (gold, 10 days after drug started. Avoid future
Heparin induced penicillamine), diuretics (thiazides, exposure to the causative agent.
thrombocytopenia, furosemide) tolbutamide, digoxin, ASA and NSAIDs reduce the effects or
the best alternate? methyldopa, heparin induced remaining platelets and therefore
Fondaparinux thrombocytopenia (less likely with low should be avoided during
molecular weight heparin), and quinidine. thrombocytopenia.
Pure red cell aplasia Azathioprine, phenytoin, isoniazid, The Coombs test is used to distinguish
(Total or partial penicillamine, chlorpropamide, immune mechanism also G6PD
failure or red cell chloramphenicol, erythropoietin, deficiency. Red cells usually return to
production) cephalosporin's, penicillin's, tetracycline’s, normal after 2 to 3 weeks.
insulin, methotrexate, isoniazid, quinidine,
quinine, rifampin, sulphonylureas, Marked increased of reticulocytes
methyldopa, mefenamic acid, drugs with indicates? anemia
oxidant effect on cell membrane (particularly
in G6PD deficiency).
Megaloblastic Acyclovir, alcohol, antiepileptic, methotrexate Impaired DNA synthesis usually due to
anemia (large (dose dependent), nitrofurantoin, oral folate or vitamin B 12 deficiency.
abnormal form or contraceptives, proguanil, sulphasalazine, Use folic acid supplements to treat
precursors to RBC) trimethoprim (usually due to worsening of patients taking antiepileptic drugs.
pre-existing folate deficiency) and phenytoin.
ADRs leading to psychotic problem
Psychiatric problem Causative drugs
Depression · Alcohol, amantadine, CNS stimulants (amphetamine withdrawal).
· Antimicrobials (ciprofloxacin, sulphonamides)
A person likes to · Cardiovascular (lipophilic beta blockers (Propranolol), alpha blockers, CCB,
self-harm? digoxin, methyldopa, statins).
· Benzodiazepines, carbamazepine, levodopa, phenothiazines).
· Hormones (corticosteroids, estrogens, progesterone)
· Disulfiram, isotretinoin, mefloquine, metoclopramide, and NSAIDs.
Psychosis · Amantadine, amphetamines, anticholinergics (includes 1st generation
antihistamine), antiepileptics, bromocriptine, chloroquine, clonidine, digoxin,
disulfiram, donepezil, ganciclovir, isoniazid, levodopa, mefloquine, NSAIDs,
quinidine, quinolone, zolpidem, and drugs of abuse.
Mania · Baclofen, bromocriptine, chloroquine, corticosteroids, dopaminergic agents,

isoniazid, levodopa, and antidepressants.
Behavioural toxicity · Lamotrigine (cognitive SEs), dextromethorphan (children), diphenhydramine,
chlorpheniramine, vigabatrin.
Confusion · Antiparkinson's drugs, barbiturates, beta-blockers, benzodiazepines, cimetidine,
corticosteroids, diuretics, H 2 -receptor antagonist, hypoglycemic, MAOis, NSAIDs,
opioids, and 1st generation and antihistamines.
Dementia or · Most common are benzodiazepines withdrawal symptoms, corticosteroids,
delirium opioids, anticholinergics and drug with anticholinergic effects including TCAs,
or delirium tremens antiarrhythmics, antiparkinson agents, conventional antipsychotics, ipratropium
(high doses), oxybutynin, tolterodine and sedating antihistamines.
Neuroleptic · Dopamine antagonists (antipsychotics, most common are phenothiazines and
malignant syndrome butyrophenones).
Sedation · Most common are antiparkinson’s drugs, antipsychotics (phenothiazines,
particularly chlorpromazine), barbiturates, benzodiazepines, carbamazepine,
opioids, antidepressants (amitriptyline, trazodone), 1st generation antihistamines,
and alpha blockers.
ADR leading to Neurological disorder

Neurological Causative drugs Comments
disorder
Headache Vasodilators (CCBs like nifedipine, nitrates), · Tolerance usually develops
indomethacin, MAOi interaction (hypertensive during vasodilator treatment
(ANTIHYPERTE crisis), analgesics (rebound after daily and patients should persist
NSIVE KNOWN administration, especially with caffeine), triptans with treatment if possible
FOR (overuse), ergotamine (withdrawal), and SSRIs.
HEADACHE)
Aseptic meningitis NSAIDs, vaccines, ciprofloxacin, azathioprine, · Particularly in patients with
penicillin, isoniazid, cotrimoxazole. systemic lupus erythromatus
· Difficult to distinguish
clinically from bacterial/viral
meningitis, therefore a drug
history should be considered
in all cases.
Benign intracranial Amlodipine, corticosteroids (including topical), · Symptoms include headache,
hypertension danazol, etidronate, nalidixic acid, nitrofurantoin, edema of optic nerve head,
oral contraceptives, tetracycline’s, isotretinoin, nausea, vomiting, tinnitus and
vitamin A (at high doses and deficiency) visual disturbances
· Usually resolves on cessation
of treatment
Reduction of Bupropion, 1st generation antihistamines, · Early drug withdrawal

convulsion antipsychotics, baclofen, chloroquine, improves prognosis
threshold and cyclosporine, corticosteroids (systemic), · Risk factors include diabetes
increasing the risk donepezil, isoniazid, lithium, mefloquine, ecstasy mellitus, alcoholism, vitamin
of seizures agents (amphetamines), NSAIDs, oral deficiency (vitamin B 1 , B 12 ),
contraceptives, penicillin's, quinolone antibiotics, reduced renal/hepatic
antidepressants (SSRIs, and TCAs), stimulants and function, poor acetylator
anorectics, theophylline, tramadol, vaccines. status (hydralazine, isoniazid).
Withdrawal effects of alcohol, baclofen,
barbiturates, BZD.
Guillain-Barre’ Captopril, corticosteroids, gold salts, hepatitis B · Rare paraesthesia of toes or
syndrome (disease vaccine, Q influenza vaccine, MMR vaccine, fingers progresses to upper
of peripheral oxytocin, penicillamine, streptokinase and lower limb followed by
nerve) total body weakness
Myasthenia gravis Corticosteroids (high-dose), phenytoin, amino · Avoid in myasthenia gravis
(chronic muscle glycosides, quinolone antibiotics (ciprofloxacin),
weakness beta-blockers, lithium, anticholinergic
involving reduced
activity of
acetylcholine at
neuromuscular
junction)
Extra pyramidal 1st generation antipsychotics such as haloperidol · Apparent lower risk of drug-
symptoms and (also following withdrawal), antiemetics induced Parkinsonism with
Parkinson’s (metoclopramide, prochlorperazine), CCB newer antipsychotics
disease (verapamil, amlodipine, diltiazem), lithium, (clozapine, quetiapine
"PATD" methyldopa, antidepressants (TCAs and SSRIs), risperidone, olanzapine).
and valproate · Dose-related
· Metoclopramide should be
avoided in patients with age
less than 20 years or QT
prolongation.
Tinnitus NSAIDs, including ASA, and antimalarials.
ADRs affecting Respiratory system

Respiratory disorder Causative drugs Comments
Cough ACEi; All ACE inhibitors and direct · Angiotensin receptor antagonists
renin inhibitors (Aliskiran). (ARBs) may be suitable alternatives
Nasal congestion Chronic use of topical nasal · Prolonged used of topical
(stuffy nose) decongestants (ephedrine, decongestant vasoconstrictors causes
xylometazoline, oxymetazoline) tolerance and rebound congestion due
Antidepressants, antihypertensive to in part to down-regulation of alpha-
(methyldopa, prazosin, hydralazine, adrenoceptor.
propranolol), antipsychotics, oral · Dilation of nasal vasculature produces
contraceptives, ASA, and NSAIDs. tissue edema.
Bronchoconstriction Anticholinesterases, Antibiotics (e.g. · Particularly in asthma and COPD

penicillin's and cephalosporin's), patients.
Aspirin, NSAIDs, dipyridamole, non- · Allergic reaction to penicillin's may
selective beta-blockers, (including eye also occur with other beta lactam
drops), ACE inhibitors, pharmaceutical antibiotics. (cephalosporin's,
excipients (tartrazine, benzoates, carbapenems and monobactams).
phenylmercuric salts, paraben,
benzalkonium chloride and
metabisulfite), general anesthetics
and muscle relaxants Radiological
contrast media ACE.
Reflex Ipratropium, inhaled beta2-agonist, · Direct irritation of bronchial mucosa
bronchoconstriction corticosteroids, cromoglicate,
zanamivir
Lung parenchyma- Methotrexate, nitrofurantoin, · Generally allergic reactions presenting
interstitial amiodarone, gold salts, paclitaxel, as cough, breathlessness and wheeze
pneumonitis penicillamine, sulphasalazine. · Patients on methotrexate should not
receive nitrofurantoin due to synergy
of ADR
· Early diagnosis and treatment improve
recovery
Lung parenchyma- Anticancer agents (bleomycin) · Direct toxicity causes inflammation
pulmonary fibrosis Amiodarone, gold, sulphasalazine, and fibrosis leading to significant
nitrofurantoin, bromocriptine and morbidity and mortality.
pergolide. · Dose and duration of treatment are
important
Pulmonary edema IV beta-agonists (salbutamol iv and · Increased pulmonary vascular
(adult respiratory terbutaline), amphotericin, permeability presenting as cough,
distress syndrome, haloperidol, hydrochlorothiazide, breathlessness and frothy sputum.
ARDS) mannitol, urea, indomethacin, · Close monitoring of women receiving
methadone, naloxone, and protamine IV beta-agonists in premature labour,
sulphate. especially in the presence of fluid
overload.
Pulmonary Nitrofurantoin, NSAIDs, antibiotics, · Symptoms include cough, dyspnea
eosinophilia antineoplastic. and fever.
· Patients improve on cessation of
treatment.
· May be treated with corticosteroids.
Respiratory failure Opioids overdose, CCB, beta-blockers, · Opioids depress the rate and depth of
(neuromuscular) anti-rheumatics, aminoglycoside and respiratory centre in the brain to
polymyxin antibiotics, and diuretics. increase blood CO 2 .
· Impaired respiratory muscle function.
· Patients at risk include those with pre-
existing impaired respiratory muscle
function, renal failure and myasthenia
gravis.
· Reversible on cessation of treatment.
Pulmonary and Combined oral contraceptives May present as sudden collapse, pleuritic
thromboembolism pain, breathlessness, cyanosis and
hemoptysis.
ADR affecting Endocrine System

Endocrine effects Causative drugs
Altered glucose Niacin, hypoglycemic drugs, clozapine, olanzapine, quetiapine,
control
Thyroid dysfunction Amiodarone, lithium
Adrenal function Corticosteroids, ketoconazole (reduced), rifampin (reduced)
Aldosterone synthesis Carbenoxolone, lithium, loop diuretics, oral contraceptives, spironolactone, thiazides
Hypoaldosteronism ACEi (including Angiotensin II receptor antagonist), NSAIDs, and heparins
Gonadotrophin Ovarian and testicular:
release and gonadal Corticosteroids (reduced), danazol (increased free testosterone), ketoconazole (reduced
function testicular steroidogenesis)
Gynecomastia-estrogenic:
Clomiphene, digoxin, estrogens, spironolactone
Gynecomastia - (due to reduced testosterone):
Alcohol, alkylating agents, cyproterone, flutamide, phenytoin, spironolactone,
ketoconazole, cimetidine.
Gynecomastia: Antipsychotics (chlorpromazine), CCB, isoniazid, marijuana, methadone,
methyldopa, protease inhibitors, stavudine, and TCA.
Hyperprolactinemia or Methadone, morphine, antidepressants, antipsychotics, anti ulcer drugs (e.g.
galactorrhea cimetidine, ranitidine), benzodiazepines, estrogens, methyldopa, and verapamil.
SIADH-syndrome of Psychotropics, carbamazepine, cytotoxics, and hypoglycemics (chlorpropamide,
inappropriate tolbutamide).
secretion of
antidiuretic hormone
ADR affecting musculoskeletal tissue

Musculoskeletal Causative drugs Comments
pathology
Statins, fibrates, nicotinic acid, · Myalgia presents as muscle pain,
Myalgia (muscle pain), amiodarone, carbimazole, tenderness and/or muscle weakness.
cramps or myopathy cyclosporine, cimetidine, colchicine, · Increase creatine kinase (CK-MM) is
corticosteroids (withdrawal), an indicator of muscle damage (10 x
danazol, diuretics, opioids, normal level may indicate myopathy).
penicillamine, quinine, chloroquine, · Muscle rigidity is hallmark symptom
quinolones, and zidovudine. of NMS, this can lead to
rhabdomyolysis.
Metabolic bone disease: Corticosteroids, heparin, thyroid · Lowest-effective dose of
osteomalacia (rickets, hormones corticosteroids should be used
abnormal bone · Consider vitamin D supplement for
softening). housebound and frail elderly.
Metabolic bone disease: Aluminium salts (including · A lack or defective metabolism of

osteomalacia (rickets, prolonged ingestion of antacids), vitamin D.
abnormal bone barbiturates, bisphosphonates · Poor diet and lack of sunlight are
softening). (overdose), phenytoin, long term contributing factors.
total parental nutrition.
Arthralgia (joint pain Penicillin, CCB, carbimazole, · May accompany any drug-induced
without swelling). isoniazid, procainamide, quinidine, skin eruption.
quinolone antibiotics, rubella · Severe joint pain with swelling is a
vaccine, BCG. component of serum sickness (e.g.
penicillin)
Arthralgia. Acute gout High dose Thiazide diuretics, low- · Caused by the arthritis (includes
dose salicylates, niacin and inflammation and swelling) of acute
cyclosporine gout.
Arthropathy (erosion of Quinolone antibiotics · Restricted indications in children,
articular cartilage) growing adolescents and avoid in
pregnancy.
· Usually reversible on cessation of
treatment.
Tendinopathy FLUROQuinolone antibiotics · More common in people in over 50
(particularly Achilles (ofloxacin) years of age increased risk if renal
tendon) impairment and/or corticosteroids
treatment
Retroperitoneal fibrosis ASA, beta-blockers, bromocriptine, · Symptoms include persistent pain in
(development of fibrous codeine, ergotamine, haloperidol, the loin and groin, oliguria, pain on
tissue behind methysergide. micturition, myalgia and edema.
peritoneum) · Symptoms improve on withdrawal of
treatment
Systemic lupus Hydralazine, procainamide, beta- · Symptoms include arthralgias,
erythematosus (SLE) or blockers, carbamazepine, myalgias, malaise, fever, pleurisy and
lupus like syndrome chlorpromazine, disopyramide, pericarditis, butterfly rash.
isoniazid, methyldopa, · Symptoms improve within days or
nitrofurantoin, penicillamine, weeks of cessation of suspected drug
phenytoin, quinidine, · Usually occurs after several months
sulphasalazine, sulphonamides, or years of continued therapy.
tetracycline’s (minocycline, · Presentation of drug-induced SLE
particularly young patients) differs from SLE
thiazides, thiouracil. · Leucopenia, thrombocytopenia,
anemia, elevated ESR and antinuclear
"HIPPP MCCQ" antibodies may be present.
· Increased risk in slow acetylators
ADRs affecting GI system

Adverse GI effects Causative drugs Comments
Taste disturbance ACEi, CCB, etidronate, Griseofulvin, Usually resolves on cessation of
(dysguisea) isotretinoin, levodopa, losartan, penicillamine, treatment but may take for months.
terbinafine, captopril
Zopiclone: Bitter taste
Metallic taste Allopurinol, gold, lithium, metformin,
metronidazole, penicillamine, zopiclone.
captopril
Gingival Phenytoin, dihydropyridine CCBs, cyclosporine Usually occurs within 3 months of
overgrowth starting treatment. Good oral hygiene
minimizes risk of gingival hyperplasia.
Pigmentation of Tetracycline’s Rare and particularly minocycline
the oral mucosa
Dental Tetracycline’s Avoid tetracycline in children under 12
discoloration years old
Dry mouth Anticholinergic effects, antihistamine, TCAs, May cause weight loss, candidiasis,
(xerostomia) CNS stimulants, phenothiazines dental caries, poor adherence to drug
regimens, reduced efficacy of sublingual
drug administration (e.g. nitroglycerin).
Saliva secretion Cholinergic agonist (e.g. pilocarpine, clozapine) Risk of choking at night
(Ptyalism)
Stomatitis and Aspirin, barbiturates, captopril, Griseofulvin, Usually resolve quickly when drug is
Mouth ulcers isoniazid, NSAIDs, proguanil, sulphasalazine stopped.
Esophageal Ascorbic acid, ASA, Q bisphosphonates, Usually occurs within hours to days of
disorders clindamycin, doxycycline, ferrous sulfate, taking causative drug. Most cases heal
NSAIDs, potassium salts, quinidine, tetracycline, within days or weeks of treatment
and theophylline. cessation.
Acid reflux or CCB, opioids, nitrates, and anticholinergics. Due to relaxation of the lower
heartburn esophageal sphincter.
Nausea and Many but often occurs with anticancer drugs, Symptoms may resolve with continued
Vomiting emergency contraception (Plan B), levodopa, use or occasionally by taking the drug
opioids, SSRIs, iron salts, bromocriptine, after food. It may indicate toxicity of
erythromycin, estrogens. digoxin or theophylline.
Varenicline (16%)
Gastro toxicity NSAIDs, corticosteroids, CCB, SSRIs, clopidogrel. Increased risk when coprescribing with
NSAIDs
Duodenal NSAIDs, less often corticosteroids, but likely if It may be difficult to diagnose at early
ulceration and taken with NSAIDs. stages, as the inflammation is
perforation asymptomatic. This may be a cause of
“unexplained bleeding”. Complications
include iron-deficiency anemia due to
blood loss, hypoalbuminemia due to
protein loss, ulceration and stricture
formation (results from postprandial
colicky pain). Associated with alcohol
abuse. Diagnosis may follow the
detection of iron-deficiency anemia,
usually after long-term treatment,
hypoalbuminemia (associated with
peripheral edema and other signs of fluid
retention due to protein loss from
damage intestinal mucosa). Blood loss is
not often sufficient for detection in fecal
occult blood test (FOBT)
Paralytic ileus and Acarbose, CCB, clozapine, bulk forming Physical obstruction or anticholinergic
pseudoobstruction laxatives, loperamide, opioids, phenothiazines, effects inhibiting smooth-muscle activity,
potassium salts, TCAs particularly if more than one
anticholinergic agent is prescribed
Malabsorption Cholestyramine, colestipol, orlistat, liquid Supplements of fat-soluble vitamins may
from the paraffin, metformin be required.
duodenum Serum vitamin B 12 may be reduced in
patients taking metformin but clinical
significance appears to be small
Diarrhea Many but most common are, antibiotics (most Clindamycin-induce diarrhea may be the
commonly clindamycin), acarbose, metformin, result of Pseudomembranous colitis.
bile salts, colchicine, cytotoxic, dipyridamole, Treatment should be stopped.
gold, iron salts, laxatives, magnesium- Severe diarrhea may lead to treatment
containing antacids, NSAIDs (mefenamic acid), cessation of diarrhea causing drugs.
orlistat, ticlopidine, misoprostol, olsalazine.
LEFLUNOMIDE (20%)
Colitis Amphetamines, cocaine, digoxin, ergot amine, Presents as sudden onset of severe
sumatriptan, methotrexate, methyldopa, abdominal pain, nausea, vomiting,
methysergide, NSAIDs, estrogen, salicylates diarrhea, and abdominal distension.
Tachycardia, pyrexia, leucocytosis, and
bloody stools may be present.
Constipation Many but most common are, anticholinergics, Risk factors include polypharmacy,
opioids (codeine, morphine etc), iron slats, dehydration, immobility, advance age
verapamil, TCAs, antihistamines, clozapine, and low-fibre diet.
MAOIs, peppermint oil, phenothiazines, Opioids induced constipation is treated
sucralfate, and diuretics. by stimulants laxative (Senna or
Al and Calcium antacids. bisacodyl).
Dark stools Iron slats, bismuth salts, You must counsel the patient rare but mild if causative
aminosalicylates, ACEi, agent is stopped risk factors may include gallstones, alcohol
azathioprine, furosemide, consumption, hyperlipidemia, hypercalcemia
H 2 receptor antagonist, Presents as sudden onset of upper abdominal pain,
metronidazole, estrogen, vomiting, tachycardia, fever, jaundice and rigid tender
propofol, sodium abdomen. Serum amylase is raised
valproate, sulindac,
thiazide diuretics.
ADRs involving the KIDNEY

Renal disorder Causative drugs Comments
Prerenal failure Diuretics, laxatives Due to reduced renal perfusion
Intrarenal failure NSAIDs (especially when volume is Due to effects on mechanisms controlling the tone
(changes to GFR) depleted), ACEi, and diuretics. of renal arterioles.
Increased risk in patients with bilateral renal
disease. Monitoring is essential in at-risk patients.
Intrarenal failure NSAIDs, beta-lactam antibiotics, Hypersensitive, inflammatory reaction leading to
(acute interstitial furosemide (furosemide), damage of renal tubules. Diagnosed by biopsy
nephritis AIN). allopurinol, azathioprine, captopril, presents as acute renal failure. Dialysis may be
cimetidine, cotrimoxazole, required but most patients recover up to several
phenytoin, rifampin, Thiazides, and months after causative agent is withdrawn.
sulphonamides. Intermittent rifampin therapy should be avoided
due to immunological response.
Re-exposure to rifampin should be monitored
closely.
Intrarenal failure Amphotericin, cyclosporin. A common direct toxic effect
(acute tubular Ciprofloxacin, gentamicin,
necrosis) methotrexate, radiological contrast
agents, rifampicin.
Intrarenal failure Gold, penicillamine, NSAIDs Bilateral, immunologically mediated damage to
(glomerulonephritis: hydralazine (acetylator status glomeruli
membranous, important), procainamide Presents as proteinuria, which may progress to
minimal change, edema and hypoalbuminemia (nephritic
lupus nephritis) syndrome).
Postrenal failure Chemotherapy, acyclovir (IV), Due to urinary tract obstruction
methotrexate, and sulphonamides. May also follow drug-induced rhabdomyolysis.
Chronic renal failure Chronic use of NSAIDs especially A problem particularly associated with compound
salicylates analgesic preparations including combinations of
acetaminophen with salicylates, codeine or
caffeine.
Nephrogenic Lithium Does not respond to desmopressin
diabetes insipidus Serum lithium and creatinine levels should be
monitored regularly
Hemolytic uremic Cyclosporine, mitomycin C, oral Hemolysis leading to obstruction of renal
syndrome contraceptives, metronidazole (in arterioles. Also causes anemia, Thrombocytopenia
children), and quinine with risk of severe hemorrhage
Discoloration of Rifampicin, dopaminergic This may be alarming and therefore patients

urine antiparkinsonian drugs, should be warned before starting the treatment.
metronidazole, phenazopyridine,
triamterine, bismuth subsalicylate,
pyrantel pamoate
ADRs affecting sexual function

Sexual dysfunction Causative drugs Comments
Primary infertility Cytotoxics (alkylating agents), anabolic · May include a toxic effect on the
steroids, colchicine, diethylstilbestrol, gonads or altered secretion of
methotrexate, NSAIDs (females), gonadotropin hormones by pituitary
sulfasalazine (males) gland
Anovulation and Anabolic steroids, danazol, isoniazid, · May result from drug-induced
Amenorrhea metoclopramide, cimetidine, NSAIDs, hyperprolactinemia
SSRIs, estrogens, risperidone, · NSAIDs may inhibit ovulation and
spironolactone should preferably be avoided
around the time of ovulation in
women trying to conceive
Erectile Antiandrogens (finasteride), anabolic · Other factors include smoking,
dysfunction steroids, anticholinergic, antidepressants, alcohol, diabetes, heart disease,
(impotence) antipsychotics, benzodiazepines, beta hypertension, peripheral vascular
blockers (carbamazepine, gabapentin, disease, spinal cord injury.
phenytoin) digoxin, methyldopa, · SSRIs, TCAs may be used to treat
metoclopramide, omeprazole, prazosin, premature ejaculation
spironolactone, thiazide diuretics.
Priapism (painful Anticoagulants, alprostadil, sildenafil, · Immediate treatment is required to
erection over 4 vardenafil, tadalafil antipsychotics prevent fibrosis or gangrene
hours). (includes atypical), hydralazine,
nifedipine, prazosin, trazodone.
Female orgasm Antidepressants, benzodiazepines, · Patients prescribed fluoxetine or
dysfunction, libido cimetidine, clonidine, methyldopa, clomipramine have reported
changes, reduced estrogen, propranolol, spironolactone, spontaneous orgasm
vaginal lubrication thiazide diuretics, trazodone
Reduced libido Spironolactone, cimetidine, oral · Libido may be increased rarely by
(reduce sexual contraceptives, propranolol, thiazide trazodone, moclobemide or
desire) diuretics, antidepressants (particularly levodopa
SSRIs)
Gynecomastia Cimetidine and spironolactone,
ketoconazole, anabolic steroids
Tips
1. rapid infusion of 2. Clindamycin 3. ASA
vancomycin
4. Clozapine 5. Methimazole 6. Propylthiouracil (PTU)
7. CK-MM 8. Halothane 9. abrupt discontinuation of
antipsychotic
10. hypertensive crisis 11. decrease renal 12. alpha blockers
perfusion
13. Carvedilol 14. Labetalol 15. Ticlopidine
16. Sympathomimetics/ps 17. Clindamycin 18. Mg antacids
eudoephedrine
19. statins 20. Metformin 21. Orlistat
22. anticholinergics 23. opioids 24. antihistamine
25. AlOH 26. Verapamil 27. Calcium
28. Iron 29. TCA 30. Nitroprussides
31. Nitroglycerin 32. vasodilators 33. Hydralazine
34. CCB 35. Amiodarone 36. Bromocriptine
37. Bleomycin 38. Phenytoin 39. inhibit levodopa conversion to
catecholamine in brain
40. nausea & vomiting 41. digitalis toxicity 42. low blood perfusion
· Malignant hyperthermia is caused by? ( )
· Pre-renal failure may cause due to? ( )
· Syncope is caused by? ( )
· MAO inhibitors with pseudoephedrine (sympathomimetics) gives? ( )
· Neuroleptic malignant syndrome is caused? ( )
· Nitroglycerin gives? ( )
· What creatine kinase indicates myopathy? ( )
· Gray baby syndrome caused by? ( )
· Red man syndrome caused by? ( )
· Reye syndrome is caused by? ( )
· Pseudomembranous colitis is mainly caused? ( )
· Agranulocytosis is caused by? ( )
· Hypokalemia + digoxin gives? ( )
· Levodopa + pyridoxine gives? ( )
· Levodopa + Tolcapone ( )
· Gingival hyperplasia caused by? ( )
· Pulmonary fibrosis is caused by? ( )
· Headache is side effect of? ( )
· What drugs do venous pooling? ( )
· What antiplatelets drug gives neutropenia side effect? ( )
· Constipation is a side effect of? ( )
· Diarrhea is side effect of? ( )
· Glaucoma is a side effect of? ( )
· Spironolactone side effect? ( )
· Choose a beta blocker with vasodilator action ( )
www.pharmacyprep.com Drug Interactions
66
Drug Interactions
Questions Alerts!
· DI with antacids, Ca, and Fe supplements, sucralfate, with tetracycline, bisphosphonates,
levothyroxine, and quinolones.
· CYP 3A4 inhibitors. Erythromycin and clarithromycin, itraconazole, ketoconazole, Fluconazole,
protease inhibitors grapefruit juice and cimetidine
· CYP 3A4 inducers. phenytoin, phenobarbital, carbamazepine, barbiturates, rifampin
· DI with OCP phenytoin, carbamazepine, topiramate and rifampin
· Warfarin DI. Vitamin K, NSAIDs, antiplatelet, antibiotics, dark green veg.
· Theophylline DI. Age, smoking, high protein diet.
· Lithium DI. Diuretics, ACEi, renal diseases
· Receptor & Receptor. Beta blockers and Beta agonist
· Digitalis toxicity: hypokalemia drugs, quinidine, verapamil, tetracycline
Pharmacokinetics, pharmacodynamics and pharmaceutical interactions.
Pharmacokinetic interactions (Absorption, Distribution, Metabolism and Excretion).
ABSORPTION
DISTRIBUTION
METABOLISM
ELIMINATION
Absorption.
Alteration of GI flora
Alteration of Antibiotics (e.g. tetracycline’s, Digoxin has better bioavailability after erythromycin.
intestinal penicillin, erythromycin) Erythromycin administration reduces bacterial
flora. inactivation of digoxin.
Pseudomemb Clindamycin may cause severe P. colitis
ranous
colitis. Anticoagulants and antibiotics ↓GI Cotrimoxazole increase INR in warfarin
flora, and this ↓ production of
vitamin K 2 (MENOQUINONE).
Alteration of pH
Alteration of H 2 blockers and antacids Both H 2 blockers and antacids increase gastric pH. The dissolution
gastric pH of drugs like Ketoconazole and PPIs omeprazole are reduced,
causing decreased drug absorption.
Bisacodyl and antacids Bisacodyl and antacids should not take together. Bisacodyl is taken
an empty stomach.
CaCO 3 , Fe, Gabapentin,
Rosuvastatin, sucralfate
Complexation and adsorption (drug binds in GIT)

Calcium, magnesium, or Quinolones complexes with divalent cations, causing a decreased
aluminium and iron salts. bioavailability. Tetracycline (must avoid with dairy products), complex
Complexation/chelation
with divalent and trivalent cation.

Bisphosphonates (alendronate) take empty stomach. Levothyroxine
should separate from iron supplements.
Sodium polystyrene Cation in antacids bind to sodium polystyrene sulphonate, causing

sulphonate (Kayoxylate) reduced renal clearance of bicarbonate, resulting in systemic acidosis.
Cholestyramine and Reduce absorption of all drugs, thus all drugs should be separated for 2 to
colestipol 4 hrs.
Penicillamine and Al and
iron
Charcoal Adsorb with other drugs. Higher surface area the higher adsorption. The
purer, the higher adsorption.
Alteration of motility/Rate of gastric emptying time and absorption

Increased GI Laxatives, cathartics Increased GI motility decreases bioavailability of drugs that are absorbed
motility slowly. Metoclopramide may decrease the cefprozil absorption. May also
affect the bioavailability of drugs from controlled-release products.
Mg antacids are cathartic.
Decreased GI Anticholinergic Propantheline decreases the gastric emptying of acetaminophen, delaying
motility agents acetaminophen absorption from the small intestine.
Alteration of metabolism in GI tract

Inhibition of MAOIs: MAOis inhibit metabolism of tyramine containing foods in the intestine, leading to
drug Phenelzine hypertension caused by high tyramine levels. (Hypertensive crisis with
metabolism Tranylcypro sympathomimetics pseudoephedrine).
in intestinal mine Levodopa converts into dopamine leads to peripheral side effects such as nausea and
cells vomiting.
Grapefruit Inhibit the metabolism of drugs substrate with CYP3A4. Avoid grapefruit juice with
juice atorvastatin, lovastatin and simvastatin (ALS), DHP-CCB, amiodarone, and
carbamazepine.
Distribution: Plasma protein binding and displacement
Alteration of distribution: Phenytoin and valproic acid.

Valproic acid displaces phenytoin from plasma protein binding and decreases hepatic metabolism of phenytoin
clearance by inhibiting the livers metabolism of phenytoin.
ASA reduces protein binding and inhibits the metabolism of valporate.
Tissue cellular and drug interactions. Digitalis toxicity can be enhanced by combination of digoxin and quinidine.
(Ventricular arrhythmias)
Metabolism (CYP450 substrates, inhibitors and inducers) (details in Chapter metabolism)

Stimulation of metabolism
Warfarin and phenobarbital
Warfarin and carbamazepine. Carbamazepine increase clearance of warfarin.
· Oral contraceptives and phenobarbital, CBZ, phenytoin and rifampin.
· Smoking induces CYP1A2
· Pyridoxine induce metabolism of levodopa.
· Theophylline and rifampin.
Metabolism inhibitors:
Theophylline and macrolide. Macrolides such as erythromycin, clarithromycin inhibit CYP3A4.
Phenytoin and folic acid. Phenytoin enhances folic acid metabolism can cause megaloblastic anemia.
Mercaptopurines 6-MP (azathioprine) and allopurinol. Allopurinol inhibit xanthine oxidase enzyme. This enzyme
is essential for the metabolism of azathioprine. Thus, increase concentration of azathioprine (mercaptopurine)
and this can lead to azathioprine toxicity. Reduce 1/3 or 1/4 dose of azathioprine in patient who are using
allopurinol.
Pharmacodynamic interaction: Drugs having opposing pharmacological effects.
Thiazide Diuretics and insulin gives hyperglycemia whereas insulin gives hypoglycemia.
Drugs having similar pharmacological effects.

Sedative and alcohol. Benzodiazepine and alcohol.
Anticholinergic drugs. Anticholinergic drugs with sedatives.
Antihypertensive drugs (sildenafil, tadalafil, vardenafil and nitrates). Combination of PDE 5 inhibitors with
nitrates gives severe hypotension.
NSAIDs. Two NSAIDs should not be combined.
Alteration of electrolyte interaction: Digoxin and diuretics hydrochlorothiazide and furosemide cause
hypokalemia, thus if its combine with digoxin can give digitalis toxicity.
ACEi or ARBs and potassium sparing diuretics. Both ACEi with potassium diuretics cause hyperkalemia.
Lithium and diuretics: Diuretics gives side effect of hyponatremia (↓Na), thus this increase lithium levels, and it
can lead to lithium toxicity.
Interaction at receptor site. MAOi and sympathomimetics (pseudoephedrine, xylometazoline). MAOi and
sympathomimetics such as pseudoephedrine, and xylometazoline combination can lead to hypertension crisis.
Serotonin syndrome
MAOi and TCAs combination can give serotonergic syndrome.
MAOi and SSRIs combination can give serotonergic syndrome.
TCA + SSRI combination can give serotonin syndrome
SSRI + venlafaxine combination can give serotonin syndrome
MAOi and dextromethorphan combination can give serotonin syndrome.
Smoking increase cardiovascular risk (DVT, stroke, MI) with OCP.
Alcohol and drug interactions

Must avoid alcohol
· Metronidazole gives disulfiram like reaction
· Disulfiram gives disulfiram reaction
· Chlorpropamide (sulfonylureas) gives disulfiram like reaction
· Metformin gives lactic acidosis
· Phenothiazines (antipsychotic) gives sedation
· Benzodiazepine, opioids gives sedation
· Antihistamines gives sedation
Drug that can lead to complication if combined with alcohol.

· Cimetidine may increase ethanol blood concentration (cimetidine increases alcohol absorption in GI, and
reduce activity of alcohol dehydrogenase enzyme).
· Methadone may increase sedation.
· Acetaminophen can cause liver toxicity
· Aspirin may cause increase GI bleeding
· Methotrexate may increase hepatotoxicity
· Insulinà may increase hypoglycemia
· Glyburideà prolong hypoglycemia, and disulfiram like reactions.
· Glipizideà prolong hypoglycemia, and disulfiram like reactions.
· Ketoconazoleà may results in disulfiram reaction (flushing, vomiting, increased respiratory rate,
tachycardia)
· Nitroglycerinàmay result in hypotension
· Paroxetineàmay result in increase risk of impairment of motor and mental skills.
· Sertralineà may result in increase risk of impairment of motor and mental skills.
· Venlafaxineàmay result in increase risk of CNS effects.
· Warfarinà increase INR or PT (acute alcohol) or decrease (chronic) INR or PT
· Zaleplonà may result in impaired psychomotor function
· Zolpidemà may result in increase sedation
· Phenytoinà decrease phenytoin serum concentration; increase seizure potential, and additive CNS
depressant effect.
· Morphineà may result in increased sedation (during withdrawal period, alcohol may Accelerate withdrawal
effect of medication)
· Bupropionà may increase risk of seizures.
· Cefotetan (2nd gen) àdisulfiram like reaction
· Cefometazole(2nd gen) àdisulfiram like reaction
· Cefoperazone—(3rd gen) àdisulfiram like reaction.
Food drug interactions

· Food can increase, decrease, or not affect the absorption of drugs.
· Food can influence the bioavailability of a drug from a modified-release dosage form (e.g., controlled
release, delayed released (enteric coated) rather than from an immediate-release dosage form.
· Complexation and adsorption of the drug in the GI tract with another food element is a common drug
interaction that reduce the extent of drug absorption. For example, quinolone antibiotics and tetracycline
complex with calcium (found in milk products).
· Food can be metabolized by the same liver enzymes that metabolize drugs, causing enzyme inhibition or
induction, and resulting in toxic or sub therapeutic drug levels. For example, grapefruit and valencia oranges
inhibit the CYP3A4 isoenzyme system, causing increased levels of substrate drugs such as saquinavir,
indinavir, midazolam, nifedipine, lovastatin, cyclosporine, carbamazepine, and verapamil.
· Food can pharmacodynamically antagonize the effect of some drugs. For example, spinach and broccoli
provide dietary sources of vitamin K, which antagonizes the effect of warfarin.
Tips
1. Bupropion 2. Venlafaxine 3. Fluvastatin
4. Lovastatin 5. Simvastatin 6. Atorvastatin
7. Carbamazepine 8. gives disulfiram 9. Severe orthostatic
increase clearance of reaction hypotension
warfarin
10. hypertension crisis 11. MAOI + TCA 12. MAOI + SSRI
13. MAOI + MAOI 14. Nitrates 15. alpha blockers
16. Lactic acidosis
· Sildenafil cannot be combined with prazosin because it cause? ( )
· MAOI, tranycypromine & tyramine gives? ( )
· Serotoninergic syndrome is caused by? ( )
· A patient using sildenafil should avoid? ( )
· Sildenafil + nitroglycerin can cause? ( )
· What statins should be avoided taking with grapefruit juice? ( )
· What antidepressant can be used with MAOI? ( )
· What statins should be taken with food? ( )
· Warfarin + carbamazepine ( )
· Metronidazole + alcohol ( )
· Metformin + alcohol ( )
List of drug that should be taken empty stomach

Tetracycline
Ampicillin
Zafirlukast
Alendronate, Etidronate
Cloxacillin
Penicillin V
PPIs, levothyroxine
Iron supplement
Norfloxacin
www.PharmacyPrep.Com Clinical Biochemistry and Therapeutic Drug Monitoring
67
Clinical Biochemistry and
Therapeutic Drug Monitoring
Questions Alerts!
· Renal Function Tests (RFT)àCrCl, BUN
· Liver Function Tests (LFT)àLDH, AST, ALT, ALP, bilirubin
· Cardiac Enzymes à Troponin I
· Creatinine Kinase? Enzyme add phosphate group to proteins.
· Creatinine kinase? CK-MM (myalgia), CKMB (MI)
· Urine Analysis à Ketone bodies, pH, specific gravity
· Blood works (hematological)à CBC, wbc, hematocrit, MCV, TIBC, serum ferritin, hemoglobin levels
· Anticoagulants.INR (International normalized ratio), warfarin (INR 2 to 3), heparin (aPTT), and LMWH
(no Test necessary).
· Thyroids Tests. Serum TSH (0.5 to 5 mU/L), TT4, FT4, TT3 and FT3
This chapter reviews basics of clinical biochemistry such as liver function tests, renal function tests, hematology,
acid base disorders, anemia and its application in laboratory tests to monitor diseases and monitor drug adverse
reactions.
Common tests: Renal function test, liver function test (LFT), urinalysis, common enzyme serum test, and
hematological test (blood works).
· Renal Function Tests (RFT)àCrCl, BUN
· Liver Function Tests (LFT)àLDH, AST, ALT, ALP
· Cardiac Enzymes à Troponins I, Creatinine Kinase (CK)
· Urine Analysis à Ketone bodies, pH, specific gravity
· Blood works (hematological)à CBC
· Anticoagulants à INR (International normalized ratio), warfarin (INR 2 to 3), heparin (aPTT), and LMWH (no
monitoring)
Renal Function Test: Can be measured by blood urea nitrogen (BUN), serum creatinine and creatinine clearance
(CrCl) or estimated glomerular filtration rate (eGFR).
Blood urea nitrogen (BUN): Urea is an end product of protein metabolism. It is produced in liver and excreted by
the kidneys. In normal conditions, urea clearance is equal 60 % GFR. BUN increase indicates renal disease.
Normal values for BUN range 8 mg/dL to 18 mg/dL (3 to 6.5 mmol/L). The concentration of BUN reflects renal
function, because the urea nitrogen in blood is filtered completely at the glomeruli of the kidney, then
reabsorbed and tubular secreted within nephron.
Increase in BUN indicates an acute renal failure. The BUN decrease may indicate terminal stages of liver disease,
because liver produces solely BUN. Increase BUN indicator of azotemia or uremia.
Serum Creatinine: The creatinine is a metabolic product of muscle creatinine phosphate. More sensitive
indicator for renal damage than BUN levels.
Normal values for serum creatinine range from 0.6 to 1.2 mg/dL (80 to 120 mmol/L).
Generally, serum creatinine values doubles with each 50% decrease in GFR. If a patient normal serum creatinine
is 1 mg/dL represents 100% renal function, 2 mg/dL represents 50% function and 4 mg/dL represents 25%
function. Serum creatinine solely filtered by glomerular filtration (GFR). Thereby decrease GFR, may lead to
increase in serum creatinine (SrCr). This indicates renal disease.
Serum creatinine decreased in elderly. As a person gets older muscle mass represents a small proportion of total
weight and creatinine production is decreased. In females, the serum creatinine concentration in female’s
patient is generally 0.2 to 0.4 mg/dL less than males, because females have relatively small kidneys.
Creatinine Clearance (eGFR): The rate at which creatinine is removed from the blood by the kidney, roughly
equal to GFR. Normal values for men range from 80 mL/min to 120 mL/min If it is less than <50 ml/min, it is
categorised as renal disease. Creatinine clearance reflects the GFR.
Calculation for creatinine clearance: Cl cr = C U V/C Cr

C U = concentration of creatinine in urine
V = urine volume (millilitres per minute or urine formed over collection period).
C cr serum creatinine concentration.
Cockcroft-gault equation is used to estimate creatinine clearance.
To measure creatinine clearance using Cockcroft and Gault formula, require stable serum creatinine, age, body
weight and gender.
for males (mL/min)= [(140-Age)x(body weight in Kg)]/(SrCr)X 72
for female, the above formula must be multiplied by 85%
Chronic renal failure Acute renal failure

LOW Na, HIGH PROTEIN
LOW PROTEIN HIGH CALORIE
LOW k RESTRICTED FLUID
LOW Mg
Liver Function Test (LFT): There are 4 liver enzymes, which are indicators of liver dysfunction. Levels of LDH,
ALP, AST and ALT increase with liver dysfunction. Increase levels of these enzymes indicate liver has been
damaged.
LDH = Lactate dehydrogenase, ALP = Alkaline phosphate, AST = Aspartate aminotransferase; ALT = Alanine
aminotransferase
LFT
LDH ALP LIVER SPECIFIC Transaminases (AST and ALT)

NON-SPECIFIC TO LIVER
LDH1, & LDH2 LDH3 LDH4, and LDH5

(Heart) (Lungs) (Liver, skeletal muscle)
· Lactate dehydrogenase (LDH): The glycolytic enzyme LD (100 to 190 units/L) catalyzes the interconversion of
lactate and pyruvate and present in most tissues. LDH is present in high concentration in the heart, kidney,
liver, lungs, and skeletal muscles.
· The liver will liberate LDH quickly when damaged by physical trauma, infection or ischemia. LDH therefore
useful in diagnosing myocardial infarction, hepatic disease and lung disease.
· Alkaline phosphatase (ALP). It is produced from the liver and bones. This is sensitive to mild or partial biliary
obstruction.
Transaminases (AST and ALT)

· Aspartate aminotransferase (AST). Previously known as serum glutamic oxalocacetic transaminase (SGOT),
primarily found in heart, liver tissues, and lesser extent is found in skeletal muscles, renal tissues, and
pancreatic tissues. AST is sensitive to damage to heart, such as MI, CHF, and acute hepatitis.
· Alanine aminotransferase (ALT): It is previously known as serum glutamic pyruvic transaminase (SGPT). It is
primarily found in liver, and lesser amount in heart, skeletal muscles, and kidney. ALT is sensitive to liver cell
damage, and less sensitive than AST.
ALT AST ALP bilirubin
VIRAL HEPATITIS --- --- NO/+
DRUG INDUCED -- -- NO/+
HEPATITIS
ALCOHOLIC CIRRHOSIS NO -- NO
INTRAHEPATIC -- -- --
CIRRHOSIS
JAUNDICE -- -- --- --
Drugs that cause hepatotoxicity: Acetaminophen, Statins, Methotrexate, Warfarin, Niacin, Amiodarone
Valproic acid, phenytoin, CBZ, INH, Tetracycline & Erythromycin, Levofloxacin & moxifloxacin, 6-MP, and
cyclophosphamide.
Serum Bilirubin (Bile)

It is primary breakdown product of haemoglobin and is formed in reticulocytes into stream blood. Where it is
almost completely bound to serum albumin. When bilirubin arrives at the liver at sinusoidal surface of liver cells,
the free fraction is rapidly taken up by liver and converted to bilirubin diglucuronide and monoglucuronide,
referred to as conjugated bilirubin. The conjugated bilirubin then secrete into bile, appears in intestine, where
bacterial converts bilirubin to urobilinogen. Most of urobilinogen is destroyed in feces, but some fraction
reabsorbed in blood and liver.
· Effective bilirubin conjugation and excretion depends on RBC turnover and hepatobiliary function. Normal
values of total bilirubin are 0.1 to 1 mg/dL (2 to 18 mmol/L). Direct bilirubin. 0.0 to 0.2 mg/dL (0 to 4
mmol/L).
· Increase of serum bilirubin indicates jaundice, it occurs from bilirubin deposition in the tissues.
Causes of increased bilirubin: Hepatocellular damage (liver cirrhosis), cholestasis (post hepatic), hemolysis
(prehepatic). There are 3 major reasons for increase bilirubin.
· Increase hemolysis (urine color not changed).
· Biliary obstruction (biliary stones), dark urine and bile in urine, chlorpromazine gives intra hepatic
cholestasis). Liver cell necrosis (viral hepatitis), dark urine color and bile in urine.
· Liver cell cirrhosis (necrosis) occurs in viral hepatitis.
Serum Protein (blood proteins):

· Primary serum proteins. Albumin and globulins (alpha, beta, gamma). Albumin is the major protein of the
blood, it constitutes 55% of serum proteins. Acidic drugs bind to albumin. It is primarily produced from liver.
Albumin (40 to 60 g/L) liver disease decrease albumin.
· Albumin is produced by the liver and contributes approximately 80% of serum colloid osmotic pressure.
Therefore, hypoalbuminemia associated with edema and transudation of extracellular fluid.
· Globulin are serum immune proteins. Protects from infections.
Hypoalbuminemia
· Decrease in essential amino acids due to malnutrition can lead to hypoalbuminemia.
· Albumin can be lost directly from blood because of hemorrhage, and burns.
Hyperalbuminemia
· Increase in albumin can cause shock or volume Conditions Albumin Alpha –1- acid
depletion. Plasma proteins concentration that changes glycoprotein
with some conditions. Renal failure ¯ -
Hepatic failure ¯ -
Globulins: There are several types of globulins such as alpha, Arthritis - -
beta, gamma, etc. Burns ¯ -
· The gamma globulins are the same as immunoglobulin Pregnancy ¯ -
(Ig). Stress/Trauma ¯ -
· Globulins 23 to 35 g/L. Decrease in albumin levels results
in compensatory increase of globulins.
Alpha-Fetoprotein (AFP)
The Alpha-Fetoprotein is a glycoprotein synthesized by the fetal yolk sac, fetal liver. It is primarily produced in
fetal liver and AFP test is considered as marker for diagnosis of fetal liver cancer in pregnancy.
Cardiac Enzymes (cardiac biomarkers); Troponin, CK-MB, Myoglobin, B-type natriuretic peptide (BNP).
Cardiac Troponins (Tn)
· Troponin T, C and I is complex of proteins that mediate the calcium-mediated interactions of actin and
myosin with muscles.
· Troponin T is in cardiac and skeletal muscle cells.
· Troponin I is present only in cardiac muscle.
· Troponin C is present in two distinct isoforms that are present in skeletal and cardiac muscles.
· Troponin T and I is more specific and sensitive indicator of myocardial injury.
· Troponin is a relatively new method to identify myocardial cell injury and thus assist in the diagnosis of
acute MI.
· The use of troponin as primary diagnostic tests for acute MI is widely accepted.
Serum Enzymes:
Creatine kinase (CK), previously known as creatine phosphokinase (CPK). It is primarily found in heart muscle,
skeletal muscle and brain tissue.
Creatine kinase catalyzes the transfer of high-energy phosphate group in tissues that consume large amount of
energy. Therefore, total CK can increase in exercise, IM injections of drugs that are irritating to tissue (diazepam,
phenytoin), acute psychosis episodes, and myocardial injury.
CK isoenzyme. Creatin kinase helps to diagnose of acute myocardial (CK-MB) or skeletal muscle (CK-MM)
damage diagnostic tests. Deep intramuscularly injection can increase CK levels.
CREATININE KINASE FOUND IN DIAGNOSIS
CK-MM skeletal muscle. Sensitive indictor of Myopathy
CK-BB brain tissue.
CK-MB heart muscle Sensitive indicator of myocardial necrosis or
myocardial infarction.
B-type natriuretic peptide (BNP): produced by ventricles due to increase blood pressure.
BNP 100-500 pg/mL may be congestive heart failure (CHF).
Urinalysis: Provides basic information regarding renal function, urinary tract disease, and presence of certain
systemic diseases.
· Pyuria and bacturia is symptoms of urinary tract infection
· pH: Urine pH is around 5 to 9.
· Specific gravity (SG). Normal SG is 1.003 to 1.035
· Increase SG indicates excessive blood sugars or proteins in urine.
· Decreased SG indicates diabetes insipidus.
· Fixed SG at 1.003 indicates, kidney lost its ability to concentrate or dilute urine.
Drug Color Urine Stools Body fluid Lens

Rifampin Orange red * * * *
Metronidazole Dark *
Nitrofurantoin Dark *
Bismuth Dark * *
subsalicylate
Triamterene Blue *
Pyrantel pamoate Red * * * *
Entacapone Brownish *
orange
Iron salts dark *
Metformin dark *
Proteins in urine: Normal values 50 to 80 mg/24 hours. Excessive proteins in urine (proteinuria), caused by UTI,
renal disease, fever, and venous congestion.
· Albuminuria indicates glomerular permeability.
· Microalbuminuria presence of albumin in urine at the level of higher than normal but lower than the limits
that are detected by standard test. Microalbuminuria indicates nephropathy.
· Glucose does not normally appear in urine. Glycosuria indicates diabetes.

· Diabetic nephropathy: Albumin creatinine ratio (ACR) >2 g/L
Ketones: Ketones does NOT normally appear in urine. If there is No glucose stores, fats stores begin to
metabolize to ketones. Ketonuria indicates uncontrolled DM, or starvation, and zero or low carbohydrate diets.
Components of urinalysis:
· Urine pH 4.5 to 9.0
· Protein levels 50 to 80 mg/24 hours
· Glucose levels 180 mg/dL
· Ketone levels do not appear in urine.
Hematological Laboratory Tests (Blood work): Complete blood counts (CBC): The CBC is one of the most
commonly ordered clinical laboratory test. It is package of the following laboratory tests and CBC measures.
COMPLETE BLOOD COUNT TESTS INCLUDES
· Hemoglobin (Hgb) Some CBC may or may not include:
· Hematocrit (Hct) or packed cell volume (PCV) · Platelets count
· Total white blood cells (WBC) · Reticulocytes counts
· Red blood cells (RBC) · Leukocyte differential count
· Mean cell volume (MCV)
· Mean cell hemoglobin concentration (MCHC)
The reticulocyte (incomplete formed RBC) count provide measure of immature RBCs. This test provides an index
of bone marrow production of mature RBCs.
ESR (Erythrocyte sedimentation rate) measures the rate of RBC settling of whole, uncoagulated blood overtime
and it primarily reflect plasma composition.
ESR is indicator of inflammation. E.g. RA
ESR values used to follow, the clinical course of disease, and demonstrate the presence of occult organic disease
and differentiate conditions similar symptoms (like angina ESR normal and MI ESR↑).
Hematocrit (Hct): The percentage of red blood cells to the blood volume is the Hct. (Packed cell volume). The
decrease in (↓Hct) result from anemia, bleeding, bone marrow depression by drugs, chronic diseases, genetic
anemia (sickle cell anemia), and hemolysis. An increase in Hct may result in increase RBC and cause of
polycythemia.
WBCs (leukocytes) also referred to white cell count.
· Normal levels of WBC 4,000 to 11,000 WBC/mm3.
Question Alerts!
· WBC signals infection (leukocytosis) and inflammation. 1) Increase neutrophil indicates?
WBC indicates bone marrow depression this indicates (leukopenia). 2) Bacterial infections increase?
Normal Indicator 3) Viral infections increase?
Neutrophils 55% to 75% Bacterial infection
Lymphocytes 20% to 40% Viral infection
Monocytes 0% to 7% Tuberculosis
Eosinophils 0% to 5% Parasites infection
Basophils 0% to 1% Inflammation,
Allergies, Asthma
· Bacterial infections generally increase neutrophil to 80% and decrease lymphocytes to 10%.
· Viral infections increase lymphocytes (lymphocytosis).
· Allergic reactions, such as asthma, allergic rhinitis, parasite infections, and drug allergies increase
eosinophils and basophils.
· COPD and pneumonia increase neutrophils
· Immunodeficiency, AIDS decrease T lymphocytes or WBCs (lymphopenia), or cluster differential (CD 4 count).
· Tuberculosis infection increase monocytes (monocytosis).
Measuring blood coagulation

Warfarin Heparin Low Molecular Weight Heparins (LMWH)
Oral anticoagulant iv or sc Sc or iv
PT and INR aPTT Not monitored because predictable response. However, monitor
rash, bleeding, and heparin assay.
Liver metabolism Liver Liver
· Warfarin monitoring: International normalized ratio (INR 2 to 3), and prothrombin time.
· Heparin monitoring: Activated partial thromboplastin time (aPTT) and PT.
Prothrombin Time (PT): Prothrombin is synthesized in the liver and is converted to thrombin during blood
clotting process.
· Thrombin formation is the critical event in the hemostatic process because thrombin creates fibrin
monomers that form a network of clot and thrombin activates platelets.
· Clotting time.
· Measures deficiencies in factor II, VII, IX, X (2, 7, 9 and 10)
· Not specific for liver diseases
· Normal values 10 to 13 seconds
Increase in PT (INR)
· Can occur due to inadequate vitamin K in the diet or drugs that increase PT. Warfarin, heparins, low
molecular weight heparins (LMWH), high dose of salicylates, and antibiotics. The higher the PT, the greater
the risk of bleeding.
Decrease in PT (INR)
· Increase in vitamin K supplements or diet that contains vitamin K such as dark green vegetables, broccoli,
avocado, spinach, and lettuce. Thereby increase in risk of blood clot.
Activated Partial Thromboplastin Time (aPTT)

· The aPTT measures the intrinsic clotting system, which depends on factors.
· Measures intrinsic clotting system factors VIII, IX, XI, XII and XIII as well as common pathway factors II, V, and
X.
· Monitored for heparin therapy
· Normal values 21 to 45 sec
Increase in aPTT
Caused by
· Severe liver dysfunction
· Inadequate vitamin K intake (deficiency of vitamin K)
· Poor or inadequate nutrition
· Increase in aPTT increase the risk of bleeding
International normalized ratio (INR). The INR is the PT ratio that would result if world health organizations
(WHO) international reference thromboplastin were used to test the patient sample. Normal INR is 2 to 3 in
patient using warfarin. Increase in INR is an indication of blood thinning where as decrease in INR is an
indication of blood thickening.
Increase in INR (>3): Indicate blood thinning, overdose of drugs such as Warfarin, Heparins, LMWH, ASA/NSAID,
Acetaminophen > 2 g can cause increase in INR.
Decrease in INR (<2). Indicate blood thickening
· Vitamin K supplements
· Green vegetable (avocado, broccoli and spinach)
· Oral contraceptives
Normal lipoproteins levels

· Low density (LDL) cholesterol (serum) <2.2 mmol/L or <125 mg/dL
Triglycerides <3.6 mmol/L or <160 mg/dL
· High density (HDL) cholesterol (serum)>0.9 mmol/L >35 mg/dL.
· Cholesterol/HDL ratio is 5 mmol/L.
High risk group with coronary artery disease, the LDL levels should be <2 mmol/L.
Apolipoprotein B <0.8 g/L (Apo-B). This protein found on the surface

of LDL particle. Each LDL particle only has one copy of apo-B.
This also found on all beta-lipoprotein surface such as chilomicrons,
LDL, and VLDL. This is used to predict CVD risk.
TARGET LEVEL BEST THERAPIES

LDL
TG
HDL
TOTAL CHOLESTEROL
Thyroid function tests

Normal Hypothyroidism Hyperthyroidism
Serum TSH. 0.3 mU/L Serum TSH - >6 mU/L Serum TSH ¯ <0.3 mU/L
to 6 mU/L Subclinical hypothyroidism >10
Serum TSH Serum TSH
Decrease Free T 4 and T 3 Increase Free T 4 and T 3
Thyroid stimulating hormone (TSH) 0.3 to 6 mU/L, 0.3 to 6 μU/mL.
Free thyroxine (free T 4 ) 10 to 36 pmol/L, 0.8–2.8 ng/dL
Total serum thyroxine (T 4 ) 51 to 142 nmol/L, 4–11 μg/dL
Total serum triiodothyroxine (T 3 ) 1.2 to 3 nmol/L 78 to 195 ng/dL
Thyroid disease diagnosis tests Free T 4 and Serum TSH

· Replacement therapy for hypothyroidism. Serum TSH, free thyroxin index (FTI), resin triiodothyronine
uptake RT 3 U, Total thyroxin TT 4 .
Free T 3 and FT 4
· The FT 4 is the most reliable diagnostic test for evaluation of hypothyroidism and hyperthyroidism when
thyroid hormone binding abnormality exists. In contrast measurement of
· FT 3 is expensive.
· Total T 3 and T 4 (TT 3 and TT 4 ):
· The TT 3 and TT 4 measures both free and bound (total serum T 3 and T 4 ).
· TT 3 is particularly helpful in diagnosis of Graves’s disease.
· TT 3 is not good indicator of hypothyroidism.
Thyroid stimulating hormone:

· The serum TSH is the most sensitive test to evaluate thyroid function.
· The TSH is elevated in hypothyroidism
Dehydration symptoms.
In dehydration
· Mild: normal BUN/Creatinine
· Moderate: - BUN/Creatinine
· Severe: - BUN/Creatinine, - Hb, Low sucrose.
Neoplasm screening
Prostate specific antigen (PSA); for prostate cancer
Pap (Papanicolaou) smear; cervical cancer
Mammogram. Breast cancer
Biopsy: Sampling of cell or tissue for examination
Digital rectal exam: prostate cancer and BPH screening.
GI Track tests
Fecal Occult blood: Invisible traces of blood in stool
Shilling’s test: To determine vitamin B 12 absorption.
Barium enema: To test large intestine (lower GI)
Infectious disease/Rheumatologic/immunological:
Western blot. To detect specific protein (analysis of individual proteins in protein mixture). Separated by size
and charge.
CD 4+ Tcell count: HIV
Erythrocyte Sedimentation Rate (ESR): measure inflammation
ELISA test. HIV
Therapeutic Drug Monitoring
Questions Alerts!
· Anticoagulants: Warfarin (PT, INR), Heparin (aPTT) and LMWH (No monitoring).
· Thyroid hormones: Serum TSH, TT4, FT4, TT3
· Antipsychotic drugs: Clozapine, CBC (WBC), and weight gain, blood glucose.
· Lithium: serum levels <1.5 mEq/L
· Statins: regularly LFT and CK-MM for myopathies
· Amiodarone: chest x-ray, eye exam, serum TSH
· Ticlopidine therapy monitored for CBC or WBC because it causes neutropenia
· Methotrexate therapy monitored for lung function test, LFT, folic acid
· Vancomycin. Renal function Test
· Isotretinoin baseline test: TG, LFT
· Ifiximab: Chest X ray
Laboratory test Therapeutic ranges of Monitoring guidelines

Drug
monitored test
Serum amikacin peak 20-25 mcg/ml Wait until the administration of the third dose to
trough 5-10mcg/ml check drug levels. Obtain blood for peak level 30
Amino glycosides
Serum minutes after IV. infusion or 60 minutes after I.M.

gentamicin/tobramyci 4-8 mcg/ml administration. For trough levels, draw blood just
n peak trough Serum 1-2mcg/ml 0.6 - 1.3 before the next dose. Dosage may need to be
creatinine mg/dl adjusted accordingly. Recheck after three doses.
Monitor creatinine clearance and BUN levels and
urine output for signs of decreasing renal function
Serum creatinine 0.6-1.3 mg/dl Monitor serum creatinine, BUN, and serum
BUN 5-20 mg/dl electrolyte levels at least weekly during therapy.
Serum electrolytes Potassium: 3.5-5 mEq/L Also regularly monitor blood counts and liver
(especially potassium Magnesium: 1.5-2.5 function test values during therapy.
Amphotericin B
and magnesium) mEq/L

Sodium: 135-145 mEq/L
Liver function tests Chloride: 98-106 mEq/L
CBC w/ differential
and platelets
WBC with differential Specimen cultures and sensitivities will determine
antibiotics
cultures and ***** the cause of the infection and the best treatment.
sensitivities Monitor WBC count with differential weekly during
therapy.
Serum creatinine FBSL. 5 to 6 mmol/L Check renal function & hematologic parameters
Fasting serum glucose before initiating therapy and at least annually
Glycosylated HbA1C. 5.5% to 6.5% of thereafter if patient has impaired renal function,
(metformin)
biguanides
hemoglobin (HbA1C) total hemoglobin don’t use metformin because it may cause lactic
CBC Test shows past 3 mo acidosis. Monitor response to therapy by
BSL. Test q6 mo for periodically evaluating fasting glucose and
patient on insulin. Test glycosylated hemoglobin levels. A patient’s home
q1yr for type II DM. monitoring of blood glucose levels helps monitor
compliance and response. and decrease mortality.
WBC with differential agranulocytosis Obtain WBC count with differential before initiating
Clozapine
or CBC therapy, weekly, during therapy, and 4 weeks after

discontinuing the drug.
Serum digoxin SERUM: 0.8 to 2 ng/ml Check serum digoxin levels at least 12 hours, but
Serum electrolytes Potassium. 3.5 to 5 preferably 24 hours, after the last dose is
(especially potassium, mEq/L administered. To monitor maintenance therapy,
magnesium, and Magnesium. 1.7 to 2.1 check drug levels at least 1 to 2 weeks after therapy
calcium mEq/L is initiated or changed. Make any adjustments in
digoxin
Serum creatinine Sodium: 135 to145 therapy based on entire clinical picture, not solely
mEq/L on drug levels. Also, check electrolyte levels, renal
Chloride: 98 to 106 function periodically during therapy.
mEq/L CLINICAL SIGNS OF TOXICITY: ANOREXIA, VOMITING,
Calcium: 8.6 to 10 mg/dl DIARRHEA, VISUAL DISTURBANCE
0.6 to1.3 mg/dl.
Serum electrolytes Potassium: 3.5 to 5 To monitor fluid and electrolyte balance, perform
Serum creatinine mEq/L baseline and periodic determinations of serum
BUN Magnesium. 1.7-2.1 electrolyte, serum calcium, BUN, uric acid, & serum
Uric acid mEq/L glucose levels.
Fasting serum glucose Sodium: 135-145 mEq/L
diuretics
Muscle pain Chloride: 98-106 mEq/L

Calcium: 8.6-10 mg/dL
0.6-1.3 mg/dl
5-20 mg/dl
2-7 mg/dl
70-110 mg/dl
Hematocrit Women. 36% to 48% After therapy is initiated or changed, monitor the
Men: 42% to 52% hematocrit twice weekly for 2 to 6 weeks until
erythropoletin
stabilized in the target range and a maintenance

dose determined. Monitor hematocrit regularly
thereafter.
Serum ethosuximide 4 to 100 mcg/ml Check drug level 8 to 10 days after therapy is
ethosuximide
initiated or changed
Laboratory test Therapeutic ranges of test Monitoring guidelines

monitored
Drug
Serum lipids Total cholesterol < 5 Therapy is usually withdrawn after 3 months if
mmol/L response is inadequate. Patient must be fasting to
Gemfibrozil LDL <2.2 mmol/L measure triglycerides level.
(Fibrates) HDL women: >0.9 mmol/L
Triglycerides: <3.2 mmol/L
Increase BSL
Niacin Glucose
Activated partial 1 to 2 times control When drug is given by continuous IV infusion, check
thromboplastin time aPTT q4 hours in the early stages of therapy when
Heparin
(aPTT) drug is given by deep SC. injection, check aPTT 4 to 6

hours after injection
Heparin induced thrombocytopenia (HIT) symptoms.
Serum lipids CK-MM is indicator of Perform liver function tests at baseline, 6 to 12

HMG-CoA red.
Liver function tests myopathies weeks after therapy is initiated or changed, and
(LFT) periodically thereafter. If adequate response isn’t
inh.
and creatine kinase achieved within 6 weeks consider changing the

(CK) therapy
Fasting serum Optimal blood sugar Monitor response to therapy by evaluating serum
glucose levels. glucose and glycosylated hemoglobin levels. It is a
Insulin
Glycosylated Fasting. 4-7 mmol/L good measure of long-term control. A patient’s

hemoglobin (HbA1 C ). HbA1C <7% home monitoring of blood glucose levels helps
Post prandial. 5-10 mmol measure compliance and response.
Serum lithium Serum levels. 0.8 to 1.5 Checking blood lithium levels is crucial to the safe
Serum creatinine mEq/l use of the drug. Obtain serum lithium levels
CBC >2 mEq/l can cause immediately before next dose. Monitor levels twice
Serum electrolytes toxicity. weekly until stable. Once at steady state, levels
(e.g. K and Na) K: 3.5 to 5 mEq/l should be checked weekly; when the patient is on
Lithium
Fasting serum Mg: 1.7 to 2.1 mEq/l the appropriate maintenance dose, levels should be
glucose Na: 135-145 mEq/l checked every 2-3 months. Monitor serum
Thyroid function Cl: 98 to 106 mEq/l creatinine, serum electrolyte and fasting serum
tests 70-110 mg/dl glucose levels. CBC and thyroid function test before
TSH: 0.5-5.4 mU/L therapy is initiated and periodically during therapy.
T 3 : 80 to 200 ng/dl
T 4 : 5.4 to 11.5 mcg/dl
Serum methotrexate Normal elimination: Monitor methotrexate levels according to dosing

CBC with differential <10 micromol 24 hours protocol. Monitor CBC differential, platelet count
Platelet count, post dose and liver and renal function tests more frequently
Methotrexate
liver function tests <1 micromol 48 hours when therapy is initiated or changed and when
Serum creatinine postdose methotrexate levels may be elevated such as when
Chest x-ray <0.2 micromol 72 hours the patient is dehydrated.
post dose Q. Methotrexate, except?
150 to 450 x 103/mm2 A. cardiac toxicity.
0.6 to 1.3 mg/dl
Serum phenytoin 10 to 20 mcg/ml Monitor serum phenytoin levels immediately before
CBC next dose and 2 to 4 weeks after therapy is initiated
Phenytoin
or changed. Obtain a CBC at baseline and monthly

Phenytoin toxic symptom? early in therapy. Watch for toxic effects at
Nystagmus therapeutic levels. Adjust the measured level for
hypoalbuminemia or renal impairment, which can
increase free drug levels.
Serum potassium 3.5 to 5mEq/L Check level weekly after oral replacement therapy is
Potassium
initiated until stable and every 3 to 6 months

chloride
thereafter
Serum procainamide 4-8mcg/ml (procainamide) Measure procainamide levels 6-12 hours after a
5-30mcg/ml (combined continuous infusion is started or immediately before
Procainamide
Serum N- procainamide and NAPA) the next oral dose combined (procainamide and
acetylprocainamide **** NAPA) levels can be used as an index of toxicity
when renal impairment exists. Obtain CBC
CBC periodically during long-term therapy.
Serum quinidine 2-6mcg/ml Obtain levels immediately before the next oral dose
CBC **** and 30-35 hours after therapy is initiated or changed
Liver function tests * periodically obtain blood counts, liver and kidney
Serum creatinine 0.6-1.3mg/dl function tests values and serum electrolyte levels
Serum electrolytes K:3.5-5 mEq/L
(esp K) Mg: 1.7-2.1mEq/L
Quinidine
Na:135-145mEq/L
Cl: 98-106mEq/L
Fasting serum 70-110mg/dl Monitor response to therapy by periodically

Sulfonylureas
glucose 5.5-8.5% of total evaluating fasting glucose and glycosalated

Glycosylated hemoglobin hemoglobin levels, patient’s home monitoring of
hemoglobin blood glucose levels helps measure compliance and
response.
Serum theophylline 10 to 20 mcg/ml Obtain serum theophylline immediately before next

dose of sustained-release oral product and at least
Theophylline
days after therapy is initiated or changed.
Thyroid function Serum TSH: 0.3 to 6 mU/L Monitor thyroid function tests every 2-3 weeks until
tests T 3 : 80 to 200 ng/dl appropriate maintenance dose is determined.
hormone
Thyroid
T 4 : 5.4 to 11.5 mcg/dl
Serum vancomycin 20-35 mcg/ml (peak) Serum vancomycin levels may be checked with the
5-10 mcg/ml (trough) third dose administered, at the earliest. Draw peak
levels half hour after the IV infusion is completed.
Draw trough levels immediately before the next
Serum creatinine dose is administered. Renal function can be used to
0.6-1.3 mg/dl adjust dosing and intervals.
Vancomycin
For an acute MI, atrial Check INR daily beginning from 3 days after therapy
fibrillation, treatment of is initiated continue checking it until therapeutic
pulmonary embolism, goal is achieved and monitor it periodically
prevention of systemic thereafter. Also, check levels 7 days after any
PT and embolism, tissue heart change in warfarin dose or concomitant, potentially
INR 2 to 3 valves, valvular heart interacting therapy.
Warfarin
disease, or prophylaxis or
treatment of venous
thrombosis (DVT).
2 to 3 for mechanical
Prosthetic valves or
recurrent systemic
embolism 2.5-3.5.
Note: ***** For those areas marked with asterisks, * For those areas marked with one asterisk
the following values can be used: the following values can be used:
Hemoglobin: Women: 12-16 g/dl Differential: Neutrophil: ALT: 7-56 units/L
Men: 14-18 g/dl Bands: 0%-8% AST: 5-40 units/L
Hematocrit: Women: 37%-48% Lymphocytes: 16%-45% Alkaline phosphatase:17-142 units/L
Men: 42%-52% Monocytes: 4%-10% LDH: 6-220 units/L
RBCs: 4-5.5 x 106/mm3 Eosinophills: 0%-7% GGT: <40 units/L
WBCs:5-10 x 103mm3 Basophills: 0%-2% Total bilirubin: 0.2-1 mg/dl
Monitoring
Antibiotics aminoglycosides
vancomycin
Cardiovascular drugs Digoxin, amiodarone, BBs, ticlopidine
CNS drugs Lithium, Phenytoin, Carbamazepine,
clozapine
Other Theophylline, methotrexate,
Tips
1 80-120 ml/min 2 bleeding 3 bilirubin
4 does not change 5 parathyroid hormone 6 3.5 to 5 mEq/L
7 2 to 3 8 troponin 9 aPTT
10 AST>ALT 11 Creatinine kinase CK-MB 12 Stop warfarin, monitor INR and give oral Vit K
13 No monitoring
required
· Normal range of serum potassium levels? ( )

· Hypothyroidism can be monitored by? ( )
· What is normal INR level in patient taking warfarin? ( )
· Increase INR indicated the risk of? ( )
· Normal levels range of creatinine clearance ( )
· What substance levels are increased in jaundice? ( )
· What enzyme ration increases in alcoholic hepatitis? ( )
· What is monitored in patient taking LMWH? ( )
· If INR is more than 5 indicates ( )
· What is monitored by heparin? ( )
· Name the enzyme most likely to increase in levels suggesting a myocardial infarction? ( )
· What cardiac enzyme exclusively elevated after MI? ( )
· Osteoporosis can change calcium level by? ( )
· Calcitonin opposes action of? ( )
· Phosphorylation of creatinine by creatinine kinase requires, what?
· Lithium normal serum levels ( )
· Warfarin monitoring ( )
· Statin monitoring ( )
· Serum levels of phenytoin ( )
· Factors that affect theophylline clearance ( )
· HbA1c test monitoring ( )
· Symptoms of renal disease ( )
· Monitoring hypothyroidism ( )
· What laboratory tests indicates myopathies? ( )
· What supplements recommended with phenytoin therapy? ( )
· Amino glycosides have? ( )
· Metformin is contraindicated in? ( )
· What is true about erythropoietin’s? ( )
· What is Clozapine mechanism & monitoring ( )
· Propylthiouracil and methimazole should be monitored for? ( )
· Vancomycin is monitored for? ( )
· What is monitored in patient using pioglitazones?
www.pharmacyprep.com Therapeutic Drug Monitoring
68
Quality Assurance in Pharmacy
Practice
Quality assurance refers to program for systemic monitoring and evaluation of various aspects of pharmacy
practice, services, or facility to ensure that standards of quality are being met.
The purpose of quality assurance in pharmacy is to protect the health and well-being of the public by ensuring
and promoting safe, effective, patient centred and progressive pharmacy in collaboration with other health-care
providers.
Aspects/areas of quality assurance applicable to the retail or community pharmacy.
Premises à Dispensary à stock and storage à The Pharmacy Team
Patient Care Services à Data Management à Special Servicesà Regulations and QA
Premises
Premises must be easily identifiable as healthcare facility.
The pharmacy must be safe and accessible to public and comply with appropriate legislations.
Security must be maintained in pharmacy.
Patient must have access to appropriate medical, pharmaceutical and health promotion information.
Signage to should reflective of pharmacy services.
Dispensary
The physical environment and layout of the dispensary should be according to regulatory agency legislations.
Equipment
Must have adequate equipment to carry out the operation of pharmacy.
All apparatus must be routinely assessed and replaced if not a suitable standard.
Stock and Storage

Stock must be sourced from a licensed supplier to ensure that the requirement of safety, quality and efficacy are
upheld.
Stock must be stored in appropriate conditions of light, humidity, ventilation, temperature, and security should
be ensured.
The pharmacy teams
The professional activities of pharmacy at any time are the responsibility of the pharmacist in-charge.
Patient care services

NAPRA Professional Competencies for Canadian Pharmacists at Entry to Practice #2: Patient Care.
Pharmacists, in partnership with the patient and in collaboration with other health professionals, meet the
patient’s health and drug-related needs to accomplish health goals.
Counseling
New Prescriptions: A licensed pharmacist, academic registrant, intern or student (under the direct supervision of
a licensed pharmacist) provide patient counselling on the release of all new prescriptions.
Refills: A licensed pharmacist, academic registrant or intern exercises professional judgement as to the content
of the dialogue on repeat and refill prescriptions. Possible topics for discussion include: Changes in dosage
regimes, Compliance and efficacy and presence of adverse effects.
Non-prescription drugs recommendations;

Prior to recommendation NAPRA schedule 2 and 3 drugs, pharmacist gather patient information, such as
· History of complain, and length of present symptoms
· Conditions and symptoms to be treated.
· Allergies and contraindications.
· Current medication and medical conditions.
Documentation and Data Management

Decisions made by pharmacist and reasons for decision are documented in patient records.
Ongoing and documentation of interventions recorded in the patient profile includes
· Adverse effects
· Actual and potential drug interactions
· Compliance and drug discontinuation
· Changes to dosage regimen and quantity.
· Pharmacist reason to fill/refuse to fill a prescription
· Counseling refusals
· Change on package size upon patient request.
· Permission from the patient or caregiver for using non-child resistant packaging is documented and kept on
the patient’s file.
Medication Services
Administration of drugs including vaccination
· Pharmacist who administers drug to patient must
· Do so with patient authorization
· Have policies and procedure to respond medical emergencies such anaphylaxis, and drug reactions.
Quality Assurance
Medication incidents and Discrepancies or Near Misses.
A pharmacist must expeditiously address, document and report incidents, discrepancies and adverse events in
dispensing drugs and in providing patient care.
· Medication incidents are given priority over any other non-emergence tasks.
· Patient must be contacted, and in the event patient cannot be contacted, every effort is made to locate the
patient.
· The patient is contacted as soon as medication incident discovered and provided correct medication in a
timely manner.
· After an incident has been discovered, the pharmacist ensures that the incorrect medication is quarantined
and/or returned to the pharmacy to avoid risk of harm or further harm
· Pharmacy manager and prescribers are notified about all medication incidents
· The pharmacy has policies and procedures for addressing, reporting, investigating, documenting, disclosing
and learning from medication incidents.
· All medication incidents are documented on a pharmacy incident report form
PharmacyPrep.com OTC and Prescription drugs for Dermatological Conditions
69
OTC and Prescription Drugs for
Dermatological Conditions
Questions Alerts!
· Head lice mode of transmission and treatment
· Acne and rosacea symptoms and treatments
· Dermatitis, diaper rash self care, uncomplicated and complicated therapy.
· Psoriasis symptoms (red scaly patches) and treatment
Head lice
Drugs to treat head lice Brand Name Brand Name
(parasites) and scabies
Permethrin 1% Nix Permethrin
Lindane 1% (shampoo) Isopropyl mersteate Resultz
Sulphur 6% in petrolatum Pyrethrin 0.33% with R&C
piperonyl butoxide 3%)
· Transmission: Hair to hair contact, commonly shared items such as combs, brushes, hats and
stuffs toys. It does not fly.
· Lice live on the skin with short or long hair. Scalp and back & sides.
· Hygiene is not criteria of head lice transmission.
· All physical contact should be treated, if head lice or nits are found.
· Female lay eggs daily, these nits hatch after 7 to 10 days.
Non-pharmacological
· Infected fomites, soak combs/brushes in hot water for 5 to 10 min (1:4 vinegar in water) or wash in
pediculicide shampoo.
· Store unwashable items in plastic bags for 10 to 14 days.
· After treatment with pediculicide shampoo remove nits using fine toothcomb.
Treatment: Treat all contacts if you notice head lice. Treat infected contact after close examination.
· Inform daycare but still go.
· Eggs hatch after 7 to 10 days. Once hatch nyphs must have access to the human host within 12 to 24 hr
period to survive.
Pharmacological:
Neurotoxic drugs. Permethrin, and Lindane.
Drug of choice permethrin 1%.

· Wet hair with water. Use fine teeth comb to remove nits.
· Apply drug to wet hair. Leave on for 10 min. Wash with water and repeat removal nits by fine teeth comb.
Permethrin 1% applied day 1 and day 7 may be effective for cases resistant to all topical pediculicides.
· Best ovicidal activity among all treatment with 70 to 80% efficacy.
· Re treatment after 7 to 10 days.
Lindane (shampoo) 1%
· Contraindicated in seizures.
· Caution in under 2-year age and nursing mothers, pregnancy and elderly, inflamed skin.
· Apply for 4 minutes to dry hair.
Non-neurotoxic products. Isopropyl mersteate IPM (Resultz)
Scabies
· Infestation of the skin with human mites. Highly contagious of the skin. Human mite Sarcoptes
scabiei var hominis.
SCABIES LIFE CYCLE

Scabies infestation on the skin can cause the following manifestations?
· Burrows (linear tunnel)
· Papules and blisters
· Pruritus (eczematous), the most severe at nights.
· Pustules
· Clothes/linens should be cleaned with soap and hot water or stored in bags for 5 to 7 days
(separate from host die in 2 to 3 days).
· Vacuum all surfaces (rugs, carpets, furniture).
· Avoid contact with others.
· All close contacts should be treated. It is a hygienic problem.
Treatment
Treat infested individuals and all close physical contact with topical scabicides Permethrin 5%.
· Drug of choice in adults and children >2-month-old.
· Less than 2 months require prescription (medical supervision).
· Effective 96 to 100%. Low systemic absorption.
· Caution individual with ragweed Question alerts!
chrysanthemum allergy. Scabies treated by permethrin 5% cream.
· Applied to entire body neck down to toes (include toes, nails, genital areas), except in eyes, mouth. In
children head down to toes. Must be washed off after 12 hours. Retreat after 7 to 14 days to prevent ping-
pong effect.
Sulphur 6% in petrolatum
· DOC in pregnancy, lactation, and children under 2 months
· Apply bid for 10 days
· Unpleasant odor and local irritation
How to use: Massage into all skin areas, from the neck down to the soles of the feet; every bit of the skin must
be treated, including the fingernails, waist, and genitalia; leave on for 8 to 14 h, then wash off (shower may be
the best way).
Lindane cannot be used by children <10 yrs old, elderly, pregnancy and lactation, seizure disorders.
· Patients with extensively excoriated skin, elderly & children may be enhanced percutaneous absorption and
increased potential toxicity
· 10% systemic absorption & accumulates with repeated exposures
· Killing time 6 h can repeat treatment in 7 to 10 days
· Sulfur 5 to 10% ointment is used in small children and pregnant woman.
Acne
Acne treatment
Generic Name Dosage Generic Name Dosage form
Benzoyl peroxide, gel, lotion topical Tetracycline oral
Salicylic acid 2% topical Minocycline Oral
Clindamycin (solution) topical Doxycycline oral
Erythromycin (gel, lotion, Oral & Tretinoin Topical
solution, pads) topical
Isotretinoin Oral
Steps in acne pathogenesis.

· Increase sebum production (microcomedone)
Pore orifice remains close (close comedone) (Proliferation of Propionibacterium acne, gram +ve anaerobic). The
other name of P. acne is Corynebacterium parvum.
· Antibody to P. acne develops and inflammation rupture follicule wall.
· Papule (Pore orefice remains close)
· Nodule or Cyst (foreign body response)
Increase sebum (Sebacious gland)à sebum+keratinocytes à Microcomedone à (inflammatory

lesions Propionibacterium acne) [Open comedone (blackhead)] [(white head pimples are closed
comedone] --> papule, pustule, nodule -->
Acne is due to
· Increased follicular keratinization.
· Increased sebum production
· Propioni bacterium acne or
Corynebacterium parvum. Increased
(bacterial) lipolysis of sebum
triglycerides to free fatty acids.
· Inflammation
· Acne is not caused by dust
Nonpharmacological
· Squeezing pimples may increase risk of scarring, avoid excessive cosmetic use and use only non-
comedogenic water-based products. Washing; not more than twice daily with mild soap.
· For shaving use safety razors (soften with soap)
· Comedone extractionàWash with hot water and place extractor on acne.
· Ultraviolet light currently not recommended
· Shampoo hair regularly keep from falling on to face. Reduce hair spray use.
· Keep nails short and clean.
· Balanced diet is good for overall health, but there is no evidence that acne is caused by specific food.
Food does not aggravate acne.
MILD-MODERATE SEVERE
Minor pimples, black head, white heads Papules/Pustules/Cyst nodules
NON-INFLAMMATION INFLAMMATION
Benzoyl peroxide Topical retinoids.
Topical retinoids (tretinoins, Adapalene) Antibiotics (topical/oral antibiotics), oral
isotretinoin
Treatment:
Topical acne preparations:
· Benzoyl peroxide (Exofoliant and antibacterial). Populopustular acne
· Cream, Alcohol or acetone Gel, lotion, foams, paste and washes.
· Is a peeling agent that also has some antibacterial action, mainly used in Papulopustular acne.
· Apply at bedtime
· Topical Retinoids (Tretinoin 0.01%, 0.025%, 0.05%, 0.1%), and Adapalene cream (0.1%), Gel (0.1% and
0.3%)
· Cream, Gel, solution. Apply at HS
· Used in comedogenic acne, not used in pregnancy
· Antibiotics
· Erythromycin 1.2%, 2% (gel, lotion, solution, pads), and clindamycin 1% (solution, gel).
· Used to decrease colonization of skin mainly in papulopustular acne.

· Salicylic acid 2%: Available without prescription.
Systemic Antibiotics and drugs: (Tetracycline, minocycline, Erythromycin, isotretinoin).
Tetracycline
· The most commonly prescribed oral agent. Reduce the number of acnes and may exert an anti-
inflammatory effect by inhibiting leukocyte chemotaxis.
· Contraindicated in pregnancy.
· Side effects: GI effects, photosensitivity, may exacerbate azotemia in patients with pre-existing renal
disease.
· DI. GI absorption of tetracycline may be impaired by iron, bismuth, aluminum, calcium, magnesium in drugs
and foods (e.g. dairy products) separate doses by 2 hours.
Minocycline
· Once daily
· Can be given with food or milk
· SE: dizziness, vertigo, ataxia, abnormal cutaneous pigments
Doxycycline
· Contraindicated in pregnancy and child < 8 years of age
Erythromycin
· Alternative to tetracycline due to its excellent safety.
· SEs: nausea, vomiting, epigastric distress, diarrhea.
· DIs: may increase blood levels of theophylline, cyclosporine, carbamazepine, warfarin, digitalis, ergotamine,
methyl prednisone.
· Concurrent use with Terfenadine or cisapride is contraindicated.
Retinoids (Tretinoin and Isotretinoin)

Isotretinoin. Oral
· Side effects: Teratogenicity, dry skin, lips, ocular effects (conjunctivitis, might decrease vision), increase TG
level, increase cholesterol level, increase liver function, reversible hair loss.
· Drug interactions: No adverse reaction known between retinoids and oral contraceptives. Avoid taking
vitamin A supplements.
· Contraindications: Completely contraindicated in pregnancy and planning to be pregnant.
Hormonal Therapy
· Used for women with moderate acne.
· Used for several months to see improvement
Rosacea or Acne rosacea
Caused by Pityrosis R (common in age over 30 y)
Symptoms: Erythematic (redness)
Treatment: Metronidazole 0.75% gel or cream or 1% cream
Rosacea two types;

1. Papulopustular lesions and eye involvement with or without flushing.
2. Telangiectasia or facial edema or rhinophyma (refer to dermatologist).
Dermatitis
Drugs to treat dermatitis
Generic Name Generic Name Brand Name
Hydrocortisone 0.5% (Topical) generics Hydrocortisone 1% (Topical) generics
Zinc oxide 40% Tacrolimus
Zinc oxide 15 to 20% Pimacrolimus
Three different forms of dermatitis.

· Atopic dermatitis or eczema
· Contact dermatitis (e.g. poison ivy)
· Diaper dermatitis (diaper rash)
ATOPIC DERMATITIS CONTACT DERMATITIS DIAPER DERMATITIS (DIAPER RASH)
or ECZEMA (immune response)
Dry skin Detergent, (e.g. poison ivy) Wet diapers
Olive oil or Coconut oil Avoid contact Avoid wet diaper
is helpful Avoid alcohol wipes
oat meal bath can help Allow air drying
Hydrocortisone 1% Calamine (ZnO+ Ferric Uncomplicated diaper rash: ZnO,
0.025% oxide) petrolatum/hydrocortisone 0.5%
beclomethasone Complicated: (tomato red, silvery lining)
Tacrolimus hydrocortisone/petrolatum/antifungal
clotrimazole 1% cream
Pimacrolmus
Atopic dermatitis or eczema is chronic inflammatory pruritic dermatosis associated with personal or family
history of allergic disease.
· Affects up to 1% of population and common in young people
· Flare-ups initiated with emotional stress, irritants such as soaps or chemicals, environmental factors such as
heat or humidity, trauma or food allergies
· Prone to viral, bacterial and fungal skin infections.
Olive oil after bathing or oat meal bath can help
Signs and symptoms

· Pruritus
· Lesions due to scratching
· Weeping erosions, vesicles and excoriated, reddened, scaling papules or plaques
· Skin may be thickened with pigmentation changes
Differential diagnosis
· Contact dermatitis – pattern of lesions, distribution, and identification of allergic, chemical or physical cause
can differentiate it from atopic dermatitis.
Nonpharmacological treatment
· Minimize use of bath soaps and solvents
· Reduce laundry soap residue in clothing
· Avoid bleach and fabric softener
· Use cool air humidifiers to reduce room dryness
· Avoid wool, nylon or rough fabrics
· UV lights may be helpful
Pharmacological treatment
· Topical hydrocortisone is mainstay therapy
· Oral antihistamine
· Coal tar
· Burrow’s solution for weeping lesions. Compress for 2 to 3 days for astringent and antibacterial effects
· No antibiotics
Pharmaceutical agents
Bath products; soothing to itchy, irritated skin
Emollients
· Cover tiny fissures in skin
· Provide soothing protective film
Topical hydrocortisone 0.5% - relieve the itching associated with atopic dermatitis
· Most common local side effects: contact dermatitis, allergic reactions, pain and pruritus
Oral antihistamines
· Older sedative types may help relieve itching associated with dry skin
· May cause drowsiness, gastrointestinal disturbances, paradoxical excitability,
· Nervousness and difficulty in sleeping
· Contraindicated in patients with angle-closure glaucoma, kidney or liver disease, prostatic hypertrophy,
pregnant or breast-feeding women
Coal tar – best applied under an emollient due to their drying properties
· Often messy, had unpleasant odour, stains hair, skin and clothing
· May cause folliculitis, tar acne, contact dermatitis and photosensitivity
How to manage atopic dermatitis

Possible causes:
· Stress
· Skin irritants such as soaps or chemicals
· Environmental factors such as high heat or humidity.
· Foods, molds or pollens to which the person may be allergic
Allergic Contact Dermatitis

· Allergic contact dermatitis is an itchy skin condition caused by an allergic reaction to material in contact
with the skin.
· It arises some hours after contact with the responsible material, and settles down over some days
providing the skin is no longer in contact with it.
· Contact dermatitis should be distinguished from contact urticaria, in which a rash appears within
minutes of exposure and fades away within minutes to hours. The allergic reaction to latex is the best-
known example of allergic contact urticaria.
Active dermatitis is usually treated with the following:
· Emollient creams
· Topical steroids
· Topical or oral antibiotics for secondary infection
· Oral steroids, usually short courses, for severe cases
· Photochemotherapy.
· Azathioprine, cyclosporin or other immunosuppressive agent.
· Tacrolimus ointment and pimecrolimus cream are immune modulating drugs
Diaper Dermatitis (Napkin or diaper rash)

Synonyms: Diaper rash, napkin rash.
Non-pharmacological treatment.
Use warm water to clean diaper Question Alerts!
area and airdry diapering (NOT 1) Diaper rash self-care? Avoid alcohol wipes.
alcohol wipes). 2) Complicated diaper rash treatment? clotrimazole 1% cream
· Change diaper frequently.
· Maintain hygienic conditions.
· Discontinue aggravating factors.
· Allow air-drying. Avoid powders as barriers (NO cornstarch, talc, and baking soda).
· Gentle cleansing with mild soap and water. (Avoid baby wipes & acid pH cleanser).
· Avoid food that increases urinary output and fecal pH (high protein diet, caffeine, citrus juices).
Uncomplicated
· Zinc oxide 15 to 20% or silicone. Zinc oxide 40% for treatment and 15% for prevention. Use lanolin-
free protectant barrier with each diaper change.
§ Reapply every few hours in a thick layer. Remove with mineral oil or water.
Complicated
Confluent tomato red plaques, white scaly border.
Anti-yeast agent’s miconazole, clotrimazole, nystatin for 7 to 10 days.
· Nystatin. Effective only against Candida.
· C. albicans likely cause if condition present >3 days.
· Should be discontinued once inflammation has subsided.
· Anti-inflammatory agents (hydrocortisone 0.5% to 1%). Should not be used >1 wk.
Uncomplicated diaper rash Complicated diaper rash

Limited rash Confluent tomato red plaques, white scaly border.
ZnO, petrolatum, hydrocortisone Clotrimazole, miconazole, nystatin and ZnO,

hydrocortisone
Urticaria
· Urticaria refers to a group of disorders in which swelling occurs in the skin. The release of chemicals such
as histamine causes small blood vessels to leak and results in tissue swelling.
Acute urticaria
· is sometimes due to allergy. Allergy depends on previous exposure to the material, and the
development of an immune reaction to it. A protein called IgE is involved.
Treatment:
· Oral antihistamines control wealing and itching for the majority of patients with urticaria.
· Non-sedating antihistamines (loratidine, fexofenadine, terfenadine, cetrizine, and astemizole) are less likely
to cause drowsiness than the less expensive conventional antihistamines.
· Oral steroids (prednisone) – useful for severe acute urticaria but unsuitable long term.
· If you have generalized urticaria, ask your doctor if a medicine could be the cause. Avoid Aspirin and
codeine, and reduce your intake of acidic fruits
Dry, Scaly Skin

Dry skin – due to dehydration of stratum corneum
· Also called xerosis
· May be present with other dermatoses such as atopic dermatitis, in normal skin due to aging, illness or
environmental factors
· Causes: low humidity, exposure to cold winds in winter, mechanical abrasion and repeated exposure to
solvents, soaps and disinfectants that remove lipids from skin
Signs and symptoms

· Roughness, flaking, scaling and chapping in front of lower legs, back of hands and forearms
· With inflammation, pruritus and fissuring
· Atopic, contact and seborrheic dermatitis
· Dandruff
· Psoriasis
· Bathe once a week and sponge on other times
· Use emollients or protectants to maintain hydration
· Increase water intake
· Bath products and skin moisturizers that contain lactic acid, phospholipids or urea
· Oral antihistamines to help relieve itching
· Topical hydrocortisone preparations to reduce inflammation
Bath products -Contains oil such as mineral oil or lanolin, salts such as sodium bicarbonate or colloidal solids
such as oatmeal may not enhance hydration but may sooth itchy, irritated skin
Cleansing products – soaps made from saponification of animal and/or vegetable fats or soap-like synthetic
detergent cleansers
· Both emulsify fats with water to remove oil and dirt from skin
· Any type of skin cleanser can aggravate skin dryness depending on its pH, cleansing ability, composition
and additives
Emollients – bland oleaginous substances applied to skin by rubbing
· Used to replace natural skin oils, cover tiny fissures in the skin and provide a soothing protective film
· Don’t hydrate skin, they slow evaporation of moisture from skin
· Maintain hydration if applied immediately after bathing
· Common emollients: petrolatum, glycerin, urea, lactic acid, mineral oil, lanolin and fatty acids
Topical hydrocortisone 0.5% - to relieve minor itching and inflammation associated with dry skin
· Most common local side effects: contact dermatitis, allergic reactions, pain and pruritus
Oral antihistamines – relieve itching associated with dry skin
· May cause drowsiness, gastrointestinal disturbances, paradoxical excitability, nervousness and difficulty
sleeping Contraindicated in patients with glaucoma, kidney and liver disease, prostatic hypertrophy,
pregnant and breast-feeding women
How to prevent dry skin

· Use a humidifier on forced-air heating systems
· Keep the room temperature at the lowest comfortable level in the winter and use a humidifier
· Avoid air conditioning when possible
· Use a mild or superfatted soap; if dry skin continues, use soaps to cleanse only the groin, underarms and
feet
· Avoid wool and rough clothing that will irritate skin
· Protect skin from wind, extreme cold and sun
How to treat dry skin

· Add a bath oil to the water in the last 5 minutes of your bath; adding it earlier will not allow water to get
into your skin
· Add baking soda or oatmeal to your bath if skin is itchy
· Rub an ointment into your skin after your bath to help skin hold in the moisture
· Rub a moisturizer into your skin often during the day and at bedtime; special dry skin creams can be tried if
regular moisturizers are not helpful
· Oral antihistamines can help relieve itching especially at bedtime
· To correct a dry skin tendency from any cause reduce contact with soap and water and apply a moisturizer
or emollient
Hydrocortisone cream 0.5% can help relieve itching and red skin that may occur with some cases of dry skin. It
will not cure dry skin. Hydrocortisone should not be used for long term control of dry skin. If the itching and
redness do not improve after 7-10 days of treatment, see your doctor
Reduce bathing
· Reduce washing to every second day, or less often, although the body folds may be sponged daily if desired.
· Baths or showers should be kept as brief as possible.
· Water should be lukewarm.
· Minimize the use of soap. Reduce the need for bathing by keeping as clean as possible both at home and at
work.
Moisturizers and emollients . The terms 'moisturizer' (to add moisture) and 'emollient' (to soften) are
interchangeable as they describe different effects of these agents on the skin. Basically they have two
actions.
· Occlusives, which provide a layer of oil on the surface of the skin to slow water loss and thus increase the
moisture content of the stratum corneum.
· Humectants, which are substances introduced into the stratum corneum to increase its water holding
capacity.
Some moisturizers contain both occlusives and humectants. The humectants, agents adding water to the
stratum corneum, include glycerine and urea.
Alpha hydroxy acids such as lactic acid or glycolic acid. At higher concentrations these also have a descaling or
keratolytic action by thinning the stratum corneum, they are often known as peeling agents.
Psoriasis
Psoriasis is a disorder of the skin that typically consists of red scaly patches covered by silvery white
scales. Psoriasis is very common. Approximately 2% of adults have psoriasis.
· Sunshine: Sunshine may help to clear psoriasis, in many Question Alerts!

people it improves dramatically during sunny holidays. Psoriasis is red scaly
patches.
· Baths. Soaking in warm water with a bath oil or tar
solution can soften the psoriasis and lift the scale. Bland soaps or soap substitutes are useful and
detergents and antiseptics are not necessary and may irritate.
· Emollients. The psoriasis should be kept soft with moisturizing creams to prevent it cracking and
becoming sore. Vaseline, emulsifying ointment and psoralens cream are among suitable
preparations.
· PUVA = psoralens + UVA (ultraviolet light inhibits epidermal mitosis) and psoralens is
photosensitizer.
Occlusive dressing’s patches of psoriasis which are limited in extent may improve with occlusive
dressings i.e. waterproof adhesive dressings. Occlusion with plastic wrap, plastic baggies or thin
plastic gloves, covered with fabric, a sock or cotton gloves can also be used.
· Hydrogel/hydrocolloids are occlusive interactive dressings. Hydrogel contain high content of water.
Crude coal tar: Coal tar in the 'Goeckerman' regime in hospital, it is applied twice daily to the patches
after exposure to ultraviolet light. The psoriasis clears in 4 to 6 weeks and may stay away for months.
Topical steroids anti-inflammatory inhibits epidermal proliferation and alter immune reactions. Hydrocortisone
0.5% is only anti-inflammatory lacks the antiproliferative effect. Instead moderate potency clobetasone 17-
butyrate 0.5% is used.
Oral medications include methotrexate. Methotrexate tablets are taken once a week, salicylic acid,
Anthralin and biological response modifiers infliximab.
PSORIASIS + PSORIASIS (red scaly patches skin, scalp, joints)

PSORIATIC
ARTHRITIS
Anti- TNF +/- 1st line 2nd line 3rd line
Methotrexate
18 and 42% (up to Topical Phototherapy (UVB) Biologics such as
30%) corticosteroids, or psoralen + UVA or etanercept,
vitamin D 3 , retinoids, Po methotrexate, adalimumab,
calcineurin inh. cyclosporine, acitretin infliximab,
Coal tar & anthralin or apremilast secukinumab,
ustekinumab, or
apremilast.
*calcineurin: is a calcium and calmodulin dependent serine/threonine protein phosphatase. It activates
Tcells.
Dandruff and Seborrhea
Dandruff and seborrhea. Scaly dermatoses occurring in area of high sebaceous gland concentration
· Dandruff affects most adult
· Seborrhea occur most often in infants less than 3 months of age (cradle cap) and adults 30 to 60 years of age
· 2-5% of population is affected with more men than women.
· Exacerbated with stress. Low humidity and temperature
· Worse in winter
· Skin irritation, bacterial and yeast infections have been implicated
Signs and symptoms:

Dandruff: characterized by excessive scaling and itching of the scalp, dry, white, grayish scales spread uniformly in scalp.
Dry white scale scattered. (Scalp)
Seborrhea: excessive scaling and itching but found in the axilla, back, chest, ears, face and groin. Greasy,
yellowish scale over erythematous patches. (scalp, facial, groin)
· it is an inflammatory dermatosis
· Lesion is a patchy area of yellowish scales with slight to moderate redness of underlying skin.
· Cradle cap in infants is seborrheic dermatitis but not itchy
· Regular cleansing of the scalp or other affected areas with non-medicated shampoo
· Should shampoo and massage scalp at least 3 times a week to control the condition
Cytostatic/antifungal shampoo with selenium sulfide, zinc pyrithione or ketoconazole
· Keratolytics useful to soften and detach flakes
· Coal tar relieves itching and lower population of bacteria or yeast on the scalp
Antiseptics: (benzalkonium, chlorhexidine, povidone iodine
· Kill bacteria or fungi
Coal tar have astringent, keratolytic, antipruritic and antiseptic effects

· Available in ointments, lotions, gels, shampoos and bath preparations
· Tar often messy, unpleasant odour, stain skin, hair and clothing.
· May cause folliculitis, tar acne, contact dermatitis and photosensitivity.
Ketoconazole: Cytostatic effect that slows cell turnover and antifungal effect against Pityrosporum ovale.
· Not be used within 2 weeks of treatment with topical corticosteroids.
Salicylic acid (2-3%); keratolytic effect Question Alerts!

· Useful in resistant cases of dandruff and 1) Selsun blue shampoo (selenium sulfide) may
seborrhea. stain blond or grey hair.
· Not be used more than twice a week.
Selenium sulfide; cytostatic and antifungal effect

· Remove all jewelry before use and wash hands thoroughly. Not to be used within 2 days of applying hair
tints or perm solution.
· Excessive use causes oily hair and hair loss. May stain blond or grey hair
· Don’t apply to inflamed or damaged hair. Only used twice a week.
Sulfur (3 to 5%): keratolytic effect

· Useful for dandruff but not proven to be effective
· Used twice a week
· Odor or stinks
Zinc pyrithione: cytostatic and antifungal effects

· More effective than others
· Can be used daily to control dandruff and seborrhea
Antiperspirants (anti body odour)

· Aluminum salts. Aluminum chloride, Al-chlorhydrate.
· Aluminum acetate (used in excessive sweating or hyperhidrosis).
· Zinc oxide corn starch

· potassium alum and ammonium alum.
Foot Conditions
Fig 69.1
Athlete’s Foot
Athlete’s foot (Tinea pedis) is common cutaneous fungal infection. Secondary bacterial infection may
cause inflammation and additional maceration.
Prevent transmission to other by no going bare foot around home or in public area.
Signs and symptoms
· Itching, peeling, scaling, vesiculation, patchy hyperkeratinization and inflammation occurs between the toes
are the main clinical signs. Malodor may be present.
· The acute form is characterized by fissuring, scaling and peeling and the skin between toes appears white,
macerated and soggy.
· Chronic form is characterized by hyperkeratotic, scaly eruptions on weight bearing surfaces of feet, heels,
soles and borders of the feet.
· Should be differentiated from contact dermatitis, pustular psoriasis and drug eruptions
· Patients failing to respond to non-prescription antifungal preparations used correctly for several weeks
should be referred to a physician.
· Nail involvement requires prescription treatment
Athlete's foot occurs between toes

· Antiperspirant or absorbent powder (talcum or aluminum chloride) CAN be applied to feet to
decrease sweating.
· Patient with history of athlete’s foot may dust an antifungal (e.g. tolnaftate) powder on their feet to prevent
further reoccurrence.
· Antifungal powder should NOT be placed in shoes, as coagulation of powder and moisture create an
unfavorable environment.
· Drug of choice to treat athlete's foot? Clotrimazole 1% cream
· Cochrane review concluded that "Tea tree oil" has NO evidence of effect for T. pedis.
· Athlete’s foot is transmittable to other.
ATHLETES FOOT
CLOTRIMAZOLE 1% CREAM Apply twice daily for four weeks. Recommend
MICONAZOLE 2% CREAM using for one week after resolution of symptoms
TOLNAFTATE 1% to prevent reoccurrence.
· Counsel patients on proper foot hygiene.
· Bathe daily and dry feet well between the toes. Wear absorbent socks (cotton 60% less blend with
synthetic fiber, nylon) changed daily or twice daily if the patient is susceptible to hyperhidrosis (sweating).
· Wear shoes that “breathe” (sandals, if possible).
· Change shoes daily and wear different shoes for sports.
· Dust with talcum powder or cornstarch, especially between the toes.
Pharmacological Treatment
· Expose feet to the air to dry them and suppress bacterial proliferation.
· Soak feet with an astringent or dust with a medicated powder (talcum powder)
· Use a topical antifungal agent such as clotrimazole, miconazole, tioconazole, tolnaftate or undecylenic acid.
· Clotrimazole, miconazole or tioconazole are the preferred agents since they have both bacterial and
antifungal activity and there is less chance of recurrence.
· Use a topical antifungal agent such as clotrimazole, miconazole, tioconazole, tolnaftate or undecylenic acid.
· Clinical improvement should be apparent within 2 weeks
Clotrimazole 1% cream, Miconazole 2% cream, spray powder, oxiconazole and tioconazol, imidazole
antifungal agents. Tolnaftate 1% cream, gel, aerosol, topical powder, topical solution.
· Have some antibacterial activity.
· Adverse reactions are infrequent like mild skin irritation, burning, stinging and erythema.
· Sensitivity reactions occurs rarely.
Naftifine and butenafine; effective antifungal but no antibacterial activity

· Mild burning or stinging, dryness, redness, itching or local irritation may occur.
Tolnaftate; effective antifungal agent, no antibacterial activity

· Recurrence and treatment failure is common
· Rarely cause irritation or hypersensitivity reaction
Undecylenic acid; oldest antifungal agents

· Can be as effective as tolnaftate, but characteristic odour is objectionable
· Hypersensitivity reactions and skin irritation are rare
How to prevent athlete’s foot

Athlete’s foot fungi prefer moist, warm places, they thrive on the feet and between the toes of people whose
feet are often hot and sweaty.
Individuals with history of athlete's foot may regularly dust an antifungal powder such as tolnaftate
once or twice daily on their feet to prevent further reoccurrences. Antifungal powder should NOT be
placed in shoes, as coagulation of powder or moisture create unfavorable environment.
All antifungal preps apply to affected areas once or twice daily.
This can be prevented by few simple measures:

· Wash the feet once or twice a day with soap and water and dry them thoroughly, especially between toes
· Wear sandals or shoes and socks that allow adequate ventilation
· Avoid socks made of synthetic fibers as they retain heat and moisture. Light cotton socks are best.
· Do not wear occlusive footwear such as rubber boots or athletic shoes for any longer than necessary.
· Change shoes daily to allow them to dry inside
· Change socks regularly and wash them thoroughly in hot water
· Dust the feet, especially between the toes, with a foot powder to aid drying
Viral skin infection (all types of warts are associated with HPV infection): Common warts, flat wart,
plantar warts and genital warts.
Common wart caused by HPV 2, 4, 27 and 29 (knee, hands, fingers, around nail.) Warts found on sole
of the feet are called plantar warts (verrucae plantaris)
Flat wart caused by HPV 3, 10, 28 and 49. (face or neck)
The drug of choice is topical products.

CUTANEOUS WARTS GENITAL
COMMON WARTS FLAT WARTS PLANTAR WARTS WARTS
FACE & NECK FOOT & SOLE

Verruca vulgaris Verruca plana Verruca plantaris
Salicylic acid Salicylic acid (<17% OTC) Salicylic acid Imiquimod
Cryotherapy and Rx can use up to 70% Cryotherapy
GARDASIL is indicated in boys and men 9 through 26 years of age for the prevention of infection caused by
HPV types 6, 11, 16, and 18 and the following diseases associated with the HPV types included in the vaccine.
Tips
1. sebaceous gland 2. Diane & Alesse 3 Erythromycin or Clindamycin
4. cool humidifiers, 5. petroleum jelly, ZnO 6 cleaning w/ alcohol wipes
moisturizer cream
7. it transmits by head to 8. Permethrin 1% 9 avoid sharing combs,
head contact or common brushes, hats & pillows
shared items
10 gives blisters, hot 11 full thickness, painless 12 superficial, sunburn
H 2 O, flame oil leathery, flame & hot metal
13 UVB 14 SPF 15 UVA
16 coal tar 17 sulfur 18 anthralin
19 UV light 20 salicylic acid 21 corticosteroids
22 Methotrexate 23 antifungal + ZnO 24 petroleum jelly, ZnO
25 Propioni bacterium 25 Second application after 7 to
acne 10 days of 1st application
· How do the head lice transmit? ( )
· What is correct self care measure for head lice? ( )
· Drug of choice for head lice? ( )
· How often head lice treatment should be applied? ( )
· What bacteria cause acne? ( )
· What gland secretions can cause acne? ( )
· What is pharmacological therapy for acne in pregnancy? ( )
· What oral contraceptives can be used for acne treatment? ( )
· What is self care measure should be recommended for dermatitis? ( )
· What is the treatment for uncomplicated diaper rash? ( )
· What is pharmacotherapy for complicated diaper rash? ( )
· What self care measure is not recommended for diaper rash? ( )
· What is pharmacotherapy for psoriasis? ( )
· What topical dermatological agent that gives stains? ( )
· What topical dermatological agent gives odor? ( )
· 1st degree burn examples ( )
· 2nd degree burn examples ( )
· 3rd degree burn examples ( )
· Photo toxicity, photoaging, immunosuppressant & skin cancer can cause ( )
· Sunburn, immunosuppression & skin cancer ( )
· Sun protection factor (SPF) 15, 30 or 50 ( )

· Clouds, snow, beach gives high sun burn (True)
· High altitude have high sunburn (True/False)
· Water, beach areas, snow have high sunburn (True/False)

· Atopic dermatitis or eczema. Olive oil is applied directly to rehydrated skin after bath.
· Colloidal oatmeal bath, Soaps are made from animal or vegetable (glycerine soaps (transparent soaps).
· Treatment of atopic dermatitis Burrows solutions (aluminum acetate), Hydrocortisone 0.5%
and Tacrolimus cream
www.Pharmacyprep.com Ophthalmic, OTIC and Mouth Conditions
70
Ophthalmic, Otic and Mouth
Conditions
Questions Alerts!
· Ophthalmic preparations to treat red or pink eye, and dry eye.
· Eyelid conditions. Hordeolum, chalazion and blepharitis.
· When to refer? Pain and vision changes, diabetic dry eye, foreign object.
· Prescription directions of ophthalmic (OU, OD, OS), otic drops (AU, AD, AS).
· Hard and soft lenses and lens solutions.
· Vertigo or Meniere disease treatment. Otitis externa and otitis media.
· Mouth conditions like canker sores, and cold sores therapy.
Fig 70.1
Eye problem: Mild blepharitis, single hordeolum (stye), conjunctivitis and dry eye.
Blepharitis: Inflammation of the eyelid margin

· Burning, irritation, itching and hyperemia along lid margins
· Crusting and scaling around eyelashes may be present hordeolum. Acute inflammation in the eyelash
follicle or eyelid gland
· Tenderness, edema and redness
· Pus may appear along the eyelid margin in a few days
· Blepharitis and hordeolum
· Commercial eyelid cleanser useful for blepharitis
· Indiscriminate use of nonprescription ophthalmic anti-invectives should be avoided
· Thorough cleansing sufficient for self-limited disorders
Question Alerts!
1) Ophthalmic conditions that require referral to doctor?
1) Red irritated eye with purulent discharge is probable bacterial conjunctivitis tried self care and >
72 h then refer
2) Red irritated eye with watery discharge and itching is probable allergic conjunctivitis, self care >72
hr then refer
3) Red irritated eye and NO itching and NO discharge than probable viral refer to doctor.
4) Gritty, sandy feeling is probable dry eye > 5days refer
5) Pain and vision changes refer to doctor
6) Blepharitis refer to doctor.
Conjunctivitis (red or pink eye). Inflammatory condition of the membrane that lines the inside of the eyelids
and covers the exposed surface of the sclera. Conjunctivitis can be allergic, bacterial, and viral.
Conjunctivitis diffuse redness in both eyes

· Redness is more marked in the outer aspects of the eye and less around the cornea
· Muco purulent discharges is more common with bacterial conjunctivitis
· Clear discharge in viral or allergic conjunctivitis
· Intense itching occurs with allergic conjunctivitis
Red Eye Bacterial or viral Allergic
Symptoms Abrupt onset, purulent or Burning sensation, itchy eyes watery discharge, mild
mucopurulent discharge, lids redness +/- lid swelling.
endomatus +/- stuck AM. Self resolved
in 7 to 10 days, chronic if >2 wks.
Minimal itching.
Non-Rx Clean gauze compresses avoid cleanser Allergen avoidance, cold compresses over the eyes,
and avoid eye patches. water irrigation BID, and avoid contact lenses.
Schedule
Polymyxin B/gramicidin (eye drops),
III (OTC) polymixin B/bacitracin (ointment).
Rx Trimethoprim/polymyxin B (drops), Artificial tears 4 to 6 times a day, ophthalmic
erythromycin or bacitracin (ointment), antihistamine, oral antihistamine, mast cell stabilizers,
sulfacetamide 10% solution and for chronic corticosteroids
Bacterial conjunctivitis: Common causes are S. aureus, S. pneumonia (most common in children), H. influenza
(most common in children).
Symptoms: Abrupt onset, purulent or mucopurulent discharge, lids endomatus +/- stuck AM. Self resolved in 7
to 10 days, chronic if > 2wks. Minimal itching.
Non-prescription therapy: Clean gauze compresses, avoid cleanser and avoid eye patches. Polymyxin
B/gramicidin (eye drops), polymixin B/bacitracin (ointment).
Rx therapy: Trimethoprim/polymyxin B (drops), erythromycin or bacitracin (ointment), Sulfacetamide 10%

solution
Viral conjunctivitis
Common cause: Adenovirus, herpes simplex virus
Symptoms: Itchiness is minimal, redness is generalized. Discharge is profuse, serous
Non-pharmacological: Give warm or cold compress to increase comfort.

NonRx therapy: Ocular decongestants and/or lubricants may be useful.
Rx therapy: Trifluridine (topical), Acyclovir, Famciclovir, and Valacyclovir (oral).
Allergic conjunctivitis
Common cause: ragweed, Grass pollen, Itchiness is severe
Symptoms: Burning sensation, itchy eyes watery discharge, mild redness +/- lid swelling
Non Pharmacologic therapy: Allergen avoidance, Cold compress over the eyes, water irrigation BID, and avoid
contact lenses.
Rx therapy: artificial tears 4 to 6 times a day, ophthalmic antihistamine, oral antihistamine, mast cell stabilizers,
and for chronic corticosteroids
Levocabastine; emedastine (H1 antagonist) for itchy and watery eye, Olopatadine (antihistamine and mast cell
stabilzer), Nedocromil, Iodoxamide (mast cell stabilizing agent)
alleviates. Ketorolac (Nonsteroidal anti-inflammatory eyedrop) for
itching & redness. Drugs that cause dry eye
Other types of Conjunctivitis include: Chlamydial Conjunctivitis: · Anticholinergics: Antimuscarinic
Trachomatis Fungal conjunctivitis: In rare cases: Rickettsial drugs
conjunctivitis: Rare: Parasitic conjunctivitis: Rare · First generation antihistamines
· B-blockers: propranolol, timolol
· Diuretics: hydrochlorothiazide,
Dry eye
indapamide
· Isotretinoin
Symptoms: Dry eye, sandy, gritty sensation, photosensitivity and · Niacin (in hyperlipidemia)
difficulty moving the eyelids · Phenothiazine antipsychotics (e.g.
· Etiology: Aqueous deficiency. Decrease lachrymal gland Chlorpromazine)
secretion. · TCA’s (amitriptyline)
· Mucin deficiency: Damage or inflammation of goblet cells can
be cause by condition erythema multiforme.
· Lipid deficiency: decrease lipid layer is common in patients with blepharitis.

· Epitheliopathies: defects in the corneal epithelium that can impair tear film stability.
Nonpharmacologic treatment
· Cleanse eyes thoroughly
· Blepharitis and hordeolum benefit from warm, moist compresses applied for up to 15 minutes, 3 to 4 times
a day
· Cool, moist compresses have a soothing effect for conjunctivitis and dry eye.
Treatment
Nonprescription Therapy: Artificial tear solutions: An ideal tear replacement product would posse:
· Electrolytes in concentration similar to that normal tear.
· An osmolality of 2000 to 280 mOsm
· Viscosity of less than 20 centipoise
· No cytotoxic
· Preservative free.
Pharmacotherapy: Substituted cellulose ethers (Carboxymethylcellulose 1%): Polyvinyl Polymers (Polyvinyl

alcohol 1.4% and sodium hyaluronate)
· Ointments: Petrolatum and carbomer
· Artificial tear inserts – hydroxypropylcellulose
· Pilocarpine, Acetylcysteine, Methylprednisolone
· Instillation of artificial tears every 1-6 hours for a trial period of 48 hours
· Emollients can cause blurring of vision and are better suited at night
Any eye irritation that fails to respond to nonprescription therapy within 48 hours should be referred to an eye
care professional for proper diagnosis
Antihistamines – may cause photophobia or allergic reactions
· Antazoline, pheniramine, pyrilamine
Anti-invectives – polymyxin B combined with bacitracin or gramicidin
Artificial tears – chemically inert and coat the eyes
· Help them retain moisture
· Protect from irritation
· Slow turnover of tears
· Examples dextran, methylcellulose, and hydroxypropyl methylcellulose,
· Polyethylene glycol, polyvinyl alcohol and sodium carboxymethylcellulose
Astringents – not to be used for hordeolum or allergic conjunctivitis
· Zinc sulfates a mild astringent that clears eye secretions.
Decongestants – can cause rebound hyperemia if overused
· Contraindicated in patients with glaucoma
· Examples naphazoline, oxymetazoline, phenylephrine, tetrahydrozoline, xylometazoline.
· Emollients, soften eye tissue and protect it from drying such as Lanolin, mineral oil, petrolatum
How to administer eye drops

· Wash hands thoroughly.
· Tilt the head back or lie down.
· With eyes open, gently pull the lower lid below the eyelashes away from the eye to form a pouch.
· Approach the eye from the side and hold the container near the lid (at least 2 cm away). Do not touch the lid
or lashes.
· Look toward the ceiling. Looking up moves the center of the eye away from the instillation site, minimizing
the blink reflex.
· Instill one drop into the pouch. Hold this position to let the drop fall as deep as possible into the pouch.
· Look down for several seconds and then slowly release the lower lid. Looking down brings the cornea into
maximum contact with the drop.
· Gently close (don’t squeeze) the eyes for 1 to 2 minutes while applying gentle pressure to the bridge of the
nose for 30 to 60 seconds. Gentle pressure prevents the drops from being drained from the eye.
· A tissue may be used to blot around the eye, but do not rub. Closing the eye helps prevent loss of solution
caused by blinking. If the eye is closed too tightly, the medication may be expelled.
· Don’t rub the eye. Try not to blink.
· To apply several drops, wait 3-5 minutes after the instillation of each drop
· Never contaminate the dropper tip or the top o the container by allowing it to touch the eye, eyelid,
eyelashes, and fingers or counter
surface.
Question Alerts!
Eye care products 1) Difference of soft and hard lens?
2) What is purpose of adding surfactants in contact lens
Contact Lenses solutions? Removing contaminant, debris, facilitate
Types of contact lenses disinfection.
· Hard (rigid) gas permeable lenses or
Rigid gas permeable (RGP) and hydrophobic. Silicone, fluorosilicone acrylate, polymethyl methacrylate
(PMMA).
Soft lenses are hydrophilic. Hydroxyethyl-methacrylate (HEMA).
Hard lens (RGP) Soft lenses (most commonly use)

Poly methyl methacrylate (PMMA) Hydroxyethyl-methacrylate HEMA
HYDROPHOBIC HYDROPHILIC
LIFE 5 YEAR UNTIL LOST 1 DAY TO 1 YEAR
DAILY WEAR TIME <12 HR DAILY WEAR TIME >12 HR
RISK OF MICROBIAL HIGH
CONTAMINATION IS LOW
STRONG FRAGILE
Disposable are opened for each day. No regular solution requires.
Contact lens solutions (cleaning solutions)

Two types: Surfactants remove loose debris and protein cleaners. In other words, remove proteins from soft
lens.
Surfactants: Disinfect and remove contaminants.

Protein cleaners or enzyme cleaners
contain papain, pancreatin, or
Question Alerts!
subtilism (enzyme). Remove protein
1) Administering eye drops?
deposits by catalyzing the natural
While instilling all ophthalmic drop, contact lens should be
breakdown of debris into simple
removed!
compounds.
2) Tilt head back or lie down
3) After instilling eye drop why would you apply gentle
Wetting and rewetting solutions:
pressure to the bridge of nose? To keep the medication from
Produce cushioning and lubricant
going down the tear duct. (prevent systemic absorption)
effect between lens and eyelid,
between eye and cornea (removes dryness).
Drugs interaction with contact lens

· Oral contraceptive alters tear composition results decrease lubrication.
· Antihistamine, Hypnotics, Sedative decrease blink rate (blink increases hydration).
· Anticholinergics, antihistamines, TCA’s decrease tear volume
· Isotretinoin may cause itching and decrease wear time in soft lens users.
· ASA may cause ocular irritation, redness in soften wearers.
· Disinfecting solutions kills bacteria
· Preservative; maintain sterility of solution
· Saline solution preservative minimize the risk of contamination
· Wetting and rewetting solutions provide wetting, lubrication and cushioning functions.
· Contact lens should be stored in disinfecting solutions.
· Drying out is the major (75%) problem for soft lens users.
Drugs cause discoloration of soft lens.

Dopamine Nitrofurantoin Sulfasalazine
Tetracycline Phenazopyridine Phenolphthalein
Rifampin Pyrantel pamoate
Mouth Ulcers (aphthous ulcer):
Non-prescription Medications
· Local anesthetics (topical): Benzocaine, lidocaine.
· Oral analgesics: Acetaminophen, ASA, and NSAIDs
· Protectant: hydroxycellulose; base agent (Zilactin, Oractane).
Prescription Medications
· Corticosteroids, Fluocinonide, Clobetasole and Triamcinolone.
Dental Abscess: accumulation of puss in dental cavities.

Drug of Choice: Pen V or Amoxicillin or Erythromycin (base for adults and estolate for children)
Cold Sores
Cold sore is oral herpes infection also called fever blisters is caused by herpes simplex virus 1 (HSV 1 ).
Transmitted through direct contact. Usually appears on the lips also on hard palate or gums.
Cold sores sign and symptoms begins with prodromal symptoms of mild burning or itching on the lips.
· Small vesicles filled with clear fluid which eventually ruptures and crust over
· Last for 3 to 10 days.
· Cold sores improve without treatment.
Cold sores also known as recurrent herpes labialis.

Tingling sensation progressing to tiny painful grouped blister on lips, then crust.
· Usually caused by activation of latent herpes simplex virus type I.
· Primary infection occurs between 6 and 36 months of age. 15% of adults have primary infection.
Recurrent infection occurs in 20 to 45% of previously infected people.
· Mostly get first infection with herpes when they are infant. Virus remains in the body and spread
through physical contact.
· Abreva (docasanol) is used for treatment of recurrent cold sores.
· Acyclovir ointment.
Nonprescription medications
Pharmacotherapy
Topical anesthetics
· Ester type: Benzocaine, tetracaine; contact sensitizers
· Benzocaine: most common topical anesthetic used to relieve pain associated with canker and cold sores.
External analgesics
· Camphor, menthol, and benzyl alcohol
· Counterirritants commonly found in cold sore balms
Astringent: Burrow’s solution or cold compresses with tap water applied 3 to 4 times daily is helpful for cold
sores
· Sunscreen with SPF 15; recommended to prevent cold sores in those with recurrence after exposure to sun.
Protectants
· Petrolatum, ZnO, cocoa butter, allantoin, and calamine
· Prevent drying of lesions from cracking or fissuring
Heparin sodium and zinc sulfate (lipactin) – reduces pain duration
· Shorten time required for lesions to heal
Prescription medication. Antivirals like acyclovir
CANKER SORES
Recurrent aphthous stomatitis usually appear on the cheeks, tongue, and soft palate floor of the mouth.
Canker sores. Visible manifestation of recurrent aphthous stomatitis

· Streptococcus sanguis partly the cause
· Autoimmune mechanism is also implicated. At least 20% is affected
· Women twice as susceptible as men. Susceptibility appears to be inherited
Canker sores sign and symptom. Painful, recurrent ulcers in the oral mucosa
· 3-10 mm shallow lesions
· Round with white center and red halo
· Persist for 7-14 days.
Treatment
Topical anesthetics
· Ester type. Benzocaine (contain up to 20% benzocaine), and tetracaine; contact sensitizers.
· Applied to only small areas of the mouth to prevent a “cotton-mouth” feeling and loss of oral
sensation.
Protectants
· Petrolatum, ZnO, cocoa butter, allantoin

· Emollient mixtures or denture adhesives can alleviate pain
Rx. Chlorhexidine gluconate and tetracycline mouthwashes help resolve cankers
Oral thrush
Also known as Candidiasis caused by fungus Candida albicans. Drugs commonly cause oral thrush are inhaled
corticosteroids.
To prevent oral thrush associated with inhalers. Rinse mouth with water after inhalation of corticosteroids spray
and using aero chambers.
Treatment: Nystatin suspension.
Xerostomia (dry mouth): Xerostomia is a dry mouth conditions in which there are no salivary secretions and also
caused by improper functioning of the salivary gland (Sjogren’s syndrome).
Nonprescription medication: Ice chips, artificial saliva, and sugarless candies.

Treatment. Artificial saliva
Teething pain
Nonpharmacological
· Hard, smooth and clean products may be given to the child to bite and chew on such as frozen face cloth.
Safe tethers cooled in refrigerator before use can be helpful.
· The Canadian dental association recommends rubbing the back of a small, cold spoon on the gum.
Non-prescription medication
Oral analgesic. Acetaminophen and ibuprofen
Topical anesthetic. Benzocaine 7.5% and 10% gel
Treatment of eruption cysts

· In general cysts rupture, spontaneously.
· Rare cases surgically removed, if significant discomfort or interferes with feeding occurs.
Dental Caries: Destruction of calcified tissue resulting from an infection. Dental caries most commonly caused by
Streptococcus mutans. This bacterium produces acids that demineralized the enamel.
Treatment
1. Tooth paste contains
· Detergents or surfactants (sodium laurel sulfate, sodium N-lauryl sarcosinate)
· Humectants (glycerin, propylene glycol)
· Whitener (peroxides; sodium triphosphate)
· Fluorides – reduce caries formation
2. Mouth wash contains
· Cetylpyridinium chloride may cause staining of teeth
· Chlorhexidine; may cause stains, taste change, discoloration of tongue
3. Triclosan
· Antiplaque
· Antimicrobial agent that helps prevents gingivitis, plaque cavities and tartar.
Trench mouth. This can cause acute necrotizing ulcerative gingivitis (ANUG) is caused by overgrowth of
spirochete and fusiform microorganism.
Gingivitis/periodontitis
The infection of gingival tissue is gingivitis. Gingivitis mouth rinse

· Chlorhexidine mouth rinse
Non-prescription
· Mouth hygiene
· Anesthetics; Benzocaine, and eugenol
· Analgesic; Acetaminophen.
Endocarditis
Caused by S. viridan and S. aureus.
Prophylaxis
· Amoxicillin 1 g before (1 hr) surgery, followed by 500 mg TID for 3 days.
· Azithromycin 1 g/day followed by 500 mg OD x 2 to 3 days (for patients allergic to betalactam).
· Clindamycin 600 mg followed by 300 mg QID x 3 days (for patients allergic to betalactam).
Reference. Canadian Pharmaceutical Specialties
OTIC disorders
Excessive/impacted earwax
· Overactive ceremonious
glands Question Alerts!
· Narrowed ear canal 1) Ceremonius gland produce? earwax
· Large amount of hair in the 2) Earwax is removed by carbamide peroxide and mineral
canal occurs often in oil.
elderly.
· Ineffective or insufficient chewing or talking, especially in elderly.
· Improper removal methods.
Earwax softening agents

· Carbamide peroxides the only approved as safe and effective agent for earwax removal.
· To prevent vertigo, medication in the vial should be warmed in the hands and put 5-10 drops in the ear BID
for 4 days.
· Do not use if ear drainage, discharges, pain, and irritation or rash occurs.
· Do not use if there is injury of perforation of eardrum.
· If the patient feels pain or severe fullness upon instilling the drops, this might be an indication of ruptured
tympanic membrane.
Altitude and ear pressure:

· This is caused by not functioning the Eustachian tube properly
· Pain can be reduced or prevented through: Swallowing (chewing gum or eating candies) to activate the
muscle that pull open the Eustachian tubes and helps to unblock the ear. Giving a bottle of milk or juice to
the baby may reduced or prevent ear pain among babies.
· Yawning is effective in opening Eustachian tubes.

· Pinching the nostrils using the cheek and throat muscles, and forcing air back of the nose, may help in
unblocking the ear.
· Decongestant may be a great help either an oral agent (Sudafel) taken an hour before descent, or topical
agent (oxymetazoline) should be administered 10-15 minutes before descent.
Otitis Externa (swimmer ear)

It is the inflammation of ear canal. This is commonly known as swimmer’s ear or hot weather ear. Most often it
occurs during summer. 50% of this is cause by Pseudomonas aeruginosa, other common microbes include Staph,
Bacillus, and Proteous organisms.
Symptoms includes itching, moving pain in air, and fluid discharge from canal in severe cases, decrease or loss of
hearing.
Ear drainage:
Clear or cloudy drainage ----> Otitis media, or CSF
Bloody drainage---> ear trauma
Drainage resulting from eczematous mild otitis externa can be self treated.
Non-pharmacological
· Hot compresses; pain, discontinue sticking
· Cold compresses; swelling, itch
· Avoid using shampoos
· Do not manipulate with swabs
· Removal earwax
· Use blow drier after shower. Bath not shower
OTC; Aluminum acetate 0.5% (Burosol), Benzothenium chloride 0.03% and Acetic acid 2%
Prescriptions
· Gentamycin otic solution (amino glycosides active against gram –ve, (Pseudomonas), and S. aureus (side
effect: ototoxicity).
· Ciprofloxacin ophthalmic solution (no ototoxicity)
Otitis Media (OM)

· Otitis media is the infection of middle ear. Symptoms. Pain in the ear, and fever
· Acute otitis media (most common cause S. pneumonia, H. influenza, and M. catarrhalis). However, the types
of OM chronic suppurative otitis media Otitis media with effusion.
· Drug of choice. Amoxicillin or +/- clavulanate, ceftriaxone, cefuroxime axetil, azithromycin.
· Children with frequent otitis media should vaccinated by pneumococcal vaccine.
Vertigo and dizziness

Dizziness is refers to variety sensations such as light-headedness, fainting, spinning, and giddiness.
Vertigo is defined as sensation of motion in response given bodily movement. Nausea and vomiting, pallor, and
perspiration accompany vertigo. It is vestibular disease as result of lesions or disturbances in inner ear. e.g.
Meniere's disease.
Meniere's disease prophylaxis; Diuretics (HCTZ, Triamterene), Betahistine (histamine agonist) is commonly used.
Diet salt restrictions and avoid coffee, and smoking.
Boils: Infected hair follicles in the ear canal that usually cause by S. aureus. This is self-limiting and is best treated
by application of warm compress.
Tips
1. 1 gtt OU 2 1 gtt AU 3 Carbamide peroxide
4. otitis externa 5 cold sores 6 wax removal
7. antibiotics & 8 inflammation of the eyelid 9 HSV 1
corticosteroids margin
10. HSV2 11 CMV 12 Epstein barr virus
13. VZV 14 pain in eye 15 blurred vision
16. blepharitis 17 dry eye 18 diabetes
19. polyvinyl alcohol 20 hydroxypropylmethylcellulose 21 Thimerosal
(HPMC)
22. 0.01% 23 sterile & isotonic 24 Tropicamide
25. emollients, anesthetics, 26 Acyclovir 27 cerumenous gland
astringents and Acyclovir
· What ophthalmic conditions require referral to doctor? ( )

· What is added in ophthalmic preparation to increase eye contact? ( )
· the most allergic ophthalmic preservative? ( )
· Benzalkonium chloride concentration as preservative in ophthalmic drops? ( )
· Ophthalmic preparation should be? ( )
· What eye drops that are used in eye exams? ( )
· Cold sores are caused by? ( )
· What is treatment of cold sores? ( )
· What is not a treatment cold sores? ( )
· Both eyes is directed as? ( )
· Both ear is directed as? ( )
· Earwax removal is? ( )
· Swimmer’s ear is? ( )
· Abreva is used for? ( )
· What is active drug of valacyclovir? ( )
· Ear wax glands are also known as? ( )
· Mineral oil in ear is used as? ( )
· Acyclovir is effective against? ( )
· Blepharitis is? ( )
· An autoimmune disease characterized by destruction of the lacrimal and salivary glands resulting in the
inability to produce saliva and tears. ( )
· Stye (hordeolum) require warm compress where as blepharitis require cold compress
Latanoprost side effect (Eye pigmentation and lengthening of eye lashes)
www.Pharmacyprep.com OTC Drugs, antihistamine, decongestants and antitussive
71
OTC Drugs, Antihistamine,
Decongestants, Antitussives,
and Expectorant
Questions Alerts!
· Topical xylometazoline and oral decongestant pseudoephedrine, phenylephrine precautions and
contraindications with MAOi (phenelzine, tranylcypromine, selagiline, rasagiline) hypertensive crisis.
· Antitussives like dextromethorphan, codeine DIs with MAOi can cause serotonin syndrome.
· What OTC drugs have abuse potential? Dextromethorphan, pseudoephedrine, diphenhydramine,
and Tylenol # 1.
Pharmaceutical Agents
1. Analgesics/antipyretics; acetaminophen, ASA or ibuprofen
· Treat pain and fever.
· Don’t administer ASA to infants, children, teenagers or young adults because of Reye’s syndrome.
Antihistamines: Relieve rhinorrhea, sneezing and watery eyes associated with cold
· Often cause drowsiness and drinking alcohol or taking other antihistamines or sedatives can increase
effect.
· Paradoxical excitability, nervousness and difficulty sleeping sometimes occur in children.
· Contraindicated in patients with glaucoma, kidney or liver disease, prostatic hypertrophy and pregnant
or breast-feeding.
1st gen 2nd gen

Rapid onset and short duration Slow onset and long duration
Highly lipophilic Less lipophilic
Diphenhydramine Q6-8h Cetrizine Q24h
Fexofenadine Q12h 60 mg, SR Q24 120mg
No decongestant Desloratadine is approved for relief of
nasal decongestant.
Drug of choice to allergic rhinitis.
PM AM or day time use
Can use for allergies, anaphylaxis, Allergies, common cold and runny nose
common cold, runny nose, and as
sedative.
Motion sickness and antiemetics
Antitussives. Dextromethorphan indicated only for dry, unproductive coughs when congestion is not present.
· Contraindicated in patients with chronic, persistent cough, patients with lung disease and in women
who are pregnant or breast-feeding
Decongestants: pseudoephedrine, Questions Alerts!

phenylephrine Phenylephrine or pseudoephedrine with MAOi cause
· Oral agents are more hypertensive crisis.
effective but caution in 2) Systemic decongestant in normotensive patient BP increases
patients with heart disease, only in high doses. Whereas high BP patient increase BP in
hypertension, thyroid normal doses.
disease, diabetes, glaucoma 3) topical decongestants SEs are mainly local and >3-5 d can
and prostatic hypertrophy, rebound congestion.
patients taking
antidepressants, and women who are pregnant and breast feeding.
· Topical agents can cause rebound congestion if used for more than 3 to 5 days.
· Oral decongestant should avoid in first trimester of pregnancy.
ORAL DECONGESTANT TOPICAL DECONGESTANT

Pseudoephedrine, phenylephrine, Oxymetazoline 0.05%
ephedrine
Po Nasal drops, and spray, ophthalmic solutions
Schedule II OTC
decongestant For sinus and red eye
As decongestant from colds, flu, hay fever, &
sinusitis.
AVOID WITH MAOI (- BP) AVOID WITH MAOI (- BP)
Expectorant. Guaifenesin is the only one available in Canada

· Adverse effects are rare.
· Overdose can cause nausea and vomiting
· Contraindicated in patients with chronic, persistent cough, patients with lung disease and in women
who are pregnant or breast feeding.
Antihistamine: To treat Allergies, Allergic rhinitis, Question Alerts!

Insomnia, Motion sickness, Nausea and vomiting. 1) Dextromethorphan concurrent with
Precaution. driving, operating machine, anticholinergic MAOi, SSRIs, TCAs can cause serotonin
side effect, and constipation. syndrome
Diphenhydramine or dimenhydrinate is the drug of 2) Diphenhydramine can be taken 25-50 mg
choice for motion sickness. Q4-6h PRN
Meclizine have long half-life is the drug of choice in 3) All of the antihistamine are taken once
pilots and navigator. daily, except?
Decongestants. pseudoephedrine, xylometazoline,
saline drops
· Congestions and cough, shortness of breathe.
· Caution. Uncontrolled blood pressure, uncontrolled diabetes, glaucoma.
· DI. MAOi is not taken with oral decongestants.
Antitussives: dextromethorphan, codeine used to treat cough or dry cough.

Drug interactions: MAOi and SSRI can cause serotonin syndrome.
Expectorants: Guaifenesin used to treat productive cough (cough with sputum).
DEXTROMETHORPHAN CODEINE Guaifenesin

Contraindicated in children <6 Contraindicated in children For mucus and phlegm
years age. <12 ages use only
The Common cold
Common cold: self-limiting viral infection

· Involves mainly the nose, throat and chest
· Transmitted from person-to-person through sneezing, coughing, hand-to-hand contact and contact with
objects handled by a person with cold
· No cure for the common cold
· Available treatments lessen the severity of symptoms
Most frequently caused by:

· Rhinovirus (30-50%) and coronavirus (10-20%)
Less frequently caused by:

· Respiratory syncytial virus (RSV), Adenovirus, Para influenza, Enterovirus
Infection is transmitted by:

· Hand to hand (Virus contact nasal mucosa) and via aerosol particle.
Signs And Symptoms
· First sign is usually sore throat, described often as dry or scratchy sensation
· Rhinorrhea and nasal congestion follow the sore throat.
· Fever is common in children, but not in adults
Prevention:
· Wash hands often
· Cover mouth while coughing
Avoid direct contact with contaminated objects

Treating the common cold
· No cure for common cold. Remedies that may help relieve some of the discomfort
· Stay at home if possible and rest in bed
· Drink plenty of fluids (up to 8 glasses of water or other fluid a day). Hot liquids are particularly helpful
for a stuffed up nose
· Keep the air around you well humidified to make breathing easier
Pharmacological Treatment
· Salt water gargles and throat lozenges – soothing to a sore throat
· First generation antihistamines – relieves rhinorrhea and watery eyes
· Topical and oral nasal decongestants – relieves stuffy nose and sinuses
· Oral decongestants more effective than topical but produces more adverse systemic effects
· Expectorant, guaifenesin – treats productive cough with chest congestion
· Dextromethorphan – to suppress dry, unproductive cough
· Analgesic/antipyretic – for body aches and fever in adults
· Zinc – controversial but zinc gluconate lozenges may reduce some symptoms of common cold but may
cause nausea and impart bad taste
Recognizing A Common Cold
Typical signs and symptoms:

· Sore throat: often dry, scratchy feeling rather than a painful feeling
· Runny or stuffed up nose: appears just after sore throat. Nasal discharge is clear and watery at first and
become thicker as cold progresses
· Watery eyes: common in early stages of cold
· Headache and sinus pain: discomfort usually arises from inflammation of the sinuses
· Dry cough: usually follows the nasal congestion. Becomes watery as the cold progresses
Fever
Fever: Body temperature, which is above the normal range (37oC) resulting from an elevated thermoregulatory
set point in the anterior hypothalamus.
Signs and symptoms.

· Mild fever can cause chills, dehydration, headache, and
Question Alerts!
loss of appetite, nausea and vomiting.
1) Children less than 6 months should be
· High fever in children can cause convulsions (febrile referred to doctor for all fever symptoms.
seizures) while in adults can cause confusion or even
delirium. Neurological damage can occur at body
temperatures of 41.7 ᴑC (107 ᴑF) and greater.
Differential diagnosis: Hyperthermia, increase in body temperature without an increase in the thermoregulatory
set point.
· Sponging with tepid water may soothe but won’t reset the hypothalamic set point
· Alcohol sponge is not recommended
· Remove all excess clothing and bedding to allow for heat dissipation
· Give fluids to ensure adequate hydration
· Antipyretics – reduce body temperature by reducing the hypothalamic set point to normal
· Don’t administer ASA in infants, child or teenager because it can cause Reye’s syndrome
1. Acetaminophen – effective antipyretic
· Treatment of choice for fever in infants, children and teenagers

· Patients with liver disease or who consume 3 or more alcohol containing drinks per day should consult a
physician before taking acetaminophen.
2. Acetylsalicylic acid (ASA) – useful antipyretic in adults

· Can cause stomach irritation leading to heartburn, bleeding and ulcers
· Has marked antiplatelet effect
· Patients with asthma or kidney disease or taking other medications should consult a physician before taking
ASA
3. Ibuprofen – fever in adults, children and infants

· Can cause stomach irritation, leading to heartburn, bleeding and ulcers
Allergic Rhinitis (Hay fever)

· Acute inflammation of the mucous membrane of the nose usually accompanies the common cold
· Hypersensitivity response to airborne allergens mediated by immunoglobulin IgE. (Mediated by Ig E)
· Allergic rhinitis can be seasonal or perennial
· Seasonal allergic rhinitis begins in spring and ends in fall.
· Perennial allergic rhinitis is caused by allergens present year-round, such as house dust, mites, animal
dander, cockroaches, and indoor molds.
Allergens Pollens, molds, house dust mites, cockroaches, and insect allergies stimulate the release of chemical
mediators such as:
§ Histamine Allergic rhinitis Symptoms
§ Leukotrienes LTC 4 , LTD 4 and LTE 4 , Runny nose, Pruritis of eye ear and
§ Prostaglandins D 2 , throat, Sneezing, Cough
§ Kinins No fever and no sore throat
Watery eyes, Fatigue
Risk factors:
· Gender, childhood, male, age before 20 years (80%), family history
of atopy increases risk for rhinitis, asthma and eczema
Environmental control: Pollens, Molds, House dust mites, Animals and Insect allergies
Treatment:
· Antihistamines; sneezing, itching of eyes, ears, nose, and throat, runny nose, tearing.
· Decongestant; desloratadine relieves nasal congestion.
· Corticosteroids
· Mast cell stabilizer
Others: Anticholinergics, Antileukotrienes, Mast cell stabilizers, Sodium cromoglycate (side effects: sneezing,
nasal stinging, irritation, bad taste in the mouth
Influenza (Flu)
Caused by viral infection. Two types of virus cause serious infections Influenza A (most common and more
severe) and Influenza B. Effects are on the superficial epithelium of the airway tract.
Symptoms. Dry cough, sore throat, nasal discharge. Chills and fever (immune response), and sweat, muscle
pains, weakness/fatigue.
Flu mist nasal spray can be used in children.
Persons at high risk of flu

· Persons over 65 year’s age.
· Any resident of nursing home or other care facilities regardless of age.
· Adults and children with chronic cardiac or pulmonary disorders sever enough to require regular medical
condition.
· Adults with chronic condition such as asthma, COPD, diabetes mellitus, cancer, immunodeficiency or
immunosuppression, renal disease, anemia or hemoglobinopathy.
· Children over 6 months of age to 2 years.
· Pregnancy
Flu vaccine contraindications

· Less than 6 mo age
· Allergies to eggs (can be given in clinic in doctor supervision)
· Person with flu symptoms should avoid flu vaccine until symptom resolve.
Treatment
· Nasal decongestants
· Antihistamines
· Antitussive
· Expectorants
Flu shot are given annually
· Influenza season between October through April
· Immunization season from October through November
Sinusitis
§ Inflammation of sinus in response to infection or allergy and may be influenced by anatomical
abnormalities.
§ Sinusitis is more common in children.
Caused by (70%): S. pneumonia, Influenza, Catarrhalis
Symptoms persist more than three months consider as chronic sinusitis: Caused by
· H. influenza (50%, S. aureu, P. aeruginosa, Fungi (diabetic patient)
Treatment:
· Nasal decongestants, Antihistamines, Antitussives, Expectorants and Analgesic
Drug of choice:
· Acute sinusitis: Amoxicillin
· If allergic to b-lactamsàTrimethoprim/Sulfmethoxazole (TMP/SMX)
· Ref: Formulary for general practice drug of choice, p.104, 1998
Pharyngitis
Inflammation of pharynx. (Part of other illnesses cause by infections)
Viral pharyngitis: Epstein-bar infection, Influenza, Common cold, Measles, Vericella
· Allergic rhinitis, Sinusitis, Or allergies.
Bacterial pharyngitis: Beta hemolytic streptococcus (Group A Strep-GAS) (15-30%)-during winter or early spring.
Symptoms:
· Sore throat
· Fever, headache
· Swollen lymph nodes, usually in neck
· Runny nose
Medications: Nasal decongestants,Antihistamines, Antitussives, Expectorants, Analgesic
Treatment:
· Bacterial pharyngitisàPenicillin V
· If allergic to lactams –Erythromycin base (adults), erythromycin estolate (children)
· Ref: Formulary for general practice drug of choice, p.98, 1998
Cough
Symptoms of many respiratory diseases. Can result from many chemical or mechanical effects.
Common causes of cough are: Asthma, Chronic bronchitis, Congestive Heart Failure (CHF), Drugs (eg. ACE
inhibitor), Emphysema, Foreign body, GERD, Post nasal drip, Upper/lower Respiratory Tract infection.
Treatment: antitussive such as Dextromethorphan, expectorants:
Antitussives (for cough): Non-narcotics antitussive: Dextromethorphan, Diphenhydramine
Narcotic Antitussive: Codeine and hydrocodone

Codeine is used in children age >12 year and older.
Dextromethorphan: Widely used in OTC cold remedies to suppress non-productive cough

P.O onset 15- 30 min
Duration 3 to 6 hours
Used in children > 6 year age.
Side effects: Nausea, Drowsiness, Dizziness

Contraindications: CNS depression will increase if drug used with: Alcohol, Narcotics, Sedatives-hypnotics,
Barbiturates, and depressants.
Narcotics Antitussive:
Codeine: 15-30 mg of dextromethorphan = 8 -15 mg of codeine
Side effect: Drowsiness, Sedation, Constipation (Stimulant laxative bisacodyl or senna), nausea, and vomiting
Expectorants
§ Gauifenesen (extract of tar)
§ Ammonium chloride
Expectorants reduce sputum viscosity and allow more effective removal of secretions from the respiratory tract.
Gauifenesen (extract of tar)

Mechanism:
· Increase ciliary action
· Fluid from the respiratory tract less viscous
· Facilitate the removal of mucus

· High doses cause emesis
Side effects. Rare (drowsiness, nauseas, vomiting)
Ammonium chloride:
Mechanism: Irritant to stomach, Causes reflex increase in airway mucus secretions. High doses will
cause acidosis in individuals with renal failure
Decongestant
Topical decongestants. Oxymetazoline and Xylometazoline
· Decrease nasal airway resistance and nasal blood flow, but usually do not cause systemic
sympathomimetic action.
· Act rapidly within 10 min
· Lead to rebound nasal decongestion (rhinitis medicamentosa) which usually occurs 5-10 days of
treatment.
· Short term treatment, 2-3 days
· Topical: Onset of action 5-10 min.
· Phenylephrine, Naphazoline, and Xylometazoline
Side effects. Local burning sensation, Sneezing, Dryness of the nasal mucosa. Bradycardia, Tachycardia,
Hypertension
Nasal decongestants. Phenylephrine, and Propylhexedrine
Systemic decongestants:
· Pseudoephridine, Epinephrine, Phenylephrine and Phenylpropamine
· Cause nasal vasoconstriction and decreased nasal edema within 30 minutes and continues for 6 hours
(regular formulation)
· Oral (onset of action 30 min)
· Caution with patient, Hypertension, heart disease, hyperthyroidism, diabetes, narrow angle glaucoma,
BPH.
Side effects. CNS stimulation (mild), Insomnia, Headache, Irritation, Tachycardia or palpitation, Increase of BP in
hypertensive patient. Affects blood sugar levels in diabetics.
Contraindication. Uncontrolled hypertension, Severe coronary artery disease, MAOI, Glaucoma, BPH
Tips
1. glaucoma 2. hypertension crisis 3. runny nose
4. uncontrolled BP 5. diabetes 6. sore throat
7. BPH 8. watery eyes 9. sneezing
10. low grade fever 11 self-limiting viral infections of 12 malaise
rhinovirus (30 to 50%) & corona virus
(10 to 20%)
· Common cold is caused by? (self-limiting viral infections of rhinovirus (30 to 50%) & corona virus (
)
· Common cold symptoms(runny nose, sore throat, watery eyes, sneezing, low grade fever & malaise) (
)
· Contraindications of oral decongestants ( )
· MAOI + sympathomimetics like pseudoephedrine give --> ( )
· Echinacea purpurea probably can be effective in the prevention and treatment of common colds in adults.
· Expectorants examples are? à
· Topical antihistamine examples à
· High risk groups for flu vaccine à
· Who should NOT take flu vaccine à
· Flu vaccine is taken every à
· When is the flu season in Canada à
· Flu immunization season à
· Contraindications of antihistamines à
· Cautions of oral decongestants à
· Nonpharmacological treatment common cold? Bed rest, Drinking plenty of fluids and Humidifying
the air
www.Pharmacyprep.com OTC Drugs for Nausea
72
OTC drugs for Nausea, Vomiting,
Diarrhea Constipation, and
Hemorrhoids
NAUSEA & VOMITING
Non-prescription anti emetic drugs
· Dimenhydrinate is used for all types of nausea and vomiting (N&V) (except post chemotherapy N&V).
Given 30 min before exposure
· Meclizine is used for all types of N & V
· Promethazine
· Diphenhydramine is alternative for dimenhydrinate
· Pyridoxine (vit. B 6 ) used only for pregnancy induced N&V (PANV)
· Scopolamine: used only for motion sickness
· Ginger root
Sedation is common side effects of non-prescription antiemetic drugs (except pyridoxine). If alertness is
required, scopolamine or promethazine + ephedrine or dexamphetamine (used by airline pilots).
Pregnancy associated nausea and vomiting also known as “Morning Sickness”.
Self-care measure
Alter diet emphasize on small & frequent meals, avoid fatty or spicy foods.
· Eat at all times of the day when nausea is less severe.
· Eat before getting up from bed (in the morning).
· Discontinue iron supplements (temporarily) because this causes nausea and vomiting.
· Ginger root 250 mg qid may reduce nausea and vomiting.
Nonprescription
· Dimenhydrinate use only for 2 to 3 days refer to physician if ineffective.
· Pyridoxine (vitamin B 6 ) can be used alone. No side effects & drug interactions.
Prescription
· Drug of choice Diclectin (pyridoxine 10 mg + doxylamine).
Opioid induced nausea and vomiting (OINV)

Opioid induced nausea and vomiting is caused by stimulation of chemoreceptor center and decreased GI
motility.
Alter administration schedule (make sure nausea does not interfere with meal).
· If pain does not decrease, attempt an increase in opioid dosage (pain could be caused by nausea and
vomiting).
· Switch to another narcotic drug
· Use other anti-emetic. Metoclopramide (drug of choice), and prochlorperazine, diphenhydramine,
dimenhydrinate, ondansetron, haloperidol.
Post chemotherapy nausea and vomiting (PCNV)

Alter diet (emphasize on small & frequent meals. Avoid fatty or spicy foods).
Non-prescription medicines are not useful. Prescription medicines are metoclopramide, dronabinol also known
as THC (cannabinoids) and prochlorperazine.
Low emitogenic drugs: Treatment start with dexamethasone as needed.

Delayed nausea and vomiting: The drug of choice for moderate emitogenic is dexamethasone
Drug of choice for acute emitogenic is 5HT 3 antagonist ondansetron+ dexamethasone.
High emitogenic drugs: The drug of choice for high nausea and vomiting is dexamethasone + ondansetron +
aprepitant
Anticipatory nausea and vomiting: The drug of choice is benzodiazepine (lorazepam).
Motion sickness
Self-care measures
· Avoid eating large meal within 3 hours of travel.
· Avoid dairy products or food high in protein content, high-calories, or high in sodium before travel.
· Avoid alcohol, smoking and bad smells.
Treatment
For short duration of exposure, dimenhydrinate is effective for most patients. Diphenhydramine is an
alternative. Take oral medication at least 60 min in advance. Because motion induces gut stasis. The second
dose can be used after 6 hrs.
Scopolamine Trans dermal patch: Placed behind ears. 1 patch every 72 h, can be removed and reused within 72
h but should rotate site of application.
· Side effects include constipation, dry mouth, blurred vision, skin rash, disorientation, delirium.
· Should not be used in children.
DIARRHEA
Management
· Rehydration and maintain electrolyte balance can reduce diarrhea symptoms
· Children: Continue breastfeeding & oral rehydration solution (ORS) should be offered; otherwise,
discontinue all food and drinks and give ORS.
· Give ORS as soon as diarrhea begins until diarrhea is less frequent
· Rapid re-feeding should immediately follow rehydration

· If diarrhea with vomiting, give ORS 15 ml every 10 to 15 minutes (using a spoon).
· Oral rehydration therapy (ORT) is the most effective treatment for children with acute diarrhea.
· Pregnant: Maintain fluid intake. Loperamide is safe in pregnancy.
· Elderly. Prompt rehydration is essential.
· Fruit juice pop, or tea with sugar are not suitable due to high carbohydrate content.
Symptoms of dehydration: Dry mouth (increased thirst), crying without tear, sunken eyes, less or low frequency
or decreased urination and skin turger. Sunken soft spot in infants. Feeling weak and lightheadedness.
Sweating or frequent urination is NOT a dehydration symptom.
Treatment
Nonprescription
Loperamide (Imodium):
· Not given to children under 2 years old also in children less than 12 years old without doctor’s advice.
· Not recommended for acute dysentery/infections diarrhea (bloody stool with fever).
· SEs include abdominal cramps, drowsiness, dry mouth, and skin rash.
· Maximum dose is 16 mg/day (4 mg start then 2 mg after each loose bowel movement).
Attapulgite (Kaopectate) may be used for drug-induced (mild to moderate) diarrhea. Not to be used for less than
2 days.
Bismuth Subsalicylate
· The bismuth subsalicylate (BSS) should be avoided in patients taking anticoagulants, salicylates, probenecid,
or methotrexate.
· Avoid in NSAIDs or ASA allergies
· Not for children less than 2 years old due to Reye’s syndrome
· Used in chronic diarrhea, for travelers diarrhea & H. pylori management
· SEs. include black tongue and stools, and tinnitus
Psyllium (Metamucil)
· Should be taken within 2 hours of other medications because it reduces absorption of other medicines
· Should be taken with at least 250mL water to prevent fecal impaction and/or esophageal obstruction
Prescription
· Cholestyramine – for treatment of bile acid induced diarrhea
· Codeine – for patients who do not respond to non-prescription medicines
· Clonidine – for diarrhea associated with opioid withdrawal and diabetic neuropathy
· Diphenoxylate with atropine (Lomotil) less effective than loperamide
· Octreotide – for chemotherapy-induced and AIDS-associated diarrhea
· Herbal and other Remedies:
· Herbal – chamomile, carob, marshmallow, slippery elm, bayberry
· Probiotics – live microorganism (bacteria and yeast)
· Refer to physician if diarrhea does not improve in 48 hours with high fever, blood in feces, severe pain in
belly, children less than 6 months old, with vomiting for more than 4 to 6 hours with sign of rehydration;
more than 6 BM in one day.
Most cases, diarrhea in children is self-limiting and non life threatening.

Focus on dehydration with ORT.
Breast feeding should be continued during episodes of diarrhea.
If not breast feeding appropriate food should be continued (avoid BRAT " banana, rice, apple sauce, toast' diet.
is complex carbohydrate diet). After 24 hr normal condition can resume normal diet. take 7-10 days to become
stools completely formed.
If child vomiting and diarrhea does not stop in 4-7 hr should receive medical attention.
NONINFECTIOUS diarrhea: Drug induced diarrhea could be caused by:

· Antibiotics
· Chemotherapeutic agents
· Anti-inflammatory agents (NSAIDs, Colchicine)
· Anti-arrhythmic (Quinidine)
· Anti-hypertensive (Beta-blockers, ACE inhibitors)
· Antacids (Mg-containing antacids, ranitidine, omeprazole)
· Miscellaneous; Misoprostol and theophylline
TRAVELLERS DIARRHEA caused mainly by E. coli, Shigella sp and Campylobacter jejuni

Prevention.
· Hot and cooked meals, cooked vegetables (no salad or no fresh salad).
· Peeled fruits, boiled/bottled water, carbonated beverages without ice cubes, pasteurized milk (properly
stored).
· Bismuth sub salicylates as prophylactic agent.
· Typhoid vaccine recommended for travelers.
· Cholera vaccine for healthcare workers in endemic areas.
Nonpharmacological: Children and elderly should use oral rehydration solution. Adults maintain hydration with
canned juices, purified boiled or bottle water, clear salty soup, carbonated water.
Prevention: Dukoral vaccine can be recommended by pharmacist. Prior to departure, travelers should see
physician for appropriate antibiotics.
Treatment (prescription)
· Drug of choice is ciprofloxacin 500 mg BID X 3 days
· Alternative azithromycin, and cefixime.
· Cotrimoxazole of limited use due to widespread resistance
CONSTIPATION
Self-care measures
· High-fiber diet (for children less than 2 years old should have dietary levels of fiber equal to or greater than
their age + 5 g/day, 25 to 30 g intake for adults).
· Minimum fluid intake of 1500 ml daily. Moderate physical activity.
· Regular toilet routine (children should be encouraged to defecate 5 to 15 min after meal).
· Heed the urge to defecate, weight loss for overweight patients.
· Prune and other juices with sorbitol may also help.
Drug inducing constipation.

· Anticholinergic agents: antidepressants, antipsychotics, antiparkinson's (levodopa).
· Cation containing agent’s aluminum containing antacids, sucralfate, CaCO 3 , and Ca supplements,
bismuth, and iron supplements.
· Other drugs. Verapamil, clonidine, diuretics, cholestyramine, NSAIDs, opiates, vinca alkaloids,
sympathomimetics agents, and ganglion blockers.
Pharmacological treatment: laxatives

Bulk-forming (psyllium, bran, and methylcellulose)
· Adsorb water to soften the stool and increase the bulk, which stimulates peristalsis.
· Should be taken with at least 250 mL water to prevent esophageal obstruction and/or fecal impaction.
· Side effects include flatulence, bloating. Safe to use in pregnancy.
· Contraindication in patients with fluid restriction and mechanical obstruction of the GIT.
· Not to be taken within 2 hours with other medications because it reduces drug absorption.
Osmotic laxatives. (Lactulose, and glycerin)

· Mechanism: Retains water and allow the stool to pass easier through the bowel.
· Osmotic laxative preferable for constipation in infants and children.
· Lactulose not tolerated by most patients because of too much sweetness in taste. Can be used by
diabetic patients.
· Side effects include flatulence, abdominal cramps, and N&V.
· Contraindicated in patients on galactose free diet.
· Taken with fruit juice or milk only to improve palatability.
· Lactulose is the drug of choice for hepatic encephalopathy, because it absorbs ammonia.
· Glycerin: Softens the stool and lubricates the bowel by increasing water retention (osmotic properties)
in the intestinal lumen. Also stimulates rectal contractions. SEs rectal irritation.
Saline laxatives (Mg hydroxide, and Mg sulfate)

· Mechanism: Same mechanism of action as osmotic laxatives.
· Mg hydroxide (Milk of magnesia).
· Side effects: Diarrhea, dehydration and electrolyte imbalance, hypermagnesemia
· Contraindicated: Patients with cardiac or renal disease
· Chilled before administration to increase palatability
· Mg sulfate (Epsom salt)
· Na phosphate (Fleet enemas)
· Best administered on an empty stomach, 30 min AC or HS
· SEs. includes hyperphosphatemia, hypocalcemia, hypokalemia, hypernatremia
· CIs. for pregnant and lactating women.
· Enemas
· It is not recommended in children <2 y and caution in children below 2-5 y.
· Not recommended in Na restricted patients
· Use with caution in patients with renal or cardiac disease
Stimulant laxatives
· Mechanism: Increase the secretions of water and ions into the lumen and stimulate the bowel wall to
contract. (Produces rhythmic muscle contractions in intestine). Recommended if osmotic laxative is fail
or not tolerated.
· Side effects: abdominal cramping. Can cause dependency.
· Senna
· May discolor the urine from red to pink or brown to black, excreted into breast milk.
· The drug of choice for opioids induced constipation
· Faster onset of action than bulk laxatives.
· Bisacodyl
· Preferred stimulant laxative for long term use in patients on H 2 antagonist and should not be taken
within 1 h of antacids.
· Tablets should not be crushed, or broken, or chewed (swallowed whole).
· Cascara sagrada (“sacred bark”)
· CI: In children
· Excreted in breast milk
· May discolor urine red to pink or brown to black
· Castor oil
· Not recommended in children <2 yrs
· CIs. in pregnancy due to purgative action
· Used in emergency procedures
· Stool softener. (Docusate sodium)
· Soften hard stools
· Used in combination with bulk laxatives
· Primary rule is in prevention of constipation
· SE: include abdominal cramps, diarrhea, nausea, and rash.
· Lubricant/Emollient, mineral oil. not recommended in children < 1 y old

· Warning: Can decrease absorption of fat-soluble vitamin (ADEK)
· Increase anticoagulant effect due to decrease absorption of vitamin K
· Risk of lipid pneumonitis
· Can lead to hepatotoxicity
· Can cause anal seepage and perianal discomfort
· Should be taken on empty stomach
** Best Laxatives for:

Infants: Recommended: glycerin supplement, lactulose or sorbitol (as stool softener)
Children: Mg hydroxide, mineral oil, lactulose and sorbitol, polyethylene glycol.
· NOT recommended: enemas, mineral oil, stimulant laxative

Pregnancy: Bulk-forming agents, stool softener, osmotic, or Mg laxatives
Avoid: stimulant laxative, mineral oil, castor oil
Breastfeeding: Bulk forming and osmotic laxatives (1st line therapy),
· Mg Sulfate, cascara and Senna (2nd line therapy)
Cancer patients: Stimulant laxatives with enemas intermittently; avoid bulk laxatives
Elderly patients: Lactulose or glycerin supplements (initial treatment)
· Bulk laxatives for prevention; stool softener
· Avoid stimulant and saline laxatives Long-term use (in opioid patients)
· Bisacodyl (with physician supervision)
** See physician if no BM for 7 days, pain or bleeding in Question Alerts!
rectum, fever, pain in belly, and feeling of vomiting. Simethicone is an antiflatulant
Flatulence (Gas) and Cramps

Non-prescription treatment
· a-D-galactosidase is taken with 1st bite of food
· Lactase; taken with or before ingestion of lactose
Simethicone: The simethicone acts by preventing bubbling of liquids in the stomach. Does not absorb from
GIT. Does not have significant side effects.
· Peppermint, garlic, ginger are alternative therapy.
**Refer to physician if symptoms persist for more than 1 to 2 weeks or non-prescription therapy is ineffective.
Hemorrhoids (Pile): Abnormally swollen veins in the rectum and anus, caused by too much pressure in the
rectum forcing the blood to stretch and bulge the walls of the veins, and sometimes rupturing them.
Treatment.
· Anti-inflammatory agents. Hydrocortisone 0.5% (should not be used >7 days).
· Astringent. ZnO (relieves irritation and burning sensation), calamine (5 to 25%). Hamamelis water (witch
hazel) 50% gel available as pads or wipes.
· Local anesthetic: Dibucaine 0.5 to 1% ointment/cream, Pramoxine 1% ointment
· Antiseptics. Domiphen (0.05% cream/ointment).
· Protectants. Glycerin, white petrolatum and ZnO.
· Vasoconstrictor. Phenylephrine 0.25% gel.
· Wound healing. Shark liver oil 3% ointment/cream 66 mg supp. yeast 1% ointment
· Pregnancy: Correct constipation and taking sitz bath.
· Analgesic: Menthol, and camphor.
Prevention.
· Avoid constipation
· Increase fiber diet, fluids, and physical exercise
· Regularize stool habits and minimize strain and time on seat
Intestinal worms. (Pinworm, ascariasis, and whipworm)
PINWORM
Question Alerts!
Nonpharmacological measure
Pinworm self care
· Take shower every morning.
· Regular cleaning or bedding, nightclothes, under wear and hand towels.
· Hand wash, and nail cleaning mainly before meals.
· During week the following treatment, all family members should wear cotton underpants. (Washed in soap
water). Worn day and night change twice daily.
· Cleaning of floors of sleeping place.
· Clean bedroom articles, curtains where high concentration of eggs.
· Avoid shaking linens, curtains before wash.
· Avoid thumb sucking in children.
· Not effective. Cleaning or vacuuming entire house or washing sheets every day is probably not effective to
prevent re-infection.
· Avoid sharing dishes.
· Avoid sharing undergarments
All close contacts should be treated. Avoid treatment in pregnancy.
Prevention. Proper hygiene
Treatment: Drug of choice pyrantel pamoate

· Side effects: Nausea, vomiting, dizziness, headache, and anorexia
· Avoid in pregnant and with liver disease
· Liquid should be shake well before use.
Pyrvinium pamoate
· SEs. Nausea, vomiting, abdominal pain, photosensitivity
· Tablets should be swallowed whole to avoid staining the teeth
· Will color stool red for 24 to 48h after dose; also stain vomitus and clothes
Piperazine adipate: Can be used in pregnancy

Prescription.
Mebendazole
· Drug of choice (100 mg single dose, repeated after 1-2 weeks)
· For adults and children >2 y
· SEs. abdominal pain and diarrhea
· Taken with meal
Tips
1 Psyllium 2 Diclectin Vit B6 + 3 Docusate sodium + senna or bisacodyl
Doxylamine
4 Dexamethasone 5 Ciprofloxacin 6 Benzodiazepines
7 Bismuth subsalicylate 8 uncooked food 9 contaminated water
10 ice cubes 11 fresh salads 12 dry mouth
3 sunken eyes 14 less frequent urine 15 loss of skin turger
16 crying without tears
· DOC for pregnancy induced nausea and vomiting ( )
· DOC for low emitogenic chemotherapy induced N& V( )
· DOC for delayed chemotherapy induced N&V( )
· DOC for anticipated nausea and vomiting ( )
· symptoms of dehydration ( )
· traveler’s diarrhea mainly caused by? ( )
· black stools and tongue is side effect of? ( )
· DOC for traveler’s diarrhea ( )
· DOC in pregnancy for constipation ( )
· DOC for opioids induced constipation ( )
· What is the drug of choice for pregnancy induced nausea and vomiting à
· What are the self care measures recommended for N&V associated with PCNVà
· DOC for low emitogenic chemotherapy induced N&V à
· DOC for delayed chemotherapy induced N&V à
· DOC for anticipated nausea and vomiting à
· Symptoms of dehydrationà
· Traveler’s diarrhea mainly caused by à
· Black stools and tongue is side effect of à
· What type of food should be avoided by travelers to prevent infectious diarrhea à
· Drug of choice for travelers’ diarrhea à
· What are the most important self-care measure is recommended relieve constipation?
· Drug of choice in pregnancy for constipation?
· Drug of choice for opioids induced constipationà
· What are the self-care measures to relieve hemorrhoidsà
www.pharmacyprep.com Analgesics and Topical Pain Relievers
73
Analgesics, and Topical Pain Relievers
Questions Alerts!
· NSAIDs side effect and maximum dose
· Triptans mechanism and onset of actions (sc is fastest)
· Migraine prophylaxis. Amitriptyline, propranolol, verapamil, and nortriptyline.
Conditions Types of pain

Migraine Throbbing pain
Angina Thrusting pain, can cause referred pain to left arm & finger
Neuralgia Nerve pain, numbness, burning, tingling
Ulcers Epigastric pain
Liver cirrhosis Upper right quadrant
Referred pain (visceral pain) Pain perceived a location other than the site. (e.g. angina)
Appendicitis Lower right quadrant
Urinary tract infections Flank pain (between ribs and hip)
(pyelonephritis or pelvic)
HEADACHE
TENSION MIGRAINE CLUSTER
Associated with Unilateral headache (throbbing pain), often A series of relatively short
stress, tension etc. No associated with nausea and vomiting. Decrease cyclical pattern or cluster.
nausea and vomiting. quality of life by interrupting activities. This can be painful and can
Associated with nausea and vomiting, triggers by wake up from sleep.
light, smell, noise, and food etc.
Headache: Generally, headache is characterized as tension, cluster and migraine.

Tension: Associated with stress, tension etc. No nausea and vomiting.
The drug of choice for tension headache? Acetaminophen or NSAIDs.
Cluster headache: A series of relatively short cyclical pattern or cluster. This can be painful and can wake up
from sleep.
The drug of choice is verapamil.
Migraine
· Unilateral headache (throbbing pain), often associated with nausea and vomiting. Decrease quality of
life by interrupting activities.
· Associated with nausea and vomiting, triggers by light, smell, noise, and food etc.
Migraine Therapeutic Plan

· Mild migraine attacks. ASA, ibuprofen, adjunctive dimenhydrinate, metoclopramide, and acetaminophen
(weak evidence).
· Moderate attacks. NSAID, triptans (the drug of choice), dihydroxy ergotamine (DHE) (weak evidence).
Combination drugs acetaminophen + codeine+ caffeine, ASA + codeine + caffeine or ASA + butalbital +
caffeine.
· Severe and ultra severe attacks. Butraphanol, chlorpromazine, dexamethasone, ketorolac, meperidine,
metoclopramide, prochlorperazine, and sumatriptan.
Mild Migraine attacks

· ASA. Dose 650 to 1300 mg q4h buffered or soluble tablets (not enteric coated)
· Ibuprofen: Dose 400 to 800 mg q6h, rapid dissolving tablets available
· Acetaminophen: Weak evidence of benefit. Monitor AST/ALT.
Moderate to severe migraine attacks

· NSAIDs (ibuprofen, naproxen, mefenamic acid).
· Triptans 5HT 1b/d agonists: Sumatriptan, rizatriptan, zolmitriptan, almotriptan and naratriptan.
Sumatriptan side effects are chest tightness. Contraindicated: pregnancy.
· Oral 25 to 50 mg, MR q2h (max 200 mg/24 h).
· Intranasal 5 to 20 mg, 1 spray in 1 nostril per dose.
· MR in 2 hours (max 40 mg/day). Do not shake and prime.
· SC 6 mg, MR 1 hr/max 12 mg/24 hr.
· Take at first sign of headache or at aura.
· If NO relief first dose, DO NOT use second use. If it relieved, and second attack, use only after 2 hours.
Avoid other triptans use with 24 hours.
TRIPTANS. All triptans available as tablets.

Sumatriptan subcutaneous is fastest onset of all triptans 10-15 min
Oral disintegrating tablets (wafers), rizatriptan and zolmitriptan
Inter nasal spray. Sumatriptan and zolmitriptan.
Dosage forms Half- MAOi &
life SSRI, SNRI Propranolol Cimetidine
Sumatriptan Tab, sq, spray 2.5hr ü

Zolmitriptan RDT, wafers, spray 3 hr ü ü
Naratriptan tab 6 hrs
Rizatriptan RDT, wafers 2-3 hrs ü ü
Fravotriptan tab 26 hrs
Almotriptan tab 3-4 hrs
Combination analgesics
· Acetaminophen 300 mg + codeine 8 mg + caffeine 15 mg (Tylenol #1)
· ASA+ codeine + caffeine (222)
· ASA+ butalbital + caffeine (Fiorinal). Regulated as control drug part 2.
Migraine prophylaxis: Propranolol, atenolol, metoprolol, nadolol, verapamil, amitriptyline, nortriptyline,

topiramate, valproic acid, divalproex sodium and carbamazepine. Venlafaxine and pizotifen (serotonin
antagonist) and lithium.
Low Back Pain

· Avoid unnecessary bed rest for uncomplicated back pain. As well as premature physical therapy.
· For acute uncomplicated low back pain, NSAIDs are effective for pain relief particularly during the first few
weeks.
· For back pain and chronic soft tissue pain, tricyclic or other types of antidepressants have equivocal efficacy,
but may be useful for their antidepressant effect.
Pharmacological treatment Question Alerts!

· Acetaminophen Low back pain? Keep normal
· NSAIDs: ASA activity, and minimize bed rest.
· Skeletal muscle relaxant (chlorzoxazone, methocarbamol)
· Acetaminophen + methocarbamol (Robaxacet)
· ASA + methocarbamol (Robaxasal)
Sports Injuries
Goals of therapy.
· To reduce acute symptoms (pain, inflammation) and recurrences
· To correct contributing factors (e.g. malalignment, muscle weakness)
· To return the athlete’s weight-bearing capability, flexibility, range of motion, strength and proprioception to
normal
· To enable that athlete to participate comfortably and fully in all pre-injury activities
General approach
· R – Rest the injured part
· I – Ice application to the injured part for 15 to 20 minutes ≥4 x/day for the 48 hours or longer.
· C – Compress the injured part with elastic bandage if there is swelling.
· E – Elevation
· Other injuries requiring immediate medical attention eye, head, and nosebleed.
· Along with the R-I-C-E therapy ASA or NSAIDs could be used for short period for pain and swelling.
· Note: A patient with DVT and injury should not follow the full “RICE Therapy” because ice and compression
could lead to stasis hence rests and elevation of limb would be options for such kind of patient.
1. Introduction to Wounds
2. Prevention and Management of Venous Leg Ulcers
3. Prevention and Management of Pressure Ulcers
4. Prevention and Management of Diabetic Foot Ulcers
Pressure Ulcers: Also known as decubitus ulcers (rectal ulcer), and bedsores.
Common sites of pressure ulcers are buttocks, thighs, back, ankle etc.
Ulcer care.
· Wound debridement, wound cleansing and dressing of wound.
· Note that for wound cleansing, antiseptic agents/hydrogen peroxide and other wound cleaners may be toxic
to the wound and should be avoided.
· Cleansing or irrigation of wound should be done with normal saline.
Stages of Symptoms treatment
pressure ulcers
Stage 1 Skin unbroken but inflamed Skin sealants
Stage 2 Skin is broken to epidermis or dermis Hydrogel
Stage 3 Ulcer extends to subcutaneous fat layer Moist saline gauze

Stage 4 Ulcer extends to muscle or bone Moist saline gauze
Multiple sclerosis
Immunomodulators. Glatiramer, interferon beta1a, interferon beta 1b, fingolimod (spingosine-1-phosphate
receptor agonist), dimethyl fumarate.
Adhesion molecule inhibitor; Natalizumab
Anti-CD52 monoclonal antibody. Alemtuzumab
Tips
1. Propranolol 2 NSAIDS or 3 Triptans, alternatively
Acetaminophen ergot alkaloids
Avoid prolong bed 5. Throbbing pain; feels 6 Unilateral
4. rest hitting w/ a hammer headache
7 Nausea & vomiting 8. 5HT1 b/1d agonist 9 R-I-C-E
10 Amitriptyline 11 Valproic acid 12 Verapamil
· What are the symptoms of migraine headacheà

· What is drug of choice for acute migraine attackà
· What are the drugs used to treat migraine prophylaxis -->?
· What is prophylaxis is recommended for migraine in-patient experiencing 3 to 4 migraine attacks every
month and having constipation à
· What is mechanism of action of triptans à
· General approach for sports injuries ( )
· What drugs are used for migraine prophylaxis? ( )
· What are recommended self measures for back pain? ( )
· What is the treatment for back pain? ( )
· Migraine pain is? ( )
· Pressure ulcers also known as à
· Mechanism of muscle relaxants à
· Drugs used in multiple sclerosis à
Select True or False statements

· A 45 yo man diagnosed with benign prostatic hyperplasia, and migraine prophylaxis. Propranolol
appropriate therapy for migraine prophylaxis?
· after taking sumatriptan migraine headache does not relieve than double the dose of sumatriptan
· after taking sumatriptan migraine headache does not relieve than decrease the dose of sumatriptan
· after taking sumatriptan migraine headache does not relieve than do not use sumatriptan
www.PharmacyPrep.Com Asthma and COPD
74
Asthma and COPD
Questions Alerts!
· Asthma triggers
· Mild, Moderate and Severe asthma therapy
· Theophylline drug interaction
Predniosone side effects and dose
Asthma. Chronic inflammatory disorder of the airways, ↑ airways responsiveness, causes reversible
obstruction. In asthma esinophils, mast cells and T lymphocytes plays significant role. Sensitivity, and
hypersensitive of airways to specific and non-specific stimuli, such as air, odour, allergens, virus etc.
Diagnosis:
Spirometer (preferable method of diagnosis) (Forced expiratory volue per second (FEV 1 normal >80%)
Peak flow meter (home monitoring)
Bronchoprovocation challenge test, using methanacholine or histamine if diagnosis is in doubt.
Sequence of asthma therapy SABA PRNà ICS à LABA à LTRAà PO CTS à iv CTS.
MILD MODERATE SEVERE EMERGENCY
FEV >80% FEV1 60-80% FEV1 <60%
SABA PRNà SABA PRNà ICS SABA PRNà ICS à LABA iv CTS + O 2
ICS à LABA à LTRAà PO CTS
Asthama management
A = Adrenergic agonist (beta2 agonist)
S = Steroids (inhaled)
T = LABA; LTRA, Theophylline,
H = Hydration (IV steroids)
M= Mask O 2
A = Anticholinergics
Beta 2 Adrenergic Agonist

MOA: beta 2 stimulation causes increase camp in smooth muscle leading to bronchodilation
Short acting beta 2 agonist (SABA)

· Inhaled: Albuterol (salbutamol), terbutaline, isoproterenol
· Onset within 5 min
· Therapeutic use as relieve branchoconstriction, the acute symptoms of cough, wheezing and chest tightness,
asthma emergencies and exercise induced asthma.
· Regular use can lead to decline in lung function.
Oral Beta 2 agonist: Albuterol (salbutamol), and Terbutaline

More SE and less bronchodilation effect than inhaled preparations
Long acting beta2 agonist (LABA)

· Inhaled: Formoterol (full B 2 agonist), salmeterol (partial agonist)
· Onset: 14 min and duration upto 24 hours. Regular BID treatment
· Therapeutic use Maintenance therapy and exercise induced asthma NOT for acute. Used in patients already
taking corticosteroids
· Formoterol can be used for acute and maintenance
Anticholinergic: Ipratropium bromide: useful as alternative for patients who are already susceptible to tremors
or tachycardia from B 2 agonist
Tiotropium is long acting anticholinergic once daily, it is administered by handihaler
Corticosteroids
· ICS: Benefit ↑ lung function, ↓ airway hyperreponsiveness, ↓ symptoms of excerbations
· Max clinical effects in 2 to 4 wks. Fluticasone in few days
· Given 2 to 4 pf BID
· Side effects: oral pharangeal candidiasis, dysphonea from vocal cord myopathy, and cough.
· Mouth rinsing and using spacer can minimize SE,
Oral corticosteroids (Po CST)

TU: Severe asthma with intensive airway inflammation
Leukotriene antagonist. Montelukast and Zafirlukast

· Only oral available
· TU: Asthma maintenance (steroid sparing agents), and ASA induced asthma
Chronic Obstructive Pulmonary Diseases
COPD: Chronic obstructive pulmonary diseases; COPD is due to chronic obstruction of the airway. There are two
types of COPD.
· Emphysema (high altitude sickness)
· Chronic bronchitis.
Emphysema is a disease in which the small air exchange sacs (alveoli) in the lungs become permanently enlarged
and damaged (alveoli walls destroyed) thus decreasing oxygen absorption and resulting in shortness of breath.
Chronic bronchitis is an inflammation of the airways that causes lungs to produce excessive amounts of mucus
(phlegm), associated with chronic productive cough. This reduces the flow of air to the lungs. Onset age 45
years.
Risk factors that cause COPD: Smoking (80 to 90%), Family history, Occupational exposures to certain ducts and
fumes, Air pollution, Second hand smoking and asthma,
Diagnosis: spirometer (FEV1 = <80%), peak flow meter, bronchoprovocation test.

alpha1-antitrypsin level: for family history of COPD
Chest X-ray
pulse oximetry+/- arterial blood gas (SpO 2 ): determines the requirement oxygen therapy.
SpO 2 >95% = normal
SpO 2 91-94% = borderline
SpO 2 85-90% = Immediate intervention
SpO 2 <85% = administer 100% oxygen
COPD FEV1
MILD >/- 80%
MODERATE <50 TO <80%
SEVERE <30 TO <50%
VERY SEVERE <30% OF PREDICTED
*Canadian Thoracic society guidelines.
Recommend: flu vaccine (annually) and Pneumococcal vaccine
Treatment sequence for COPD?

SABD (salbutamol and ipratropium)
¯
LABD (ANTICHOLINERGIS & LABA+/- ipratropium)
¯
Theophylline
¯
Oral steroids or inhaled ICS and antibiotics (exacerbation)
SABD = salbutamol, ipratropium
LABD = salmeterol, formeterol, tiotropium
ASTHMA AND COPD DRUG AVIALBLE DOSAGE FORM

Drug Dosage form
Salbutamol MDI, turbuhaler, nebulizer
Montelukast Chewable and granules
Theophylline Tab, Xl tabs
Advair (fluticasone/salmeterol) Diskus, turbuhaler
Symbicort (Budosenide/formeterol) Turbuhaler
Zenhale (mometasone/formeterol) Inhaler
Tips
1. Salbutamol 2. short acting beta2 agonist 3. Terbutaline
4. Corticosteroids 5. 5Prednisone/ 6. Zafirlukast
Prednisolone
7. Theophylline 8. Diphenhydramine 9. Codeine

10. Ephedrine 11 Cromolyn sodium 12 Ipratropium bromide
13. Exercise 14 Emotional stress 15 Cold air
16. montelukast
· Rescue medications or treatment of acute exacerbations and prevention of exercise-induced asthma (

)
· What drugs relieves the symptoms of asthma, chronic bronchitis and emphysema ( )
· Which drug may interact with MAOIs and cause a dangerous rise in blood pressure ( )
· Rinsing mouth and using spacer can minimize the side effect of this drug ( )
· It is use for the treatment of skin diseases, rheumatic disorders and certain blood disorders ( )
· It is the drug of choice for Aspirin induced asthma ( )
· This drug should be use with caution in patients with peptic ulcer and seizure diseases ( )
· It is a non narcotic antitussive ( )
· What narcotic antitussive that causes addiction and tolerance ( )
· What causes slight increase in blood pressure and has both alpha and beta effects ( )
· What is use for prophylactic treatment and not used for acute asthma attack ( )
· What is the drug of choice for chronic obstructive pulmonary disease ( )
· Indications of short acting beta 2 agonists include à
· Indications of long acting beta 2 agonist include à
· Sequence of asthma therapy: SABA prn à
· When LABA are initiated in asthma patient? à
· What are asthma triggers? à
· What is NOT a trigger? à
· Leukotrienea areà
· Theophylline clearance in 3 year old? à
· Omalizumab is? à
www.pharmacyprep.com Smoking cessation
75
Smoking Cessation
Questions Alerts!
· Nicotine withdrawal and overdose symptoms
· Bupropion mechanism and side effects
· Varenicline (Champix) mechanism and side effects.
Pharmacological aids to smoking cessation
Nicotine Replacement Therapy (NRT) Prescription Therapy
Nicotine gum Nicotine patch Bupropion Varenicline

Nicorette Nicoderm or (Zyban) (Champix)
Nicorette plus Habitrol
Nicotine inhaler
Nicotine spray Question Alerts!
What is NOT nicotine withdrawal
symptoms? Myalgia
Nicotine withdrawal symptoms: Severe craving, anxiety or irritability, restlessness, nervousness,

difficulty with concentration. Sleep disturbance, headaches, increase appetite (weight gain) or eating
habit and constipation.
Symptoms to be monitored in case of nicotine withdrawal are severe craving, Anxiety or irritability
· Restless, nervousness, difficulty with concentration
· Sleep disturbance, headaches,
· GI symptoms, increase appetite or eating behavior
· Symptoms are peak after 24 to 72 hours of last cigarette
· Smoking is single most common preventable cause of death and disability in Canada
Nicotine overdose symptoms: Palpitation (heart racing), difficulty in breathing, nausea, vomiting, and diarrhea.
Drug of choice
· Bupropion could be used with or without nicotine replacement therapy.
· Nicotine inhaler is contraindicated if allergy to nicotine or menthol. Use with caution in patients with
bronchospastic disease.
· If patient has CVS disease, weight less than 45 kg, or smokes less than ½ pack/day begin with 17 to 24
for 6 weeks then decrease to 7 mg/24h for 2 weeks.
· NICOTINE BASED: Nicotine patch or gun; Stop smoking completely.
· NON-NICOTINE BASE: Bupropion (Zyban); Can smoke for first two weeks of treatment.
Nicotine replacement therapy

· Almost every smoker can benefit from using
nicotine replacement therapy. In pregnancy Question Alerts!
and heart or blood vessel problems, its use 1) Nicotine patch storage conditions? Room
requires precaution. Temp
· The nicotine replacement therapy available 2) Available dosage forms of nicotine
in patch, gum, nasal spray and inhaler forms. replacement therapy? Inhalers, spray, gum,
patch and lozenges.
Nicotine Patch
· Most smokers should start using a full-strength patch (15 to 22 mg of nicotine) every day for 4 weeks
and then a weaker patch (5 to 14 mg of nicotine) for another 4 weeks.
· Directions for use. At the start of each day, place a new patch on a part of your body between the neck
and the waist. Put the patch on a new spot each day to lessen skin irritation.
· Treatment period. The patch is usually used for up to 8 weeks.
· Side effects. Some people who use the patch get a rash on their body where the patch is placed. Skin
rashes are usually mild and easily treated. Moving the patch to another area of the body helps.
Nicotine Gum
· Start using the 2 mg dose. However, start with 4 mg gum if you smoke more than 20 cigarettes a day.
· Use gum if you smoke as soon as you wake up in the morning.
· Have severe withdrawal symptoms when you don't smoke.
· Have tried to quit on a lower dose and failed.
· If you are a very light smoker (less than 10 to 15 cigarettes a day)
Directions for use.

· The gum must be chewed in a special way to make it work. Chew it slowly until you feel a "peppery"
taste. Then stop chewing and move the nicotine gum between your cheek and your gum. Each piece of
nicotine gum should be kept in your mouth for about 30 minutes.
Treatment period.
· A regular schedule (at least one piece of nicotine gum every 1 to 2 hours for 1 to 3 months) may give the
best results. Some people don't chew enough pieces of gum a day and or they don't chew the gum for 8
weeks. They might not get the most benefit from nicotine gum.
· Maximum 6 months
Side effects: mild side effects such as hiccups, stomach upset or sore jaws. Most of these side effects
disappear if the gum is used correctly.
Nicotine Nasal Spray

· Directions for use: Apply one spray in each nostril. Use the spray one to two times each hour while you
are awake. Use the spray at least 8 times a day. Don't use it more than 40 times a day.
Side Effects:
· The nasal spray may cause nasal irritation, diarrhea and a fast heart rate. If you have hay fever or sinus
infection.
Nicotine inhaler
· Directions for use: Inhale from a cartridge when you have a desire for a cigarette. Use no more than 16
cartridges a day for up to 12 weeks.
Side Effects:
· You might have irritation of throat and mouth when you first start to use the inhaler. It might make you
cough. You should get over this after a while.
Nicotine lozenges: available
Bupropion (Zyban)
· 150 mg daily x 3 days than 150 mg BID for 7 to 12 weeks.
· Begin 1 to 2 weeks before the selected quid date.
· Monitor in hypertensive patients
Contraindicated in:
· Pregnancy
· History of seizure
· Anorexia nervosa
· Bulimia nervosa
· Precaution in taking MAOi’s
Side effects: More common. Dry mouth (19%), and insomnia. Less common, hypertension, myalgia,
arthralgia, dizziness, tremor, somnolence, bronchitis, pruritus, rash, and taste prevention
Varenicline (Champix)
· Mechanism of action: Act on nicotinic receptors. It is partial agonist that binds selectively to alpha4, beta 2,
nicotinic acetylcholine receptors with a greater affinity than nicotine.
· Used in combination with quit smoking and education. Helps to relieve the craving and withdrawal
symptoms associated with stopping smoking.
· Starting dose is 0.5 mg once daily for the first 3 days, then 0.5 mg bid for next 3 days and then 1 mg bid daily
thereafter. Treatment for 12 weeks. Stop smoking in 1 to 2 weeks of starting this med.
· Side effects: Dizziness, drowsiness, dry mouth, flatulence (passing gas), gingivitis, headache, Nausea (16%),
Vomiting, rash, insomnia, unusual weakness and constipation.
nausea (40% vs 8% placebo); and the pooled terms of: abdominal pain (17% vs 3% placebo), and
increased blood pressure (11% vs 6% placebo).
· Contraindications: Pregnancy, breastfeeding, and children.
Drug Interactions: Insulin, NRT, warfarin, and theophylline. Contact doctor if constipation, abdominal pain,
appetite changes.
Tips
1. Severe craving 2. Anxiety or irritability 3. Dry mouth
4. Insomnia 5. Restlessness 6. Nervousness
7. Difficulty with 8. Sleep disturbance 9. Headaches
concentration
10. Nicotine gum 11. Nicorette 12. Nicorette plus
13. Nicotine patch 14. Nicoderm or habitrol 15. Champix
16. Increase appetite or 17. Bupropion 18. Room temperature
eating behavior
· What drugs are used for smoking cessation? ( )

· How nicotine patches are stored? ( )
· What is incorrect about nicotine patch? ( )
· The types of nicotine dosage forms? ( )
· Nicotine replacement therapy products ( )
· NRT used in combination with quit smoking education (True/False)
· Nicotine withdrawal symptoms ( )
· This could be used with or without nicotine replacement therapy ( )
· More common side effect of bupropion ( )
· Varenicline mechanism of action ( )
· Bupropion side effects include?
· Bupropion contraindications?
www.pharmacyprep.com Sleep Related Disorders
76
Sleep Related Disorders
Questions Alerts!
· Insomnia self care (avoid exercise before bedtime)
· Benzodiazepine classification and side effects
Some examples of primary sleep related disorders:

· Insomnia (10-30%)
· Restless Leg Syndrome (RLS) (2 -15%)
· Sleep Apnea (4-8%)
Insomnia Non-pharmacological SLEEP HYGIENE

· Sleep hygiene · Keep regular sleep wake schedule for 7 days/wk.
· Relaxation exercises · Restrict sleep time to average sleep time.
· Sleep restriction and stimulus · Avoid extensive horizontal rest or daytime napping
control. · Get regular exercise every day (avoid exercise before bedtime).
· Aerobic exercise. decreases · Avoid heavy meals just before bedtime.
daytime rest and increase · Do something which is boring before bedtime Avoid before
exercise bedtime; Caffeine, alcohol, heavy meals, hungry. Minimize noise
and light, high temperatures. Minimize drinking fluids. Avoid
vigorous exercise 2-3 hours before bed.
Nonprescription therapy Prescription therapy

· Diphenhydramine · Benzodiazepines (SHORT ACTING)
· Valerian · Barbiturates (NOT used because of narrow therapeutic index).
· Melatonin · Antidepressants (TCA’s)
· Chloral hydrate
Restless leg syndrome (RLS): Desire to move limbs (creepy crawly sensation, itchy, aching feeling, cramp and
painful) with motor restlessness, worse at rest, temporary relief by activity, and worse at night. Diagnosis based
on periodic limb movement (PLMS). Rule out; iron deficiency, peripheral neuropathy, Akathisia (drug induced or
positional): peripheral neuropathy, nocturnal leg cramps.
Treatment:
The drug of choice selective dopamine agonist ropinirole or pramipexole.
Selective Dopamine D2 agonist; ropinirole (D 2 agonist) 0.5-3 mg; pramipexole (D 2 and D 3 agonist) 0.12 -0.15 mg.
www.pharmacyprep.com Sleep Related Disorders
Bromocriptine 5 to 20 mg
Levodopa-carbidopa 25 to 400 mg
Opioids, benzodiazepines, gabapentin, carbamazepine, clonidine, baclofen, Vitamin B 12 and folate.
Sleep apnea: Cessation of breathing lasting at least 10 seconds (no spontaneous breathing can cause multiple
episodes of low oxygen or hypoxia) with desaturations and arousals. Symptoms are snoring, gasping for air,
stopping breathing at night, memory complaints, irritability, depression, morning headaches, sexual problems,
restless sleep, and sedation or tiredness during the day.
Treatment: Continuous Positive Airway Pressure (CPAP) machine
Tips
1 Temazepam 2. Short acting 3 Lorazepam
4 Midazolam 5. Zopiclone 6 Oxazepam
7 Diazepam 8. Triazolam 9 Exercise before bed
· What benzodiazepine is indicated for initiating sleep? (4 and 8 )

· What drug may cause less rebound on withdrawal? ( 5 )
· What is inappropriate self care measure ( 9 )
www.pharmacyprep.com Eating Disorders
77
Eating Disorders
Questions Alerts!
· Definitions of bulimia (loves to eat then purge) and anorexia (fear of eating) nervosa.
· Drug related problems orlistat
Anorexia Nervosa: It is characterized by deliberate loss of weight (to <85% of expected weight), refusal to
maintain normal body weight, fear of weight gain and amenorrhea.
There are 2 sub types. Restricting, non-purging, excessive exercise or fasting.
Drug of choice is domperidone, metoclopramide reduce the feeling of fullness.
Bulimia Nervosa: It is characterized by repeated episodes of binge eating followed by inappropriate

compensatory behavior such as self-induced vomiting, misuse of laxatives, diuretics, emetics, other medication,
long time fasting, or excessive exercise.
There are two subtypes. Purging by using laxatives, or emetics. DOC is SSRI, and venlafaxine
Medications: Appetite suppressant. Diethylpropion
Satiety enhancers
· Sibutramine (Meridia). Serotonin and norepinephrine reuptake inhibitor (SNRI)
· Lipase inhibitor. Orlistat (Xenical): Gastric lipase inhibitor reduces 30% fat absorption
Cannabinoid type 1 receptor antagonist.

Rimonabant: Blocks the central and peripheral effects of the endocannabinoid system mediated by cannabinoid
(CB)-1 receptors.
Drugs that are used for weight loss therapy Drugs that cause anorexia (loss of appetite)
Orlistat Metformin
Sibutramine Amiodarone
Bupropion CNS stimulants (amphetamine and methylphenidate)
Topiramate
Liraglutide (Saxinda), Exenatide
Drugs that increase appetite Drugs that cause weight gain

TCAs Insulins
Corticosteroids TCAs
Oral contraceptives MAOI
www.pharmacyprep.com Eating Disorders
Sulfonylurea's Antipsychotics (2nd gen) clozapine, olanzapine

Sulfonylurea's
Meglitinides
Note: Long acting Insulin Detemir (weight neutral or weight loss)
Tips
1. Domperidone 2. Metoclopramide 3. Orlistat
4. Anorexia nervosa 5. Bulimia nervosa 6. Purging
7. Non purging 8. Loves to eat 9. Fear of eating
· It is characterized by deliberate loss of weight ( )

· Excessive exercise or fasting ( )
· Reduce the feeling of fullness ( )
· It is characterized by repeated episodes of binge eating ( )
· Intestinal lipase inhibitor ( )
· Using laxatives or emetics ( )
· What type of eating disorder patient use purging? ( )
· Bulimia nervosa =
· Anorexia nervosa =
www.PharmacyPrep.Com GERD, Ulcers, IBD, and IBS
78
GERD, Ulcers, Inflammatory Bowel
Disease, Irritable Bowel Syndrome
Questions Alerts!
· GERD symptoms and heart burn management
· Ulcers: causes of ulcer and triple therapy to treat H. pylori ulcer
· Ulcerative colitis and Crohns disease treatement
· Irritable bowel syndrome symptoms
This chapter review the symptoms and therapy of gastroesophageal reflux disease (GERD), ulcers, irritable bowel
syndrome (IBS), and inflammatory bowel disease (IBD).
GI CONDITIONS SYMPTOMS
GERD (heartburn) Substernal burning, regurgitation & pain radiating
to throat
Ulcers Epigastric pain, GI bleeding
Irritable bowel syndrome (IBS) GI upset, diarrhea, constipation. (NO GI bleeding)
Crohn's and Ulcerative colitis Abdominal pian, diarrhea, GI bleeding
(Inflammatory bowel disease IBD)
gastrointestinal diseases with GI bleeding?
Gastroesophageal Reflux Disease: It is defined as (heart burn, regurgitation) chronic symptoms or mucosal
damage produced by the abnormal reflux of gastric content into the esophagus.
Risk factors: High fat meal, carbonated drinks, pregnancy, obesity and increase age.
Symptoms: Heartburn (pyrosis), it is a substernal burning or pain that may radiate to the neck, back, or throat.
Symptoms occur shortly after meals or when reclining after meals, or upon lying down at bedtime. Often
symptoms may awaken one’s sleep. Symptoms are exacerbated by eating a large meal (high fat meals), and
bending over.
Nonpharmacological measures
· Quit smoking & reduce alcohol and caffeine intake

· Take smaller, more frequent meals (avoid high fat and spicy foods)
· Avoid exercising/bending on full stomach
· Avoid tight fitting clothes around the waist
· Elevate head of bed 10 cm high
· Avoid lying down after meal
**Refer to the physician if symptoms are more than 2 weeks. Avoid smoking and limit alcohol and caffeine
intake.
Gastroesophageal reflux disease (GERD) is categorized into mild and severe.

· Mild GERD, relief of symptoms is with antacids, alginates or non-prescription strength H 2 RA.
· Severe GERD PPI are the drug of choice. Use PPI for 2 to 4 weeks
· The goal is to raise the intragastric pH 4 during periods when reflux is likely to occur.
PATTERN OF HEARTBURN RECOMMENDATION

Intermittent, short term heartburn needing fast relief. Antacids, alginates
Longer lasting episodes (night time) needing a longer duration H 2 RA
of effect.
Predictable heartburn after trigger food. H 2 RA taken before unavoidable exposure.
Frequent heartburn or episodes needing treatment for more PPI
than few days
Pharmacologic treatment: Symptom control for minor or intermittent symptoms use antacid alginic acid, or
H 2 RA. Moderate to severe GERD use PPI, H 2 RA, or metoclopramide.
· Food induced GERD, drug of choice is H 2 RA.
· Special populations: Pediatric. Non-prescription H2 RA are CI. in children <12 yrs old.
· Pregnant can be used antacids, except sodium bicarbonate
· Elderly. Can use antacids and non-prescription H 2 RA
Antacids: Al hydroxide, Ca carbonate, and Mg hydroxide and Na bicarbonate

· Al hydroxide SEs constipation and hypophosphatemia (in prolonged use)
· Ca carbonate SEs constipation, milk alkali syndrome (hypercalcemia); causes rebound hyperacidity.
· Mg hydroxide SEs diarrhea and hypermagnesia (in renal failure)
· Shake or chew well; quick acting with cathartic effect. Should be avoided in renal failure and limited use in
elderly due to risk of hypermanesemia.
· Al-Mg combination products, SE; diarrhea (in long term use)
· Na bicarbonate: Not often used because of sodium can be hypertensive.
· All antacids have drug interactions with quinolones, tetracycline, digoxin separate dosing by 2 hours.
Alginic acid: It works as foaming agent. Tablets must be chewed with full glass of water taken when patient is in
upright position. Should not be taken at bedtime.
Prokinetic agent: Metoclopramide and domperidone
H 2 - receptor antagonists (H 2 RA): cimetidine, ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid)
· equally effective: usually effective in mild GERD, BID
· the efficacy is limited by the rapid development of tachyphylaxis & the inability to properly suppress meal-
related acid secretion.
· Step-down therapy: H 2 RAs are instituted after symptomatic relief has been achieved with PPIs
· SE: diarrhea, constipation, headache
· Cimetidine SE: gynecomastia, impotence (rare)
· Famotidine; potent
· DI: Ranitidine: decrease clearance of theophylline, phenytoin and warfarin Cimetidine; CYP450 inhibitors,
· Use H 2 RAs to reduce the “night-time awakening” caused by GERD
Proton pump inhibitors (PPI): omeprazole (Losex capsules, MUPS, tablets), esomeprazole (Nexium), lansoprazole
(Prevacid), pantoprazole (Pantoloc), rabeprazole (Pariet)
· Drug of choice in the most GERD patients
· Side effects: abdominal pain, diarrhea and headach.
· take ½ hour before meals: the most effective acid suppression, once daily
· acid rebound occurs with discontinuation (tachyphylaxis is not a problem)
· At equivalent doses, available PPIs offer similar efficacy and safety
· DI: ↓ efficacy of drugs requiring an acid medium for absorption (ex. Itraconazole, atazanavir, indinavir)
· Omeprazole: DI; Omeprazole may decrease metabolism of warfarin, diazepam and phenytoin (require
dosage adjustment), and clopidogrel
· Esomeprazole; may confer a modest advantage over other agents for severe erosive esophagitis
· Pantoprazole; rapid onset
· Rabeprazole; ↑digoxin level
Ulcers or dyspepsia (pain sharp 30-60 min after a meal)

and discomfort in the upper abdomen) GI bleeding.
Ulcers are categorized as
Peptic ulcers
· Gastric ulcers; Due to reflux since it has weak pyloric sphincter Question Alerts!
· Duodenal ulcers; Excessive acid secretion from parietal cells Excessive acid
· Acute stress ulcers (Curling’s ulcer). Tumors. secretion cause?
· Pathologic acid-hypersecretory states (Zollinger-Ellison syndrome).
· Chronic peptic ulcer disease is the most commonly caused by H. pylori.
Common Risk Factors: Stress, smoking, alcohol, NSAIDs and H. pylori.
Symptoms: Epigastric pain occurring 1 to 3 hours after meals that is relieved by ingestion of food or antacids is
classic symptoms of peptic ulcer disease. Pain can occur and episodes lasting from weeks to months and may be
followed by variable periods of spontaneous remission and reuccarence.
Diagnostic for gastric ulcer, or duodenal ulcer is Endoscopy or EGD (esophagogastroduodenoscopy)
Treatment of peptic ulcers

The drug of choice to treat pepetic ulcer is PPIs as empiric therapy for 4 to 8 wks.
· For neutralization of gastric acid use antacids. To reduction of gastric secretion use H 2 receptor blocker, and
proton pump inhibitors
· For cytoprotection use sucralfate. For ASA/NSAIDs use prevention with PPI or misoprostol
Treatment of peptic ulcer disease due to Helicobacter pylori, infection.

H. pylori confirmation test is urea breath test (UBT)
· Goal of therapy is to eradicate H. pylori use triple therapy of 2 antibiotics + PPI
· Losec 1-2-3 A. Clarithromycin 500 mg bid + omeprazole +amoxicillin

· Losec 1-2-3 M. Clarithromycin 250 mg bid+ omeprazole + metronidazole
· Hp-Pack
· Quadruple therapy. Tetracycline+ metronidazole + bismuth subsalicylate + Omeprazole
· clarithromycinàLosec 1-2-3M. If patient is allergic to amoxicillin or if patient is having diarrhea or if
patient is more prone to having anaerobic infection
Gastritis: The gastric ulcers are associated with a corpus predominant (diffuse predominant) gastritis. This
pattern gastritis is associated with low acid output, gastric atropy, and adenocarcinoma.
Inflammatory Bowel Disease (IBD): Consist of two conditions ulcerative colitis and Crohn’s. The ulcerative colitis
mainly colon and chrons disease in all over GI tract.
Causes of inflamatory bowel disease:

· Infection with Mycobacterium and other pathogens
· Genetic factors
· Environmental conditions
· Non-pathogenic intestinal flora
Crohn’s disease: Inflammation is present from the esophagus to the anus but predominantly in the small bowel
or colon. Obstruction of the bowel abscess formation.
Drug of choice to treat mild Crohn's disease 5ASA or oral budosenide.

¯
Drug of choice moderate oral budosenide and severe iv steroid
¯
Drug of choice to treat fistula? Azathioprine or 6-MP, infliximab
Drug of choice to treat NO remission (not cured) from initial therapy? AZA, 6MP, or MTX and in severe biologics
(infliximab, adalimumab, cetrolizumab).
Drug of choice for maintenance therapy? 5ASA, Infliximab, adalimumab, Azathioprine, 6MP.
Ulcerative colitis: Relapsing inflammatory condition in the colon with symptoms of bleeding, urgency, diarrhea
and tenesmus.
· Erosion and ulceration of the mucosa
· Decrease in the number of goblet cells
· Frequent infection secondary to fever and anemia
· Drug of choice in mild to moderate is 5-ASA
· Drug of choice in severe ulcers is oral prednisone
Aminosalicylates. Sulfasalazine and 5-ASA.

· Sulfasalazine metabolized to sulfapyridine + 5-ASA (mesalamine)
· Sulfpyridine has systemic absorption and is responsible for SE’s N/V, headache, anorexia, and folate
malabsorption.
· Sulfa free compounds. Mesalamine (5-ASA), olsalazine (two molecules of 5-ASA linked to diazo bond).
· The side effects experienced with mesalazine and olsalazine are less then sulfasalazine
Irritable Bowel Syndrome (IBS): It is defined as abdominal discomfort associated with altered bowel habits. It is
characterized by symptoms of abdominal discomfort, bloating, cramping, constipation or diarrhea. (NO
BLEEDING SYMPTOM)
Non-pharmacological therapy
· Regulating dietary fibre and lactose intake.
· Stress management.
· Probiotics may help.
· Dicyclomine. It has anticholinergic side effects
· Loperamide: Used for diarrhea
· Magnesium hydroxide: Used for heartburn
· Lactulose: Used for constipation
· Psyllium.Bulk laxative
· Cholestyramine: For patients with bile salts malabsorption
Barium swallow is used for media of esophageous

Barium enema is infused as contrast media for endoscopy diagnostic test for lower GI tract.
Tips
1. High fat meal/ carbonated drinks 2. pregnancy 3. increase age

4. obesity 5 Al antacids 6. Mg antacids
7. Ca antacids 8 Alginic acid 9. Sucralfate
10. Famotidine 11 Cimetidine 12. Omeprazole
13. Esomeprazole 14 Lansoprazole 15. Pantoprazole, Rabeprazole
16. Misoprostol 17 GERD 18. IBS
19. H. pylori 20 Ulcerative colitis 21. Chrons
22. 5-ASA 23 Prednisone 24. Infliximab
25. Ulcers 26 Colon 27. Simethicone
· What are triggers of heartburn or GERD ( )

· Symptoms are heartburn, epigastric pain( )
· What is defined as abdominal discomfort associated with altered bowel habits? It is characterized by
symptoms of abdominal discomfort, bloating, cramping, constipation or diarrhea. ( )
· Symptoms are relapsing inflammatory condition in the colon with signs of bleeding, urgency, diarrhea and
tenesmus. ( )
· Symptoms of inflammation are present from the esophagus to the anus but predominantly in the small
bowel or colon. Obstruction of the bowel abscess formation. ( )
· Takes ½ hour before meals. The most effective acid suppression, once daily ( )
· What gram negative bacteria may cause gastric ulcer ( )
· What is active metabolite of sulfasalazine ( )
· What is an antiflatulence agent ( )
· What antacids may cuase side effect as diarrhea( )

· What antacids may cuase side effect of constipation ( )
· What drug is an isomer of omeprazole ( )
· What drug can cause rare side effects as gynecomastia, impotence ( )
· Do not take with ciprofloxacin, tetracycline, biphosphonates and thyroxin ( ).
· What PPI is rapid onset of proton pump inhibitors ( ).
· Decrease efficacy of drugs requiring an acid medium for absorption( ).
· Usually effective in treatment of mild GERD, as BID ( ).
· Step down therapies are instituted after symptomatic relief has been achieved with PPIs (H 2 RA).
· Lactulose is used in what type of chronic liver disorder à hepatic encephalopathy.
· What drug is an example of ecosanide isà ( )
· Misoprostol is analogue of à PGE 1
· Type of pain in GERD is characterized as à Substernal
· What disease increases bilirubin levels à Jaundice
· What are the side effects of aluminum salts à Constipation
· What are the side effects magnesium antacids àDiarrhea
· H. pylori infection may cause à 25
· What type of hepatitis is chronic à Hepatitis B and C
· What is treatment of hepatitis B, or C? Interferons alpha
· NSAIDs induced ulcers can be treated byà PPI
· Azathioprine or 6-MP cause pancreatitis (3%)
· What is the drug of choice for fistula? Infliximab
· When infliximab is used? Refractory case it means in patient who have continuing symptoms despite the
optimal use of steroids, immunosuppressant (AZA, 6MP, MTX).
· Epsom salt is? Magnesium sulfate
· Ulcerative colitis occurs at? Colon
· An example of antiflatulance agent? ( )
· What vaccine can be used for prevention of traveler’s diarrhea (E. coli, cholera)? Dukoral
· Symptoms of ulcers include? Epigastric pain, and weight loss
· Symptoms of irritable bowel syndrome (IBS)? Bloating, cramping, constipation, and diarrhea, NOT bleeding.
· Symptoms of ulcerative colitis? diarrhea, bleeding, pain
· Symptoms of Crohn’s disease? diarrhea, bleeding and pain
· What test is done to confirm H. pylori? Urea breath test (UBT), Serology and endoscopy.
· Laproscopy is? examination of the abdominal cavity using endoscopy.
· How many days prior patient should stop PPI before UBT? 3 weeks
· What gives fastest relief of heartburn? Antacids
· Antibiotics used for treatment of ulcers? Amoxicillin, clarithromycin, metronidazole and tetracycline. (Not
used are quinolones).
· Adalimunab is used to treat? Crohns disease, and psoriasis)
· Crohn's disease maintenance therapy? Azathioprine, 6-MP, and Methotrexate and infliximab.
PharmacyPrep.com Diabetes
79
Insulin and Antidiabetic Drugs
Questions Alerts!
· Long actin Insulin (glargine)
· Insulin dose management
· Long acting sulfanyl ureas such glyburide, gliclazide and glimepride.
· Metformin side effects like stomach upset and rare SEs lactic acidosis
· Sitagliptine and saxigliptine is DPP4-inhibitor
· Rosiglitazone cardiovascular side effects
· Incretin hormone analogs like Liraglutide
· Acarbose mechanism
This chapter review of insulin therapy for diabetes mellitus and antidiabetic drug for the treatment of type II
diabetes.
Diabetes mellitis, type I and type II.

Type I. Insulin dependent DM (IDDM) 5 Type II. Non-insulin dependent DM (NIDDM) >90%
to10%
Juvenile onset Adult onset (40 yrs)
Destruction of beta-cells in pancreas Milder form
No production of insulin associated with Very strong genetic predisposition
treatment is by diet and insulin. Inability of beta cells to produce adequate insulin and
Ketoacidosis occurs doesn’t meet the body’s requirements.
NOT RELATED TO GENETICS OR FAMILY Mainly due insulin resistance
HISTORY. Family history related or genetic
Autoimmune.
Normal Blood Sugar Levels (BSL)

· Fasting blood glucose 5 to 6 mmol/L (conversion factor mg/dL is 18)
· Random blood glucose <11.1 mmol/L
· Post prandial <11.0 mmol/L
HbA1C is 4 to 6%, Measures past three months blood sugar levels. Used to determine antidiabetic drugs
compliance of patient
Types of Insulin
Ultra rapid Rapid Intermediate Long-acting
Insulin lispro Regular NPH Glargine

Detemir
Types of insulin are categorized by their onset of action, and these relative positions hold true for their
effectiveness and their duration of action as well.
Insulin Duration Onset Peak (hours) Duration of Action
(hours) (hours)
Humalog (H) (lispro) Very short 5-10 30-40 min 2-3 h
synthetic (Fastest) min
SC or iv form
Clear solution
Regular (R) Rapid (short) ½ -1 h 1-3 h 5-7 (dose-dependent;
(suitable for iv dose). Both SC or iv (in may be longer)
human and animal source emergencies)
clear solution
NPH (N) Isophane Intermediate 2-4 h 6-10 h 14-18 hr
Amorphous precipitate of Semilente (30%) not suitable for iv dose
insulin with zinc ion acetate
buffer
Glargine Longest acting 24 hr

Detemir Single daily dose Should not be mixed
with other insulins.
Insulin SE: Weight gain and hypoglycemia, lipohypertrophy at site of injections.
Very Rapid-acting Insulin Analogues: clear Question Alerts!

· insulin aspart (NovoRapid) All insulins are clear solution, except?
· insulin glulisine (Apidra) What types of insulins can be adminstered
· insulin lispro (Humalog) as iv.
Rapid-acting Human Insulin-clear:

· insulin regular (HumulinR, Novoline ge Toronto): 15 min before meal
Intermediate-acting Human Insulin– cloudy
· insulin NPH (Humulin N, Novoin ge NPH)
Long-acting Insulin Analogues: clear

· Clear, don’t mix with other insulins, duration 24 hr (no discernible peak)
· insulin detemir (Levemir)
· Insulin glargine (Lantus); acidic solution (pH4), microprecipitates form (slowly released), NO im or iv.
Mixed (regular/NPH) Human Insulin– cloudy

· Insulin regular/insulin NPH (Humulin 20/80, 30/70), Novolin qe 10/90, 20/80, 30/70, 40/60,50/50)
Mixed Insulin Analogues– cloudy

· Insulin lispro/lispro protamine (Humalog Mix25)
Insulin storage conditions

· Should be stored in refrigerator
· Can be stored at room temperature 28 days (1 month), Except Detemir pen can stay for 42 days.
· Do not shake vigorously
· If you notice turbidity or vapors or precipitation, do not use, discard it
Type 2 DM: HbA1c > 6.5% + hyperglycemia symp; FPG > 7 mmol/L
First line therapy is metformin
If not controlled, then add sulfonylureas, or new antidiabetic drug (sitagliptine,

liraglutide, canagliflozin).
If not controlled 2 drugs, then add 3rd drug or insulin (basal insulin).
At diagnosis A1c > 9% or DKA or severe symptoms of hyperglycemia, the drug of choice is INSULIN.
ORAL ANTIDIABETIC DRUGS

Sulfonylureas; Chlorpropamide, gliclazide (Diamicron), gliclazide long-acting, glimepiride, glyburide (Diabeta)
· Mechanism: Stimulate release of endogenous insulin thus increase insulin secretions.
· SE: hypoglycemia and weight gain avoid obese or over weight patients
· Avoid in sulfa allergies
· CI: pregnancy
· SEs : hypoglycaemia, weight ↑ Question Alerts!
· Chlorpropamide; dose adjustment in real Glimepiride is long acting in 3rd gen sulfanylureas
impairment, once daily long half life Glyburide has the highest hypoglycemia and less
Associated with disulfiram reaction with hypoglycemia with glimipride
alcohol may give nausea, vomiting,
headache, flushing upon ingestion of alcohol. SIADH (Syndrome of Inappropiate antidiuretic hormone) this
leads to edema.
· SE: alcohol-associated flushing, and ↓Na.
· gliclazide – produce an earlier insulin release than others.
· gliclazide long-acting – once daily
· glimepiride (Amaryl) – once daily
· glyburide (Diabeta): dose adjustment in real impairment, lowest risk of cardiovascular events and high
hypoglycemia.
Meglitinides: Nateglinide (Starlix), repaglinide (GlucoNorm)

· MOA: Increase insulin secretions, Decrease post prandial blood glucose levels
· SE: hypoglycemia and weight gain, hypoglycaemia (esp. if not take meal). CI: pregnancy
· May be taken prior to meals (skip dose if you miss meals) à take at first bite of meals
· take 0 to 30min before meal → lowering postprandial glucose levels
· Repaglinide – DI: gemifibrozil (↑repaglinide conc. - avoid)
Biguanides: metformin (Glucophage)

· MOA: Reduce gluconeogenesis, and increase glucose utilization, Increase glucose uptake into cells
SE: Less common but more serious SE is lactic acidosis. No hypoglycemia, can give weight loss. To avoid GI SEs,
start low & titrate up q2-4wk. Metformins rare SE lactic acidosis risk is increased by? Alcohol, renal and hepatic
diseases.
Alcohol in diabetic patient potentiates hypoglycemia
·
· Dose adjustment in real impairment, SE: lactic acidosis, diarrhea (most), VB 12 ↓
· ONLY oral, NO weight↑ → good for obese patient, NO hypoglycaemia on its own. Take with food or after
food
· DI: alcohol (potentiates hypoglycemic effect)
· CI: hepatic impairment, renal impairment, CHF, hypoxemic states patient
· Caution if CrCl 60 ml/min
· Decrease mortality
· Does not cause sulfa allergy
Alpha-glucosidase Inhibitors: acarbose (Glucobay)

· MOA: Inhibit alpha glycosidase intestinal enzymes
· Decrease absorption of starch and sucrose (do not stop absorption of Question Alerts!
glucose) Mechanism of acarbose?
· Decreases the postprandial plasma glucose level Acarbose do NOT decrease
· SEs: It causes bloating and flatulence and diarrhea absorption of glucose
· With meal, not used as monotherapy.
· Meal-time dosing; may take several weeks for maximum effect. Taken
with the first bite of food.
· Maximal effect takes weeks↑ dose q4-8wks
· Sulphanilureas + acarbose
· Does not by itself cause hypoglycemia
· GI intolerance: flatulence >41%, diarrhea >28%, sucrose not absorbed.
Thiazolidinediones (TZDs): Pioglitazone (Actos), and rosiglitazone (Avandia)

Rosiglitazone/glimepiride (Avandaryl), metformin (Avandamet)
· Mechanism: PPAR-g receptors agonist. Increase peripheral insulin sensitivity, and reduce gluconeogenesis.
· Effective in lowering HbA1C
· Contraindications: Liver disease, and CHF
Side effects: Weight↑(most), fluid retention edema 4.8% (HF; HTN), anemia ~1% mild
↑ HDL, NO hypoglycaemia on its own.
· DI: gemifibrozil (↑repaglinide conc. avoid). CI. CHF pts, can use renal impairment pts
· ↑ risk of pregnancy if adequate contraception not used (ovulation resumes)
· NO use with insulin (not approved by health Canada)

· Pioglitazone. ↓ TG, have more +ve lipid effect. More DI than rosiglitazone
· Mon: If baseline ALT is elevated (>2.5 times normal), do not use glitazones
· Rosiglitazone. ↑ LDL Decrease TG, Increase HDL, Once daily with or without food
· Monitor liver function (ALT) when indicated;
· Delayed action… Onset ~2-4wks Max effect in 8-16 wks.
· Rosiglitazone / metformin – associated with overall lower glucose & HbA1c
Dipeptidyl peptidase-4 Inhibitors (DPP-4): Sitagliptin, saxagliptine and linagliptine

Mechanism: Inhibitor of dipeptidyl peptidase enzyme (DPP-4) that enhances the incretin hormone.
· Side effects: Nasopharyngitis DIs. low potential (do not inhibit CYP450), can cause hypoglycemia with
sulfonylureas. Weight neutral.
· Take with metformin, with or without food, do NOT potentiate hypoglycaemia.
· 100 mg once daily taken with or without food.
· Not used in type I diabetes, there is no clinical studies.
Incretin analogs: Glucagon Like-Peptide 1 (GLP1) agonist.

Liraglutide (Victoza): once daily inj. with/without meals
Exenatide: twice daily, 60 min before meals
Exenatide LAR: once weekly with/without meals
GLP-1 is released from GI and act on stomach, liver & pancrease;

Stomach: inhibit gastric emptying time.
Pancrease: ↓blood glucose and glucogon secretion and ↑insulin secretion.
(SGLT2) inhibitor. Sodium Glucose Co-transporter 2

Canagliflozin (Invokana): 100 mg qd, empagliflozin, dapagliflozin
SGLT2 is enzyme in the renal tubule that causes glucose reaborption back into the blood. Therefore canagliflozin
reduces the reabsorption of glucose from renal tubule leading to more excretion of glucose in urine.
Intestinal Lipase Inhibitors. Orlistat (Xenical)

· SE: Diarrhea, steatorrhea, abdominal discomfort, and oily leakage.
· Take with food, impair absorption of fat soluble vitamins (A, D, E, and K).
Antidiabetic Drugs How to take?

Metformin Take with meals
Sulfonylureas Take with meals
Acarbose 30 min before meals/with first bite of meals
Meglitinides 30 min before meals/with first bite of meals
DPP-4 inh With or without food
PPAR-g receptor agonist With or without meal
GLP-1 analogs Before breakfast
Regular Insulin Before meals
SGLT2 inh. Empty stomach in the morning
Tips
Tips format 002: Find answers from the table

1. FBG >7.1 mmol/L 2. HbA1c >7.0% 3. Random >11.1
4. Polyurea 5. Polydipsea 6. weight in Kg/(height in m)2

7. Weight loss 8. Sweating 9. Palpitation
10. Rapid acting Insulin 11. Insulin regular 12. Intermediate (NPH)
13 Long acting insulin 14 Premixed insulin 15. Sulfonyl ureas 1st gen
16 Sulfonyl ureas 2nd gen 17 Meglitinides 18. Metformin
19 Thiozolidinediones 20 Acarbose 21. Incretin enhancers (DPP-4
Inhibitor)
22 Diabetic complications 23 Insulin 24 Intestinal lipase inhibitors
25 Waist line >102 cm 26 Waist line >86 cm 27 Confusion
· What hormone act on cell membrane receptors to increase glucose uptake ( )

· Blood sugar levels if a person is diabetic ( ) HbA1C >6.5%
· Symptoms of hyperglycemia ( )
· Symptoms of hypoglycemia ( )
· All insulins are clear solutions, except ( )
· Sitagliptine and saxigliptine are ( )
· What drug may give lactic acidosis if taken with alcohol and renal diseases, liver disease ( )
· Diabetic complications are retinopathy, nephropathy, cardiovascular diseases, and foot amputation,
except, hepatic cirrhosis ( )
· What waist line that have risk of diabetes in men ( )
· What waist line that have risk of diabetes in women ( )
· What drugs increase glucose uptake ( )
· What drugs increase insulin secretion ( )
· Drugs that should be taken with first bite of meals or effective to treate postprandial blood glucose (
)
· Drugs that are withdrawn due to heart failure side effects ( )
· What drug used for weight loss therapy ( )
· Liraglutide is (incretin hormone analogue)
· What is correct about NPH insulin? Taken BID
· Glitazone mechanism? Increase sensitivity receptor (PPAR-g).
· PPAR-g receptors are located on the cell nucleus.
· Lipohypertrophy is? Accumulation of fat at injection site.
· Lipoatrophy is? Loss of subcutaneous tissue injection site.
Injection site sequence faster absorption to slower absorption? Abdomen, arms, thighs, buttocks). Massage
to the site. Cold insulin absorbs more slowly. Opened insulin vial that has been stored in fridge should be
discarded after 1 month.

· A 65 yo uncontrolled diabetic patient have got foot ulcers. Patient wants to know diabetic foot care. The
pharmacist should refer this patient to Podiatrist? (True)
· premixed insulins Used for stable lifestyle patients (True)
· premixed insulins Can be self adminstered by patient (True)
· premixed insulins Cartridges cannot be exchanged with different mixture of insulins (True)
· premixed insulins is an expensive than insulin (True)
· premixed insulins Require insulin pen to adminster (True)
Pharmacyprep.com Thyroid disorders
80
Thyroid Disorders
Questions Alerts!
· Symptoms of hypothyroidism and hyperthyroidism
· Monitoring of thyroxine. Serum TSH, FT3, FT4
· DI's of thyroid hormone with antacids, Ca, Fe supplements
HYPOTHYRODISM HYPERTHYROIDISM
The drug of choice LEVOTHYROXINE, The drug of choice ANTITHYROID METHIMAZOLE AND PTU
(SYNTHROID, ELTOXIN)
First prescription for 4 to 6 wks.
TREATMENT IF serum TSH >10 Mu/l TREATMENT IF severe hyperthyroid symtpms
Hoshimoto Graves disease
The drug of choice for thyroid toxicosis. Is lugol solution.
HYPO ↑TSH (>10) = ↓ free T 4 <0.6 ng/dL), or (T 4 , T 3 resin uptake) monitor Q 6 go 8 wks.
HYPER ↓TSH = ↑T 3 , T 4
Hypothyroidism. Symptoms that are caused by deficient thyroid hormone production, thus resulting into
slowing down of all body metabolic functions.
Types of hypothyroidism
· Primary hypothyroidism caused by thyroid gland failure.
· Hoshimoto disease. It is an autoimmune disease resulting from cell and antibody mediated thyroid injury.
· The hyposecretion of the thyroid hormone causes myxedema, goiter and cretinism.
· Symptoms: Sensitivity to cold, constipation, bradycardia, and weight gain
· Signs. Dry flaky skin, coarse hair, slurred speech, puffy face, hands, feet, and hearing loss. Decreased libido,
slow return of deep tendon reflexes, if untreated myxedema and coma will develop.
· Diagnosis: Initial test is serum TSH assay and TSH levels are elevated in primary hypothyroidism and low
serum free T 4 .
Pharmacotherapy: Levothyroxin (Eltroxin, Synthroid) and dessicated thyroid hormone.

· Levothyroxine: T 4 dosage, 1.6 µg/kg/day (adults), 12.5 to 25 µg/day (patient with coronary artery disease or
elderly).
· Pregnancy. Dose↑ (thyroid binding globulins↑), check TSH each trimester & 4 to 6 wk after any dosage
adjustment.
· It takes 6 weeks to attain a new steady state
· Take empty stomach. Taken in morning.
· Side effects. Exacerbation of angina and in overdose hyperthyroid symptoms.
· Drug interactions: Absorption↓ by Fe, Ca, Al, Mg, sucralfate separate 2 h, cholestyramine, colestipol
(separate administration by 6 hours).
· Blood sugar control may decline with initial therapy (dosage adjustment of antihyperglycemic agents)
liothyronine, triiodothyronine (T 3 )
· Use for short-term management of patients with thyroid cancer undergoing withdrawal of levothyroxine
(T 4 ).
· In the elderly (because of age) or in patients with coronary artery disease, start with a dose as low as 12.5
mcg/day as tolerated and titrated every four weeks. TSH levels changes after 6 to 8 weeks.
· Iron salts, clacium and sucralfate decrease absorption of levothyroxine thus separate 2 hours. Resins like
cholestyramine, cholestipol separate 6 hours. Do not take aluminium compounds with thyroid preparations.
Dessicated thyroid hormone may contain pork proteins.
Hyperthyroidism: The hypersecretion of the thyroid hormone may cause thyrotoxicosis or Grave’s disease and
Plummer’s disease.
· Type of hyperthyroidism. The hyperthyroidism normaly is divided into two categories: Grave’s disease or
diffuse toxic goiter and toxic nodular goiter.
· Grave’s disease. The most common form of hyperthyroidism. It is an organ specific autoimmune disorder in
which antibodies produced against autoantigens stimulates the secretion of the thyroid hormone. It may
cause protrusion of the eyeballs. Hasimoto’s disease is completely opposite, as the resultant antibodies due
to autoantigens inhibit the secretion of the thyroid hormone.
· Symptoms: Intolerance to heat, and weight loss, weakness and anxiety. Signs. heart palpitation,
nervousness, diarrhea, and tachycardia.
· Diagnosis: ↓serum TSH, (sensitive TSH) and ↑T 4 and T 3
Pharmacotherapy: Anti thyroid drugs (methimazole, propylthiouracil), and lugol solution (KI + I 2 ).
Antithyroid Agents
· Methimazole. MMI, propylthiouracil PTU
· Stop about 5 days prior to a thyroid scan, RAIU or treatment with 131I.
· Side effects: Allergy, rash, agranulocytosis, hepatotoxicity and nephrotoxicity (rare)
· Stop if rash, fever, sore throat (agranulocytosis) or jaundice develop.
· PTU. daily, block theconversion of T 4 to T 3 , DOC. pregnant & lactation women
· MMI: TID
· Anti thyroid drugs (methimazole, propylthiouracil). Both cross the placental barrier and can accumulate in
the thyroid gland of the fetus.
· Methimazole. Monitor TSH sensitivity test. Side effects are cough, fever and agranulocytosis.
· Propylthiouracil is preferred in pregnancy.
· More agranulocytosis seen than that of methimazole. Rapid absorption after oral administration. Drug
choice in pregnancy. Monitor complete blood count
Lugol solution (KI + I 2 ). Given as oral drops, and it may cause stains
Iodine
· Oral Lugol’s solution, iv sodium iodide
· Blocks thyroid hormone production, use in the acute management of severe hyperthyroidism.
· Administer 1 h after PTU or MMI; blocks radioactive iodine uptake
· iv sodium iodide used for thyroid storm
· Lugol’s solution used for thyroid storm & prior to thyroidectomy (2 to 6 drops TID 7d preceding operation),
6.3 mg iodide/drop
Iodine, radioactive
· sodium iodide 131I (Iodotope)
· SE: hypothyroidism, CI : pregnancy, in patients with significant ophthalmopathy – with caution or steroids
· Use to ablate thyroid tissue in patients with Graves’ disease, toxic autonomous nodules and toxic
multinodular goitres
· Giving as single oral dose (usually only one dose required)
Beta 1 -blocker, nonselective: propranolol

Selective
· atenolol, metoprolol
· use adjunctively in the management of Graves’ disease or toxic nodules
· CI: asthma patients
· Propranolol; ↓ the conversion of T 4 to T 3
· Selective Beta1 -blocker; foster onset of action than propranolol
Corticosteroids, systemic
· dexamethasone, hydrocortisone sodium succinate
· Use adjuvant therapy in treatment-resistant cases for hyperthyroidism
· dexamethasone used for thyroid storm
· hydrocortisone used for Myxedema coma
Tips
Tips format 002: Find answers from the table:
1. Bradycardia 2 Hypotension 3 Constipation
4. Diarrhea 5 Dry skin 6 Sensitive to heat
7. Weight loss 8 Weight gain 9 Sensitive to cold
10. TSH < 0.5 11. TSH > 5.5 12 Graves disease
13. Hashimoto disease 14. Thyroxin 15 Methimazole
16. Propylthiouracil 17. Lugol solution 18
· Symptoms of hypothyroidism ( )
· Symptoms of hyperthyroidism ( )
· Hyperthyroidism ( )
· Hypothyroidism ( )
· What is the drug of choice for hypothyroidism ( )
· What is the drug of choice for hyperthyroidism ( )

· What is the drug of choice for hyperthyroidism in pregnancy ( )
· What drug that are taken empty stomach ( )
· Drug absorption is decreased if taken with calcium supp or dairy products, iron, antacids ( )
· What drugs that stain ( )
· Severe fever, sore throat and agranulocytosis are the side effects of ( )
· Calcitonin is stimulated byà
· TSH is secreted from à
· In treatment of hypothyroidism with T 4 have effect on à
· Hypothyroidism is monitored by à
· T 4 metabolized to T 3 by deiodinase enzyme in -->
· Sweating is symptom of à
· Lugol solution is an oral drops of? à
· Thyroxine absorption is decreased by à

· Hyperthyroidism in pregnancy: PTU is drug of choice, with the lowest possible doses used to maintain
the maternal T4 level in the high normal range. (True)
· A 55 yo women using levothyroxin 75 mcg to treat hypothroidism. She is experiencing sweating, heat
sensitive and diarrhea. Indicates overdose. (True)
· levothyroxin take in the morning empty stomach(True)
· levothyroxin take with full glass of milk (False)
· Lugol solution used to treat thyrotoxicosis, (Graves disease) (True)
· hypothyroidism, Total T 4 decrease(True)
· hypothyroidism, Free T 4 decrease(True)
· hypothyroidism, Total T 3 decrease(True)
· hypothyroidism, Serum TSH decrease(False)
· hypothyroidism, Free Thyroxine index decrease(True)
· FT4, TT4, TT3 and FTI decrease in hypothyrodism, only serum TSH increase. For hyperthyroidism, exactly
opposite changes. (True)
· Myxedema; In this disease, the patient may have slow speech, a puffy face, slow pulse, low BMR and
scanty hair. (True)
· Cretinism: The growth and height of the child is stunted. The patient has low BMR and a bloated face.
The patient is also mentally retarded. (True)
· Goitre: It is also known as simple or non-toxic goiter. A dietary deficiency of iodine may be responsible
for this. The neck of the patient is swollen. (True)
· Toxic nodular goiter: It is due to benign neoplasm or adenoma or may be because of long standing
normal goiter. (True)
· Hoshimoto thyroiditis: It leads to hypothyroidism(True)
· Discontinue antithyroid if patient notice even a single rash (Pruritis Maculopapular rashesh associated
with vasculitis)
· Why is it beneficial to add propranolol to a drug regimen of a patient diagnosed with hyperthyroidism?
decrease heart rate, anxiety, tremors, and heat intolerance
PharmacyPrep.Com Contraception
81
Contraception
Questions Alerts!
· Side effects of oral contraceptive pills
· OCP DIs with phenytoin, carbamazepine, topiramate, rifampin, antibiotics.
· OCP CI's. Coronary artery disease, DVT, PE and liver diseases.
· What if patient miss one pill? What to do?
· Emergency contraception like plan B side effects (N&V)
Short term prevention (<1 yr planning for pregnancy) Long term prevention (>1 yr planning for pregnancy)
Barrier methods IUD, Medroxy progestin inj
Combined oral contraceptive pills, Nuvaring
Breast feeding: progestin only
Barrier methods: condoms. Male (latex, polyurethane, lambskin)
· Protect against STIs including HIV (latex condoms only).
· Lambskin: no protection against STIs.
· Latex SEs: hypersensitivity in either partner, use water lubricants (oil-based ↓ integrity).
Condoms: female
· Not to be used with male condoms, shelf-life of up to 5 years.
· inserted up to 8 h prior to intercourse & removed immediately after
Diaphragm
· Side effects: Toxic shock syndrome
· Use with spermicidal, can be inserted 6 h before intercourse & used in breastfeeding women.
· Use silicone diaphragm (allergy to latex).
Sponge
· Side effect: Toxic shock syndrome, spermicidal is released in a sustained fashion for 10 to 12h
· Do not use during menstruation
Cervical cap
· Side effect: Toxic shock syndrome, can be left in place for up to 48h for multiple acts of intercourse.
· Can be used in breastfeeding women, not to be used within 6wk of delivery
Spermicides: nonoxynol-9 (Vaginal Contraceptive Film)
Not effective against HIV or STI
Intrauterine devices (IUD). copper-T IUD (Nova-T, Flexi-T)
Contraceptives, oral combination

· Avoid in lactating women during the first 6 wk postpartum, with caution in the first 6mo postpartum
· SE: chloasma, hypertension, breakthrough bleeding or spotting, N/V, breast tenderness, and mood changes.
· DI. rifampin & griseofulvin use backup barrier method during therapy
· Obesity affects metabolism to compromise contraceptive efficacy. May decrease the effectiveness of
contraceptive.
· "ACHES" danger signal Abdominal pain/Chest pain & shortness of breath/Headaches/Eye problems/Severe
leg pain (DVT).
Diane-35 (EE 35 µg / cyproterone 2 mg)

· Drug of choice in severe acne (Not for birth control)
· Discontinue 3 to 4 mo after signs of acne have completely resolved
Contraceptives, transdermal patch: EE/norelgestromin (Evra)

· Apply a new patch once a wk on the same day of the wk for 3 wks
· If off for >24 h start new patch & use backup method for 7 days
· OCPs→ patch. The first patch on the first day of withdrawal bleeding
· If later than the first day of withdrawal bleeding, use backup method for 7 days
· Depot MPA→ patch, start on day of scheduled injection.
· Not effective. Weight 90 kg or more
· Do not apply on chest.
Contraceptives vaginal ring: EE/etonorgestrel (NuvaRing)

· Contraindication: <6 wk postpartum if breastfeeding
· Do not use diaphragm or cervical cap as backup, vaginal tampons (ok: after removing vaginal ring)
· Can be left at room temperature for 4 mo, 3 wk inside vagina then removed for a 1wk for menstrual periods.
· Left out longer than 3h → efficacy ↓, use backup method for 7 days.
Contraceptives, progestin only oral: norethindrone (Micronor).

· Inhibits cervical sperm penetration by thickening the cervical mucus
· Can use over 35 years old smoker, and intolerate ethenyl estradiol, and patient have unwanted side effects
with COCs, breast feeding, and migraine with neurologic symptoms
· SEs. ectopic pregnancy, irregular bleeding, DOC. Lactating women, contraindication to EE
· Contains 28 tablets of active drugs
Contraceptives: Progestin only injectable: Medroxyprogesterone acetate (Depo-Provera)

· Depot injection, can use in the postabortal state (5 days postpartum), during lactation (6wk postpartum).
· Can use over 35 years old smoker, and intolerate ethenyl estradiol
· Contraindications: Pregnancy, breast cancer.
Side effects: Wt↑, BMD↓ (long-term)
· Injected within first 5days of onset of menses, interval between injections must not exceed 13 wk
· Ovulation & regular menstrual periods may not resume for up to a year after the last injection.
Contraceptives, progestin only intrauterine system (IUS) levonorgestrel (Mirena)

· Inserted within 7 days of onset of menses, remains in place for 5 y.
· Highly efficacious (≤0.2%).
Emergency contraceptive methods: EE 50µg + levonorgestrel 0.25mg/dose (Ovral) and
· Levonorgestrel 0.75 mg/dose (Plan B).
· Side effects: Nausea & Vomiting, dizziness, and fatigue.
· Single dose of 1.5 mg used within 24hr (prevent 95%) can take up to 5 days after unprotected intercourse.
· copper-T IUD (Nova-T) consider up to 7 days after unprotected intercourse
Contraception and breast feeding

· Oral contraception should be avoided in postpartum women and breast-feeding until 6 weeks after delivery.
Barrier contraceptives can be used.
· IUDs should be avoided with 4 to 6 weeks postpartum (until ovulation occurs)
· Progestin contraceptives can only be used during lactation (without increase of thromboembolic events).
Low dose combination of OC’s may be used once the milk supply is well established (progesterone unlike
estrogens do not inhibit the binding of prolactin to its receptors hence no decrease in breast milk, therefore
Progestin is preferred.
Starting OC’s
· 1st tablet either on the day of menses (eliminates the need for alternate means of contraception) or take 1st
tablet on the first Sunday after beginning of menses and use and use extra contraception method for 1st 7
days of OC’s
· Oral contraceptives are best taken in the evening (before bedtime, to decrease the side effects such as
nausea, breast tenderness, chloasma (exacerbated by sunlight when estrogen concentration are high and
can be prevented by the use of sunscreen wide hats).
Missed pills
· If 1 pill, then take as soon as you remember and next pill as per schedule (no need for extra contraception
method). If 1 pill missed take 2 pills next day.
· If 2 pills missed, in a row 1st/2nd week take 2 pills when remember
Question Alerts!
and 2 pills the next day, and use alternative method of
What if missed one pill?
contraception for 7 days from the day missed.
· If 2 pills missed in 3rd week, discard pack and start new pack or
continue a pill everyday till Sunday and then start a new pack and use alternate method for 7 days.
· The same applies for 3 pills in a row for any week.
Tips
Find answers from the table
1. Ovral 2. Plan B 3. Condoms
4. Nonoxynol-9 5. Pregnancy 6. Breast cancer
7. Deep vein thrombosis 8. Vaginal bleeding 9. Alesse
10. Dian 25 11. Nausea and vomiting 12. Dimenhydrinate
13. Chloasma 14. Breast tenderness 15. Chest pain
16. Headache 17. Eye problems 18. Severe leg pain
19. Tampons 20. Evra patch 21. Nuva ring
22. IUDs 23. Depo provera 24. Abdominal pain
· Spermicidal: Vaginal contraceptive film ( )

· Contraception method may protect STIs and HIV ( )
· Contraindications of oral contraceptive pills ( )
· Oral contraceptives approved to treat acne ( )
· What is the common side effect of plan B ( )
· What is used as treatment for nausea and vomiting for contraceptives ( )
· What contraceptive methods and hygiene product that can cause toxic shock syndrome ( )
· Contraceptive method that applied for once a week, ( )
· The side effects of oral contraceptive pills ( )
· The danger signals of oral contraceptive pills ( )
· Emergency contraceptive methods ( )
· Emergency contraception plan B side effects ( )
· If missed one pill, what should be done ( )
· Contraceptive method that used once a month (removed after 21 days) ( )

· Non-contraceptive health benefits of OCs include decrease endometrial cancer, ovarian cyst, endometriosis
pain, fibroids, dysmenorrhea, and pelvic inflammatory disease. (True/False)
· Oil based lubricants should not be used for latex condoms (male), diaphragms, cervical caps. (True/False)
· Diaphragm and cervical caps do not require a prescription but need a trained health professional to insert.
(True/False)
· Spermatocides are used along with condoms, diaphragm, and cervical cap. (diaphragm requires spermicidal
for every intercourse where cervical cap does not require extra spermicidal for subsequent intercourse.
(True/False)
· STI are only prevented transdermal patch contraceptives. (False)
· STI are only prevented subdermal progesterone implants (False)
· STI are only prevented by condoms contraceptive methods (True)
· Transdermal contraceptive Evra patch should be applied to the abdomen, buttocks upper torso, and upper
arm at the beginning of menstrual cycle (True)
www.pharmacyprep.com Gynaecological and genitourinary conditions
82
Gynaecological and Genitourinary
Conditions
Questions Alerts!
· Risks associated with endometriosis, symptoms and treatment of endometriosis.
· Menopause symptoms and management
· Toxic shock syndrome infection is caused by? S. aureus
· Drugs to treat erectile dysfunction like sildenafil, tadalafil and vardenafil DI with nitroglycerin
Dysmenorrhea
· Painful menstruation is referred to as dysmenorrhea
· Increase levels of prostaglandin during ovulation cycles, in endometrium it gives cramps, this leads to
menstrual pains. Thus, problem can be treated by prostaglandin inhibitors.
· Drug of choice is mefenamic acid or diclofenac.
Endometriosis
· Endrometriosis can cause pelvic pain (up to 80%), dysmenorrhea (40%) and infertility (40%), deep
dyspareunia (44%) and fatigue, dysuria, hematuria, rectal bleeding, shoulder pain.
· Treatment for pelvic pain. NSAIDs (mefenamic acid), oral contraceptives, progesterone only oral
contraceptives, androgen agonist. Danazol and gonadotropic releasing hormone (GnRH) analogs
· Treatment of fertility clomiphene.
· Treatment of dyspareunia by vaginal moisturiser. PELVIC PAIN: pain below belly button
in the anterior lower abdomen including
Male sexual dysfunction the sex organs).
· Erectile dysfunction treatment. PDE 5 inhibitors Sildenafil, vardenafil, and tadalafil.
· Side effects. Headache, flushing, dyspepsia, nasal congestion, transient visual disturbance, dizziness, and
skin rash. Rarely priapism, and permanent visual loss.
· Drug interactions: Nitrates, alpha blockers, CYP3A4 inhibitors, grapefruit juice, and erythromycin.
PDE 5 inhibitors: sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis)
Contraindications: Nitrates (seek emergency care if chest pain present within 24 to 48 hr of taking PDE 5
inhibitors, or use for 5 days after stopping long-acting nitrates).
· Non-selective α-blockers, CYP3A4 inhibitors
· Side effects: Headache (15%), flushing (10%), dyspepsia (5%), nasal congestion (5%), transient visual
disturbances (2%) and Priapism.
Sildenafil is used 30 to 60 min before sexual activity. Taken with fatty meal has higher bioavailability
· Dose adjustment. Hepatic or renal disease (<30 ml/min) & in the elderly.
· Priapism & permanent vision loss (go to see a doctor).
· Up to 12 hr duration of effect
Vardenafil. 30-60 min before sexual activity
· Dose adjustment. In moderate hepatic or renal disease & in the elderly
· Side effects: Priapism & permanent vision loss (go to see a doctor)
· Up to 12 hr duration of effect, take empty stomach
Tadalafil – long half-life and long duration of action. At least 60 min before sexual activity
· Dose adjustment: No need in the elderly.
· Tadalafil 5 mg daily is approved for benign prostatic hyperplasia
· Side effects: visual disturbances & permanent vision loss (go to see a Dr)
· Up to 35hr duration of effect – no more frequently than every 2nd day
· Contraindications: sever hepatic impairment
· PGE 1 analogues: alprostadil; intracavernosal injection (Caverject), intraurethral pellet (MUSE)

· Use to Pts with taking nitrates or α-blockers
· Injection – not use more than once daily or 3times /wk, at least 24hr between each dose
· Pellet - not use more than once per 24hr period, MO: BP (detect asymptomatic hypotension)
Menopause
· Cessation of menstrual periods is referred as menopause. The average age of menopause in Canada is 51
years.
Symptoms: vasomotor symptoms: Hot flushes, night sweats, sleep disturbances, lethargy, depression, vaginal
dryness, dyspareunia (painful sexual intercourse). These symptoms are mainly due to the depletion of estrogens
and progesterone.
Menopause symptoms treatment: Hormone replacement therapy: Estrogen, (vaginal suppositories), estrogen
patch, progestin.
Vasomotor and Hot flashes treatment: hormone replacement therapy (oral, patch and vaginal estrogen and
progestin), if estrogen/progestins cannot use then venlafaxine can use.
Hysterectomy: Removal of uterus. Hysterectomy patient use estrogen only: Progestin are not used.
Intact uterus: estrogen and progestin hormone replacement therapy.
Toxic shock syndrome (TSS)

· It is an infection resulting from toxin producing strains of S. aureus.
· TSS is a severe life-threatening condition, can evolve clinically in rapid fashion becoming severe ill in less
than 12 hours.
· TSS is associated with use of tampons, reservoir types of contraceptives such as sponges, IUD, and cervical
caps. However, condoms are not associated with TSS.
Benign prostatic hyperplasia (BPH)

· It is a condition where a male prostate becomes enlarged to the point that it causes discomfort. There are
two categories of symptoms:
· Obstructive symptoms. Weak urinary stream, difficulty initiating stream, stream starts and stops, inability to
terminate, post void dripping, urinary retention, and sensation of incomplete empty bladder.
· Irritative symptoms: Urinary frequency, nocturia, pain during urination, urinary urgency
· Treatment: finasteride and dutasteride (5a reductase inhibitor) and  1 adrenergic antagonist tamsulosin,
prazosin, doxazosin, and terazosin.
· 5 a reductase enzyme catalyzes testosterone to dihydrotestosterone.
· The drug of choice to treat BPH, is Proscar: Finasteride 5 mg
· Propecia: Finasteride 1 mg is used to treat alopecia.
Pre-menstrual symptoms (PMS)

· Cyclic re-occurrence of physical, behavioral, and psychological symptoms during the luteal phase of
menstrual cycle (after ovulation).
· PMS symptoms occur 1 to 2 days before periods may be due ↓ progesterone, or estrogen.
A sever PMS include, and mood changes.

· Luteal phase of menstrual cycle
· All women have no PMS.
· There is no treatment for PMS
· Evening prime rose oil is used for PMS.
Vaginitis or vaginosis or vaginal infection

· Infection of vagina caused by vaginal microorganisms or overproduction. Question Alerts!
· Bacterial vaginosis Color and odor in discharge is
· Creamy and fishy odor discharge (yellow/grey) symptoms of?
· Most common form of vaginitis
· Sexually transmitted disease thus partner requires treatment.
· Vaginal candidiasis
· Severe pruritus, with white cottage cheese discharge (only recommended for self treatment).
· It is not sexually transmitted disease thus partner does not require treatment.
· Over the counter antifungals miconazole, clotrimazole, nystatin are the drug of choice.
· Trichomoniasis
· Frothy, wet discharge
· It protozoa infection.
· It is a sexually transmitted disease thus partner require treatment.
Atrophy
· Vaginal discharge, spotting, and soreness, burning.
· Drug of choice is metronidazole
Vaginal candidiasis Bacterial vaginitis Trichomonas

White, or curdy discharge, Yellow Color discharge Frothy wet discharge
pruritus Fishy odor
The drug of choice Clotrimazole The drug of choice PO/pv The drug of choice
1-10%, miconazole, nystatin and Clindamycin Metronidazole po or vaginal
fluconazole Po/pv metronidazole
Partner require treatment
Urinary incontinence in adults

· Bladder symptoms involve the leakage of moderate to large amount of urine due to hyperactivity, stress,
and over distended bladder.
· Stress incontinence. loss of urine due to an increase in intra-abdominal pressure. Examples cough, and
exercise.
· Urge incontinence. symptoms of overactive bladder which caused by inability delay voiding when urge is
perceived. Examples CNS condition, like Parkinson's disease and stroke.
· Overflow incontinence. Involves the leakage of urine due to an over distended bladder, commonly resulting
from outlet abstractions. Examples such as BPH or neurogenic causes such as diabetic neuropathy or
multiple sclerosis.
· Functional incontinence; loss of urine caused by the inability to get to toilet. Example physical disabilities,
difficulty removing clothing, cognitive factors such as dementia, depression, or environmental factor such as
distance to toilet, and positioning.
Drug of choice is oxybutynin (Ditropan) and is an anticholinergic drug act M3 receptors.

· Drug that should be avoided in urinary incontinence diuretics (furosemide), glucocorticoids,
thiazolidinediones.
Enuresis in children (bed wetting)

· Drug of choice is antidiuretic hormone derivatives desmopressin (DDAVP)
· Smooth muscle relaxant, oxybutynin and imipramine
Tips
Find answers from table:
1. Mood changes (swing) 2. Flushing 3. Night sweat
4. Vagina dryness 5. PDE 5 inhibitors 6. oxybutynin
7 Luteal phase 8. Urinary incontinence 9. Benign prostatic hyperplasia (BPH)
10 Premenstrual syndrome (PMS) 11. dysmenorrhea 12. Jet urination
13. Difficulty in urination 14. Finasteride 15. Dutasteride
16. Prazosin 17. Tamsulosin 18. irritation
19. Saw palmetto 20. Pelvic pain before periods 21. S. aureaus
22. Contraceptive sponges 23. IUD 24. Cervical caps
25. Sildenafil
· Symptoms of dysmenorrhea à
· Symptoms of endometriosis à
· What microorganism cause toxic shock syndrome à
· What contraceptive methods can cause TSS à
· What drugs are inhibitors of PDE 5 enzyme à
· Nitrates + sildenafil should not take together because à
· Menopause symptoms à
· Benign prostatic hyperplasia symptoms include all except à
· What phase of menstrual cycle does PMS symptoms occur à
· What drugs should be avoided in urinary incontinence à
· What is the drug of choice enuresis in children à

· Symptoms of menopause ( )
· Sildenafil, tadalafil, vardenafil are ( )
· The drug of choice of urinary incontinence ( )
· Occurs in premenstrual syndrome (PMS) ( )
· Symptoms of benign prostatic hyperplasia ( )
· The drug of choice for BPH ( )
· The drugs that used to relieve the symptoms of BPH ( )
· What is not symptoms of BPH ( )
· What anticholinergic drug that acts on M 3 receptors ( )
· Herbal product that is used to treat prostatic hyperplasia ( )
Select True or False Statement

· A customer of your pharmacy presents with symptoms of vaginal discharge, yellow and fishy odour.
Refer to doctor is appropriate? (True)
· Color discharge and fishy odour is indicator of bacterial infection, thus refer to doctor.
· If a patient is not treated for asymptomatic sexually transmitted infections. Can cause pelvic
inflammatory disease and infertility (True)
· pre menstrual symptoms occur during luteal phase. (True)
· toxic shock syndrome caused by infections of S. aureus. (True)
· toxic shock syndrome can cause by tampon use. (True)
· toxic shock syndrome Can cause by condom use (False)
· toxic shock syndrome can cause by candida infections. (True)
· toxic shock syndrome Can cause cervical cap contraceptives. (True)
· patients experienced priapism condition avoid using sildenafil? (True)
· patient have reported visual disturbances condition avoid using sildenafil? (True)
· patient using nitrates condition avoid using sildenafil? (True)
PharmacyPrep.Com Osteoarthritis, Rheumatoid arthritis and Gout arthritis
83
Osteoarthritis, Rheumatoid
Arthritis and Gout Arthritis
Questions Alerts!
· Osteoarthritis therapy acetaminophen 650 mg q4-6h
· Rheumatoid arthritis therapy methotrexate and Infliximab
· Methotrexate dose to treat rheumatoid arthritis max 25 mg/wk
· Acute gout attack therapy Indomethacin, colchicine and prednisone.
· Acute gout risk factors, high protein diet, low dose ASA.
Osteoarthritis (OA) is a degenerative joint disease caused by a breakdown of the cartilage between
bones. and degradation of articular cartilage in synovial joints.
OA. Aging of cartilage and trauma
Sex distribution, OA. Equal in both sex
Symptoms: Painful joints, restricted joint movements
OSTEOARTHRITIS
Selfcare: weight bearing exercise, physical therapy, weight loss, orthotics, nutraceuticals, bracing.
The drug of choice is Acetaminophen 650 mg q6h
+/- topical NSAIDs +/- Codeine
If no relief, then use NSAIDs or COX-2 inh.

¯
If no relief then use corticosteroids (Po or intraarticular) or Hyaluronic acid
Non-prescription
· Acetaminophen is initial drug of choice for symptom relief. Maximum therapeutic dose should be tried for 2
to 3 weeks
· Acetaminophen 650 mg 4 to 6 times a day
· ASA/NSAIDs/Ibuprofen is 2nd line therapy

· Acetaminophen + caffeine + codeine
· Glucosamine/Chondroitin
· Topical counter-irritants (Methyl salicylate/Menthol/Capsaicin)
COX-2 inhibitors (Celecoxib) as effective as NSAIDs but lower incidence of GI side effects.
· Intraarticular corticosteroids (3 to 4 injections year)
· Hyaluronic acid injections only for those who failed other therapies
· Narcotic analgesics
RHEUMATHOID ARTHRITIS
Rheumatoid arthritis: A chronic systemic, autoimmune inflammatory condition. Symmetric synovitis affecting
similar joints bilaterally. Symptoms: Inflammation of joints with frequent acute attacks. Rheumatoid arthritis
occurs when body’s immune system attacks the tissue lining and results in the joints causing cartilage to erode.
Weight bearing and non weight bearing joints. Soft tissue effected.
· It is non-organ specific autoimmune disease
· Type III hypersensitive reaction
· Blood contain rheumatoid factor Question Alert!
· Stiffness occurs in the morning Lab investigations of RA.
· Large areas of joints are effects
· Not associated with frequent of use of joints
· It effects on weight bearing and non-weight bearing joints.
RA STAGES: CONNECTIVE TISSUE AFFECTED AND CHRONIC INFLAMMATION OF SYNOVIAL JOINTS

SYNOVITIS PANNUS FIBROUS ANKYLOSIS
Thicken synovial membrane Cartilage destruction Fibrous tissue involves into scar tissue
Inflammation
Diagnosis: Rheumatoid factor, erythrocyte sedimentation rate (ESR), x-ray, antinuclear antibody, and c-
reactive protein (CRP).
RHEUMATHOID ARTHRITIS
The drug of choice is methotrexate max 25 mg once week. (add folic acid supplement)
If NO relief methotrexate, add or switch to other DMARD or infliximab

Refractory RA add infliximab
Patient with active tuberculosis, active bacterial infections, hepatitis B & C, live vaccine
avoid TNF alpha inh.
RA pain treatment prednisone.
The drug of choice in pregnancy sulfasalazine
Disease modifying anti-rheumatic drugs (DMARDs)

· Methotrexate is the gold standard for the treatment of RA
· Should be started within 3 months of disease onset (max effect in 3 to 6 months)
· Initial dose of 20 to 25 mg po/wk, do not exceed >25 mg/wk
· Minor SEs oral ulcers can be reduced by concurrent use of folic acid
· Should be avoided in patients with hepatitis B and C, renal insufficiency, or lung disease, serious SEs are
cytopenia, and hepatic toxicity.
· Hydroxychloroquine; SE corneal and retinal Question Alert!
deposition Methotrexate dose.
· Sulfasalazine Drugs that cause corneal deposits?
· Leflunomide: Can be used in combination with Hydrochloroquine, amiodarone
methotrexate (CI in pregnancy) or in place of it for
patients who have failed or have contraindications to
methotrexate.
· Should be stopped in both males and females at least 3 months before attempting conception (patient must
undergo drug elimination by taking cholestyramine 8 g TID for 11 days.
· Azathioprine a purine analog immunosuppressive agent
· Cyclosporine
· Minocycline
· Penicillamine
· Gold sodium thiomalate
NSAIDs and Glucocorticoids. Prednisone/Triamcinolone – safest therapy during pregnancy and lactation
Biological response modifier: Infliximab, etanercept, adalimumab
Infliximab
· Biological response modifier act as TNF a inhibitor. It is chimeric monoclonal antibody.
· Only available as iv. Stored in refrigerator.
· Approved for ulcerative colitis and It is always used with methotrexate.
· Side effects: The most common SEs are headache, fever, chills, fatigue, diarrhea, pharyngitis upper
respiratory tract and UTIs.
GOUT ARTHRITIS
Gout is a disease in which monosodium urate monohydrate (MSU) crystal are deposited in joints, soft tissues
such as cartilage, tendon and bursa or renal tissues such as glomeruli, interstitium tubules. Gout arthritis
involves 4 stages Asymptomatic hyperuricemia (female >360 mmol/L, men >420 mmol/L), Acute gouty attacks,
Intercritical gout, Tophaceous gout.
Risk factors: Protein diet, purine foods, meat, beer and male gender, low dose of ASA, obesity, sea
food. (NOT RF smoking)
Drug that cause hyperuricemia: Thiazides, low dose ASA, niacin, alcohol, levodopa, iv nitroglycerine,
ethambutol, and pyrazinamide. (NOT cause losartan and fenofibrate)
Acute gout attack

Abrupt onset of excruciating pain and inflammation of joint at night or early morning. Patient cannot
tolerate even light pressure such as a bed sheet on the affected joint. Attacks often resolve
spontaneously over 3 to 10 days.
ACUTE GOUT ATTACK

DRUG OF CHOCE: No consensus on which of the available treatment is the most effective for
acute attack
1. colchicine’s: 0.6mg every hour; continue until symptoms begin to settle; nausea, vomiting,
vertigo develops; or max 6 mg has been reached.
2. NSAIDS: indomethacin, 25-50 mg tid; ibuprofen, 400-600 mg qid; naproxen 250-500 mg bid
SECOND LINE THERAPIES

Systemic glucocorticoids have been used effectively in the management of polyarticular gout
when colchicine and NSAIDs are contraindicated.
Prednisone 30-50 mg once daily x 3-5 days then taper by 5 mg/day.
Intraarticular injections are useful in treating acute gout when one joint or bursa is involved.
NSAIDS. Indomethacin
· It is prostaglandin type I NSAIDS
· It has the highest anti-inflammatory action in all NSAIDs. It does not decrease uric acid
· It has high GI irritation SE (add gastroprotection with PPI for patient with risk increases for GI bleed).
Colchicine Question Alert!

· It is anti-inflammatory drugs What drugs are NOT used to treat acute gout
· It has no analgesic action attack? Allopurinol or acetaminophen
· The most common SE is GI irritation
Corticosteroids
· Given intra-articular injections for monoarticular pain
· Given oral for polyarticular pain
Asymptomatic hyperuricemia
· Normal serum urate levels: Woman 360 micromol/L and men 420 micromol/L. More common in men over
40 years of age.
· Hereditary metabolic disease that is a form of acute arthritis and is marked by inflammation of the joints.
· Gout is associated with increased body stores of uric acid.
· Acute attacks involve joint inflammation caused by precipitation of uric acid crystals.
· Hyperuricemia à Urate crystal in joints à inflammatory response
Treatment of hyperuricemia. Antihyperuricemic agents as allopurinol, sulfinpyrazone and probenecid
Allopurinol
· Inhibit xanthine oxidase (XO)
· Allopurinol and azathioprine drug interactions is due to which enzyme XO
· Side effects: Rash is the most common, can form urate crystal in kidney. Take with plenty of fluids
· DIs: Half life of azathioprine and 6 mercaptopurine increased by allopurinol so this may increase toxicity
from increased plasma concentration of these drugs.
· Oxypurinol is metabolite of allopurinol
Febuxostat: Can be used in allopurinol allergy patient.
Sulfinpyrazone
· Side effects: can from kidney stones
Probenecid
· Side effects: Can from kidney stones
Tips
1. Acetaminophen 2. Methotrexate 3. Minocycline
4. Hydroxychloroquine 5 Infliximab 6 Allopurinol
7. Sulfinpyrazone 8 Colchicine 9 Indomethacin
10 Weight bearing joints 11 Non-weight bearing joints 12 Obesity
13 Family history 14 Inadequate Ca & Vitamin 15 Deficiency of
estrogen
16 Hyaluronic acid 17 Intra articular 18 Probenecid
19 RA 20 Osteoarthritis 21 Gout
22 25 mg/WK 23 TNF alpha blocker 24 Etanercept and adalimumab
25 DMARDs 26 Anti-inflammatory action 27 Full glass of water
28 Capsicum 29 Rash 30 penicillamine
· Morning stiffness is symptoms of à

· Rheumatoid arthritis can occur on à
· Examples of DMARDs à
· Biological response modifiers à It blocks TNF
· Examples of TNF-alpha blockers à
· Biological response modifier that blocker IL-1 à anakinra
· Methotrexate maximum dose for rheumatoid arthritis treatment is à
· Infliximab is a murine chimeric antibody act on à
· Acetaminophen has least activity as à
· Probenecid, sulfinpyrazone and allopurinol should be taken with à
· Drug that may cause renal damage or bone marrow depression ( )
· What is the drug of choice to treat osteoarthritis ( )
· What anticancer drugs used for the treatment of rheumatoid arthritis ( )
· What drug is used to treat rheumatoid arthritis and malaria ( )
· A broad-spectrum antibiotic used in the treatment of rheumatoid arthritis ( )
· What drug used for rheumatoid arthritis and Crohn’s disease treatment ( )
· What is a suicide inhibitor of xanthine oxidase (XO) ( )
· Drugs that promotes uric acid excretion in urine ( )
· What drugs are used to treat acute gout attacks ( )
· Long term use acetaminophen is associated with --> primarily hepatotoxicity and probably renal toxicity.
· Capsaicin is obtained from? ( )
· Gout arthritis risk factors? purine rich diet, Low dose ASA, protein diet, sea food, beer and meat.
· Febuxostat is? xanthine oxidase inh.
· What are the onset of action of DMRDs? Methotrexate, and other DMARDs 1.5 to 6 months. Leflunomide
after 4 wks produce significant greater improvement (The meantime for clinical response).
· What is the common side effect of allopurinol? ( )
www.PharmacyPrep.Com Osteoporosis
84
Osteoporosis
Questions Alerts!
· Risk factors of osteoporosis age, menopause, and family history, thin and small build.
· Calcium and vitamin D supplements dose and DI's.
· Bisphosphonates like alendronate, residronate, etidronate and zolendranoic acid
· Bisphosphonates doses
Osteoporosis: Overall reduction of bone mass (osteopenia), resulting in thin, fragile bones that is prone to
fracture.
There are 4 common sites of fracture in osteoporosis. Wrist, shoulder, hip and spine.
Spine fracture also know "vertebral compression fractures" results due to falls, sneezing, coughing, reaching,
lifting or carrying.
Paget’s disease: Bone remodeling disorder, resulting in excessive bone resorption followed by disorganized.
Risk Factors
Non-Modifiable Modifiable
· Age >65 y · Low calcium intake (<1000 mg elemental
· Vertebral compression fractures calcium per day)
· Postmenopausal woman (not on estrogen · Inadequate sun exposure.
therapy). · Cigarette smoking
· Premature menopause (<45 years) · Excessive alcohol intake
· Gender (Female) · Caffeine containing beverages.
· Family history · Sedentary life style
· Thin and small boned (overweight or obesity · Excessive heparin therapy
is NOT risk factor) · Oral corticosteroid therapy
· Hypogonadism
· Race. Caucasians, Asians
· Hyperparathyroidism
· Hypocalcemia
Nutritional Supplements: Ensure adequate intake of both Calcium and vitamin D of these nutrients when
prescribing pharmacologic therapy
· Ca - Premenopausal women: 1000 mg/day, menopausal women & men > 50 y 1500 mg/day
· SE : constipation & nausea

Calcium Salts
Calcium carbonate (40% elemental calcium) Question Alerts!
· Tricalcium phosphate (calcium phosphate, tribasic) 39% The highest elemental calcium
· Calcium chloride 27% is present in? CaCO3
· Calcium citrate (21%)à good choice for seniors
· Calcium lactate (13%)
· Calcium gluconate (9.3%)à least elemental calcium
Vitamin D
· Vitamin D. <50 y 400 IU/day, >50 y 800IU/day
· SEs. hypercalcemia, hypercalciuria, renal calcification, renal stones (usually at very high doses).
· Vitamin D 3 (cholecalciferol) is preferred over vitamin D 2 (ergocalciferol).
Diagnosis.
Bone mineral density measurements by Dual Energy X-ray Absortiometry (DEXA).
T-score -2.5 or lower is osteoporosis.
Non-pharmacologic
Reduce risk of falling (recommended weight bearing exercise walking, jogging, running).
Adequate dietary calcium and vitamin D
Stop smoking, reduce alcohol <2drink/day, caffeine 2 cups.
Women Men Corticosteroid induced osteoporosis

Estrogen/progestins +
Raloxifene +
Bisphosphonates (drug of choice) + + +
Calcitonin + +
Teriperatide + + +
RANK lingand (Denosumab) + + +
Pharmacotherapy:
The DOC for osteoporosis is bisphosphonates.
Bisphosphonates: Antiresorptive agents.
Tips
1 Alendronate 2 Calcium carbonate 3. Risedronate

4 Raloxifene 5 Calcium citrate 6. Calcitonin
7 Family history 8 Inadequate Ca & Vit D 9. Deficiency of estrogen
10 Swimming 11 Weight bearing 12 Obesity or overweight
13 Osteoblast 14 Androgen 15 Osteoporosis in men
16 800 IU/day 17 Achlorhydric 18 Abnormal bone
formation
· Risk factors of osteoporosis ( )

· Approved for prevention and treatment of postmenopausal bone loss, treatment of established
osteoporosis and glucocorticoid-induced osteoporosis ( )
· 40% elemental calcium provides the most calcium ( )
· Selective estrogen receptor modulator (SERM), estrogen like action on bone and lipid metabolism ( )
· A hormone secreted from thyroid gland ( )
· Calcium supplement recommended in elderly ( )
· This drug should be taken first thing in the morning on an empty stomach ( )
· What is NOT a risk factor of osteroporosis à ( )
· Bone remodeling occurs, which is presentà ( )
· Osteoporosis is caused by à ( )
· Androgen deficiency cause à primary hypogonadism and 15
· Recommended daily allowance of vitamin D over 50-year-old is à ( )
· Elderly may absorb calcium poorly due to à ( )
· Paget diseaseà ( )
· Calcium carbonate (40% elemental calcium)à Provides most calcium, usually requires an acidic
environment for absorption.
· What excercise is the least beneficial for bone mineral density (BMD) for osteoporosis --> swimming
· Which dose intervals are not available for bisphosphonate? biweekly
· Therapeies of vertebral and non-vertebral fracture? Bisphosphonates, HRT, denosumab
Bone formation thrapy? Teriperatide (for vertebral and non-verterbal but NOT hip)
· Epigastria is SE of ? Bisphosphonates
· Dual energy x-ray absorptometry (DXA) test shows? T-score
· Residronate dose is? 35 mg weekly, 75 mg tab on two consecutive days Qmonth, and 150 mg Qmonth.

· Inadequate Ca and vitamin D can cause osteoporosis (True)
· Smoking increase risk of osteoporosis? (True)
· Physical activity like weight bearing excercises like stair climbing, walking, and jogging decrease risk of
osteoporosis. (True)
· Increase in dietary soy intake decrease risk of osteoporosis. (True)
· Increase intake of broccoli decrease risk of osteoporosis. (True)
· A 35 yo women get the prescription of 50,000/wk unit of vitamin D. What to do? talk to doctor and
dispense. (True)
· protein diet like dietary are plant derived phyoestrogen present in soy proteins. (True)
· Drugs that cause osteoporosis: Corticosteroid, prednisone, levothyroxine. (True)
anticonvulsants, phenytoin, heparin (long term use), and Al-containing antacid (True)
www.pharmacyprep.com Hypertension
85
Hypertension
Questions Alerts!
· Cardiovascular risk factors.
· Clinical practice guidelines of hypertension monitoring
· Drug of choices to treat high blood pressure in patient with diabetes, renal, and coronary
artery disease, stroke patients.
Hypertension is defined as a systolic blood pressure >140 mm Hg, a diastolic blood pressure >90 mm
Hg. Diagnosis criteria from joint national committee (JNC8) report recommendations for follow up in
adults.
Question Alerts!
· <130/85 à Recheck in 2 yrs
The normal blood pressures?120/80
· 130-139/85-89 à Recheck in 1 yr
· 140-159/90-99 à Confirm within 2 months
· 160-179/100-109 à Evaluate or refer to source of care within 1 month
· >/-180/110 à Evaluate or refer to source of care immediately or within 1 week depending clinical
evaluation
Maintain BP below
· 140/90 uncomplicated hypertension (therapy starts)
· 140/90 with target organ damage or CV disease
· Isolate systolic hypertension >140/<90
· Diabetic or renal impairment <130/<80
· <125/75 with proteinuria >1 g/24 hrs
BP Measurement
· Patient should avoid smoking or caffeine for 30 min prior to BP
measurement
· Rest 5 min before BP measurement
· Position arm (bronchial artery) at heart level
· Uncover arm, do not put cuff over cloths
· Position cuff 1 inch above antecubital crease
· Ask patient about previous reading. Inflate cuff rapidly to approximately 30 mm Hg above previous
readings.
· Deflate cuff slowly, and completely. Measure pressure in both arms.
· Wait 1 to 2 min before repeating, and take average of 2 reading. If second reading differ by >5 mm,
additional reading should be performed.
1st line therapy
Thiazide ACEi ARBs Calcium Beta

>60 yrs DOC for DM Channel Blockers
and renal Blockers <60 yrs
disease
Combining antihypertensive: Preferably combine from type 1 and type 2

Type 1 Type 2
ACE Inhibitors Thiazide
ARBs Beta blockers
Alpha blockers
K sparing CCB
Thiazide Diuretics
· Thiazide Diuretics. Hydrochlorothiazide, chlorthalidone, indapamide, metolazone and
combinations.
· MOA: Direct arteriole dilation, inhibit Na reabsorption in the distal tubule.
· SE: HYPERGLUC
· Increased lipid (cholesterol); increased LDL and increased TG.
· Increased uric acid; Hyperuricemia
· Increased glucose; Hyperglycemia (Mon: BSL)
· Increased Ca2+ = Hypercalcemia
· Decreased K+ = Hypokalemia
· Decreased Na+, Cl- = metabolic alkalosis
Beta blockers (BBs)

· non-selective BBs à Nadolol, propranolol, and timolol
· Cardio selective BBs are à Esmolol, Metaprolol, atenolol, acebutolol (selective beta blockers).
· Cardioselective BBs with ISA à Acebutolol, pindolol (non selective)
· Beta and alpha1 blockers à labetalol and carvedilol
· MOA: ↓ Cardiac contractility à ↓ CO
· ↓ HR à ↓ CO
· ↓ central sympathetic output
· Block rennin secretion
· SE: Increase LDL and TG
· CI: Peripheral vascular diseases (Reynaud's and claudication), prinzmetal angina (vasospastic
angina)
· DOC: stable angina, hypertension (<60yr), post MI (STEMI), CHF (pulmonary edema) in general
avoid CHF because of bradycardia.
· Beta blockers à DOC: stable angina, hypertension (<60yr), post MI (STEMI), CHF (pulmonary
edema) in general avoid CHF because of bradycardia.
· Propranolol (Inderal LA) indicated for àSocial anxieties (stage fear) migraine prophylaxis, and
hyperthyroidism
· Beta blockers precaution and CIà Peripheral vascular diseases (Reynaud's and claudication),
prinzmetal angina (vasospastic angina)
· The most beta 1 selective BBs that has been studied in lung dysfunction à Bisoprolol
Angiotensin converting enzyme inhibitors (ACEi):

Benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, and
trandolapril
· MOA: Inhibit conversion of ACEI to ACEII thereby ↑ peripheral vasodilation
· and ↓ fluid volume
· SE: angioedema, dry cough treat by switching to other class of drug. It has NO effect on LDL, TG and
HDL, gives hyperkalemia (do not combine K sparing)
· CI: in pregnancy, initially increase serum Cr up to 30% is OK, if more discontinue ACE I
· MON: K+ level should not exceed 5 mEq/mL
Question Alerts!
· TU: BP, CHF, posts MI, diabetic nephropathy, Captopril require BID or TID dosing
(microalbuminurea > 1 g), intermittent and taken empty stomach.
claudication.
· Captopril and fosinopril are NOT prodrug
· ACEI à Inhibit conversion of AT 1 to AT 2 thereby ↑ peripheral vasodilatation
· and ↓ fluid volume
· Captopril à Taken Q8H, All ACE I daily single dose, except captopril
· Take on an empty stomach, 1h a.c.
· Enalapril à is 3 time more potent used once daily and NO sulfhydril group
Angiotensin receptor blockers (ARBs)

ARBs: Candesartan, eprosartan, irbesartan, losartan telmisartan, and valsartan
· Direct Renin Inhibitors àAliskiren (Rasilez)
· Alpha 1 blockers à doxazosin, prazosin and terazosin
· Why is bedtime the best time to dose terazosin?à syncope
· Alpha 1 blockers à avoid with PDE 5 inh. (Sildenafil, vardenafil, tadalafil)
Calcium channel blockers (CCBs)

· DHPs à amlodipine, felodipine, nifedipine XL. SEs. Ankle edema, flushing, headache, and
palpitation (reflex tachycardia) Amlodipine à Long
acting DHP Question Alerts!
· NDHP à diltiazem, verapamil. SEs. Headache, Dihydropyridine cause reflex tachycardia
dizziness, bradycardia, 2nd and 3rd degree heart block, Verapamil & Diltiazem causes bradycardia
new onset or worsening of heart failure and
constipation.
· Verapamil à SEs. Constipation and take with or after meals
· Felodipine à DOC Reynaud phenomenon
· Non dihydropyridines à Additive effects with beta blockers (bradycardia), digoxin, amiodarone,
· Diltiazem SEs. stomach irritation. Take regular tab before meals and SR: with or without food.
· Dihydropyridines à SEs. reflex tachycardia, headache and ankle edema
Alpha 2 agonist
· Methyldopa and clonidine
· MOA: ↑ alpha2 action and ↓ sympathetic outflow to heart
· Methyldopa Drug of choice for pregnancy
· SE: hemolytic anemia Mon: CBC
Tips
1 Propranolol 2. Thiazide diuretics 3. Clonidine
4 Hydrochlorothiazide 5. Methyldopa 6. Triamterene
7 Captopril 8. Furosemide 9. Enalapril
10. Minoxidil 11. Sodium Nitroprusside 12. Hydralazine
13. Felodipine 14. Terazosin 15 Losartan
16. BP >160/80 17. Ramipril
· What is the recommended sodium intake for a patient diagnosed with hypertension?( )
· The drug of choice against uncomplicated hypertension age over 65 yo is ( )
· The drug of choice against uncomplicated hypertension age less than 65 yo is ( )
· The drug of choice for hypertension in pregnancy ( )
· Use in non complicated hypertension and also indicated in opioids and benzodiazepine withdrawal
symptoms ( )
· Decrease BP in both supine & standing position, especially in elderly ( )
· Diuretics that gives ototoxicity, hypokalemia, dehydration, allergy, nephritis and gout ( )
· What drug turns urine into blue color ( )
· What antihypertensive drug should be taken 1 hour before meals ( )
· it is 3x more potent and used once daily and no sulfonil group ( )
· it is use for hypertension and alopecia treatment ( )
· The drug of choice for hypertensive crisis ( )
· It causes salt and water retention which may lead to CHF ( )
· The drug of choice for Reynaud phenomenon ( )
· This drug may cause a sudden drop in blood pressure that can result in loss of consciousness ( )
· Drugs may increase the effects of potassium supplements, potassium sparing diuretics,
cyclosporine, leading to raise of potassium in the blood ( )
· Hypertension with diabetes drug of choice is à
· Hypertension with renal disease drug of choice is à
· Isolated systolic hypertension which drugs should not useà

· Cardio selective beta blockers are à
· The most beta 1 selective blockers that has been studied in lung dysfunction; à
· Name the cation most prevalent in the extracellular fluid of the body.à
· Why is bedtime the best time to dose terazosin?à
· It is an antihypertensive drug which is also used prophylaxis migraine ( )

A customer of your pharmacy checked two times blood pressure in your pharmacy blood pressure
monitor and found to have average 190/95. What is appropriate to do? talk to him first and refer to
doctor
PharmacyPrep.Com
86
Coronary Artery Diseases
Questions Alerts!
· Atherosclerosis and plaques (Caused by high LDL)
· Examples of coronary artery diseases angina, and myocardial infarction
· Risk factors and investigations (biochemical marker CK-MB, Troponin-i, ECG)
· Treatment of NSTEMI (Non ST segment elevated MI). ASA, BB
· Treatment of STEMI (ST segment elevated MI). Alteplase, ASA
PharmacyPrep.Com
Types of angina
Stable/Exercise induced angina Prinzmetal/Varian/ Vasospastic Unstable/Crusendo angina

Due to coronary partial blood angina
clot Acute with platelet aggregations.
↓ Coronary blood flow. Due to non-occlusive thrombus in
↓ ST segment (subendothelial) an area of coronary
↑ ST segment (transmural) atherosclerosis / or disrupted
Due to vasospasm effect of TXA2 plaques
Definition: Angina is those symptoms of myocardial ischemia that occur when myocardial oxygen availability is
insufficient to meet myocardial oxygen demand.
Symptoms: discomfort or pain in the chest, arm, shoulder, back or jaw. Frequently worsened by physical
exertion or emotional stress.
Diagnosis: ECG and exercise stress test with echocardiography.
Stable angina
· Caused ↓ O 2 (Ischemia) supply due to ↓ blood flow. Precipitating factors exercise, cold weather, sexual
activity and emotional stress.
· Symptoms: Pain located over sternum and may radiate to left shoulder or arm, right arm or neck, or jaw.
Duration 0.5 to 30 min. Patient description of symptoms pressure or heavy weight on chest, burning,
tightness, deep, suffocating, squeezing, aching, and crushing. Symptoms occurring for weeks without
worsening consider stable angina. Usually relieved by rest or nitroglycerin SL.
· Approximately 75% of ischemic episodes are silent and not detected especially in diabetes.
· Treatment: Acute angina chest pain use nitroglycerine SL spray or tab or Chewable ASA 80 mg.
· The drug of choice angina with hypertensionà cardio selective BBs, or NTG-LA or CCBs,
· Angina with hypertension and diabetes or chronic kidney diseaseà ACEi
Drug of choice Second line therapies

1. Secondary prophylactic treatment for all 1. If patient contraindication to beta blockers, such
patient; ASA 325 mg enteric coated daily as reactive airway disease or experience side
2. Initial treatment of symptom with nitrates; effects with beta-blockers,
nitroglycerin SL tablets 0.3-0.6 mg PRN or Verapamil 80 mg tid or Verapamil SR 240 mg
nitroglycerin SL spray 0.4 mg PRN once daily
3. All patient who require regular treatment of 2. If patient intolerant to beta blocker and
symptoms should receive a beta-blocker; verapamil
Metoprolol 25-100 mg bid, nadolol 20-240 Nitroglycerine transdermal 0.4 mg/hr apply
mg once daily. morning, remove after 12 hrs.
or isosorbide mononitrate 20 mg in morning and
afternoon 7 hr apart
(Long acting nitrates to be used for a maximum
12 h/day. Nitrates should be used during high
risk periods e.g. times when angina is common
and overnight into early hours of morning.
PharmacyPrep.Com
Prinzmetal angina (vasospastic)

· Caused by spasm, do not increase MVO 2 Question Alerts!
· Mainly due to atherosclerosis Drug of choice to treat prinzmetal
· Symptoms. Pain usually occurs at rest awakens from angina?
sleep.
· Characterized by recurrent, prolong attacks of severe
ischemia.
· Treatment. The drug of choice is CCBs (nifedipine, amlodipine)
· Acute chest pain use nitroglycerine SL spray or tab
Acute coronary syndrome (ACS): Term describes the symptoms that may lead to acute myocardial infarction
(acute MI) or heart attack. Acute MI further characterized as STEMI and NSTEMI and as well as unstable angina.
Diagnosis:
· Chest pain: Generally lasting for >30 min Question Alerts!
· 12-lead ECG. ST segment elevation What are the biochemical
· Cardiac isoenzymes: cardiac troponin T or I elevated. and CK- markers for MI diagnosis?
MB elevated
· Echocardiogram to identify the site and severity of wall motion abnormalities.
· Patient presentation: Diaphoresis (sweating), nausea, vomiting, weakness, and shortness of breath, arm
tingling, and syncope. May confuse as heartburn symptoms.
NSTEMI. STEMI
Partial blockade of coronary blood flow. Completely occlusive thrombus
Involves only subendocardial myocardium Effect entire thickness of myocardial wall. Cause
ST depression or NO ST elevation on ECG myocardial necrosis.
Positive: CK-MB and Troponin-I ST segmen
Drug of choice anticoagulants Heparin. or t elevation on ECG
Antiplatelet (ASA or/and clopidogrel More extensive damage
Positive. CK-MB and Troponin I
Drug of choice. Thrombolytic (Alteplase) are time
dependant therapy or angioplasty.
Stent: ASA + clopidogrel for 1 yr
PharmacyPrep.Com
UA: Unstable angina, STEMI: ST segment elevated myocardial infarction, NSTEMI: Non-ST segmented elevated
Myocardial infarction, GPI; Glycoprotein IIb/IIIa receptor antagonists.
NSTEMI
· Caused by disruption of an atherosclerotic plaque or formation of platelet aggregation thrombus.
· Symptoms: Crushing chest pain that can radiate to neck, back, shoulders, arms and jaw. Pain is similar to
angina but more severe. May occur at rest and may be caused by less exertions.
· Pain is NOT relieved by NTG
· Diagnosis: Chest pain is NOT relieved by NTG and persist longer than 5 min.
· Treatment: MONA therapy: Morphine à Oxygen à Nitrates à ASA; BBs without ISA or CCBs à Heparin or
LMWH
STEMI
· The most common type MI (85%) is due to thrombus formation caused by precipitated by atherosclerosis
plaque rupture. This propagated thrombus leads to occlusive thrombus.
· The complete blockade due to occlusive thrombus results in persistent ischemia that clinically manifest as
STEMI. If this is not treated, occlusion of coronary arteries can lead to sudden cardiac death.
· Symptoms: similar to UA/NSTEMI, however it is common in women, elderly, and DM.
Post MI
Patient with stent gets ASA 81-325 mg+ clopidogrel 75 for one year.
Tips
1. Nitroglycerin 2. Amlodipine 3. Ca channel blockers
4. Nitrates 5. Nitrites (Na Nitroprusside) 6. ASA
7. Heparin 8. Dihydropyridine 9. Clopidogrel
10 LDL >2.2 mmol/l 11 Beta blockers 12 Thrombolytic
13 Diltiazem 14 verapamil 15 Ticlopidine
16 Atherosclerosis 17 Nitric oxide (NO) 18 Room temperature
19 Neutralization
· What is the most common cause of ischemic heart diseases (atherosclerosis) LDL
· What drug is effective for acute and chronic angina ( )
· What are the treatment of choice in patients with coronary arterial spasm ( )
· What is used for STEMI treatment (ST-segment elevation MI) ( )
· What is used for NSTEMI treatment (Non-ST-segment elevation MI) ( )
· What drug acts on peripheral vascular system that causes reflex tachycardia ( )
· What appropriate drug for those who cannot take ASA ( )
· Symptoms of stable angina à Chest pain, shortness of breath, pain radiating to left arm
(True/False)
· What is the drug of choice for stable angina à ( )
· Prinzmetal angina may causes due to à vasospasm
· What is the drug of choice for prinzmetal angina is à
· What antiplatelet drug has Neutropenia side effectà
· A patient is intolerant or allergic ASA, should get alternate drug of prophylaxis for vascular diseases
à
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· Nitroglycerin act as smooth muscle vascular dilator due to à

· Venous pooling effect is caused by à
· Nitroglycerin storage conditions à
· What is the drug of choice for STEMI à
· What are the examples of LMWH à Enoxaparin, Dalteparin, Tinzaparin, Nadroparin
· Mechanism action of LMWH àBlocks blood clotting factor 10a and IIa
· What laboratory test is used for monitoring LMWH à None
· Headache is side effect of à
· Protamine sulphate is antagonist of heparin, which react by à
· What kind of pain occurs in heart attack? Referred pain
· Referred pain is? pain localized at one location however origin is from another organ
· Patient with asthma and stable angina, the drug choice is? CCBs
Select True or False statements:

· Symptom of coronary artery diseases? chest pain, sweating, shortness of breath (True)
· IV dosage of form of nitroglycerin is the fastest acting or have rapid onset of action? (True)
· Nitroglycerin onset of iv ( 1 to 2 min), SL ( 1 to 5 min), oral (40 min), ointment (20- to 60), patch (
40 to 60) (True)
· Alteplase is least likely used after myocardial infarction after 6 hr of acute attack? (True)
· Nitroglycerin SL spray is used to relieve angina symptoms (True)
· nitroglycerin SL spray should spray on or under the tongue(True)
· nitroglycerin SL spray should store at room temperature(True)
· nitroglycerin SL spray do NOT require shaking before use(True)
· nitroglycerin SL spray relieve angina symptoms(True)
· nitroglycerin iv is faster acting than nitroglycerin SL (True)
· LMWH have predictable response thus no monitoring required(True)
· Heparin is the drug choice anticoagulant in pregnancy(True)
· Warfarin is monitored by PT and INR(True)
· warfarin should not be taken with vitamin K supplements(True)
· Protamine sulphate is antidote of heparin(True)
· With isoniazid take vitB 6 , with levodopa avoid vitamin B 6 , with warfarin avoid vit. K. (True)
· Isotretinoin and tretinoin avoid vitamin A because analogs of vitamin A and Phenytoin &
methotrexate take folic acid(True)
· Coumarin derivatives anticoagulants is used as rat poisoning? (True)
· Angina, MI, transient ischemic stroke medical conditions are associated with ischemia.
· Omega 3 polyunsaturated fatty acids are abundant in fish oils? (True)
· Ecosapentanoic acid (EPA) and docosahexanoic acid (DHA) are derived from Omega 3(True)
www.pharmacyprep.com Stroke
87
Stroke
Questions Alerts!
· Symptoms of stroke sudden dizziness, headache, confusion, blurred vision, and
fainting.
· Stroke risk factors. Coronary artery disease, DVT, high cholesterol, and age.
· Transient Ischemic attack ASA.
· Acute stroke therapy. Alteplase or anticoagulant
Stroke symptoms: Headache, dizziness, blurred vision, confusion, and incoherent speech.
F = face changes (ask patient to smile, one side drops)
A = arms drifting (raising hand can drift)
S = speech change (cannot repeat the same sentence)
T = Time (every second 1 brain cell die)
Lab tests: CT brain scan (to rule out hemorrhagic process).

ESR (to test hypercoagulable state)
ECG (exclude atrial fibrillation)
MRI to confirm the diagnosis.
Primary prevention of vascular diseases: Secondary prevention of vascular disease

(Transient ischemic attack)
Early recognition and management of Management of risk factors after patient has
modifiable risk factor such as poor diet, suffered vascular event.
sedentary lifestyle, obesity, high BP,
cholesterol, DM and smoking.
Drug of choice for the transient ischemic

attack? ASA 81-325 mg
The drug of choice for the secondary

prevention in patient with atrial fibrillation?
Warfarin or anticoagulants
What is the drug of choice to prevent
cardiogenic stroke? Warfarin or
anticoagulants.
Transient ischemic attack (TIA); Acute stroke:

deficiency of oxygen (ischemia) in brain cerebral hemorrhagic, thrombotic and embolic
tissues. The drug of choice is ASA 81 mg stroke.
Pharmacotherapy
Anti-platelets. ASA, Clopidogrel, Ticlopidine, Dipyridamole/ASA
DOC: 2nd prevention of Noncardioembolic ischemic strokes
ASA. initial therapy (50-325 mg/day for prevention)
Clopidogrel – 75mg/daily, alternative agent, somewhat more effective < ASA alone Avoid grapefruit juice
ASA + Clopidogrel; should NOT be used for long-term secondary prevention of ischemic events (-bleeding)
Ticlopidine; 250mg bid, SE: diarrhea, skin rash, neutropenia (need monitoring). Not routine use
Dipyridamole SR/ASA; 200/25g bid, ¯ risk of stroke (mostly for ischemic stroke)
Anticoagulants; Warfarin, nicoumalone

DOC : 2nd prevention of Cardioembolic ischemic strokes prevent cerebral and systemic emboli in patients with
acute MI, valvular and nonvalvular AF and prosthetic cardiac valves. Nonvalvular AF and prior TIA/stroke ®
require INR of 3.0 instead of 2.5.
Drug of choice for stroke prevention? ASA

Drug of choice to treat acute stroke? Thrombolytic (alteplase)
Tips
________________________________________________________________________
Tips format 002: Stroke
1. Headache 2. Dizziness 3. Blurred vision
4. Confusion 5. Incoherent speech 6. Warfarin
7 ASA 8 Clopidogrel 9. Ticlopidine
10 Alteplase 11 BP>140/90 12 LDL>2.6 mmol/L
13 Chest pain
· The artery that supply blood to brain? Internal carotid artery
· What is not a stroke symptom? ( )
· Symptoms of stroke ( )
· What is the initial symptoms of stroke ( )
· What are the drugs of choice for long term prevention of atherothrombotic events ( )
· What are risk factors for stroke ( )
· What is the drug of choice for transient ischemic attack (TIA) ( )
· What is the initial therapy for stroke prevention ( )
· What drugs combination of drugs increases the risk of bleeding
( )
· What drug may give neutropenia infrequently but is potentially serious and require monitoring of CBC every
1 to 2 wks ( )
· What is not recommended routine protection of stroke ( )
· What drug prevents cerebral and systemic emboli in patient with acute MI ( )
· What drugs are used in within 3 hrs of acute ischemic stroke ( )

· Dizziness and head ache are the initial symptoms of stroke. (True)
· Pathophysiologic of cerebral ischemia are associated with carotid atherosclerosis that can result
into stroke. (True)
· ASA is the drug of choice for transient ischemic attack (TIA)? (True)
· Migraine headache is least documented risk factor of stroke? (True)
· Thrombolytics like alteplase should be used within 3 hours of stroke
· Seizures is not a symptom of stroke? (True)
PharmacyPrep.Com
88
Congestive Heart Failure
Questions Alerts!
· CHF symptoms dyspnea, fatigue, edema, weight gain
· CHF Treatment. ACEi. furosemide, digoxin
· Digoxin mechanism. + ve inotropic, -ve chronotropic and vagomimetic
· Digitalis toxicity. Quinidine, thiazides, loop, erythromycin, tetracycline, verapamil
· Digoxin CI's. Ventricular arrhythmias
· Digitalis toxicity symptoms: severe nausea vomiting, anorexia, muscular weakness, bradycardia, and
ventricular premature contractions. Severe toxic symptoms include: blurred vision, disorientation,
diarrhea, ventricular tachycardia, AV blockade which progress to ventricular fibrillation.
Symptoms: Typical symptom of CHF include dyspnea, fatigue and fluid retention (edema).
The primary manifestation of heart failure are dyspnea and fatigue that may limit exercise tolerance,
and fluid retention the may lead to pulmonary or peripheral edema. Other symptoms may include
paroxysmal nocturnal dyspnea, orthopnea (shortness of breath that prevents lying down), tachypnea
(rapid breathing), cough, ascites and nocturia.
Other symptoms include jugular venous distention, hepatojugular reflux, hepatomegaly (enlarged
liver), bibasilar rales, pleural effusion (increase in fluid in pleural surfaces), tachycardia, pallor (pale
skin) and S 3 gallop. Symptoms of advanced heart failure are the same but more severe.
Causes of CHF. In 65% of patient’s coronary artery disease is the cause of heart failure, other causes
include nonischemic cardiomyopathy example hypertension, thyroid disease or valvular disease. These
patients usually have reduced left ventricular dysfunction; usually ejection fraction is <40%.
Nearly 20 to 50% of patient with heart failure is secondary to diastolic dysfunction. This is often seen
in elderly.
Diagnostic tests
· The echocardiogram is one of the most useful diagnostic tests in CHF.
· B-type natriuretic peptide (BNP) is often in acute care at emergencies. The test is useful in
differentiating CHF exacerbations and other causes of dyspnea such as COPD, asthma or
infections. Patient dyspnea secondary to CHF will have elevated plasma BNP concentrations.
The most common type of CHF is left ventricular ejection fraction <40% is indicates systolic
dysfunction.
PharmacyPrep.
PharmacyPrep.Com
CO BP Renal Blood Flow Renin

&
Angiotensin II
CHF
Venous Aldosterone
Pressure
Capillary Na/H2O retension

Filtration
EDEMA
DRUG OF CHOICE
ACEi + Beta blockers titrate to target dose in all patient without contraindications.
(adjust therapy dose to control symptoms)
Ramipril 2.5-10 mg once daily + bisoprolol or carvedilol
Lisinopril 5-20 mg once daily
PERSISTANT SYMPTOMS
ADD ALDOSTERONE ANTAGONIST
If symptoms are uncontrolled by diuretics and ACEi+BB despite increasing dose (even
in patient with sinus rhythm add) digoxin 0.125-0.250 mg once daily.
If unable to use ACEi, ARBs

Use combination isosorbide dinitrate 20-40 mg tid with eccentric dosing AND
Hydralazine 25-75 mg tid.
Pharmacotherapy.
ACE Inhibitors (captopril, enalapril, lisinopril, ramipril, and trandopril)

· MOA: Inhibit potent vasoconstrictor ACEII, reduce mortality 20 to30%, ↑ CO, ↓BP and HR
· ACEi is assumed to be class effect . Aall patient with left ventricular systolic dysfunction should
receive.
ARBs (Candesartan, and valsartan). Same as ACEi
Beta blockers (Bisoprolol and carvedilol, labetalol, Metoprolol)

· MOA. Antagonize sympathetic activity and reduce mortality. Negative inotropic effect is a
disadvantage.
· Therapy. Bisoprolol and metoprolol b 1 selective and carvedilol a 1 , a 2 and b 1 receptor inhibitor are
effective.
Diuretics (hydrochlorothiazide, metolazone, furosemide, bumetanide, and ethacrynic acid,)

· MOA: ↓ Na/H 2 O retention by inhibiting reabsorption of Na in loop of henle
PharmacyPrep.
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· Side effects: hypotension, hypokalemia and hypo magnesia
Spironolactone and eplerenone

· Added to patient with chronic HF who remain symptomatic despite optimal use ACEi and BBs.
Aldosterone inh. Reduce mortality and morbidity.
Digoxin
· Does not decrease mortality only produces symptomatic relief and reduce rate of admissions to
hospital both overall and for worsening heart failure.
· Digoxin potentially more useful in patients with functional class III-IV or cardiomegaly or chest
roentoenogram.
· Drug interactions: verapamil, amiodarone, tetracycline, erythromycin, quinidine, and hypokalemic
drug loop and thiazides gives digitalis toxicity
CCBs (amlodipine, felodipine).

CCBs: Only dihydropyridine CCBs are used or least likely used and non dihydropyridine CCBs diltiazem
and verapamil are not used in CHF.
Verapamil and diltiazem are not used because –ve inotropic effect
Vasodilators: Hydralazine, isosorbide dinitrate, nitroglycerine, and nitroprusside

Inotropic agents (digoxin, milrinone, and dobutamine).
Tips
1. Digoxin 2. Digifab 3 Loop diuretics

4. Captopril 5. Verapamil 6 Thiazides
7 Dyspnea, fatigue 8 Impaired left ventricular (LV) function 9 Fluid retention
and ¯ LV reserve
10 Systolic HF 11 Edema 12 Milrinone
13 Dobutamine 14 ACEi 15 Beta blockers
Symptoms of congestive heart failure ( )

· Characterized as congestive heart failure ( )
· Initial CHF symptoms include à ( )
· What is the common type CHF characterized by decreased pump function, dilatation of LV, and
decreased LV ejection fraction ( )
· What is the most widely used cardiac glycoside ( )
· What drug should be avoided in ventricular arrhythmias ( )
· What it is the antidote for digoxin toxicity ( )
· What drugs that increase digoxin levels ( )
· Decrease Na/H 2 O retention by inhibiting reabsorption of Na in loop of henle ( )
· What drugs has the most common side effect of cough ( )
· What drugs decrease K levels ( )
· Examples of positive (+ve) inotropic agents à
· Examples of negative (-ve) inotropic agents à
PharmacyPrep.
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· The drug of choice for CHF ( )

· What is the major cause CHF? MI or CAD
· ACEi monitor? renal function test (serum creatinine), K+ and BP.
· Pulmonary edema? Left ventricular heart failure.
· What cardiovascular drug causes salt and water retention which may lead to CHF ( )

· Symptoms of left ventricular heart failure cause à pulmonary edema (True)
· Symptoms of right ventricular heart failure cause àperipheral edema
· Weight loss is NOT a symptoms of congestive heart failure? (True)
· ACEI, furosemide, and digoxin are the drug of choice for CHF? (True)
· Beta blockers are NOT a positive inotropic drug? (True)
· Digoxin, beta agonist and phosphodiesterase inhibitors
PharmacyPrep.
www.PharmacyPrep.Com Antiarrhythmic drugs
89
Arrhythmias
Questions Alerts!
· Mechanism of Class Ia, Ib, Ic, II, and III drugs
· Examples of Class Ia, Ib, Ic, II, and III drugs
· Atrial fibrillation is an irregularly, irregulary supraventricular rhythm with consistant atrial activity (P
Wave). Atrial flutter is regular supraventricular rhythm with characterisitic of flutter wate (saw tooth
wave).
· Treatment of atrial fibrillation (P Wave) and atrial flutter
· Amiodarone SEs, drug interaction and Monitoring
Symptoms: It is mainly related to poor cardiac output i.e. dizziness, syncope, chest pain, fatigue, comfusion and
exacerbation of heart failure.
· Tachyarrhythmias. May have palpitation.
· Atrial fibrillation/flutter. May experience signs and symptoms of transient ischemic attack or stroke.
· Ventricular tachycardia and ventricular fibrillation may be asymptomatic.
ECG, holter monitor or loop monitor.

Echocardiography to assess left ventricular function, and left atrial size valvular status.
Types of arrhythmias
Supraventricular (atrial) SVA Ventricular arrhythmias (VA)

· Premature atrial contraction Premature ventricular contraction (PVC)
· Atrial flutter Ventricular tachycardia (VT)
· Atrial fibrillation (left atrium) Ventricular fibrillation (VF)
· Paroxysmal supraventricular tachycardia (PSVT)
· Sinus tachycardia
· Sinus bradycardia
Atrial fibrillation: Atria beat irregularly
Atrial flutter: Atria beat faster than ventricles (like atrial beat 4 time and ventricular beat 1 time.)
RATE CONTROL DRUGS RHYTHM CONTROL DRUG

DRUGS THAT ¯HR DRUGS THAT CONTROL RHYTHM
BETA BLOCKERS AMIODARONE, DRONEDARONE,
CCB (VERAPAMIL & DILTIAZEM) AV NODE QUINIDINE, SOTOLOL
Supraventricular Tachycardia. The drug of choice is rate control drugs such as verapamil and beta blockers.
Atrial fibrillation: the drug of choice for mild is dronedarone, procainamide, or sotolol.
The drug of choice for moderate to severe is amiodarone and anticoagulants (heparin or warfarin)
Ventricular fibrillation (ventricular rate > 250 bpm), managed by cardioversion.
Cardioversion Defibrillation
Elective procedure Emergence procedure
Used to change the heart from atrial Electrical shock treatment use to change the heart
fibrillation to a normal rhythm from life threatening cardiac rhythm to normal.
praventricular (atrial) SVA treatment. Rate control drugs

· Cardiac glycoside (digoxin), Beta blockers (Propranalol, atenolol, metoprolol, nadolol), CCBs (verapamil and
diltiazem), Antiarrhythmic class 1C: flecainide, propafenone; Antiarrhythmic Class III: Sotalol, Amiodarone,
and dofetilide
Ventricular tachycardia treatment

· Class 1A (quinidine, procainamide); Class 1B (mexiletine); Class 1C (flecainide, propafenone); Class III
(sotalol, Amiodarone); Beta blockers (metoprolol)
Antiarrhythmic Drugs Classification
Class I Class II Class III

Ia-Na+ channel b-blockers K+ channel Class IV
blockers inhibitors Ca2+ channel
Esmolol
Quinidine Amiodarone blockers
Propranolol
Procainamide Bretylium Verapamil
Timolol
Disopyramide Dofetilide Diltiazem
Atenolol
Sotolol Nifedipine Miscellaneous
Metoprolol
Ib: Lidocaine Nadolol Adenosine
Mexiletine Magnesium
Tocainide
Ic: Flecainide
Propafenone
1a Quinidine, procainamide Slows phase 0 depolarization

disopyramide
1b Lidocaine Shortens phase 3 repolarization (shortens duration of refractory
period)
1c Flecanide, propafenone Significantly slow phase 0 depolarization (slow conduction)
II Propranolol Decrease phase 4 depolarization (beta 1 blocker action)
III Amiodarone and sotalol Prolong phase 3 repolarization (increase refractory period)
IV Verapamil Shortens action potential (increase refractory period AV node)
Tips
1. Quinidine 2. Amiodarone
3. Propranolol 4. Lidocaine
5. Procainamide 6. K Channel blockers
7. phase 1 to 3 8. Phase 3
· Slows phase 0 depolarization ( )

· What class drugs prolong phase 3 repolarization (increase refractory period) ( )
· What drugs is used to treat cardioversion related arrhythmias ( )
· Competitively block catecholamine induced stimulation of beta receptor thereby suppress phase IV
depolarization ( )
· Chronic use of this drug may cause lupus like syndrome( )
· When taking this medication grapefruit juice should be avoided ( )
· Drugs that cause QT prolongation (torse des pointes) ( )
· What phases of action potential curve have no effect of stimuli à ( )
· What is relative refractory period is à ( )
· Phase I action potential is 40 (+ve) due to à
· What drug causes QT prolongation (torse des pointes)à ( )
· Digoxin is contraindicated in what type of arrhthmiasà
· Class Ia drugs act on à
· Proarrhythmic drugs are à

· Amiodorone side effects are: Photosensitive reactions, skin pigmentation, blurred vision, pulmonary toxicity,
and pneumonitis. (True/False)
www.PharmacyPrep.Com Peripheral Vascular Diseases
90
Peripheral Vascular Disorders
Questions Alerts!
Deep vein thrombosis symptoms and treatment.
DVT risk factors: Immobility, age >50 y, history of DVT, obesity, major surgeries (Hip, knee), paralysis (after
stroke), CHF, CAD, deficiency of protein C and S and smoking.
· Reynaud's phenomenon treatment AND intermittent claudication.
· Drug should avoid in peripheral vascular disorders and BBs, ergot alkaloids
Fig 90.1
Peripheral vascular disease occurs in arteries and veins of periphery, other than heart and brain.
Peripheral Vascular Diseases
Disease of Veins Disease of Arteries

Venous blood clots Arterial blockage
Pulmonary embolism Aortic aneurysms
Phlebitis Buerger’s disease
Varicose veins Reynaud's phenomenon
Intermittent claudication
Venous Thromboembolism (Fig 90.1)

Deep vein thrombosis (DVT) is obstruction of vein by blood clot. It is most common within the deep veins of calf
muscles of the leg. The affected leg may become swollen and tender. The main risk is that the clot may become
detached and give rise to pulmonary embolism.
DVT symptom can cause pain in popliteal area. Calf swelling, pitting edema, entire leg swelling. Localized
tenderness along the distribution of vein system.
Diagnosis: Doppler Test and ultrasound.
Non-pharms: Regular exercise of leg and anticoagulant therapy are used for prevention and treatment.
The drug of choice for prevention and treatment if LWMH or heparin.
Drug of choice for prophylaxis (prevention) of DVT in hip replacement or knee replacement surgeries? LMWH
(enoxaparin) or heparin
The drug of choice of DVT in pregnancy? LMWH or heparin.
Treatment: LMWH (enoxaparin, dalteparin, tinzaparin, nadroparin), specific factor Xa inhibitors (fondaparinux)
and unfractionated heparin (heparin) and warfarin.
LMWH are approved for prophylaxis and treatment of DVT.

Heparin is prophylaxis only.
Warfarin is to target INR 2-3.
Prophylaxis Drugs (LMWH & heparin). Graduated compression stockings and intermittent
pneumatic compression devices, and caval interruption by filters.
Treatment For treatment of established DVT and/or PE start oral warfarin together with sc
LMWH, or iv UHF. The LMWH or UHF is continued for minimum of 5 days or until the
INR is therapeutic for at least 2 days. The duration of oral anticoagulant is dependent
on the risk of recurrence of VTE.
LMWH In most analysis of treatment of VTE, LMWH use has typically more effective and less
costly overall compared to unfractionated heparin.
During LMWH or heparins is the anticoagulant of choice during pregnancy. Injection sc twice
Pregnancy a day to achieve the therapeutic levels. Warfarin or UFH may be used for about 6
weeks after delivery for secondary prevention.
Arterial Thromboembolism
Acute Heparinized (80 u/kg) followed by thromboembolectomy (thrombolytic treatment in
therapy all patients).
Chronic Warfarin (maintain INR 2-3 for cardiac source; 2.5-3.5 for prosthetic mechanical
therapy valve). If the risk of recurrence become high (e.g. cardiac source, significant vascular
disease or abnormality of coagulation cascade) we can consider ASA in combination
with warfarin
Combination of glycoprotein IIb/IIIa receptor inhibitors with thrombolytic therapy
may improve outcomes for arterial thrombosis
Intermittent Claudication (Fig 90.1)
Intermittent claudication is a cramping pain, induced by exercise and relieved by rest, that is caused by
inadequate supply of blood to the affected muscles. It is most often seen in the calf and leg arteries. The pulses
are absent and feet may be cold.
Antiplatelets Antiplatelets agents reduce vascular death in high-risk patients about 25% and
agents are equally effective in those with coronary artery disease and PAD.
ASA is the drug of choice.
Clopidogrel Clopidogrel may be more effective than ASA in patients with PVD but is usually
reserved for those who cannot tolerate ASA or continue to have events while on
ASA
ACE inhibitors ACEi reduce the risk of ischemic events beyond that expected from lowering
blood pressure in patients with (PAD).
Ramipril Ramipril demonstrated similar effects in patients with or without PAD.

Contraindications Beta blockers (use cautiously in sever disease with hypertension).
Rheologic modifiers à pentoxifylline
Reynaud's Phenomenon
Reynaud's phenomenon is a condition in which arteries of the fingers

Question Alerts!
become spastic (vasospastic). This may result from atherosclerosis,
Reynaud's Phenomenon is NOT
connective tissue disease, ingestion of ergot alkaloids, or frequent use
caused by plaques!
of vibrating tools.
Reynaud’s phenomenon is due to result of over sensitive blood vessels
in the body extremities. It is characterized by a pale to blue to red sequence of color changes in extremities.
Non-Pharmacological Choices. Minimize cold exposure, and use warm gloves

Therapy. The drug of choice is CCBs (nifedipine XL, felodipine, amlodipine) and diltiazem
· Alpha blocker à prazosin

· PGI 2 analog à iloprost
· Peripheral vasodilator may relieve this condition.
Contraindications: Avoid prescribing medications with vasoconstrictive potential: ergot derivatives,
methysergide and beta-blockers.
Medication taken daily (as opposed to PRN) during the winter will increase tolerance
to side effects (headache).
CCB of DOC is CCBs
dihydropyrid CCB of dihydropyridine class (e.g. nifedipine XL 30 mg or felodipine 5 to 10 mg)
ine should be used 60 minutes before cold exposure.
PGI 2 analog i.v. iloprost (PGI 2 analog) may be useful for short term use; oral iloprost is less
effective
CI Ergot alkaloids, methysergide and beta blockers?
Tips
Find answers from the table
1. Smoking 2. Obesity 3. Increase age
4. Immobility 5. Severe pain in legs 6. Pale finger tips
7. Effects extremities 8. Plaques 9. iv heparin
10 sc LMWH 11 Warfarin 12 fondaparinux
13 Embolism 14 Pulmonary embolism 15
· Risk factors of venous thrombosis ( )

· Symptoms of deep vein thrombosis ( )
· Symptoms of Reynaud's phenomenon ( )
· What is not a cause of Reynaud's phenomenon ( )
· What is the initial treatment of established DVT or PE ( )
· What is the first of a new class of antithrombotic agents, the specific factor Xa inhibitors. ( )
· Examples of vascular diseases à
· Symptoms of deep vein thrombosis à
· What is the pharmacotherapy for deep vein thrombosis à
· Intermittent claudication symptoms à
· Reynaud's phenomenon symptoms à
· What is the drug of choice in Reynaud's phenomenon à
· What drugs should be avoided in Reynaud's phenomenon à
Select True or False Statements:

· LMWH is the most important drug is used to prevent peripheral vascular diseases? (True/False)
· Anticoagulants like warfarin is commonly used to treat acute peripheral embolic disorders. (True/False)
· Beta blocker are least likely used to treat peripheral vascular diseases? (True/False)
· beta blocker cause vascular constriction thus it is contraindicated in peripheral vascular diseases
(True/False)
· Reynaud phenomenon symptoms occurs in limb extremities (True/False)
· Calcium channel blockers are the drug of choice (True/False)

· Reynaud phenomenon can be trigger cold exposure (True/False)
· Reynaud phenomenon is may occur in old age (True/False)
· arterial plaques risk factor intermittent claudication (True/False)
· estrogen/progesterone have risk of blood clots in peripheral vascular system(True/False)
· LMWHs like enoxaparin, dalteparin, tinzaparin, and nadroparin are approved for both prophylaxis and
treatment of venous thromboembolism (VTE) (True/
91
Chronic Pain Conditions
Three types of pain
Nociceptive pain: Caused by injury to body tissue. Aching, sharp, throbbing. E.g. osteoarthritis.
Psychogenic pain: Related psychological factor.
Neuropathic pain: Due to damage or dysfunction nerve, spine or brain. (touch sensitive). Examples diabetic
neuropathy, post herpetic neuralgia, trigeminal neuralgia.
Trigeminal neuralgia
· Trigeminal neuralgia is a cranial nerve disorder that involves malfunction of the trigeminal nerve
(cranial nerve V), which carries sensation from the face to the brain. Malfunction of the trigeminal
nerve produces bouts or severe, piercing pain lasting seconds to minutes.
· Since bouts of pain are brief and recurrent, typical pain medications are NOT usually helpful.
Carbamazepine (which works by binding to, and inhibiting the sodium channel) is the first line
choice, but phenytoin may be prescribed if carbamazepine does not work, or if it produces severe
side-effects. Baclofen, gabapentin, clonazepam, and valproic acid also help in some cases,
although these are inferior to CBZ. CBZ diminishes the pain associated with trigeminal neuralgia
within 24-48 hours.
· CTC7 neuropathic pain. Clinical experience shown that other therapies are inferior than CBZ but
may be helpful in adjunctive therapy.
· if some relief from TN, but SEs are not tolerable good strategy is to try oxcarbazepine, or lower the
CBZ dose or add beclofen.or phenytoin.
· Dose for trigeminal neuralgia 200 mg bid. stat, increased by 200 mg daily to max 1000 mg daily (in
divided doses).
Post herpetic neuralgia (PHN)

Herpes zoster (HZ), also known as shingles is a distinctive syndrome caused by reactivation of varicella
zoster virus (VZV). The risk of HZ increases with age, approximately half of all cases occur in persons
older than 60 years. One of the most common and debilitating sequele of HZ is post herpetic neuralgia
(PHN), defined as pain persisting more than 3 months after the rash has healed.
Herpes zoster lesions contain high concentrations of VZV, which can be spread by contact and by the
airborne route and which can cause primary varicella in exposed, susceptible persons. Less contagious
than primary varicella. Herpes Zoster contagious 2 days prior to infectious lesions and until the lesions
crust. Risk of transmission is reduced further if lesions are covered.
PHN drug of choice TCAs/ gabapentin/pregabalin

2nd line. SNRI duloxetine or venlafaxine/topical lidocaine 5% patch.
3rd line. Opioids, tramadol, fentanyl, methadone, marijuana (cannabinoids).
Acyclovir, famciclovir, and valacyclovir are nucleoside analogues that inhibit replication of human
herpes viruses, including VZV. When taken orally, these agents reduce the duration of viral shedding,
hasten rash healing, reduce the severity and duration of acute pain, and reduce the risk of progression
to PHN. Antiviral are the most effective if started within 72 hours of rash.
www.Pharmacyprep.com Anxiety Disorders
92
Anxiety Disorders
Questions Alerts!
· Common questions in pharmacy exam is to ask!
· Antidepressants mechanism and DI with MAOi
· Benzodiazepine classifications (intermediate acting BZDs daily) for max 2 to 4 wks.
· Anxiety is a normal response to fear, threat, or psychological stress and is experienced occasionally by every
one.
· Anxiety disorder involves a state of distressing chronic but fluctuating nervousness that is inappropriate in
certain circumstances.
· Anxiety disorder can be categorized into several types, such as panic attack, social anxiety disorder, social
phobia, obsessive-compulsive disorder, generalized anxiety disorder etc.
Cognitive behavioral therapy
Thought = what we think affects how we act and feel. E.g. I will not cope
Emotions = What we feel affects what we think and do. E.g. sweating, anxious
Behavior = What we do affects how we think and feel e.g. want to get away or not attend at all.
Panic attack and panic attack with or without agoraphobia

Panic is acute, short lived, extreme anxiety with some physical symptoms. This could occur any anxiety disorder
person with any specific situations. For example, a person with phobic of snake may panic when encounter with
snake. Patient may actively avoid situations in which panic attacks are predicted to occur. Intolerance of physical
symptoms of anxiety.
1s line SSRI, or SNRI
2nd line Benzodiazepine
Often clinically a small dose of long acting BZD is prescribed with SSRI/SNRI to provide more immediate
relief.
Social anxiety disorder (SAD) and (or) social phobia

· Excessive or unrealistic fear of social or performance situations. Intolerance of embarrassment or scrutiny by
others.
· Specific phobia: Excessive or unreasonable fear of a circumscribed object or situation usually associated with
avoidance of the feared object (for example, an animal, blood, injections, heights, storms, driving, flying, or
enclosed places).
The drug of choice for Generalized social anxiety SSRI or SNRI
Specific phobia like stage fear propranolol
Obsessive compulsive disorder (OCD)

· Presence of obsessions. Recurrent, unwanted, and intrusive thoughts, images, or urges that cause marked
anxiety (for example, thoughts about contamination, doubts about actions, distressing religious, aggressive,
or sexual thoughts).
· Compulsions. Repetitive behaviors or mental acts that are performed to reduce the anxiety generated by
the obsessions (for example, checking, washing, counting, or repeating).
The drug of choice is SSRIs.
· 2nd line clomipramine
· Generalized anxiety disorder (GAD)

· Uncontrollable and excessive worry occurring more days than not, about a number of everyday, ordinary
experiences or activities. Often accompanied by physical symptoms (for example, headaches or upset
stomach). Intolerance of uncertainty.
Post traumatic stress disorder (PTSD): Occurs after a traumatic event to which patient responds with intense
fear, helplessness, or horror; patients relive the event in memory, avoid reminders of the event, and experience
emotional numbing and symptoms of increased arousal. Intolerance of experiencing trauma.
The drug of choice for PTSD SSRI or SNRI.
The drug of choice for Nightmare, prazosin.
Reference: DSM-5. Diagnostic and statistical manual of mental disorder 5th ed.
Anxiety clinical practice guidelines

Cognitive behavioral therapy + BZD (daily) for 2 wks à SSRI or SNRI + CBT
Anxiety Cognitive PD SAD OCD GAD PTSD

disorders behavior therapy
(CBT)
SSRIs
Fluoxetine (Prozac) Y
Fluvoxamine (Luvox) Y
Paroxetine (Paxil) Y Y Y Y Y
Paroxetine (Paxil CR) Y Y Y
Sertraline (Zoloft) Y Y
Dual action antidepressant
Venlafaxine (Effexor XR) Y Y Y
Azapirones
Buspirone (BuSpar) Y
5HT1a agonist
Benzodiazepines
Propranolol Y (stage
ear)
Reference: Can J Psychiatry, Vol 51, Suppl 2, July 2006

The Merck Manual of medical information
Treatment choices are modified from data from Compendium of Pharmaceuticals and Specialties 2016
Tips
1 Benzodiazepines 2. Flumazenil 3 Fluoxetine
4 Sertraline 5. Paroxetine (Paxil) 6 Fluvoxamine
7 Venlafaxine 8 Paroxetine (Paxil CR) 9 Buspirone
· What are minor tranquilizers used to treat insomnia and anxiety ( )

· What it is the antidote for benzodiazepine ( )
· What drugs that are use for Obsessive-Compulsive Disorder (OCD) ( )
· What drugs that are use for Post Traumatic Stress Disorder (PTSD) ( )
· What drugs that are use for Generalized Anxiety Disorder (GAD) ( )
· What drugs that are use for Social Anxiety Disorder (SAD) & social phobia ( )
· Paroxetine is indicated for à
· Obsession is à
· Compulsion is à
www.PharmacyPrep.Com Depression
93
Depression
Questions Alerts!
· Antidepressants first line SSRI, Bupropion, venlafaxine, Mirtazepine, mocolbamide.
· Second line Tricyclic antidepressants
· Third line MAOi
· Serotonin syndrome. DIs with MAOi gives serotonin syndrome
· Dual acting antidepressants like venlafaxine, desvenlafaxine, bupropion, mirtazepine
· MAOi drugs interactions with sympathomimetics and antidepressants
· Side effects SSRI, SNRI, TCAs like amitryptiline, MAOi.
Depression is a feeling of intense sadness. It may follow a recent loss or other sad event but is out of proportion
to that event and persists beyond an appropriate length of time.
Signs and symptoms. Sadness, tearfulness, dejection, self-criticism, loss of ability to experience pleasure, loss of
appetite, inability to sleep and loss of libido. Depression can be categorized into major depression, and bipolar
depression.
The first line treatment of major depression is SSRIs, dual acting venlafaxine, mirtazepine and moclobemide. (if
one therapy fails try from the 1st line).
The treatment duration for one episode of major depression is 1 year.
The 2nd line therapy for major depression is TCA (Amitriptyline, nortriptyline)
3rd line is MAOi (phenelzine, tranylcypromine)
The drug of choice for the treatment depression and anxiety? Fluoxetine or SSRI
SSRIs: Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram, Fluvoxamine.

· SEs. Sexual dysfunction, GI, CNS. Nausea is the common.
· Discontinuation: taper slowly over four to 6 weeks. (particularly important for Paroxetine and venlafaxine).
· Fluoxetine can be used in children & adolescents & pregnancy. SEs: insomnia, potent CYP2D6 inhibitor
· Sertraline; least DI, Take with food, breastfeeding, SE : diarrhea
· Citalopram; least DI, breastfeed patient
· Paroxetine; breast-feed
· Escitalopram: isomer of citalopram
SNRIs: Venlafaxine, desvenlafaxine and duloxetine.

· SE: BP-(If dose >225 mg/day)
Dual action: Bupropion, mirtazepine, and trazadone
Bupropion: NE&DA reuptake inhibitor

· DOC: depression & smoking cessation
· CI: anorexia or bulimia nervosa, head trauma or prior seizure.
· SE: insomnia, sexual dysfunction (low rate)
Mirtazepine act on NE (directly) & serotonin (indirectly), alpha2 antagonist

SEs. Sadation, weight gain (GI & sexual dysfunction is less).
Trazadone: 5HT 2 antagonist with some serotonin reuptake inhibitory properties

· Excessive sadation (300 to 400 mg daily) ®as a hypnotic (50-100 mg)
· With other antidepressants
· SEs. drowsiness, priapism
TCAs: Desipramine, Nortriptyline, Amitriptyline, Imipramine, Clomipramine, Doxepin, Trimipramine

· 2nd or 3rd line agent
· SEs. Anticholinergic, orthostatic hypotension,
· Clomipramine. obsessive-compulsive disorder
· Amitriptyline: chronic pain, neuralgia, migraine prophylaxis, and depression.
· Nortriptyline – elderly depressed patients
Tetracyclic antidepressants – Maprotiline

· Higher risk of seizures than the others
MAOIs;
Reversible: Moclobemide
· Dietary precautions are NOT required at standard doses
· SE: nausea, insomnia (persist)
· Drug interactions: Avoid sympathomimetics (pseudoephedrine, ephedrine), meperidine.
· Caution with opioids, antihypertensives, antipsychotics, SSRIs, Selegiline, excessive tyramine, alcohol.
Reduce dose with cimetidine.
Irreversible: Phenelzine, Tranylcypromine

· Reserved for the treatment of resistant depression
· Food and drug cautions must be followed during treatment and for 2 weeks after the last dose of the
MAOi.
· DI: Sympathomimetics may ↑ BP, Meperidine may cause agitation, hyperpyrexia, circulatory collapse
· SSRIs, TCAs, levodopa may ↑ effects and side effects
· Tyramine containing food may cause hypertensive crisis.
Washout period
Generally, there is no need for a washout period, and a crossover technique can be applied (i.e., tapering one
agent while titrating the other).
· Exception
· Irreversible MAOI (phenelzine/tranylcypromine)® other antidepressants 2 weeks
· Moclobemide ® other antidepressants 5 days
· Fluoxetine ® an irreversible MAOI 5 weeks
· Caution: when starting other antidepressants after fluoxetine discontinuation.
Serotonin syndrome is an acute condition due to increase serotonin levels and develops within minutes to hours
(typically within 6 hours) after starting a medication, increasing the dose of a medication, or overdosing.
Signs and symptoms of Serotonin syndrome

Neurobehavioral confusion, agitation, coma, seizures
Autonomic Hyperthermia (fever), diaphoresis (sweating), tachycardia, hypertension, diarrhea
Neuromuscular myoclonus, rigidity, tremor (shivering), ataxia, nystagmus
Most cases are mild and resolve spontaneously within 24 to 72 hours. Cardiac arrest, coma, and multiorgan
system failure have been reported as consequences of serotonin syndrome.
Serotonin Syndrome
Serotonin syndrome occurs with the following agents. T =tremor
All SSRIs Miztazapine H = hyperpyrexia
Venlafaxin Moclobemide e = excessive muscle tone
Non selective MAOi S = shivering, seizure
Dextromethorphan H = hypertension
Linezolide A = agitation
N = neuromuscular pain
The syndrome is possible when these agents are combined with. C = coma
-each other D = Death
-MAOIs
-lithium, meperidine, pentazocine, and dextromethorphan
Discontinued symptoms. Fatigue, nausea, dizziness, and lightheadedness, tremors, chills, insomnia, anxiety and
diaphoresis are the most common effects of abrupt discontinuation of SSRIs.
Serotonin syndrome are tremors, delirium, excitement, anxiety, diaphoresis, rigidity, increase temp
(fever), clonus, increase reflexes, increase HR, either increase or decrease blood pressure.
Withdrawal. Flu, insomnia, nausea, imbalance, sensory disturbances, and hyperactivity. Tremors
Symptoms Serotonin syndrome Withdrawal symptoms (FINISH)
Autonomic Diarrhea, Fever, Shivering, Flu like fever, chills, dizziness, light
symptoms change in BP, and & N, V headed, N &V, sleep disturbances
Neuromuscular Tremors, seizure, myoclonus, Myalgia, lethargy, sensory disturbances
Dysfunction hyper reflexes
Cognitive Agitation, Confusion, Not present
hypomania
Trazodone: potent postsynaptic serotonin (5HT 2 ) receptor antagonist, with weak serotonin reuptake inh.
SNRI: Venlafaxine, duloxetine and desvenlafaxine.

Desvenlafaxine is active metabolite of venlafaxine.
Antidepressants Highs Side effects Lows side effects

Mirtazepine Weight gain Nausea & vomiting
Bupropion Low Sexual dys. & low weight gain
Trazadone Sedation Insomnia
Fluvoxamine Drug interaction
Sertraline Drug interaction.
Fluoxetine T 1/2 , Washout period Weight gain
Moclobamide DIs Sexual dysfunction
Tips
1. Phenelzine 2. Moclobemide
3. Mirtazepine 4. Venlafaxine
5. Bupropion 6. Lithium
7. Trazodone 8. Fluoxetine
9. Amitriptyline 10. SSRI
11 TCAs 12. MAOInh.
· Drugs selectively blocks the prejunctional neuronal reuptake pumps in the CNS ( )
· What is the most anticholinergic and sedative TCA ( )
· What drug is used to treat depression with insomnia, what is therapy ( )
· What antidepressant requires 5 weeks washout period ( )
· Antidepressant also used for smoking cessation ( )
· What drug is used to treat depression in sexual dysfunction, what is the best therapy ( )
· An example of an irreversible non selective MAO ( )
· it is the only reversible & selective inhibitor of MAO that is currently available ( )
· Drugs acts directly on noradrenergic system & has low rate of GI and sexual side effects but is associated
with sedation and weight gain ( )
· Antidepressant also use for generalized anxiety disorder (GAD) ( )
· Its is used in prophilactically in treating manic-depressive patient, treat manic episodes & bipolar depression
( )
· What drug serum level should not exceed 1.5 mEq/L (6)
· SSRI onset of action is à
· Fluoxetine washout period à
· Drug of choice in depression with sexual dysfunction à
· Depression with insomnia à
· Depression with diabetes à
· Depression with diabetes, the drug of choice for major depressionà
· Higher dose of venlafaxine (225mg/day) have effect on à
· A patient on antidepressants and shows with dilated pupil, may be due toà
· TCA onset of action is à
· A substance found commonly in fermented foods which can be toxic when MAO inhibitors are usedà
· MAO is classified as à
· SSRI like fluoxetine inhibit cytochrome CYP2D6 (True/False)
· Mirtazepine may cause higher weight gain (True/False)

· Avoid cheese with à
· Milk + MAOI à
· St. John wort has antidepressant effect (True/False)
· Serotonergic symptomsà
· The drug of choice against bipolar disorders and manic depression -->
· Lithium toxicity symptoms -->
· What antidepressant is used as pharmacotherapy for smoking cessation à
· Paroxetine therapeutic use -->
· What antidepressants are NOT used to treat bulemia and anorexia nervosa -- à
Select TRUE OR FALSE Statements

· Buprapion, trazadone and mirtazepine have least sexual dysfunction (True/False)
· Take SSRI in the morning and TCAs in evening or bedtime (True/False)
· Normal blood levels of lithium in adult should not exceed is 1.5 mEq/L (T/F)
· Lithium concentration varies with Na+ ions (True/False)
· Li+ conc. increases with decrease Na+ and Li+ conc. decreases with Increase in Na+ (T/F)
· ACEI, NSAID, Thiazides, decreased renal perfusion à increase Li toxicity
· Fluoxetine (SSRI), dehydration and renal dysfunction increase Li+ toxicity(T/F)
Pharmacyprep.com Antipsychotic Drugs
94
Anti Psychotic Drugs
Symptoms: The schizophrenic individual is out of touch with reality, hallucinates, hears voices and exhibits
bizarre behaviour. These symptoms are only one aspect of schizophrenia. Other symptoms are social
withdrawal, and an inability to communicate or to concentrate.
Positive Symptoms Negative Symptoms

Reality distortions: Delusions persecution Blunted affect: Lack of expressed emotion,
Grandiosity, thought broadcasting, thought Poor eye contact and inattentiveness, and Reduced
insertion, loose associations, gestures, mind- spontaneity.
reading, and being controlled.
Alogia: Lack of spontaneity of conversation and poor
Hallucinations: Auditory (most common) ability to concentrate
Olfactory, somatic, and visual.
Avolation/apathy: Lack of interest in activities, no
Disorganizations. Disorganized speech motivation, social withdrawal and poor hygiene.
Incoherent speech. Tangentiality and Loose
association Anhedonia: Loss of pleasure and Few recreational
Disorganized behavior: Agitation, Hostility activates
Assaultiveness, Uncooperativeness, Inappropriate
sexual/social behavior, Inappropriate dress and Attentional impairment. Lack of ability to concentrate
catatonia. on tasks or conversation
Treatment. 1st & 2nd genereration Treatment. 2nd generation
· Severe case of psychosis (schizophrenia) or bipolar disorder à add mood stabilizers (Valproic acid,
carbamazepine)
· Drug of choice for acute agitation in seniorsà Quetiapine or heloperidol
· 1st or 2nd generation 4 to 8 weeks no response, change to 2nd line
· Severe case of psychosis (schizophrenia) or bipolar disorder à add mood stabilizers
· For 1 episode of psychosis, continue for 1 to 2 yrs and for 2 episodes, continue treatment for 2 to 5 yrs
Antipsychotics side effects are associated extrapyramidal

symptoms. Parkinsons like symptoms (tremors), akthisia (motor Parkinson's Symptoms
restlessness), tardive dyskinesia (inappropriate postures of neck, T = Tremor
trunk and limbs), and dystonia. R = Rigidity
Parkinson’s symptoms include T = Tremor, R = Rigidity, A = A = Akinisia
Akithisia, P = Postural instability P = Postural unstability
· 1st gen (haloperidol, loxapine, chlorpromazine, thioridazine) is
effective in positive schizophrenic symptoms. However, 2nd gen Extrapyramidal symptoms
(clozapine, risperidone, olanzapine, quetiapine) covers negative P = Parkinson's symptoms
schizophrenic symptoms. Olanzapine, not effective for the A = akthisia
treatment of resistance, and risperidone works for negative and D = dystonia
positive symptoms. T = Tardive dyskinesia
· Orthostatic hypotension is SEs of 2nd generation antipsychotics
(can cause additive effects with other antihypertensive drugs).
1nd generation Antipsychotics

Low potency
· Chlorpromazine. SEs. QT c prolongation
· Methotrimeprazine
Intermediate potency
· Loxapine, Perphenazine
· Zuclopenthixol –injectable FGA , long T 1/2, Do not use in antipsychotic-naïve patients
High potency
· Fluphenazine, Flupenthixol
· Haloperidol: with Lorazepam im for acute phase. SE: QT c prolongation
· Pimozide; SE : QT c prolongation with dose > 8mg/day (avoid use with sertraline)
· Thiothixene and Trifluoperazine
2ndgeneration Antipsychotics (SGAs)

· Advantage in first-episode psychosis, in improving negative symptoms, mood and cognitive deficits and in
preventing relapse and rehospitalization.
· First line treatment
· Depression in the acute phase effectivity SGAs>FGAs
· SEs. -glucose abnormalities
Clozapine: Only antipsychotic with proven efficacy in treatment-resistant schizophrenia

Not first-line (SEs. agranulocytosis, need for regular blood monitoring).
· Mechanism. Inhibit D (less), 5HT, H 1 , M and a1
· Side effects: Weight gain (greatest), hyperlipidemia, agranulocytosis > (1%), increase risk of diabetes,
dyslipidemia, orthostatic hypotension, and high weight gain
· Therapeutic use: Drug of choice in resistance psychosis, -ve and +ve symptoms
· MON: CBC q week
Risperidone:
· Risperidone-tabs oral disintegrating – do not split.
· Side effects: high hyperprolactenemia (dose-related). EPS
Olanzapine: SEs. Weight gain (greatest), hyperlipidemia, EPS (especially akathisia), least hyperprolactenemia
· Use for acute phase: do not combine with parenteral BDZs. (cardiac & respiratory problems)
· Olanzapine- orally disintegrating may stir into 125 mL of water, milk, coffee, orange juice or apple juice
consume immediately.
· Approved for acute treatment of mania
Quetiapine: SEs.Increase risk of diabetes, hyperlipidemia (-TG), and ¯ thyroid hormone levels. Least EPS.
Paliperidone is the active metabolite of risperidone.

Least sedation
Ziprasidone: Agonist activity at 5T 1A receptors and unlike other SGAs has antagonist activity of 5HT 1D . Must be
taken with food.
Aripiprazole: Partial agonist of D 2 and 5HT 1A . and potent antagonist activity at 5HT 2A receptor. Potential efficacy
in -ve symptoms.
least sedation.
Extrapyramidal side effects. (EPS. dystonia, Parkinsonism, akathisia, tardive dyskinesia, tardive dystonia).
Management. Prevention, use SGAs as first-line therapy.
if EPS occurs, first reduce dose, consider switch to SGA if on FGA, anticholinergics (benztropine, procyclidine and
trihexyphenidyl) should NOT be used prophylactically even with FGAs, and should usually only be used on a
short-term basis to treat parkinsonism associated with FGAs, anticholinergics are generally not recommended
with SGAs
Akathisia - if dose reduction is not effective® b-blockers (e.g., propranolol 10 to 120 mg/day); anticholinergics
are ineffective
Dystonia (acute torticollis or oculogyric crisis) ® IM benztropine or diphenhydramine (acute), followed by
reduction in dose or switch to SGA.
Neuroleptic malignant symptoms: Fever, muscle rigidity, Autonomic disturbance, fluctuation in BP, Tachycardia,
elevated WBC, and CK.
NMS is treated by dantrolene, or bromocriptine
Comparison of antipsychotic drug side effects

Typical (1st generation) Atypical (2nd generation)
High sedation (Chlorpromazine) Low sedation (respiradone)
High sedation (clozapine)
Low weight gain (haloperidol) High weight gain (clozapine)
High tardive dyskinesis Low tardive dyskinesia – clozapine
Low anticholinergic and sedation high anticholinergic side effects
High Sexual Dysfuntion Low sexual dysfuntion (quitiepine)
High EPS Low EPS (Clozapine, quetiapine)
Tips
1. Zuclopenthixol 2. Haloperidol 3. Chlorpromazine
4. Risperidone 5. Clozapine 6. Olanzapine
7. High EPS 8. Tardive dyskinesia 9. Weight gain
10. Agranulocytosis 11. WBC 12.
· 1st generation 4 to 8 weeks no response, change to 2nd generation.
· Severe case of psychosis (schizophrenia) or bipolar disorder à
· 2nd gen (clozapine, olanzapine) increase risk of lipids and diabetes, EXCEPT: Respiridone
· Least extra pyramidal symptoms à
· Highest EPS à
· Patient experiencing hallucination à
· Patient experiencing social withdrawal à
· 2nd generation coversà
· Schizophrenia is characterized by à
· Metoclopramide à
· Chlorpromazine à
· Tardive dyskinesia is caused by à
· TD symptoms à
· For resistance schizophrenia DOC à
· Mechanism of clozapine à
· Drug of choice for acute agitation in seniorsà
· it is not use in antipsychotic-naïve patients ( )
· it is the only antipsychotic with proven efficacy in treatment-resistant Schizphrenia ( )
· the most widely used treatment for psychotic agitation ( )
· it is used in patients experiencing withdrawal ( )
· this can cause lupus like syndrome ( )
· this should not combine with parenteral benzodiazepines ( )
· highest extrapyrimidal symptoms ( )
· WBC should be monitored because of high agranulocytosis ( )
· act on dopamine & serotonin receptors almost equally ( )
www.PharmacyPrep.Com Dementia
95
Dementia
· Dementia is a decline in mental ability that usually progresses slowly, in which memory, thinking, judgment,
and ability to pay attention and learn are impaired, and personality may deteriorate.
· Delirium: Acute mental disorder, with symptoms of acute agitation, hallucination, extreme excitement, and
disorientation.
· Delirium tremens: Acute psychosis caused by alcohol withdrawal.
· Dementia is a decline in mental ability that usually progresses slowly, in which memory, thinking, judgment,
and ability to pay attention and learn are impaired, and personality may deteriorate.
· Delirium: Acute mental disorder, with symptoms of acute agitation, hallucination, extreme excitement, and
disorientation.
· Delirium tremens: Acute psychosis caused by alcohol withdrawal.
5 A OF ALZEHEIMERS
APHASIA INABILITY TO EXPRESS ONSELF THROUGH SPEECH
AMNESIA MEMORY LOSS
ANOMIA INABILITY TO REMEMBER NAMES
AGNOSIA INABILITY TO RECOGNIZE OBJECT
APRAXIA MISUSE OF OBJECTS DUE TO FAILURE TO RECOGNISE
Severity of dementia
· Mild dementia. Forgetting daily activities. Example taking medicines, tel. phone number, finances,
directions.
· Moderate: Forgetting personal activities. Bathing, dressing, eating (remember upon reminders).
· Severe: Forgetting personal activities but cannot recall upon reminders.
· Terminal: Patient must be fed, immobile and mute.
· Alzheimers dementia is due to? Deficiency of acetylcholine.
Levy body dementia associated with psychosis.
Diagnosis: MMSE. Minimental scale exam is used to assess cognitive impairment.
Beta Amyloid plaques are found in? Alzheimers dementia.
Drug of choice of Alzheimer dementia? Donepazil

Drug of choice of Levy body dementia? Rivastigmine
Symptoms: Memory loss, disorientation, impaired executive functions, behavioural distrubances,

depression, psychotic disturbances, and inability to care for self.
reproduce without permission. This manual is being used during review sessions conducted by PharmacyPrep. 95-1
Risk factors. Age, family history (genetic link), head injury, and cardivascular risk factors.
To slow the progression of Alzheimers disease in patients with mild to moderate dementia.
Donepezil 5 mg once daily, if no improvement after 4 to 6 weeks increase to 10 mg once daily.
· Donepezil. Centrally active reversible, non-competitive. It selective and have greater affinity for AchEI in
brain than periphery. Little or no hepatotoxicity.
· Rivastigmine: is centrally selective arylcarbamate AchEI, it has short half life of 2hours, but able to inhibit
AchEI upto 10 hours. Because of slow dissociation of carbamate enzyme it is referred as pseudo-
irreversible AchEI.
Donepezil
Drug of choice for Alzheimer's dementia.
Mechanism · Centrally active reversible, non competitive. It selective and have greater
affinity for AchEi in brain than periphery. Little or no hepatotoxicity.
· Reduces the hydrolysis of acetylcholine, increasing the amount available in
the synaptic cleft.
Side effects GI effects. Nausea, vomiting and diarrhea.
DUMBLESS · CNS effects. Fatigue, insomnia, headache
· Other effects. Muscle cramps, anorexia, and difficulty in passing urine.
Dosage · Daily one dose in the morning or evening

· Initial 5 mg/day, target 10 mg/day adjust dose after 4 wk
Advantage · Toxicity may be ↑ by inhibitors of CYP2D6 or CYP3A4 (e.g. paroxetine,
erythromycin, prednisone, grapefruit juice, nefazodone).
Drug and Drug · Effectiveness may be ↓ by inducers of CYP2D6 or CYP3A4 (e.g.
Interactions carbamazepine, phenytoin, rifampin).
Monitor · Periodic checks may be performed to see benefit of drug.
Rivastigmine
Mechanism · Inhibits non specific butyrylcholinesterase and reversible

acetylcholinesterase or centrally selective arylcarbamate AchEi,
· It has short half life of 2 hours, but able to inhibit AchEi up to 10 hours.
Because of slow dissociation of carbamate enzyme it is referred as pseudo-
irreversible AchEi.
Side effects · Weight loss due to reduced appetite. Nausea, abdominal pain.
· Depression, agitation, confusion, drowsiness, dizziness
· Weakness, trembling, sweating, malaise, convulsions (rare).
Therapeutic · Drug of choice to treat Lewy body dementia.
use · Treatment of Lewy body dementia. Avoid antipsychotics
· Acute pain such as dysmenorrhea (painful periods).
Dosage · For rivastigmine, the initial dose is 1.5 mg PO BID, and can be doubled to 3
mg PO BID after 30 days, which is the minimum effective dose.
Galanthamine
Mechanism Selective, competitive, reversible acetylcholinesterase inhibitor and also

enhances the action of acetylcholine on nicotinic receptors.
Therapeutic use Effective in Alzheimer’s and vascular dementia.
Side effects Nausea, vomiting, abdominal pain, diarrhea, indigestion, decreased
appetite and weight loss, headache, dizziness, tiredness, sleepiness or
sleeplessness, confusion, runny nose, urinary tract infection, and falls.
Dosage 16- 32 mg bid.
Memantine. NMDA receptor antagonist.
Tips
1 Donepezil 2 Rivastigmine
3 Galanthamine 4 Memantine
5 Tacrine 6 Mild dementia
7 moderate dementia 8 decrease Ach
· Amyloid plaques are seen in which disease?
· What is non-selective & limited use because of its hepatotoxicity ( )
· What causes Alzheimer’s dementia ( )
· What is the drug of choice of Alzheimer’s dementia ( )
· The drug of choice or Effective in Alzheimer’s & vascular dementia ( )
· The drug of choice or Effective in Lewy body dementia ( )
· The drug that has anorexia side effect ( )
· What is effective for patients with dementia associated with Parkinson’s disease ( )
· N-methyl D-aspartate (NMDA) blocker (4) Memantin (Ebixa)à NMDA inhibitor.
· Forgeting instrumental activities of daily living (phone#s, driving direction, finances) ( )
· Forgeting daily personal activities (bathing, feeding, dressing), recalls upon reminders. ( )
· Alzheimers disease cause due to ( )
· Delirium is à acute agitation, lack of judgement and thinking.
· Amnesia isà short loss of memory
· What are the risk factors for Alzheimers disease à Age, gender, and family history, genetic?
· Levy body dementia à dementia with hallucination, the DOC is rivastigmine
· Galantamine is classified as à competitive, reversible acetylcholinesterase inhibitor
· Rivastigmine mechanism? Inhibits non specific butyrylcholinesterase and reversible acetylcholinesterase.
Terminology
· Aphasia : Impaired ability to communicate
· Amnesia: short time loss of memory
· Dysarthia: difficulty of speech
www.PharmacyPrep.Com Epilepsy
96
Epilepsy
Simple Partial: CONSCIOUSNESS IS NOT IMPRAIED like somatosensory warning also called auras.
Complex Partial: With alteration of consciousness. The patient may have periods of memory loss, automatism,
and aberrations of behaviour.
Generalized seizures. Have loss of consciousness and involvement of both Question alerts!
hemispheres. Generalized seizure can be sub divided by EEG and clinical What type of seizure conscious
manifestation. is NOT impaired?
Partial Seizure
Comments Drug of choice
Simple Seizures begin locally 1st Carbamazepine
partial Consciousness not impaired 2nd Phenytoin
With motor symptoms jerking, lip smacking, 3rd Primidone
chewing motions 4th Gabapentin
With autonomic symptoms. Sweating, pupil
dilation.
With behavioral symptoms
Complex Seizure begin locally Drug of choice
partial With conscious impairment 1st Carbamazepine
Begin as simple 2nd Phenytoin
With or without automatism (automatism: picking 3rd Phenobarbital
at cloths is common may follow visual, auditory 4th Valproic acid
hallucinations)
Generalized seizures
Absence True absence seizures (petit mal)à10 to 30 seconds, causes alteration of consciousness,
seizures (Petit starts with occasional blinking (Nystagmus).
mal) The drug of choice is ethosuccimide. Avoid phenytoin and carbamazepine use in absence
seizure.
Myoclonic Valproic acid, lamotrigine, and topiramate.

seizures Sudden very brief involuntary jerking of facial, limb, and trunk muscles or all body.
Tonic-clonic Tonic seizures generally occur in children, muscle stiffening (tone)
seizure (grand Clonic seizures. Sustained muscle contraction altering with relaxation.
mal) Sudden loss of consciousness, become rigid, falls to the ground, last about 1 minute.
Status Single prolonged seizure lasting more than five minutes. In some cases, no regain of
epilepticus consciousness between attacks. The drug of choice is iv diazepam.
Contraception
Enzyme inducing drugs such as carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone and
topiramate may - metabolism of both estrogen and progestins thereby may reducing their concentration by up
to 50%. Suggest need to increase the dose of estrogen from 35 mcg to 50 mcg. Midcycle bleeding may indicate
that estrogen levels are too low to block ovulation. Drugs that has no interactions with oral contraceptive
include gabapentin, valproic acid.
Anti-Epileptic Drugs Therapeutics

Iminostilbene Derivatives: Carbamazepine (initial dose 25-33% of projected maintenance dose; increase dose
q2-3 wks), adult 600-1600 mg/day divided bid to qid. Children 10-30 mg/kg/day bid or qid suspension. First line
therapy for DOC for partial seizures, tonic clonic seizures, treat trigeminal neuralgia
Carbamazepine: Side effects include transient neutropenia may worsen absence (petit mal) seizures Stevens
Johnson syndrome. Strong drug interactions ↑ clearance of warfarin, OCs, TCAs and risperidone
· Oxcarbazepine: SEs: hyponatremia, skin rash cross-reaction with carbamazepine and NO auto induction of
liver enzymes.
Hydantoin Derivatives: Phenytoin 300-400 mg/day, hs. Children

· Available as: Phenytoin 100% suspension & chewable. Phenytoin sodium (capsule & iv) are phenytoin 90%
sodium 10%
· SE: Skin rash, gingival hyperplasia, and nystagmus
· NOT effective for absence (Petit-Mal) seizures.
· Phenytoin suspension and chewing tablets are 100% phenytoin
· Gingival hyperplasia, recommend mouth hygiene and 0.15% chlorhexidine mouth rinse
· Space 30 min before or after food
· Swish and swirl then spit out.
Benzodiazepines (BDZs): Clobazam, Clonazepam, Diazepam, Lorazepam, Nitrazepam

· Rapid onset, tolerance
· Tolerance to therapeutic effects.
· Diazepam iv; used for status epilepticus
Succinimide Derivatives: Ethosuximide. The drug of choice for absence seizures only, few DI and least
teratogenicity. Initial dose 500 mg once daily, maintenance 1-2 g/d bid.
GABA Derivatives: Gabapentin, Vigabatrin

· SE: vision changes and trmors, and visual changes,
· Gabapentin: No DI, can use in liver failure, “add on”drug, TID dosing
· Vigabatrin: few DI, can use in liver failure, worsen absence seizures
· DI: No interaction with oral contraceptives
· Safe in pregnancy. Not metabolized. Can be used in liver failure.
· Gabpentin: Administration with Al/Mg, Ca antacid may ↓bioavailability.
· Gabapentin: drug of choice to treat trigeminal neuralgia, diabetic neuropathy.
· Vigabatrin: worsens absence seizure

· Pregabalin: Post herpetic neurologia (PHN) and deiabetic neuropathy (DeP)
Barbiturates: Phenobarbital, Primidone

· Used for generalized seizure
· Tolerance is common
· Phenobarbital – take at bedtime (long t 1/2 )
· Primidone – metabolized to phenobarbital
Carboxylic Acid Derivatives: Valproic acid, Divalproex

· SE: teratogenicity, GI (Valproic acid > Divalproex). Very low incidence of rash
· No ¯OCs efficacy
· DOC: mixed 1° generalized seizures (generalized tonic-clonic, myoclonus, absence) and alternate choice for
absence seizures.
· Pregnancyà Neural tube defects
· No interactions with oral contraceptives
· Low incidence of rash, Steven Johnson’s syndrome
Other Anticonvulsants: Lamotrigine, Levetiracetam, Topiramate

· Lamotrigine. SE: insomnia, rash, no enzyme induction
· Levetiracetam – No DI
· Topiramate. SEs. kidney stones, weight ¯, cognitive problems (limit use), ↓ efficacy of OC’S, word finding
difficulties. ↓ efficacy of OC’S, expensive
· Also used as weight loss drug
Tips
1 Carbamazepine 2 iv Diazepam 3 Phenytoin
4 Gabapentin 5 Topiramate 6 Valproic acid
7 clobazam 8 phenobarbital 9 gingerval hyperplasia
10 steven jhonson syndrome 11 simple partial seizures 12 Generalised seizure
13 Petit mal (absence) seizures 14 Tonic clonic 15 Status epilepticus
· Antiepileptics drugs that have least drug interaction with oral contraceptives ( )
· What is the drug of choice for status epilepticus ( )
· What drugs used to treat partial seizures and tonic clonic seizures ( )
· Drugs that can caus Steven johnson syndrome side effect ( )
· Antiepileptic drugs not effective in absence (petit mal) seizures ( )
· What is the drug of choice for trigeminal neuralgia ( )
· What drugs enhances GABA activity, antagonizes amino acid ( )
· What is the drug of choice for generalized seizure ( )
· What antiepileptic drugs decrease the efficacy of oral contraceptives ( )
· What type of seizure in-patient is NOT unconscious? ( )
· Carbamazepine interferes with thyroid function test (T/F)
· Phenobarbital and phenytoin stimulates à Hepatic microsomal enzymes (HME) or CYP450.
· Carbamazepine is the drug of choice for à Trigeminal neuralgia
· What is the drug of choice against status epilepticus is à
· Avoid phenytoin in à
· Phenytoin overdose symptoms due to saturation zero order (saturated) kinetics? Nystagmus
· Gingival hyperplacia associated with phenytoin is treated by mouth hygiene and chlorohexidine mouth
wash.
· Chlorhexidine is mouth rinse used for the treatment à gingivitis, stomatitis (mucositis)
· Carbamazepine, phenytoin, clonazepam à ↓ efficacy of OCP
· Topiramate cause à Weight loss, and kidney stones
· Gabapentin has the least à Drug interactions with OCP
· Phenytoin available as à Suspension (100%), iv (92%), chewable tablets (100%) and capsule (92%).
· Carbamazepine available as à Chewable tablets, liquid
· Clobazam has high à Tolerance
· Gabapentin indicated for à Diabetic, and post herpetic neuralgia
· Pregabalin indicated for à Diabetic and post herpetic neuralgia
· Lamotrigine à have low teratogenic (alternate DOC in pregnancy)
· Vigabatrin + carbamazepine à worsen absence seizures
· A patient is on phenytoin but now dose is increased, when is the appropriate time to measure steady
stateà 5 to 30 days
· Phenytoin serum levels monitored for à 10 to 20 mcg/mL
· List the monitoring parameters for phenytoin.à Plasma phenytoin levels, LFT, CBC, BP, vital signs (with iv
use).
· What is the drug of choice for absence seizure or petit-mal seizure is? Ethosuccimide.
· Phenytoin plasma concentration is increased by 50%, what is the first side effect seen. Overdose of
phenytoin? Abnormal gait and nystagmus
· Enzyme inducers such as CBZ, Phenobarbital, phenytoin, oxcarbazepine, topiramate (>200 mg/day)? ¯ OCP
effectiveness
· OCP may reduce level of lamotrigine.
www.PharmacyPrep.Com Anti-Parkinson’s Drugs
97
Anti-Parkinson’s Drugs
Parkinson's diease is due to? Decrease in dopamine (DESTRUCTION OF NERVE

CELLS IN BASAL GANGLIA).
Symptoms: Dysarthria, gait disorders, postural instability, early stage resting
tremors, rigidity, and bradykinesia. (Except. eye movements, nystagmus, cognitive
impairment, hallucination, tardive dyskinesia).
EARLY STAGE TREATMENT

Patient who had PD for less than 5 yrs, treatment with MAOi-B, amantadine and
anticholinergics may modestly improve mild symptoms.
The drug of choice for MILD parkinson’s symtoms is selegiline.
The drug of choice to treat Parkinson's disease in patient age over 70 yo?
Levodopa+carbidopa
<70 yo? Dopamine agonist bromocriptine or promipixole, ropinirole.
Levodopa/carbidopa. Levodopa is the most effective pharmacologic treatment for Parkinson’s disease
symptoms, especially bradykinesia and rigidity.
· Decarboxylase inhibitor carbidopa & benserazide used to minimize acute side effects
· Motor fluctuations & dyskinesia ®develop in up to 50% of patients after 5 years
· Slow-release preparation ® good for patients having “wearing-off” or end-dose effects.
· Cognitive dysfunction ® poorly responsive to levodopa therapy
· SE: N & V, orthostatic hypotension, dyskinesias, hallucinations, confusion
· Avoid VB 6 supplements and Take empty stomach preferably
Dopamine agonists. Bromocriptine, Pergolide, D 2 selective Pramipexole, Ropinirole

· Adjunctive therapy with levodopa ® good for an advanced
patient with motor complications
LEVODOPA
· Initial therapy in younger patients (<70y).
L = Levodopa is the DOC for parkinsons
· SE: GI upset, orthostatic hypotension, psychiatric reactions E = empty stomach
(hallucinations and confusion) > levodopa. V = Vomiting and Nausea
· Ergot dopamine agonists (pergolide & bromocriptine). O = orthostatic hypotension
SEs. Pulmonary fibrosis (chest X-ray before initiating D = dyskinesia/domeperidone for N/V
therapy), erythromelalgia, cardiac valve fibrosis (pergolide) P = Protein diet interactions, so avoid
· Non-ergot dopamine D 2 selective agonists (pramipexole & A = Avoid VB6 supplements
ropinirole). SE: sudden sleep attacks, better choice than
ergot dopamine agonists
· bromocriptine: take with food
Selective MAO-B Inhibitors: Selegiline, Rasigline

· Good for the first year of treatment (very mild effects & don’t delay the development of dyskinesia or
fluctuations associated with L-dopa therapy)
· Potent. Rasagiline>Selegiline
· SE: insomnia
· Selegiline: may need ¯dose in women taking OCs
· Drug Interactions: serotonin syndrome with antidepressants, triptans, meperidine, linezolid.
NMDA receptor antagonists. Amantadine

· Improves L-dopa-induced dyskinesia in the later stages of the disease
· MOA: releasing dopamine from the presynaptic terminals or by blocking its reuptake
· SE: leg edema, erythema, livedo reticularis
· Caution: patients with cognitive deficits a (-confusion)
Anticholinergic agents: Benztropine, Ethonopropazine, Procyclidine, Trihexyphenidyl

· Effect on tremor, bradykinesia (little or no effect)
· Use as monotherapy or as adjuncts to dopaminergic therapy
· Benztropine – take with food
COMT Inhibitors: Entacapone

· COMT inhibitors (e.g., entacapone [Comtan], tolcapone [Tasmar]) decrease the degradation of levodopa and
extend its half-life, thus relieving the end-of-dose wearing-off effect and reducing “off” time.
· SEs. Relate to - dopaminergic activity in the brain (dyskinesia, confusion/hallucinations etc.)
· ¯30% dose of Ldopa with COMT inhibitor.
· Tolcapone. SEs: hepatotoxicity (only through the Special Access Program, Health Canada, for use in
exceptional cases).
· Entacapone:SEs. diarrhea (often weeks to months after initiation), discoloration of the urine, NOT appear to
cause hepatotoxicity.
Management of complications:
The drug of choice for nausea and vomiting is domperidone 10 mg QID AC and HS. (Avoid Metoclopramide)
Flucutation and dyskinesia are managed by?

change sinemet CR, add COMT.
Parkinsons+ psychosis? clozapine, quetiapine, and olanzapine.
Tips
1 deficiency of dopamine 2 Amantadine
3 Entracapone 4 Levodopa
5 Selegiline 6 Tolcapone
7 levodopa/carbidopa 8 Bromocriptine
9 does not cross blood brain barrier 10 tardive dyskinesia
11 MAO- type B inhibitor 12
· it is a non selective dopamine agonist ( )

· it is converted to dopamine within presynaptic dopaminergic neurons ( )
· it is indicated in Parkinson’s disease and also for prevention and treatment )of Influenza A viral infections (
· it a selective MAO type B inhibitor ( )
· it help prevent peripheral metabolism of levodopa, which increase its availability to the brain ( )
· PD is due to decrease in à
· Levodopa does penetrate into brain ( )
· Dopamine does not penetrate into brain ( )
· Carbidopa does not penetrate into brain ( )
· Dyskinesiaà
· Metochlopramide an antiemetic drug should be avoided in PD patient
· All antipsychotics require caution in PD
· Levodopa/carbidopa is DOC in PD
· Selegline is a selective MAO- type B inhibitor
· Akinesia à
· Bradykinesia -->
· Over treatment of Parkinsonism drugs can result into à
· Sciatic nerve: are found in all foot branches
· Why do we add entracapone to levodopa treatment in parkinson’s -->
www.PharmacyPrep.Com Antimicrobials
98
Antimicrobials
Eye Infections
Eye Infections
Blepharitis Hordeola Conjunctivitis Keratitis

Or Stye
Hordeola (external hordeolu ‘stye’) or (internal hordeolum “acute meibomianitis)

Causative agent S. aureus
Site of infection At the edge of the eyelid or underneath it. Head and it ruptures spontaneously
within days.
Treatment Warm compresses + oral antistaphylococcal agent e.g. cloxacillin or flucloxacillin.
Comments Incision and drainage are indicated and patient should be referred to an
ophthalmologist if the patient does not respond to the treatment above.
Conjunctivitis (pink eye or red eye)

Causative Viral, bacterial, chlamydial & noninfectious, allergy, foreign body.
agent
Treatment Chlamydial disease in adults. Oral tetracycline (doxycycline 100 mg 12 hourly) or
Erythromycin (safe in pregnancy) (500 mg 6 hourly) for 7 days, or Azithromycin (safe in
pregnancy) 1 g PO as a single dose. Amoxicillin (safe in pregnancy).
Gonococcal conjunctivitis in adults. Ceftriaxone 1 g IM as a single dose. Cefixime po tab &
suspension.
Comments Purulent or mucopurulent discharge suggests a bacterial or chlamydial cause.
Symptoms Watery discharge may be associated with upper respiratory infection or adenovirus.
Hallmarks of viral conjunctivitis are follicular reaction and preauricular lymphadenopathy.
Viral conjunctivitis (“pink-eye”)

Treatment Treatment is supportive
Topical corticosteroid therapy is controversial.

Comments Children are generally kept out of school for up to 2 weeks after the onset of the
infection
Bacterial Conjunctivitis
Causative agent Staphylococcus and/or Streptococcus for adults
Haemophilus influenza more common in children
Treatment Alternative agents include Gentamicin or Tobramycin eye drops (adults), and
ointment (for children), or Fusidic acid eyedrops
Conjunctivitis in newborn (ophthalmic neonatum)

Causative agent Chlamydia trachomatis or Nisseria gonorrhea
Treatment Chlamydia trachomatis. Erythromycin syrup (40 to 50 mg/kg/day) in 3 divided doses
for 14 days. If needed treat parents for genital infection.
Nisseria gonorrheae. Ceftriaxone 25 to 50 mg/kg IM as a single dose. If needed treat
parents for genital infection
Comments The best form of prophylaxis is 2.5% aqueous povidone-iodine solution.
Canaliculitis
Causative agent Actinomyces, and rarely propiobacterium, nocardia or bacteroids.
Treatment Mechanical expression of the exudative or granular material from canaliculi,
combined with probing and irrigation of the nasolacrimal system with penicillin G
(100,000 U/ml) eye drop solution.
Comments Patients should be referred to an ophthalmologist for definitive treatment.
Dacrocystitis
Causative agent Streptococci including S pneumoniae or S. aureus but culture should guide definitive
therapy
Site of infection Infection of nasolacrimal sac
Treatment Acute infection:
Oral amoxicillin-clavulanate or cefuroxime
Chronic infections:
Irrigate the outflow tract with an antibiotic solution such as penicillin G (100,000
U/ml) as a temporary measure.
Definitive surgical decompression ultimately rests with the ophthalmologist
Keratitis
Causative agent Bacteria, Fungi, Herpes simplex virus, acanthamoeba
Site of infection Infection of the cornea
Comments It is a sight-threatening ocular emergency and requires prompt recognition and
immediately referral to an ophthalmologist.
Herpes simplex keratitis (Viral) or keratoconjuntivitis

Causative Herpes simplex (HSV-1)
agent
Treatment Epithelial disease: Topical antiviral agents e.g. acyclovir ointment applied to eye 5 x day,
continued for at least 3 days after healing.
Trifluridine (Viroptic) and idoxuridine (Herplex-D) ophthalmic drops.
Stromal disease. Complex-combination of antiviral therapy and topical corticosteroids.
Ear, Nose, and Throat Infections. (Upper respiratory Tract Infections)
Common cold (acute Causative agent Viruses e.g. Rhinoviruses

rhinitis)
Sinusitis Bacteria e.g. Streptococcus pneumonia
Pharyngitis Viruses e.g. Adenovirus, Bacteria S. pyogenes.
(Sore throat) Drug of choice for sore throat is amoxicillin or cefuroxime, azithromycin
Acute bronchitis Viruses e.g. Myxoviruses
Chronic bronchitis H. influenza
Pneumonia (CAP) S. pneumonia, H. influenza, M. catarrhalis, M. pneumonia
CAP DOC.in out patient. Amoxicillin, Azthromycin, Clarithromycin,
Doxycyclin.
Otitis media S. pneumonia, H. influenza, M. catarrhalis
DOC. Amoxicillin, amoxi/clav, azithromycin, clarithromycin, cefuroxime
axetil.
Acute otitis externa. The most common etiology of acute otitis externa is bacterial infection. The
microorganism P. aeruginosa (20-60%) and S. aureus 10-70%. Antibiotics
aminoglycosides are active against both bacteria.
Prophylaxis of endocarditis prior dental surgeries:

S. viridans is present in deep of teeth and also causes cavities.
Amoxicillin 2 g 1hr before procedure or 2 hr after procedure, amoxicillin/Clavulanate. If patient is allergic
penicillin give cephalexin, clindamycin, and macrolides.
Dental abscess treatment: Amoxicillin 500 mg TID for 7 days
If patient is allergic penicillin give cephalexin, clindamycin, and macrolides.
Skin and Soft Tissue Infections
Bacterial skin infections
Cellulites Impetigo Folluculitis Erysipelas Necrotising fascitis
Normal skin Gram (-) ve and Staphylococcus viridans, Streptococcus diphteroid

flora Propionobacterium, actinobacter and yeast.
Normal person carry 1012 bacteria on the skin, including Staphylococcus epidermidis and
Propionibacterium acnes.
Cellulitis
An acute spreading infection of the dermis. Lesion is hot, usually red and swollen,
edematous.
Causative agent Strep. pyogenes and/or Staphylococcus aureus
Site of infection Dermis
Treatment Cloxacillin PO/IV and amoxicillin, cephalexin 7-10d, Clindamycin and
cotrimoxazole and azithromycin and clarithromycin.
Impetigo
Causative agents Strep. pyogenes (hemolytic group A Strep) and/or S. aureus and presents as bullous,
crusted or pustular eruption of the skin.
Site of infection Epidermis layer due to local invasion of causative agent.
Treatment Cephalexin 7–10 d, if topical fusidic acid or mupirocin 7 –10 d (only topical, because
unique mechanism (selectively bind to bacterial isoleucyl-tRNA) and no cross resistance
with antibacteria).
Follculitis, boil (furuncles) and carbuncles

Causative agent S. aureus
Site of infection Invasion of S. aureus in the hair follicles causing minor abscess
Treatment Penicillin's or amoxicillin
Erysipelas
Erysipelas is a rapidly spreading infection of the skin (dermis)
It has weel-defined spreading erythematous inflammation, usually accompanied by
fever and other systemic manifestation
Causative agent/s Streptococcus pyogenes, Occasionally S. aureus
Site of infection Dermis of the face
Treatment Penicillin or Amoxicillin, with or without Fluoxacillin as S. aureus may occasionally be
the causative agent.
Necrotising fasciitis
Is an inflammatory response to infection of the tissue below the dermis, spreading with
alarming rapidity along the facial planes causing disruption of the blood supply hence
necrosis and gangrene
Causative agent/s Streptococcus pyogenes (B-haemolytic group A Strep)
Micro aerophilic Streptococci with anaerobic bacteria
Site of infection Soft tissue below the dermis
Treatment Benzyl penicillin, and clindamycin with or without Metronidazole, in addition to tissue
debridment
Fournier’s gangrene
A form of necrotising fasciitis occurring around the groin area
Diabetes and local trauma are the main predisposing factors
Causative agent/s Coliform (E. coli), Streptococci (Group A Strep)
Treatment Penicillin and Cephalosporin's if allergic to beta lactams use Quinolones
(ciprofloxacin)
Comments Pain, fever, and systemic toxicity are usually prominent factor of the disease
Signs of gas formation and gangrene may also be seen
Infection of Skin by VIRUSES:

Causative agent Disease and Characteristics
Papilloma virus Common wart
Molluscum contagiosum (pox Fleshy papule
virus)
Pox virus from sheep, goats Paplovascular lesions, or skin lesions with systemic spread such as herpes
simplex (vesicular lesions)
Infection of Skin by fungi

Causative agent Disease and characteristics
Dermatophyte (keratin- Ring worm or skin lesions can be part of systemic manifestation of the disease such
loving fungi) as Cryptococcus neoformans and Blastomyces dermatitidis.
Tinea pedis Athlete’s foot treatment is clotrimazole 1% cream, miconozole, tolnaftate (topical).
Where does athletes foot occurs? Between toes
Infection of the CNS

Bacterial Meningitis Disease and characteristics
(Neonatal 6 weeks) Group B Empirical treatment. Ampicillin + Gentamicin or Ampicillin + Ceftriaxone
Strep, E. coli and other
Children (>3 months) and adults: Empirical treatment. Cefataxime, Ceftriaxone or ampicillin or vancomycin
S. pneumonia, N. meningitis, H.
influenza type B (can be
prevented by vaccination)
Elderly (>50 yrs), alcoholics, Empirical treatment: Ceftriaxone or ampicillin or vancomycin.
immunocompromised, head
injuries: E. coli, S. pneumonia, L.
monocytogenes
Meningococcal Infection: Spread by respiratory route, pharyngeal colonization in 5 to 10% of
Neisseria meningitis population.
Haemophilus influenza type B Affects 6 months to 5-year-old children (can be prevented by Hib vaccine).
Spread through (respiratory route ®blood®meninges)
Pneumococcus Elderly patients: pneumonia, immunosuppressed, haematological
malignancy. Very young (<3 months): Head injury with skull fracture. High
mortality (up to 30%).
Encephalitis Virus infection of brain and CNS cells.

HSV-1 (most common), CMV, rabies, mumps, measles, eschovirus,
coxsackievirus
Polio Enterovirus, faecal-oral spread; 90-95% well; 5% viral meningitis, 1%
paralytic polio destroys motor neurons of anterior lumen
Brain abscess Streptococcus; Staphylococcus;
Haematogenous Direct spread from middle ear, sinuses or mastoid
Usually mixed infection, anaerobes + streptococcus + haemophilus,
coliform
TB meningitis
Causative agent Meningococcus; Pneumococcus; H. influenzae
Site of infection CNS
Treatment Meningococcus: benzyl penicillin
Pneumococcus: benzyl penicillin/cefotaxime or vancomycin if resistant
H. influenzae – cefotaxime (start with penicillin and cefotaxime)
Prophylaxis: meningococcus – Rifampicin or ciprofloxacin (whole family/close contacts)
Respiratory infections:
Community acquired pneumonia
Causative S. pneumonia (most common)
agent
Ambulatory patients 18 to 40 yr Requiring hospital admission
Mycoplasma pneumonia (24%) S. pneumonia (17%)
S. pneumonia (5%) Mycoplasma pneumonia (14%)
Chlamydia pneumonia (2%) Chlamydia pneumonia (10%)
H. influenza (1%) H. influenza (7%)
Legionella pneumophilia (1%) L. pneumophilia (1%)
Staphylococcus aureus
Treatment Emergency treatment for pneumonia
S. pneumonia. Amoxicillin or Macrolide
High level resistant. Cefotaxime, ceftriaxone, po or iv fluoroquinolones.
H influenza: 2nd and 3rd generation cephalosporins or amoxicillin + clavalunate
MRSA: Staphylococcus aureus
Methicillin susceptible - - - Cloxacillin
Methicillin resistant - - - - - Vancomycin
M. pneumonia & C. pneumonia. Doxycycline or Macrolide
Legionella sp.: Fluoroquinolones, macrolide + rifampin
E. coli (aerobic gram -ve bacilli) and proteous sp. 2nd and 3rd Gen cephalosporins (initial
therapy should be with Cefoxitin or piperacillin + tazobactam)
P. aurigunosa ------- Ciprofloxacin or aminoglycosides
Pneumonia
PNEUMONIA AMBULATORY HOSPITAL WARD ICU
PCI <90 >90 CURB-65 >2
AZITHROMYCIN AMOXI-CLAV BETA LACTAM IV
DOXYCYCLINE LEVOFLOXACIN PO /IV +CLARITHROMYCIN IV
AMOXICILLIN MOXIFLOXACIN PO/IV
RENAL DOXYCYCLINE MOXIFLOXACIN CEFUROXIME Na iv +
gentamycin
p. aeruginosa Ceftazidime +
aminoglycoside
Bronchitis
Bronchitis
Viral Bronchitis Etiology based on age group
(95%) <1 year: RSV (respiratory Syncytial Virus), Parainfluenza, Corona virus
1-10yo: Parainfluenza, Enetrovirus RSV
>10 years: Influenza, RSV, Adenovirus
Bacterial Bronchitis Chlamydia pneumoniae, Mycoplasma pneumoniae
Treatment: Routine antibiotic treatment is not recommended
Antipyretic/analgesic: Acetaminophen
Antitussives: Dextromethorphan
Beta-agonist: Salbutamol
Urinary tract infection
Lower UTI Upper UTI
Urethra (urethritis)
Bladder (cystitis) Ureteritis Pyelonephritis
Urinary Tract Infection

Causative agent The most common causative agen is E. coli.
Cystitis Cotrimoxazole 3d, Nitrofurontoin 5d, Trimethoprim 3 day or Cephalexin 7d. If
ineffective or allergic use ciprofloxacin 3 d.
Urethritis Acute urethral syndrome (urea plasma and chlamydia infection). Doxycycline. During
pregnancy used erythromycin.
Pyelonephritis Bacterial infection of kidney substances.
Ciprofloxacin 7-14 d, cephalosporin's, cotrimoxazole or amino glycosides + ampicillin
(for severe).
Uncomplicated UTI Complicated UTI

Infection in healthy patient with normal Factors that aqcuire bacteria and decrease efficacy of therapy
GU Tract such as abnormal genitourinary tract (BPH, stone, bladder
cancer, and multidrug resistance)
DOC cotrimoxazole 3 days, DOC ampicillin+aminoglycoside
nitrofurontoin 5 days. Ampicillin + vancomycin
Blood/pus in urine (TURBID URINE)
Sexually Transmitted Infections

Causative Nisseria gonorrhea
agents Chlamydia (in children Chlamydia neonatrum)
Syphilis
Lymphogranuloma
Trichomoniasis. vaginitis (colored discharge)
Bacterial vaginosis. vaginitis (fishy smell)
AIDS
Condylomata acuminate
Hepatitis B and C
Chancroid (syphilis)
Genital herpes
Genital warts (papilloma virus)
Comments Candida infections (Vulvovaginitis) is not STI thereby sexual partner does not require treatment.
Symptoms of candida infections are white curdy discharge. If reoccur within 2 months, partner
need treatment.
Question Alerts!
1) Chancroid (ulcer) are present in?
2) Trichomonas infection symptoms are?
3) In which STI’s partner require treatment?.
Infections of the joint and bones
Joint and bones infections
Arthritis infections Lyme disease Osteomyelitis
Infectious arthritis
Male/female The gonococcus bacteria may cause different symptoms in women than in men. Women
differences may develop red sores on the hand feet, in addition to severe pain in the wrist and ankles.
In men, the gonococcus will frequently attack only a single joint, most often the knee.
Treatment Arthritis due to gonococcus can be treated with oral ampicillin.
Surgery is generally not necessary or particularly helpful
Lyme disease
A tick-borne infection can cause arthritis and, in severe cases, heart and/or CNS complications.
Causative agent Spirochete (Borelia burgdorferi) is transmitted to humans via deer tick (a tiny insect
found not only in deer but in squirrels, rabbits, other rodents, birds, and household pets).
Comment Prevalent during July to August
The drug of choice doxycycline, amoxicillin, or cefuroxime auxetil
Osteomyelitis
It is a bacterial infection of the bone and bone marrow
Causative Agent Staphylococcus aureus. Sequential therapy require (begin with IV and than changed
to oral) for 3 weeks.
Gastrointestinal Infection
Normal person carries 1014 bacteria in his GI tract, 95 to 100% of which are anaerobic.
The gut has a resident bacterial population.
Stomach Infection with Helicobacter pylori is common and is associated with peptic ulcer
disease and gastric cancer.
The large These are predominantly anaerobes (99.9%) and an apparent negligible 0.1%) of
intestine aerobes.
Anaerobes Bacteriosides, Bifidobacterium, Clostridium, anaerobic cocci
Aerobes Enterobacteriaceae, E. coli, Klebsiella, Proteus, Enterococci.
Bacteria Food poisoning

Shigella Dysentery (traveler’s bloody diarrhea)
Campylobacter jejuni Traveler’s diarrhea
Salmonella Eggs, poultry, meat
Clostridium difficile Pseudomembranous colitis
Escherichia coli Meat food poisoning and traveler’s diarrhea

S. aureus Meat, mayonnaise, custard
Clostridium perfringens Acute gastroenteritis, reheated dishes
Norwalk virus Diarrhea in hospitalized patient, cruises.
Entomoeba Amoebiasis
Bacillus cereus (B. cereus) Reheated rice (Be Serious!!!)
Vibrio parahaemolyticus Contaminated sea food
Listeria Meat
Tips
Steven-Johnson’s Syndrome (SJS). Rash, skin peeling, and sores on the mucus
membrane. In Steven Johnson’s syndrome, a person has blistering of mucus SJS may cause by: SASPAN
membrane, typically in mouth, eyes and vagina. Patchy areas of rash. SJS can S = sulfonylureas
occur in all age groups. A = anticonvulstants
Due to SASPAN (sulfonylurea, anticonvulsant (phenytoin, carbamazepine, S = sulfonamides
valproic acid), sulphonamide, penicillin, allopurinol and NSAIDs). Topical P = penicillin
sulfadrugs are contraindicated because it may cause disease like SJS, this A = Allopurinol
disease is life threatening. Treatment of SJS is cortisone N = NSAIDs
EYE INFECTIONS
1 Amoxicillin 2 Penicillins 3 Amoxicillin

4 Type 1 allergies 5 Type 2 allergies 6 Azithromycin
· Methicillin is only IV and IM
· Penicillin G benzathine has long half life
· Naficillin is mainly hepatic elimination
· Beta lactamase sensitive drugs: Pen G, Amoxi, Pen V and Ampicillin
· Endocarditis prophylaxis is (Dental extraction prophylaxis) à
· A child less than 2 y allergic penicillin, what is the drug choice for otitis media treatmentà
· A patient has heart diseases and underwent prostatic valve surgery. Dentist plan to tooth extraction, what
antibiotic is suitable for endocarditis prophylaxisà
· Chewable antibioticsà
· Beta lactams that should be taken empty stomach à
· Aminopenicillins are:
· Penicillin allergic patient, alternate drug of choice is?
· Penicillins are ineffective in treatment of bacterial infections associated with à
· MRSA infections are treated by à
· P.colitis associated diarrhea is treated by à
· Bacteria is inhabitant in GI, what location of GI tract is commonly found à
· Type of bacteria mainly present in colon is à
· Penicillin hypersensitive reactions
· If allergic penicillins the best alternate choice of antibiotics is macrolide.

· Penicillins gives what type hypersensitive reaction à Type 1 to V
UPPER RESPIRATORY INFECTIONS

4 Type 1 allergy 5 Type 2 allergy 6 Gastric upset
· Azithromycin suspension stored at à

· Clarithromycin suspension stored at à
· Which macrolide suspension have to refrigerate after reconstitution à
· What antibiotics should caution and require monitoring in patient receiving warfarin -
· What antibiotic potentiate the effect of digoxin and can cause digitalis toxicity à
· Azithromycin is the drug of choice in traveler diarrhea for patient traveling to à
LOWER RESPIRATORY TRACT INFECTIONS

1 Tetracyclin 2 Doxycyclin 3 Minocyclin
4 Photosensitive 5 Must take empty stomach 6 CC/PC
10 Calcium supplements 11 Dairy 12 Cotrimoxazole
· Tetracyclin are contraindicated are contraindicated in pregnancy and children.

· Tetracyclin can stain teeth causing discoloration.
· Oral or topical tetracycline are drug of choice for acne treatment
· Tetracyclin MUST BE taken on empty stomach.
· Tetracyclin binds à
· GI distress (abdominal discomfort, diarrhea) are most common SE. This can be prevented by taking with
food or decreasing dose.
· Expired tetracycline can lead à
· Doxycyclin is the DOC à
· Doxycyclin should be taken à
· Minocyclin maybe taken with or without food.
· Phototoxic reactions (sever skin lesions) can develop with exposure to sunlight. Photoxicity is the most
common side effect of doxycyclin or demeclocyclin.
· Epimerization is a à
Tetracyclins = Take empty stomach
Doxycyclins = Take with or after food
Minocyclins = Regardless of food
SKIN INFECTIONS
1 Clindamycin 2 Diarrhea 3 P. colitis
· Most common complication of clindamycin is à

· Clindamycin is active against à
· Pseudomembranous colitis symptoms include: fever, abdominal pain, bloody stools.
· Clindamycin can cause à
· Clindamycin drug associated diarrhea is treated byà
· Clindamycin suspension can be stored at à
· Clindamycin should be taken à
INFECTIONS OF JOINTS AND BONES
CNS INFECTIONS
1 Ciprofloxacin 2 moxfloxacin 3 Nor floxacin
7 Room temperature 8 Refrigerator 9 UTI
· Fluroquinolones are indicated for UTI, Infectious diarrhea (Travellers diarrhea), lower respiratory tract
infections, bone and joint infections (osteomylitis).
· Gatifloxacin, Moxifloxacin SE are à
· FluroquinolonesContraindicated in children, under 18 y, pregnant women due to itsà
· Antacids, bivalent and trivalent ions significantly decrease absorption of à
· Fluroquinolone increase INR in patient receiving warfarin, therefore monitor à
· Fluroquinolones can cause hypo or hyperglycemia, therefore monitor à
· Fluroquinolones at higher alkaline pH can cause à
· Cipro is the drug of choice in à
URINARY TRACT INFECTIONS

1 Metronidazole 2 Alcohol 3 Trichomonas
4 Amoeba 5 Must take empty stomach 6 CC/PC
7 Room temperature 8 Refrigerator 9 anaerobic bacteria
10 Calcium supplements 11 Dairy 12 Disulfiram like reaction
· Alcohol with metronidazole can cause à
· Metronidazole is classified as: Antiprotozoal drug

· Metronidazole is effective against à
· Metronidazole discolor urine
· Metronidazole caution in pregnancy
SEXUALLY TRANSMITTED INFECTIONS

1 Cotrimoxazole 2 Sulphamethoxazole 3 Minocyclin
4 Photosensitive 5 Must take empty stomach 6 PCP
7 Room temperature 8 Refrigerator 9 UTI
10 Calcium supplements 11 Dairy 12 pregnancy
· Sulfamethoxazole + trimethoprim have à

· A 22 year old patient currently using cotrimoxazole for UTI, reported sever rashes on arms, neck and back,
what are the possible reactionsà
· What are the folic acid synthesis inhibitorsà
· Patient with G6PD deficiency, takes sulfadrugs can cause à
· Hypersensitive reactions of sulfadrugs most commonly involve à
· Life threatening hepatitis caused by sulfadrug toxicity or sensitization rare SE, the signs and symptoms
includeà
· Sulfamethoxazole have high frequency of skin hypersensitive reaction in patient with
· If used in last trimester of pregnancy, can cause kernecterus in new born.
· Cotrimoxazole suspension stored at room temperature in amber color glass bottle.
· P. carinii pneumonia (PCP) drug of choice is Cotrimoxazole.
FOOD TOXICITIES
1 Vancomycin 2 Penicillins 3 Tetracycline
4 Clarithromycin 5 Streptomycin 6 Azithromycin
· use in gram +ve anaerobic bacteria Bacteroid fragilis (abdominal infection) ( )

· it should be stored at room temperature ( )
· it is not effective for Mycoplasma bacteria ( )
· it increase Warfarin INR, increase Digoxin & theophylline levels ( )
· it is effective for H. pylori (used along with PPIs in triple therapy ( )
· it is use in treatment of acne ( )
· drug for treating methicillin-resistant Staphylococcus aureus infections ( )
· it has the highest ototoxicity ( )
· it is more active against gram-ve H. influenza than Erythromycin ( )
· it is use for acne and rheumatoid arthritis ( )
· must avoid alcohol while on this drug because it cause disulfiram like reactions ( )
· it is use as prophylaxis in traveller’s diarrhea ( )
· the drug of choice for UTI 7 traveller’s diarrhea ( )
· it is use in chronic treatment of UTI ( )
www.PharmacyPrep.Com Pharmacology
99
Anticancer Drugs and Chemotherapy
Damage DNA Action of DNA Inhibit synthesis or

functions
Alkylation: Others Antimetabolites

Mechlorethamine
*Actinomycin D 5-fluorouracil
Cyclophosphamide *Etoposide Cytarabine
Ifosfamide *Teniposide Mercaptopurine
Chlorambucil *Amsacrine Thioguanine
Melphalan
Methotrexate
Busulfan
Lomustine Free radicals:
Carmustine *Bleomycin
Streptozolin
Cisplatin Topoisomerase
Carboplatin inhibitors
Dacarbazine Doxorubicin
Procarbazine Daunorubicin
Altretamine/ Topotecan
Hexamethylmelamine Irinotecan
Mitomycin
Prostate cancer. The drug of choice for prostate cancer is Docetaxel, Cabazitaxel, Mitoxantrone, Estramustine and
doxorubin.
Breast cancer. The drug of choice for breast cancer is tamoxifen after breast surgery.
Cervical cancer the drug of choice is radiation + cisplatin
Multiple myeloma the drug of choice is melphalan + prednisone
Acute myeloid leukaemia the drug of choice is cytarabine + idarubicin/daunorubicin
Skin cancer the drug of choice is topical 5-FU
Treatment of extravasation is cold compress and hyaluronidase, sodium thiosulfate, DMSO (dimethyl sulfoxide)
Definitions:
Neoplasm = New and diseased form of tissue growth
Benign neoplasms = Non-cancer form of tissue growth, which can be removed by surgery. No metastases.
Malignant neoplasms = Cancer form of tissue growth. Invasive growth of cancer.
Malignant neoplasms can be categorized as;
Bone marrow = Leukemia (cancer of cells in blood)
Connective tissue = Sarcoma
Epithelium = Carcinoma
Lymphoid tissue = Lymphoma (also named as Hodkins disease)
Myeloid stem cells = Myeloid leukemia
Endothelium = Kaposis sarcoma
Skin (melanocytes) = Malignant melanoma
Cell Cycle Phases All cells must traverse the cell cycle phases before and during cell division.
Anticancer drugs may act on specific phase. Tumor cells are more responsive to specific
drugs
G 0 phase – Resting phase

G 1 phase – Synthesis of enzymes needed for DNA synthesis
S phase –DNA replication (DNA synthesis)
G 2 phase –Synthesis of components needed for mitosis.
M phase – Mitotic tubule formation àVincristine and vinblastine
Cell cycle phase More active against cells that are specific phase of cycle:
specific drugs G 1 phaseà L-aspraginase and prednisone
S phaseà Methotrexate, 6-thioguanine, cytarabine
G 2 specificà Bleomycin and etoposide
M phaseà Vincristine and vinblastine, peclitaxol
Cell cycle specific drug Alkylating agents, Antitumor antibiotic, Cisplatin
(phase-non specific)
Cell cycle non specific Effective whether cancer cells are in cycle or resting phaseà radiation, nitrosoureas,
agents mechlorethanime
Chemotherapy
The treatment of cancer with drugs is called chemotherapy. Antineoplastic drugs, also referred to as
chemotherapeutic agents, are drugs that are used to treat cancer.
Side effects of chemotherapy
Acute:
· Extravasation (effects the adjacent tissue)
· Vessicant drugs (damage to tissue/necrosis) Example: Bleomycin, cisplatin, dactinomycin, domorubicin,

vincristine, vinblastin etc.
· Thrombophlebitis (inflammation associated with thrombus). Patient with cancer can develop thrombosis
after chemotherapy. Due to activation of fibrinogen.
· Hypersensitive reactions. Example Etopiside, peclitaxol, rituximab, trastuzumab.
· Rapid tumor lysis syndrome
· Nausea and vomiting
Chronic, organ specific:

Skinàalopecia, dry skin, nail changes, pigmentation (melanoma), and xerostomia.
Alopecia is the loss of hair: Drug that cause alopecia is doxorubicin, daunorubicin, cyclophosphamide, vincristine,
and paclitaxel.
Vessicant agents include: dactinomycin, doxorubicin, mechlorethamine, mitomycin, vincristine, and vinblastine.
Hair regrowth occurs after 1-2 months after stopping chemotherapy.
Xerostomia: Dry mouth is one of the most common complications associated with radiation therapy. Reversible
after 6 to 12 months of therapy.
Can be managed by: sugar free hard candy, chewing sugar free gum stimulates salivation. Ice chips, sugarless
candies, and commercially available saliva substitute or cholinergic agonist (Pilocarpine 5mg tab).
Bone marrow depression (Myelosuppression)

· Bone marrow depressionàNeutropenia, and thrombocytopenia
· Neutropenia à treated by colony stimulating factors (G-CSF and GM – CSF) Filgrastim or pegfilgrastim.
· Thrombocytopenia à for prevention use Oprelvekin (Inerleukin-11)
· Complications: Bone marrow suppression is the most dose limiting side effect of cancer
· Myelosuppression in general the onset is 7 – 10 days and peak is 10 – 14 days. Recovery count occurs usually
occurs in 2 – 3 weeks.
· Megaloblastic anemia by methotrexateàFolinic acid (leucovorin, 5-formyltetrahydrofolic acid).
· Neutropenia associated anticancer drugsà can be treated by filgrastim (human granulocyte colony
stimulating factor).
· Least bone marrow depression anticancer drugs is Bleomycin
· Cancer patient with anemia à Erythropoeitins are useful
Cardiotoxicity:
· Risk of CHF, commonly seen with doxorubicin, daunorubicin, epirubicin, mitoxantrone.
· 5-FU, capecitabine. Cause coronary spasms, mimicking a myocardial infarction (avoid in know coronary
artery disease patients).
· Cardiotoxicity can be prevented or lessen by using cardioprotective agent Dexrazoxane
Pulmonary toxicity:
Pneumonitis, pulmonary fibrosis commonly seen with bleomycin, carmustine, cyclophosphamide, mitomycin,
methotrexate, vinca alkaloids.
Symptoms of pulmonary toxicity include SOB, non-productive cough, and rarely low-grade fever.
Neurotoxicity:
· Common with vincristine, vinblastine, Cytarabines, Methotrexate (very little), 5FU, interferon alpha.
· Peripheral neuropathies associated with: Vincristine, peclitaxel: Peresthesia (numbness and tingling) can
occur with vincristine, which often appears within few weeks of therapy.
· High dose of cytarabin may produce cerebllar toxicity that manifest initially as loss of eye-hand coordination
and progress to coma.
· Fludrabine cause severe neurotoxicity
· Caramustine and other alkylating agents cause little or no neurotoxicity.
GI toxicity
Mucositis or stomatitis:
Mucositis: Generalized burning, and pain on the ventral surface of tongue. Floor of tongue, mouth looks
erythromatus. Stomatitis: generalized inflammation of oral mucosa.
· Mucositis or stomatitis: Common with Doxorubicin, Methotrexate, 5-fluorouracil, Actinomycin, Bleomycin
capecitabine.
· Recommend mouth hygiene, xylocaine, viscous sucralfate, nystatin, sodium bicarbonate, for severe cases
peliformin (growth factor) can be used.
· Avoid alcohol, antihitamine, steroids, spicy food
· Mucositis treatment and prevention:
· Topical anesthetics: Viscous lidocaine, or dyclonine HCL 0.5 or 1%
· Corticosteroid provides anti-inflammatory action.
· Capscisin: Produces burning and pain and ultimately desensitizes pain.
· Sucralfate suspension may provide benefit by coating.
· For Localized effect: use benzocain in orabase.
· Mucositis prevention:
· Chlorhexidine gluconate 0.12% (Peridex, Periogard) may reduce severity and frequency of mucositis
infections.
Nausea and vomitingà

· Very high emetics anticancer drugs
· Cisplatin
· Streptozocin
· Cyclophosphamide
· High emetics anticancer drugs
· Doxorubicin
· Methotrexate (250 mg to 1000 mg)
· Cytarabine
· Lowest emetic anticancer drugs
· Bleomycin
· Methotrexate (under 50 mg)
· Vincristine
· Vinblastine
· Tamoxifen
Non-pharmacological therapy
· Take small and frequent meals
· Avoid high fat and heavy aroma
· Take dry, starchy foods like crackers
Management of nausea and vomiting associated with cancer chemotherapy:

· The lowest emitogenic drugs nausea and vomiting can be treated by àDexamethasone PRN
· High and very high emitogenic drugs associated acute: nausea and vomiting can be treated byà
Dexamethasone+ Ondansetrons
· DOC for delayed nausea and vomiting à Dexamethasone
· Anticipatory nausea and vomitingà Benzodiazepine.
Hepatotoxicity
Hepatotoxicity monitor LFT, jaundice, or hepatitis: asparaginase, cytarabine, mercaptopurine, and
methotrexate.
Nephropathy:
· Elevate BUN and electrolyte abnormalities: methotrexate may precipitate in kidney. Cisplatin and
streptozocin. Amifostine may be used to protect the kidney from the nephrotoxicity associated with
cisplatin.
Sexual dysfunction:
Cyclophosphamide, melphalan, and procarbazine associated with significant infertility in men and women.
Hemorrhagic cystitis
· It is a bladder toxicity that is seen most commonly after administration of cyclophosphamide and ifosfamide.
· These drugs produce a metabolite called acrolein, which cause chemical irritation in bladder mucosa,
resulting in bleeding.
· Hemorrhagic cystitis caused by Acrolein can be prevented by excessive hydration and subsequent frequent
urination. The other method is by administering uroprotecting agent called MESNA, which bind acroleine
and prevent from contacting the bladder mucosa.
Pulmonary toxicities: The most common with bleomycin, mitomycin, and carmustine.
Rationale for combination therapy. Overcoming or preventing resistance. Cytotoxicity to resting and dividing
cells. Biochemical enhancement of effect. Beneficial drug interactions rescue host cells.
Some agents can be administered intrathecally: Methotrexate, Cytarabine’ Thiotepa
Warning: Vincristine should be labelled as Intravenous only. Intrathecally vincristine causes death.
Tips
Find the answers from the table:
1. alopecia 2. neutropenia 3. chemotherapy
4. Doxorubicin 5. Daunorubicin 6. Cyclophosphamide
7. Vincristine 8. Paclitaxel 9. Tamoxifen
10. Bleomycin 11. Methotrexate 12. Vinblastine
13. xerostomia 14. 5-fluorouracil 15. Cytarabine,
16. Mercaptopurine, 17. Thioguanine 18. Methotrexate
19. Skin cancer 20. Cisplatin 21 Streptozosin
· Examples antimetabolites include -->

· Examples of alkylating anticancer drugs -->
· Non pharmacological measures to prevent nausea and vomiting associated with caneer chemotherapy.
· Melonoma is à
· Metoclopramide and dexamethasone are more effective nausea related to à
· Methotrexate is used for à
· Which anticancer drugs cause pulmonary fibrosisà
· Hypertropy is à
· Hyperplasia is à
· Least emetic anticancer drug is à
· Cancer patient on cancer chemotherapy, reports shortness of breath, non productive cough, she may be
using drug à
· DOC for delayed Nausea and vomiting à dexamethasone
· Mesna is à
· Doxorubicin preparation should be performed in à
· Hypertropy is à
· Hyperplasia is à
· Melatonin à
· Peclitaxel and docetaxel act on à
· Cancer estimated deaths in men: Lung cancer 31% and Prostate cancer 11%
· Cancer estimated deaths in women: Lung cancer 25% and Breast cancer 15%
· Examples antimetabolites include -->*5-fluorouracil, *Cytarabine, *Mercaptopurine, *Thioguanine and
Methotrexate
100
Pharmacognosy & Natural
Products
Natural Products
Natural product Classification Use

Cranberry Antioxidant, Cleanses and stops infections in the urinary tract.
Vaccinium bacteriostatic
macrocarpon effect
Dong Quai Tonic, immuno- Used to treat all symptoms of menopause as an alternative
Angelica sinensis stimulating, anti- treatment to estrogen therapy. Regulates the hormonal system.
spasmodic Overall tonic for female reproductive system. Reduces high blood
pressure and PMS. Caution: Contra-indication in pregnancy
Echinacea Antibiotic, anti- Stimulates and boosts immune function. Has cortisone-like
Echinacea fungal immuno- activity that helps wound healing. Fights bacterial and viral
angustifolia/purpurea stimulating infections. Contra-indication in auto-immune diseases (i.e.
Multiple Sclerosis, AIDS)
Evening Primrose Anti-spasmodic Used in treatment of multiple sclerosis and PMS. Helps prevent
Oenothera biennis heart disease and stroke and maintains healthy skin. Excess
consumption can result in oily skin.
Feverfew Anti-inflammatory, Helps prevent migraine headaches and also useful against
Tanacetum emmenagogue swelling and arthritis. Stimulates digestion and improves liver
parthenium function. Caution: Not to be used by lactating or pregnant
women.
Garlic Antibiotic, anti- Reduces high blood pressure and blood cholesterol. Immune
Allium sativum fungal, anti-viral support for respiratory system. Anti-cancer and digestive tonic.
Caution: Not to be used by lactating women because it can pass
to the breast milk and cause colic in infants.
Licorice Demulcent, Gastric ulcers, adrenal insufficiency hypoglycemia. Good for
Glycyrrhiza glabra diuretic, coughs and other bronchial complaints. Caution: Contraindicated
expectorant, for those with high blood pressure or if pregnant.
laxative
Ginger Diaphoretic, Relieves indigestion and abdominal cramping. Benefit in relieving
Zingiber officinale cholagogue, motion sickness, dizziness, nausea and colds. Ginger lowers
carminative, blood clotting.
stimulant
Ginkgo Biloba Anti-asthmatic, Increases blood flow to the brain. Improves memory loss.
Ginkgo biloba bronchodilator, Alzheimer’s disease cerebral vascular insufficiency and inhibits
platelet activating blood clotting. with warfarin and Aspirin. Take with food.
factor (PAF)
inhibitor
Ginseng Tonic, stimulant, Stimulates both physical and mental activity. Anti-fatigue
Panax schin-seng demulcent, (insomnia, nervousness, poor appetite). Enhances immune
stomachic system, inhibits exhaustion of adrenal gland and anti-stress.
· Echinaceaà Common cold

· Saw palmettoà Prostate (BPH-Benign Prostate Hyperplacia)
· Garlic à lipid levels
· Feverfew à Migraine
· Gingkoà Increase memory
· St. Johns wart à antidepressant
· Bitter melonà anti-diabetic
· Prime rose oil à PMS (premenstrual syndrome)
· Atropineà anticholinergic
· Vincristine and vinblastinàanti-cancer
· Taxol (pecli-taxol)àYew plants (Himalayas)àseveral types of cancers
· Licorice can cause hypertension
www.PharmacyPrep.com Canadian Pharmacy Review
Abbreviations
Abbreviatio Meaning Latin Phrase Abbreviation Meaning Latin Phrase
n
a Before Ante bid Twice a day bis in die
ac Before meals Ante cibum q every quaque
pc After meal Post cibum qam Every morning
c with q.d Everyday Quaque die
cc With food qod Every other day
AD Right ear D= dexter qid Four times a day Quarter in die
AS Left ear S=sinister
AU Both ear
OD Right eye p.o. By mouth Per os
OS Left eye pr Per rectum
OU Both eyes p.r.n. As needed Pro re nata
dr Dram pt Pint
dx Diagnosis
g Gram Q12h Every twelve BID
hours
gr Grain qt quart
gtt Drop rx, Rx prescription
h Hour s without sine
hr Hour ss One half (1/2)
hs At bed time Hora somni stat immediately
hx History supp suppository
ID Intradermal sx symptoms
IM Intramuscular T, Tbsp or tablespoon
tbs
IU or U International units t, tsp teaspoon
unit
IV Intravenous tid 3 X a day ter in die
IVPB IV piggyback TO Telephone order
kg Kilogram tr tincture
L Liter tx treatment
lb Pound ung ointment
mcg Microgram mg VO Verbal order
mEq Milliequivalen aa/aaa Of each/ apply
t affected area
mg Milligram Ad lib As desired Ad libitum
ml Milliliter ud As directed
oz Ounce Q8H
p post post
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and 1
it is illegal to reproduce without permission. This manual is being used during review sessions
conducted by PharmacyPrep.
Prefix Meaning Prefix Meaning

a-;an-;ana No; not; without micro Small
ab- Away from Multi many
ante- Before; forward neo New
anti- against non Not
auto- self oligo Few; less
bi Two double both pan All
brady- Slow para Near; beside
carcin cancerous per Through
contra Against; opposite peri Around
Dys- Difficult; painful poly Many
Ect- Outside; out post After
en Within; in pre Before; in front of
endo Within primi First
epi Above; upon retro Behind; back; upward
Ex. Out or semi Half
extemporaneous
Gynec/o woman sub Below; under
hemi half super Above; over; excess
hyper Above; excess supra Above; on top of
hypo Below; deficient sym With
infra Below; inferior syn Together; with
inter between tachy Fast
intra within tri Three
iso Same; equal uni One
macro large xero Dry
mal Bad; poor; abnormal aa Apply affected area
meta Change; after; beyond
Suffix Meaning Suffix Meaning

ac; al; ar; ary Pertaining to otomy Incision into
algia pain ous Pertaining to
cele Hernia, herniation paresis Paralysis
centesis Surgical puncture pathy Disease
crine To secrete penia Decrease number
crit To separate pepsia Digestion
cyte Cell phagia Eating, swallowing
cytosis Condition of cells phobia Abnormal fear
desis Binding together phonia Voice; sound
ectomy Surgical removal; plasty Surgical repair
excision
emesis Vomiting plegia Paralysis
emia Blood pnea Breathing
genesis, genic, gen Producing; forming poiesis Formation
globin; globulin protein r/rhage; r/rhagia Bursting forth
gram Record rrhea Flow; discharge

graph Instrument for recording rhesis Rupture
graphy Process of recording sclerosis Hardening
ia; iac; ic Pertaining to scope Instrument for viewing
ism Condition scopy Process of viewing
itis Inflammation somnia Sleep
lysis; lytic Break down spasm Twitch
malacia Softening stasis Control; stop
megaly enlargement stenosis narrowing
oid Resembling; like therapy Treatment
(o)logist Specialist thorax Chest; pleural cavity
(o)logy Study of tocia Labor; birth
oma tumor tripsy Crushing
osis Abnormal condition trophy Growth; development
ostomy Creation of an opening tropin Nourish; development;
stimulate
Root Meaning Root Meaning

Abdomin/o abdomen Cyst/o Bladder, sac, urinary bladder
Aden/o Gland Cyt/o Cell
Adip/o Fat Dacry/o Tears
Aminio amnion Dent Tooth
Andr/o Male; man Derm/o Skin
Angi/o Vessel Dermat/o Skin
Aque/o Watery Dipl/o Two, double
Arteri/o Artery Dips/o Thirst
Arteriol/o arteriole Duoden/o Duodenum
Arthr/o joint Dur/a Dura mater
Ather/o Fat; fatty plaque Electr/o Electricity
Audi/o Hearing; sound Embry/o Embryo
Aur/o ear Encephal/o Brain
bili Bile; gall Enter/o Intestines
Blephar/o eyelid Eosin/o Red
Bronch/o bronchus Epis/i Vulva
Bronchiol/o bronchiliole Erythr/o Red
Bucc/o Inside cheek Esophag/o Esophagus
Burs/o joint Fasci/o Fascia
Calc/i calcium Femor/o Femur
Capnia Carbon dioxide Fet/o; fet/i Fetus
Carcin/o Cancer Fibul/o Fibula
Cardi/o heart Fund/o Fibula
Carp/o Wrist bone Gastr/o Fundus
Cephal/o head Gastr/o Stomach
Cerebr/o cerebrum Gingiv/o Gums
Chol/e Bile; gall Glauc/o Silver/gray
Cholangi/o Bile duct Gli/o Nerve cell
Cholecyst/o gallbladder Glomerul/o Glomerulus
Chondr/o cartilage Gloss/o Tongue
Coagul/o clotting Gluc/o Glucose; sugar

Cochle/o cochlea Gonad/o Sex glands
Col/o Colon Gravid/a/o Pregnancy
Conjunctiv/o Conjunctiva Gyn/o; gyn/e woman
Cor/o heart Gynec/o Woman
Corne/o cornea Hem/o Blood
Coron/o heart Hemangio/o Blood vessel
Cost/o rib Hemat/o Blood
Crani/o cranium Hepat/o Liver
Cry/o cold Hidr/o Sweat
Cut/o, cuti skin Humer/o Humerus
Cutane/o skin Hydr/o Water; fluid
Cyan/o blue Hyster/o Uterus
Gait imbalance

ile/o ileum Orth/o Straight
ili/o ilium Oste/o Bone
Immune/o Protection Ot/o Ear
is/o Equal Ovari/o Ovary
Jejun/o jejunum oxi Oxygen
Kal/i potassium Pachy/o Thick
Kinesi/o tears Pancreat/o Pancreas
Lact/o Milk Par/o Bear; labor; childbirth
Lapar/o Abdominal wall Patello/o Knee cap
Laryng/o larynx Pector/o Chest
Ligament/o ligament ped Children
lingua Tongue Pelv/i Pelvic
Lip/o fat Perine/o Pelvis
Lith/o stone Peritone/o Perineum
Lumb/o lymph Peritone/o Peritoneum
Mamm/o breast Phag/o Eat
Mast/o breast Phalang/o Finger and toe bones
Melan/o black Pharyng/o Pharynx
Men/o Menses, menstruation Phleb/o Vein
Metacarp/o Hand bones Phot/o Light
Metatars/o Foot bone Phren/o Diaphragm
Morph/o Form shape Pil/o Hair
Muc/o mucus Pneum/o Lung/air
Myc/o fungus Pod/o, podi Foot
Myel/o Bone marrow, spinal cord Proct/o Rectum
Miring/o eardrum Psych/o, psych/i Mind or soul
Narc/o sleep Pub/o Pubis; pubic bone
Nas/o nose Pulmon/o Lungs
Nat/o, natal Birth, delivery Py/o Pus
Nephr/o kidney Pyel/o Renal pelvis
Neur/o nerve Quadr/i Four
Noct/o night Radi/o Radius
Nyctal/o night Rect/o Rectum

Ocul/o eye Ren/o Kidney
Onych/o nail Retin/o Retina
Oophor/o ovary Rhabdomy/o Skeletal muscle; striated
muscle
Ophthalm/o eye Rheum Watery discharge
Opt/o eye Rhin/o Nose
Or/o mouth Salping/o Fallopian tubes
Orch/o Testis; testicle Sarc/o Flesh
Orchid/o Testis; testicle Semin/o semen

septi bacteria Ten/o; tend/o tendon
Sial/o saliva Tendon/o; tendin/o tendon
Sinus/o sinus Test/o Testis/testicle
Somat/o body Testicul/o Testis/testicle
Spermat/o sperm Thorac/o Chest
Sphere/o round Thromb/o Clot
Sphygm/o pulse Thyr/o Thyroid gland
Spir/o Breathe; breath Trache/o Trachea
Spleen/o spleen Tympan/o Eardrum
Spondyl/o Vertebra; vertebral Urethra/o Urethra
column
Steth/o Chest Ur/o Urinary tract
Stoma, stomat/o mouth Vas/o Vessel
Synovi/o joint Ven/o Vein
Tars/o Ankle bones Xanth/o yellow

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www.pharmacyprep.

com Evaluating Exam Review Book 2018

Misbah Biabani, Ph.D

In our teaching strategies, we utilize lecture-discussion, small group discussion,

©2000-2018 TIPS Inc. All rights reserved.

Part 1. Biomedical Sciences 15%

Part 2. Pharmaceutical Sciences 25%

26. Medicinal Chemistry and Pharmacology of Cardiovascular Drugs

53. Prescription Processing and Medication Dispensing

83. Rheumatoid Arthritis, Osteoarthritis and Gout arthritis

Body Movements (Fig 1.1)

· Abduction: Movement away from the midline of the body.

Anatomical planes (Fig 1.1)

Skeletal Joints (Fig 1.2)

Tendons: Connect muscle to bone

· Biceps brachià upper arm (biceps) and thighs.

Three types of muscle tissues

· Cardioesophageal sphincter guarding entrance from esophagus.

Stomach Secretions Purpose Source

Prokinetic drugs (metoclopramide, domperidone) decrease gastric emptying time

Small intestine: Consist of duodenum, jejunum, and ileum.

Large Intestines: It is also known as colon.

Diseases of the gastrointestinal system

Diseases of the stomach.

Diseases of the small intestine.

Diseases of the Colon

ULCERATIVE COLITIS CROHN'S DISEASE

Hernia: a perturbation of GI tract at the junction of esophagus and stomach.

Digestion and Absorption

Disorder of carbohydrate absorption. Lactose

Pepsin Trypsin and chymotrypsin

Absorption of nucleic acid:

Absorption of water (H 2 O): It is isosmotic in the small intestine and gallbladder.

Innervations of GI tract. Autonomic innervations.

· The most basic part of the GI tract ( )

Mesolimbic pathways are Frontal lobe

Vestibular ocular reflexes. Nystagmus

· The arachnoid: middle layer, transparent, flexible

Periphery can be divided into sensory (somatic) and autonomic.

PERIPHERAL NERVE COMMENTS

Oculomotor: Eye upward, medial, downward movement

Vagus Defecation, slowed heart rate

Hypoglossal: tongue movement

Pathology of neurological disorders

Akathisia = restlessness or cannot sit still.

Ataxia = lack of muscle coordination in voluntary movements.

Migraine Headache: Vasodilatation of intracranial extra cerebral blood vessels.

Heat stroke: Core body temp. >40.6 °C

Cerebrospinal fluid (CSF) sample is taken by Lumbar puncture.

FMRI. The functional MRI is used brain scanning.

Conduction System of the Heart (fig 4.4)

Myocardial action potential curve: Myocardial action potential

· Q-T interval. Mechanical contraction of the ventricles (Torse de pointes).

· Thrombus is blood clot.

Cardiac oxygen consumption: When increased size of the heart.

Laplace's Law: Laplace's law describes how tension in the vessel

Autonomic effects on heart rate and conduction velocity.

Cardiac output: stroke volume x heart rate

Pre-load = Volume of blood fills in ventricles in diastolic state

Select True/False Statements

Endocrine Types of hormone Target tissue Physiologic actions

Posterior Vasopressin (antidiuretic Kidney Causes water retention

Pancreas Insulin Most cells Promotes use and storage of nutrients

Physiological effects of some pituitary hormones