Pharmacology & Therapeutics Supplements: Ali Raza Chaudary (N67)

PHARMACOLOGY &
THERAPEUTICS SUPPLEMENTS
NISHTAR MEDICAL UNIVERSITY MULTAN
ALI RAZA CHAUDARY (N67)
www.facebook.com/humanfountainsarc
PHARMACOLOGY SUPPLEMENTS
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REFERENCES
PHARMACOLOGY AND THERAPEUTICS
1. Katzung & Trevor’s Pharmacology, Examination & Board Review, 12th Ed. (MINI
KAZUNG)
2. Lippincott Illustrated Reviews: Pharmacolog, 6th Ed.
3. Basic and Clinical Pharmacology by Katzung, 14th Ed., Mc Graw-Hill (BIG KATZUNG)
4. Kaplan USMLE Step 1 Video & Lecture Notes 2020: Pharmacology
CONTENTS
DESCRIPTION PAGE NO
MODULE NO. 1: GENERAL PHARMACOLOGY 5
MODULE NO. 2: AUTONOMIC NERVOUS SYSTEM PHARMACOLOGY 26
MODULE NO. 3: AUTOCOIDS & NSAIDS PHARMACOLOGY 34
MODULE NO. 4: RESPIRATORY & GASTROINTESTINAL PHARMACOLOGY 39
MODULE NO. 5: CARDIOVASCULAR, DIURETIC & BLOOD PHARMACOLOGY 42
MODULE NO. 6: ANTIFUNGAL, ANTIVIRAL & ANTICANCER PHARMACOLOGY 54
MODULE NO. 7: ANTI-MYCOBACTERIAL & PARASITIC PHARMACOLOGY 58
MODULE NO. 8: ANTIBACTERIAL PHARMACOLOGY 62
MODULE NO. 9: ENDOCRINE PHARMACOLOGY 72
MODULE NO. 10: CENTRAL NERVOUS SYSTEM PHARMACOLOGY 79
MODULE NO. 11: DRUGS OF CHOICE 93

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1
GENERAL PHARMACOLOGY
1 SEQ + 5 MCQs = 12 Marks
DESCRIPTION PAGE NO
PHARMACOKINETICS 6
PHARMACODYNAMICS 18
DRUG DEVELOPMENT & REGULATION 23

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PHARMACOKINETICS
(The actions of the body on the drug) OR (It is study of ADME)
Four pharmacokinetic properties determine the onset, intensity, and the duration of drug action:
1. Absorption: Absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
2. Distribution: Drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids.
3. Metabolism/Biotransformation: Drug may be biotransformed by metabolism by the liver or other tissues.
4. Elimination: Drug and its metabolites are eliminated from the body in urine, bile, tears, breast milk, saliva, sweat, or feces
ABSORPTION
(Absorption is the transfer of a drug from the site of administration to the site of action/bloodstream.)
 MECHANISMS FOR PERMEATION OF DRUGS
PASSIVE FACILITATED ACTIVE
FEATURE ENDOCYTOSIS EXOCYTOSIS
TRANSPORT TRANSPORT TRANSPORT
Movement of drug
Energy requiring
Movement of from region of Type of vesicle Type of vesicle
movement of
drug from region higher to lower transport that transport that
Definition substances across
of higher to lower concentration by moves substances moves substances
a plasma
concentration the help of carrier into a cell. out of a cell.
membrane.
or channel protein
Incidence Very Common Less Common Least Common Least Common Least Common
Process Slow & Passive Fast & Passive Very Fast & Active Very Fast & Active Very Fast & Active
Relation with Along the Against the Against the
Along the gradient Against the gradient
gradient gradient gradient gradient
Fick’s Law Applicable Not applicable Not applicable Not applicable Not applicable
Carrier Not required Required Required Required Required
Energy Not required Not required Required Required Required
Selectivity No Yes Yes Yes Yes
Saturablity No Yes Yes Yes Yes
Direction Bidirectional Bidirectional Unidirectional Unidirectional Unidirectional
Metabolic Inhibition No Yes Yes Yes Yes
Ions,
Aqueous or lipid Neurotransmitters,
Na/K ATPase Vitamin B12, Iron,
Examples diffusion in Metabolites and Neurotransmitters
pump Proteins
capillaries Xenobiotics’
transporters
 FACTORS AFFECTING ABSORPTION OF DRUGS
LOCAL FACTORS (RELATED TO BODY)
Fick’s Law
1. Area of Absorptive Surface (directly proportional) e.g. intestine > stomach

2. Contact time at the Absorption Site
 GIT Motility Absorption
 GIT Motility  Delayed absorption
3. Food/Other drugs (Dilutes the drug and slows gastric emptying i.e delayed absorption)
4. Blood Flow to Absorption Site (directly proportional) (Intramuscular, Subcutaneous & GIT sites)
5. Expression of P-glycoprotein (inversely proportional) (“pumps” drugs out of the cells & provide multidrug resistance)
6. Route of administration (affects rate and efficacy of the absorption)
7. Local pH
PHARMACOLOGICAL FACTORS (RELATED TO DRUG)
1. Solubility
2. Degree of Ionization (inversely proportional) By Henderson-Hasselbalch Equation
3. Nature of drug & pH of the medium (WHEN MEDIUM IS SAME, DRUGS CAN CROSS THE MEMBRANE)
 Acidic pH (e.g. Stomach):
Weak acidic drugs become more unionized  More lipid soluble  More absorbable e.g. aspirin
Weak basic drugs become more ionized  More aqueous soluble  Less absorbable e.g. amphetamine
 Alkaline pH (e.g. Intestine):
Weak basic drugs become more unionized  More lipid soluble  More absorbable
Weak acidic drugs become more ionized  More aqueous soluble  Less absorbable
4. Size (inversely proportional) e.g. powder form is more absorbable
5. Concentration at the site of administration i.e. by Fick’s Law

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 ROUTES OF ADMINISTRATION OF DRUGS
It is determined by
1. Properties of drug (solubility, ionization)
2. Therapeutic objectives (desirability of a rapid onset, need for long-term treatment, or restriction of delivery to a local site).
Routes of Drug Administration
Local Systemic
Topical Enteral Parenteral Others

(Skin &
Mucous
Membrane) Sub- Intra- Intra- Sub- Trans- Oral In- Nasal In-
Oral Rectal
lingual venous muscular cutaneous dermal halarional halational
Intra-
articular
Intrathecal
ROUTE PATTERN ADVANTAGES DISADVANTAGES

LOCAL EFFECTS
 Applied on skin or mucous
membranes of eye, throat,
 Low systemic effects  Not well absorbed in deeper layers
Topical ear, nose, airway or vagina
 Steady level of drugs to the system of skin
 E.g. clotrimazole applied to
skin for fungal infections.
 Difficult to hit joint surfaces
 Introduce drugs in to
 Low systemic effects  Difficult to calculate dose for joints
Intraarticular inflamed joint cavity directly
 Rapid delivery to the local tissue  Irritate joints and cause infections
 E.g. hydrocortisone
 Painful procedure, expert is needed
 Introduce drugs directly into
Intrathecal/ the cerebrospinal fluid. For  Low systemic effects
 Painful procedure, expert is needed
ventricular  E.g. amphotericin B is used  Bypasses BBB and BCB
in cryptococcal meningitis
SYSTEMIC EFFECTS
ENTERAL ROUTE (through the mouth)
 Variable; many factors
 Drugs may be metabolized before
PREPARATIONS:
 Safest, most common, convenient, systemic absorption (first pass
 Enteric-coated e.g. aspirin effect)
and economical route
Oral for protecting the stomach
 Self administered  Limited absorption due to low GIT
(by mouth)  Extended-release (ER/XR)
 Toxicities overcome by antitodes pH
e.g. morphine to prolong
e.g. activated charcoal  Food may affect absorption
duration of action for drugs
 Patient compliance is necessary
with small half lives
 Bypasses first-pass effect ,
Sublingual
Depends on the drug:  Absorb directly to systemic venous
(under tongue)  Limited to certain types of drugs
 Few drugs (for example, circulation
OR  Limited to drugs that can be taken
nitroglycerin) have rapid,  Bypasses destruction by GIT acid
Buccal in small doses
direct systemic absorption  Drug stability maintained because
(between  May lose part of the drug dose if
 Most drugs erratically or the pH of saliva relatively neutral
cheek and swallowed
gum)
incompletely absorbed  May cause immediate
pharmacological effects
PARENTERAL ROUTE (other the mouth)
Usage:
 Drugs poorly absorbed from the GI tract (e.g. heparin)
 Drugs unstable in GIT (e.g. insulin)
 Unable to take oral medications (unconscious patients)
 Require a rapid onset of action
Advantage: highest bioavailability (not subject to first-pass metabolism or the harsh GI environment)
Disadvantage: Irreversible and may cause pain, fear, local tissue damage, and infections
 Can have immediate effects  Unsuitable for oily substances
 Ideal if dosed in large volumes  Bolus injection may result in
 Suitable for irritating substances adverse effects like hemolysis and
Intravenous  Absorption not required and complex mixtures thrmobosis
(25° angle)  100% Bioavailability  Valuable in emergency situations  Most substances must be slowly
 Dosage titration permissible injected
 Ideal for high molecular weight  No antitodes like activated charcoal
proteins and peptide drugs  Strict aseptic techniques needed

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Depends on drug diluents.
PREPARATIONS:
 Suitable for slow-release drugs
 Aqueous solution: prompt  Pain or necrosis if drug is irritating
 Ideal for some poorly soluble
Subcutaneous  Depot preparations: slow  Unsuitable for drugs administered
suspensions
(45° angle) and sustained in large volumes
EXAMPLES:  Less adverse effects like hemolysis
and thrombosis as in IV bolus.
 Insulin
 Heparin
Depends on drug diluents.
PREPARATIONS:
 Affects certain lab tests (creatine
 Aqueous solution: prompt  Suitable if drug volume is moderate
kinase)
 Depot preparations: slow  Suitable for oily vehicles and
Intramuscular  Can be painful
and sustained (non- certain irritating substances
(90° angle)  Can cause intramuscular
aqueous vehicle like  Preferable to intravenous if patient
hemorrhage (precluded during
polyethylene glycol) e.g. must self-administer
anticoagulation therapy)
haloperidol & depot
medroxyprogesterone
OTHERS
 Slow and sustained
 Some patients are allergic to
depending upon thickness  Bypasses the first-pass effect
patches, which can cause irritation
of skin and lipid solubility at  Convenient and painless
 Drug must be highly lipophilic
Transdermal site of administration  Ideal for drugs that are lipophilic
(patch) EXAMPLES:  May cause delayed delivery of drug
and have poor oral bioavailability
to pharmacological site of action
 Nitroglycerin  Ideal for drugs that are quickly
 Limited to drugs that can be taken
 Scopolamine eliminated from the body
in small daily doses
 Nicotine
 Partially bypasses first-pass effect
 Bypasses destruction by GIT acid  Drugs may irritate the rectal
Rectal/  Erratic (unpredicatable)
Suppository  Ideal if drug causes vomiting mucosa
and variable
 Ideal in patients who are vomiting,  Not a well-accepted route
or comatose
 Systemic absorption may
occur; this is not always  Absorption is rapid; can have
desirable immediate effects
EXAMPLES:  Ideal for gases e.g. anesthesia
 Most addictive route (drug can
Oral Inhalational  Effective for patients with
enter the brain quickly)
 Anesthesia respiratory problems
Inhalation  Patient may have difficulty
 Albuterol  Dose can be titrated
(Oral or Nasal) regulating dose
 Fluticasone  Localized effect to target lungs:
Nasal Inhalational  Some patients may have difficulty
lower doses used compared to that
using inhalers
 Oxymetazoline, with oral or parenteral e.g.
 Mometasone bronchodilators & corticosteroids
 Desmopressin for diabetes  Fewer systemic side effects
insipidus.
 BIOAVAILABILITY (F)
( rate and extent to which an administered drug reaches the systemic circulation)
DETERMINATION
 Unity (100%) for IV administration.
 Important for calculating drug dosages for non-IV routes of administration.
 Determined by comparing;

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FACTORS AFFECTING
1. First-pass hepatic metabolism:
 When a drug is absorbed from GIT, it enters initially in portal circulation and rapidly metabolized in liver or gut wall and
amount of unchanged drug entering the systemic circulation is decreased. Eg. nitroglycerin is primarily administered
via sublingual or transdermal.
 Results in lower systemic bioavailability of parent compound, diminished therapeutic response.
 Drugs with high first-pass metabolism should be given in doses sufficient to ensure that enough active drug reaches
desired site of action.
ORAL DOSE
 > Sublingual / Parenteral

 Marked individual variation
 Oral F Liver disease or when in
competition with other drug
 Short plasma t1/2.
SITE
2. Solubility of the drug:  Liver (major site)

 Hydrophilic  poorly absorbed in lipid bilayer membranes  Gut wall & lumen
 Lipophilic  poorly absorbed in aqueous body fluids  Lungs
 For a drug to be readily absorbed, it must be largely lipophilic, yet have some solubility
Skin in aqueous solutions.
3. Chemical instability:
 Penicillin G, unstable in pH of gastric contents.
 Insulin, destroyed in GIT by degradative enzymes.
4. Nature of the drug formulation:
 Particle size
 Salt form
 Crystal polymorphism
 Enteric coatings
 Presence of excipients (such as binders and dispersing agents)
 EQUIVALENCE
FEATURE BIOEQUIVALENCE THERAPEUTIC EQUIVALENCE
Two drug formulations are therapeutically
Two drug formulations are bioequivalent if equivalent if they are pharmaceutically
they show comparable bioavailability and equivalent (that is, they have same dosage
Definition
similar times to achieve peak blood form, contain same active ingredient, and use
concentrations. same route of administration) with similar
clinical and safety profiles.
Rate Same -
Bioavailability Same -
Clinical Effect - Same
Safety Profile - Same
Pharmaceutical Equal  
Pharmaceutical Alternative  
DISTRIBUTION
(Process by which a drug reversibly leaves bloodstream and enters interstitium and tissues.)
For drugs administered IV, absorption is not a factor, and initial phase (from immediately after administration through rapid fall in
concentration) represents distribution phase, during which drug rapidly leaves the circulation and enters the tissues.

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 FACTORS AFFECTING DISTRIBUTION OF DRUGS
1. Blood flow to capillaries (Does not affect the amount of drug in the tissue at equilibrium)
 Well-Perfused Tissues: Brain, Heart, Kidney, Splanchnic organs >>> Skeletal Muscles
 Poorly-Perfused Tissues: Fat, Bone and other viscera
 Example: IV bolus of propofol  High blood flow & high lipophilicity  Rapid distribution into CNS  Anesthesia
 Hypnosis Subsequent slower distribution to skeletal muscle & adipose tissue  Plasma conc. lowered 
Diffuses out of CNS down gradient  Consciousness regained
2. Capillary permeability (determined by capillary structure i.e. fraction of basement membrane exposed by slit junctions
between endothelial cells, and by chemical nature of drug)
 Liver & Spleen: Discontinuous capillaries + Slit junctions
 Brain: Continuous capillaries + Tight junctions (Lipid-soluble drugs readily penetrate CNS but ionized or polar
drugs e.g. levodopa, fail to enter CNS as tight junction formed by endothelial cells of BBB and is actively transport
mostly)
3. Binding of drug (directly proportional to drug distribution)
 Binding to plasma proteins: Reversible binding and sequesters drugs in a non-diffusible form that slows their
transfer out of the vascular compartment. Example: Warfarin is bound to Albumin.
 Acts as a drug reservoir
 Maintains free drug concentration in plasma.
 Binding to tissue proteins: Accumulate drug in tissues by binding to lipids, proteins and nucleic acids, leading to
higher concentrations in tissues than in extracellular fluid and blood. Example: acrolein accumulates in bladder
cause hemorrhagic cystitis
 Acts as a drug reservoir
 Prolong its actions or cause local drug toxicity.
4. Lipophilicity
 Lipophilic  rapidly absorbed in lipid bilayer membranes
 Hydrophilic  poorly absorbed in lipid bilayer membranes and have to pass through slit junctions
5. Size of organ (influence concentration gradient between blood and organ)
 Skeletal muscle > Blood: Take large amount of drug and have high blood-tissue gradient
 Brain < Blood: Take small amount of drug and have low blood-tissue gradient smaller
6. Pattern of drug distribution (2 forms)
 Bound form: Inactive, Non-diffusible, Cannot be metabolized or excreted by kidneys
 Free form: Active, Diffusible, Can be metabolized or excreted by kidneys
7. Apparent volume of distribution (Vd)
 EFFECTIVE DRUG CONCENTRATION
(Concentration of drug at the receptor site)
 Readily measured in blood
 Except for topical agents, it follows;
FACTORS AFFECTING Cp or Cb
 Rate of input of drug by absorption
 Rate of distribution by Vd
 Rate of elimination by CL
 APPARENT VOLUME OF DISTRIBUTION (Vd)
(Fluid volume that is required to contain entire drug in body at same conc. measured in plasma)
 Apparent Vd has no physical equivalence that’s why it is called apparent.
 It relates the amount of drug in the body to the plasma (C p) or blood (Cb) concentration at time zero as follow;
UNITS OF Vd
 Volume
 Volume/kg of body weight (if vary with body size)
ASPECTS
1. Distribution into water compartments in body: Once a drug enters the body, it distributes into any one of these or
sequestered in a cellular site.
PLASMA COMPARTMENT EXTRACELLULAR FLUID TOTAL BODY WATER
Model One compartment Two compartment Multicompartment
Drug HMW drug LMW drug LMW drug
Features Extensively protein bound drug Hydrophilic Lypophilic
Cross slit junctions but not lipid Cross slit junctions and lipid
Crossing Cannot cross slit junctions
bilayers bilayers
Vd = Plasma Volume +
Vd Vd = Plasma Volume = 4 L (4% Vd = Total body water = 42 L
Interstitial fluid volume = ECF
Calculation of weight) (60% of weight)
Volume = 14 L (20% of weight)
Vd Low Moderate High
Example Heparin Aminoglycoside Ethanol

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2. Determination:
3. Effect on Half Life:
METABOLISM/BIOTRANSFORMATION
(Chemical alteration of drug in body that converts non-polar or lipid soluble compounds to polar or lipid
insoluble compounds)
Biotransformation
Biotransformation is required for protection of body from toxic metabolites.
SITES EFFECTS ADVANTAGES
Primary Site Active Drug to Active Drug to Active Terminate drug action
Prodrug to Active Drug
Liver Inactive Drug Metabolite (Toxic Metabolism) ↓ Toxicity
 Lipophilicity
 Renal excretion
Other Sites Stability Propranolol Phenacetin to Paracetamol  Biliary excretion
Kidney Bioavailability Morphine Digitoxin to Digoxin  Renal reabsorption
Intestine Toxicity Paracetamol
Plasma
Lungs
Levodopa to Dopamine
Methldopa to MethylNE
 TYPES OF BIOTRANSFORMATION
ENZYMATIC: ENZYMATIC: NON-ENZYMATIC
FEATURE
MICROSOMAL NON-MICROSOMAL (Hoffman’s Elimination)
Some drugs are metabolized through
Microsomal cytochrome P450,
molecular rearrangement without
Definition monooxygenase family of enzymes, Other than microsomal enzymes
involvement of enzymes from
which oxidize drugs.
quaternary to tertiary structures.
SER of Liver, Kidney, Intestinal and
Location Cytoplasm, mitochondria of Liver Plasma
Lungs
Catalyze
Monoamine oxidases (MAO),
1. Oxidation, reduction, hydrolysis
Esterases, Amidases, Transferases, Skeletal muscle relaxants
Examples (phase I reactions)
Conjugates (Atracurium and Cisatracurium)
2. Glucuronide conjugation (phase II
(All are phase 2 reactions)
reactions)
Genetic
Yes May show No
polymorphs
Inducers &
Yes No No
Inhibitors

12
 CYTOCHROME P450 SYSTEM/ MIXED FUNCTION OXIDASES
(Microsomal enzyme ranking first among Phase I enzymes with respect to catalytic versatility)
2+
Heme-containing proteins [Complex formed between Fe and CO absorbs
light maximally at 450 nm (447-452 nm)]
 Substrate: Drug that is metabolized by the enzyme system
 Inducer: Drug that increase synthesis and activity of enzyme system
 Inhibitor: Drug that decrease the metabolism of a substrate
 At least 15 P450 enzymes identified in human liver microsomes.
% of Drugs Metabolized by Enzyme System
 3A4 & 5 50%
 2D6 25%
 1A2 15%
 2C9 Small but significant interactions
 2C19 Small but significant interactions
 2E1 ?
 TYPES OF METABOLIC REACTIONS
FEATURE PHASE I REACTIONS PHASE II REACTIONS

Reactions that convert the parent drug to a more polar Reactions that increase water solubility by
(water-soluble) or more reactive product by unmasking conjugation of the drug molecule with a polar moiety
Definition
or inserting a polar functional group such as -OH, -SH, such as glucuronate, acetate, sulfate, glutathione,
or -NH2 glycine, or methyl.
Non synthetic / Functionalization Synthetic / Conjugation
Other names
(A functional group is inserted) (An endogenous radical is conjugated)
Metabolite Polar + Active, Inactive or Unchanged Polar + Usually Inactive
Half life Short Long
Consequence May result in metabolic activation Facilitate Excretion (urine/ bile/ faeces)
Selectivity Not much selective Not much selective
Enzymes Cytochrome P450 Enzymes mainly Transferases mainly
True
Detoxification No Yes
reactions
Energy Not required Required
1. Microsomal Oxidation (9 types) 1. Glucuronidation (UDP glucuronyl transferase)
 N-oxidation: Chlorpheniramine  Aspirin, Acetaminophen, Digoxin
 S-oxidation: Chloramphenicol 2. Acetylation (N-Acetyl transferase)
 O-Dealkylaton: Phenacetin to Paracetamol  Isoniazid, Sulfonamids
 N-Dealkylaton: Theophylline 3. Glutathionation (Glutathione S- Transferase)
 S-Dealkylaton (Sulphur): 6-Methyl thiopurine  Ethacrynic Acid
 Deamination: Amphetamine 4. Acylation (N-Acyl trasferase)
 Desulfuration: Parathion to Paraoxon  Niacin, Salicylic Acid
 Aliphatic Hydroxylation: Ibuprofen 5. Sulfation (Sulfotransferases)
 Aromatic Hydroxylation: Propranolol  Acetaminophen
2. Non-microsomal Oxidation 6. Methylation (Methyl transferase)
 Mitochondrial enzymes – (MAO  Dopamine, Histamine
Adrenaline, 5-HT, Tyramine 7. Ribonucleotide or Ribonucleoside Synthesis
Examples  Cytoplasmic enzymes – (Dehydrogenases)  6 Mercaptopurine
Alcohol to Acetaldehyde & Acetic Acid
 Plasma oxidative enzymes – (Histaminase)
(Xanthine oxidase)
Allopurinol
3. Microsomal Reduction
 N-reduction: Chloramphenicol
 Keto-reduction: Cortisone
4. Microsomal Hydrolysis: Pethidine
5. Non-Microsomal Hydrolysis
 Esters: Aspirin
 Amides: Indomethacin
6. Cyclization: Proguanil
7. Decyclization: Phenytoin, Barbiturates

13
 DETERMINANTS OF BIOTRANSFORMATION
1. Chemical Factors
 Enzyme Induction (increased synthesis and expression of SER containing CYP450 enzymes by drugs or other
xenobiotic factors)
Examples: Bull Shit SCRAP PG
Barbiturates
St. John’s Wort
Sulfonylureas
Carbamazepine (auto-inducer)
Rifampin (with contraceptives  therapeutic effect of contraceptivespregnancy)
Alcohol (chornic)
Phenobarbital
Phenytoin
Griseofulvin
 Enzyme Inhibition
Examples: SICKFACES.COM + AQ G
Sodium Valporoate
Isoniazid
Cimetidine (Dcreases the metabolism of propanolol leading to enhanced bradycardia)
Ketoconazole
Fluconazole
Alcohol
Chloramphenicol
Erythromycin
Sulfonamides (Decrease the metabolism of phenytoin so that its blood levels become toxic)
Ciprofloxacin
Omeprazole
Metronidazole
Amidadrone
Quinine
Grape fruit juice
 Intestinal P-Glycoprotein (P-gp or MDR-1) Inhibitors [An ATP-dependent transport molecule found in many
epithelial (intestine, BBB) and cancer cells, that expels drug molecules from mucosa to lumen or from cytoplasm
into extracellular space and contributes of first pass effect. Drugs include: Digoxin, Cyclosporine, Saquinavir]
Examples: Verapamil (Calcium Channel Blocker) Furanocoumarin (Grape fruit juice component)
2. Biological Factors
 Age
Infants CYP450 system not fully developed  Metabolism
 Chloramphenicol: Grey baby syndrome
 Diazepam: Floppy baby syndrome
Elder patients’ organs shrunkenBlood flow  Metabolism
 Gender
Males BMR > Women BMR   Metabolism (Salicylates, Ethanol, Propanolol, Benzodiazepines)
Womens on oral contraceptive   Metabolism
 Race (Antimalarials & Isoniazid)
 Diet (Deficiency of proteins, vitamins & Minerals  Metabolism)
 Genetic Polymorphs (Study of genetic factors affecting drug responses is called pharmacogenetics)
Type Functional Element Defects or SNPs Drugs Affected
CYP-3A4, 3A5 Cyclosporine toxicity 
CYP-2D6 Codeine function & toxicity
Phase I Enzymes CYP-2C9 Warfarin toxicity 
CYP-2C19 Clopidogrel metabolite 
Dihydropyrimidine Dehydrogenase 5-Flurouracil toxicity
UDP GT Irinotecan toxicity 
Phase II Enzymes Thiopurine MT Thiopurine toxicity 
G6DP Hemolysis 
Transporter Organic Anion Transporter (OATP) Simvastatin myopathy 
Receptor 1 receptor Metoprolol efficacy 
3. Altered Physiological Factors
 Pregnancy Metabolism (Phenytoin, Phenobarbitone, Pethidine)
 Hormonal Imbalance (Hypothyroidism & Hyperthyroidism)
 Disease states (CVS, Respiratory and Liver diseases impair metabolism & Renal diseases impair conjugation)
4. Temporal Factors
 Cortisterone Levels in afternoon  Metabolism & vice versa for early morning
5. Route of Drug Administration
 Lignocaine is given topically not orally to avoid first pass metabolism
6. Environmental Factors
 Smoking, Chronic alcoholism & Pesticides or Organophosphate insecticides  Enzyme inducers.
 Hot and humid climate  Metabolism
 High altitude Oxygen  Metabolism

14
 TOXIC METABOLISM
(Active drug is converted to active metabolite i.e. toxic molecule)
Examples: Methyl alcohol, Ethylene glycol & large doses of acetaminophen
Metabolism of acetaminophen (Ac) to harmless conjugates or to toxic metabolites.

Acetaminophen glucuronide, acetaminophen sulfate, and the mercapturate conjugate
of acetaminophen all are nontoxic phase II conjugates. Ac* is the toxic, reactive phase I
metabolite, N-acetyl-p-benzoquinoneimine. Transformation to the reactive metabolite
occurs when hepatic stores of sulfate, glucuronide, and glutathione (GSH, Gs) are
depleted or overwhelmed or when phase I enzymes have been induced.
 ADVERSE DRUG EFFECTS
ADVERSE DRUG EFFECTS
Unpredictable Effects Predictable Effects
Cummulation Teratogeni- Carcinogeni-

Allergy Idiosyncrasy Mutagenicity Tolerance Dependence
/ Toxicity city city
Trait that is
peculiar to a
Drug taken Decreased
group or
as antigen Drug induced Drug induced drug
individual Drug induced Drug induced Habituation/
and immune inutero fetal gene response
mainly poisoning cancer Addiction
response defects mutations due to many
because of
occurs reasons
genetic
problem
Aspirin
Penicillin causes
Large one or Aflatoxins, Coal tar,
cause hemolysis in Ethanol, Morphine, Tobacco,
small many Anticancer Vinyl
Anaphylactic people with Warfarin Nitrates Morphine
doses drugs Chloride
Shock G6DP
deficiency
ELIMINATION
(It is drug inactivation or removal from the body by metabolism or excretion)
ELIMINATION = METABOLISM + EXCRETION
Different from excretion in terms, ( drug may be eliminated by metabolism long before modified molecules are excreted from body.)
1. Most drugs and their metabolites: hepatic metabolism, biliary elimination, or urinary elimination
2. Volatile anesthetic gases: excreted by lungs.
3. Drugs with active metabolites (eg, diazepam), elimination of parent molecule by metabolism is not synonymous with
termination of action.
4. Drugs that are not metabolized: Excretion is the mode of elimination.
5. Small number of drugs combine irreversibly with their receptors: So that disappearance from bloodstream is not equivalent
to cessation of drug action: These drugs may have a very prolonged action. E.g. phenoxybenzamine, an irreversible
inhibitor of α adrenoceptors.

15
 DIFFERENCE BETWEEN FIRST ORDER AND ZERO ORDER ELIMINATION
FEATURE ZERO ORDER ELIMINATION FIRST ORDER ELIMINATION
A process that is independent of drug concentration
A process that is directly proportional to drug
Definition involved in the process and is constant with passage
concentration involved in process
of time
Process Constant Rate Process Linear Kinetic Process
Type Capacity limited elimination Flow dependent elimination
Rate Independent of drug concentration Directly proportional to drug concentration
General
Expression
Rate Constant (K) Ko K
-1 -1
Units of K mg/min min , hr
General
Equation
Graph
Clearance (CL) Not constant Constant (Rapid at first & slows as conc. decreases)
Constant (In first order kinetics, A drug infused at a
Half life (like constant rate takes 4–5 half-lives to reach steady
Not constant
CL) state. It takes 3.3 half-lives to reach 90% of the
steady-state level.)
Half life
expression
Dependence
Dependent on initial drug concentration Independent on initial drug concentration
(t½)
End At some time, comes to end Never comes to an end
At high/toxic doses:
Ethanol
Examples: Mostly drugs follows this
Aspirin
Phenytoin
 CLEARANCE (CL)
(Volume of blood or plasma that can be freed of a drug in a specific time)
 It relates the rate of elimination of drug to the plasma concentration at specific time as follow;
UNITS OF CL
 Volume/time i.e. mL/min or L/h
 CL/kg of body weight
FACTORS AFFECTING CL
 Drug
 Blood flow
 Conditions of the organs of elimination i.e. kidney, liver, intestines etc
 Clearance of a drug that is very effectively extracted by an organ is often flow-limited.

 PLASMA HALF LIFE (t½ )
(Time required for the amount of drug in the body or blood to fall by 50%)
 Determines the rate at which blood concentration rises during a constant infusion and falls after administration is stopped
 It relates as follow;
UNITS OF t½
 Time
FACTORS AFFECTING t½
 Vd
 CL

16
 EXTRACTION RATIO
(fraction or percentage of the drug removed from perfusing blood during its passage through the organ
 After steady-state concentration in plasma has been achieved,
extraction ratio is one measure of elimination of drug by that organ.
 Drugs that have a high hepatic extraction ratio have a large first-
pass effect and bioavailability of these drugs after oral administration
is low.
 It is determined as follow;
 THERAPEUTIC WINDOW
(Safe range between the minimum therapeutic concentration and the minimum toxic concentration of a drug)
 Determine the acceptable range of plasma levels when designing a
dosing regimen
1. Minimum effective concentration = trough levels of a drug
given intermittently
2. Minimum toxic concentration = permissible peak plasma
concentration
 For some drugs, therapeutic and toxic concentrations vary so greatly
among patients that it is impossible to predict therapeutic window in a
given patient. Such drugs must be titrated individually in each patient.
 DOSAGE REGIMENS
(Plan for drug administration over a period of time)
 An optimal dosage regimen results in the achievement of therapeutic levels of drug in blood without exceeding the
minimum toxic concentration and depends on;
1. Minimum Therapeutic & Toxic Concentration
2. Vd & CL
FEATURE MAINTENANCE DOSE LOADING DOSE
The dose required for regular administration to maintain a The dose required to achieve a specific
Definition target plasma level i.e. to maintain a desired steady state plasma drug concentration level (Cp) with a
(SS). single administration.
Factors CL and t½ Vd
At Steady state:
Expression
But
As for chronic therapy we give these doses once or a few
Units times per day, we convert it as follow;
Smaller and more frequent maintenance doses, if difference Loading dose is large (Vd >Blood volume)
between therapeutic and toxic conc. is small. then dose is given slowly
Dosing
Larger and less frequent maintenance doses, if difference Loading dose is small (Vd <Blood volume)
between therapeutic and toxic conc. is large. then dose is given rapidly
Graph

17
 DOSAGE ADJUSTMENTS WHEN ELIMINATION IS ALTERED BY DISEASE
RENAL IMPAIRMENT:
 GFR disturbed
 Creatinine Clearance (CLCr) disturbed
1. For drugs to be removed by renal route only
2. For drugs to be removed 50% by renal route and 50% by liver
3. Shortcut for measuring CLCr directly by Cockcroft Gault Equation
4. Shortcut for measuring GFR directly by MDRD Equation

18
PHARMACODYNAMICS
(The actions of the drug on the body)
 RECEPTORS (A molecule to which a drug binds to bring about a change in function of the biologic system)
 Selective in their ligand binding characteristics
 Modifiable
 Mostly Proteins, but also Enzymes or Nucleic Acids in nature
FEATURE TYPE-I TYPE-II TYPE-III TYPE-IV

Ligand Gated Ion G-Protein Coupled
Name Receptor Kinases Nuclear Receptors
Channels Receptors
Location Membrane Membrane Membrane Intacellular
Ligand Nature Hydrophilic Hydrophilic Hydrophilic Hydrophobic
Effector Ion Channel Channel or Enzyme Protein Kinases Gene Transcription
Monomeric or oligomeric
Single transmembrane
assembly of subunits
Oligomeric assembly of helix linking extracellular Monomeric structure
comprising 7 trans-
Structure subunits surrounding receptor domain to with receptor- and DNA-
membrane helices with
central pore intracellular kinase binding domains
intracellular G protein–
domain
coupling domain
Protein phosphorylation Protein and receptor
Changes in membrane  Gi: cAMP phosphorylation by
Protein phosphorylation
Mode of Action potential or ionic and altered gene
 Gs: cAMP formation of dimers or
concentration within cell expression
 Gq: IP3, DAG multisubunit complexes
Receptor Binding + Receptor Binding + Receptor Binding + Receptor Binding +
Domains
Channel Lining G-protein Coupling Catalytic DNA Binding
Duration of Action Milliseconds Seconds Minutes to Hours Hours to Days
 Insulin  Steroid
 Nicotinic Ach
 Muscuranic Ach  Growth Factors  Vitamin D
 Serotonin 5-HT3
 Adrenoceptors  ANP  NO
 GABAA
 Cytokines  Cytokines
Examples
 DIFFERENCE BETWEEN INERT BINDING SITE & RECEPTOR SITE

Feature INERT BINDING SITE RECEPTOR SITE
A molecule to which a drug may bind without changing Specific region of the receptor molecule to which the
Definition
any function drug binds
Play an important role in buffering concentration of a
Function drug because bound drug does not contribute directly Drug- receptor interaction initiates the drug action
to the concentration gradient that drives diffusion.
Primary receptor affinity is a basis of drug classification
Example Albumin & orosomucoid (α1-acid glycoprotein)
e.g. H1 for histamine receptors
 RECEPTOR REGULATIONS
SIGNAL AMPLIFICATION PROTECTION AGAINST EXCESSIVE STIMULATION
G-protein and Kinase-Linked Tachyphylaxis/Down-regulation: When a receptor is exposed to repeated
Receptors amplify signal duration and administration of an agonist, it becomes desensitized resulting in diminished effect.
intensity that give rise to spare  Blockage of access to G-proteins (-arrestin)
receptors.  Internalization/Sequestration of receptors ( or morphine receptors) – during recovery
Eg. unresponsive receptors are called refractory.
 Insulin receptors:  Depletion of essential substrate (thiol cofactors for nitroglycerin)
99% are spare Up-regulation: Repeated exposure of a receptor to an antagonist may result in up-
 Heart -receptors: regulation of receptors, in which receptor reserves are inserted into the membrane,
5-10% are spare increasing the total number of receptors available.
 Make the cells more sensitive to agonists
 More resistant to the effect of the antagonist

19
 EFFECTORS
(Component of a system that accomplishes the biologic effect after receptor is activated by an agonist)
1. Channel: Na/K channel for NN receptor
2. Transporter: M receptors
3. Enzyme: Adenylyl cyclase
4. May be part of the receptor molecule: Tyrosine kinase effector enzyme part of insulin receptor
 DIFFERENCE BETWEEN EFFICACY & POTENCY
Feature EFFICACY (Emax) POTENCY
The largest effect that can be achieved with a particular The amount or concentration of drug required to
Definition
drug, regardless of dose produce a specified effect
 Nature of Drug
Factors  Receptor Affinity
 Nature of Receptor
Affecting  Number of Receptors available
 Nature of Effector
Median Doses
Graded Dose
EC50; ED50; TD50
Response Can be measured by it
(Concentration or dose that causes 50% of maximal
Curve
effect or toxicity)
Median Doses
Quantal Dose
ED50; TD50; LD50
Response Cannot be measured by it
(Concentration or dose that causes a specified
Curve
response in 50% of the population under study)
Graph Y-value (Emax) X-value (Median Doses)
Represents •  Y-value =  Emax =  Efficacy. Left shifting = ED50 = Potency = Drug needed
Mathematical
Form
Graph
 DIFFERENCE BETWEEN DOSE CURVE GRAPHS

FEATUR GRADED-DOSE BINDING
GRADED-DOSE RESPONSE QUANTAL-DOSE RESPONSE
E RESPONSE
Graph between increase of Graph between receptors bound Graph between fraction of population
Definition response with increase of dose by drug with increase of dose of showing that response with increase of
of drug drug dose of drug
Potency Variables
Data  Median effective dose (ED50)
Derived (Kd = concentration of drug that  Median toxic dose (TD50)
binds 50% of receptors in  Median lethal dose (LD50)
system)
Relation Dose to intensity of effect Dose to intensity of effect Dose to frequency of effect
Graph

20
 SPARE RECEPTORS (Receptor that does not bind drug when drug concentration is sufficient to produce Emax)
 Reason
OR
 Mechanisms
1. Duration of effector activation > DR interaction
2. Receptors > Effectors
 Increases sensitivity to the agonist because the likelihood of a drug-
receptor interaction increases in proportion to the number of receptors
available
 THERAPEUTIC INDEX (TI)

(Ratio of median toxic dose (or median lethal dose) to median effective dose, determined from quantal dose-response curves.)
 Formula
 It estimates the safety of the drug.

 Safer drugs have higher TI values.
 Drugs with lower TI values frequently require
monitoring (eg, Warfarin, Theophylline, Digoxin,
Lithium)
 PHARMACOLOGICAL DRUG INTERACTIONS

CHEMICAL INTERACTIONS
Mechanims Classification
Pharmacokinetic Pharmacodynamic Additive Synergestic Potentiation Tachyphylactic Antagonism
Absorption Receptor Pharma-

cological
Distribution Non-receptor Physiological
Metabolism
Chemical
Elimination
TYPE DEFINITION EXAMPLE
Effect of substance A and B together is equal to the sum of their
Additive individual effects Aspirin and acetaminophen
i.e. A = 1, B = 1, A + B = 2
Effect of substance A and B together is greater than the sum of their
Synergistic individual effects Clopidogrel with aspirin
i.e. A = 1, B = 1, A + B > 2
Presence of substance A is required for full effects of substance B Cortisol on catecholamine
Potentiation
A = 0, B = 1, A + B > 1 responsiveness
Acute decrease in response to a drug after initial/repeated
Tachyphylactic Nitrates, niacin, phenylephrine
administration
Antagonism See below
 AGONIST (A drug that activates its receptor upon binding)
 Equilibrium is formed between Rinactive (Ri) and Ractive (Ra) state in absence of
ligand.
 The activity in the absence of agonist ligand is called constitutive activity.
 Ri state is favoured in absence of ligand.

21
 TYPES OF AGONISTS
NEUTRAL
FEATURE FULL AGONIST PARTIAL AGONIST INVERSE AGONIST
ANTAGONIST
A drug binds with equal
A drug that binds to its A drug that binds to
A drug capable of fully affinity to Ri & Ra states,
receptor but produces a non-active state of
activating the effector preventing binding by
Definition smaller effect (Emax) at receptor molecules and
system when it binds to agonist and preventing
full dosage than a full decreases constitutive
the receptor any deviation from level
agonist activity.
of constitutive activity.
Ra > Ri
Affinity for state Ra >>> Ri (in presence of full agonist, Ra = Ri Ri > Ra
it acts as inhibitor)
Intrinsic Activity (I) I=1 I >0 but <1 I=0 I<0
Apripirazole at
D-receptors with Naloxone is a
Phenylephrine at H1 and H2
Example activate underactive competitive antagonists
-receptors antihistaminics
paths and inactive the at all opioid receptors
overactive paths
Graph
 TYPES OF ANTAGONISM
COMPETITIVE NON-COMPETITIVE
FEATURE PHYSIOLOGICAL CHEMICAL
REVERSIBLE IRREVERSIBLE ALLOSTERIC
A drug that binds to A drug that A drug that
A pharmacologic
A pharmacologic a receptor molecule counters the counters the
antagonist that can
antagonist that without interfering effects of another effects of
be overcome by
Definition cannot be overcome with normal agonist by binding to a another by
increasing the
by increasing agonist binding but different receptor binding the
concentration of
concentration alters response to and causing agonist drug
agonist
normal agonist opposing effects (not receptor)
Location At receptor site At receptor site Other than receptor Different receptor With drug
Overcome Yes (By agonists) No No - -
Emax Efficacy
Emax -  (Down Shift)  (Down Shift) - -
Efficacy  
EC50 1/(Potency)
EC50  (Right shift) - - - -
Potency 
Norepinephrine
Diazepam (agonist) (agonist) + Epinephrine’s
+ flumazenil phenoxybenzamine Picroton + GABA antagonism of Dimercaprol
Examples
(antagonist) on (noncompetitive linked Cl- channel bronchoconstriction Pralidoxime
GABA receptor antagonist) on α- by histamine
receptors
Graph

22
 DIFFERENCE BETWEEN TACHYPHYLAXIS & TOLERANCE
TACHYPHYLAXIS TOLERANCE (METABOLIC/
FEATURE
(PHARMACODYNAMIC TOLERANCE) PHARMACOKINETIC TOLERANCE)
Rapid loss of drug effects caused by Decrease in clinical effects of drug after prolonged
Definition
compensatory neurophysiological mechanisms exposure to it
Onset Rapid (few minutes) Slow (days - months)
High Dose
No Yes
dependent
Effects with 
Not Seen Seen
dose
Routine Practice Not Seen Seen
Examples Ephedrine, Nitroglycerin (TD) Barbiturates, Ethanol, Opium
 Blockage of access to G-proteins (-arrestin)
 Internalization of receptors (morphine  Congenital (Negroes are resistant to mydriatic
receptor) effect of ephedrine)
Causes
 Sequestration of receptors ( receptors)  Acquired (morphine, ethyl alcohol, nitrates,
 Depletion of essential substrate (thiol cofactors ephedrine, and amphetamine)
for nitroglycerin)
CROSS TOLERANCE:
Tolerance between related drugs e.g. between ethyl alcohol and general anaesthesia.
1. Alteration in drug concentration that reaches the receptors due to an effect on absorption, distribution or elimination.
2. Variation in concentration of endogenous transmitters e.g. - blockers will slow heart rate markedly in patients with excess
endogenous catecholamines.
3. Alteration in the number or function of receptors, e.g. thyrotoxicosis increases the number and sensitivity of -receptors.

23
DRUG DEVELOPMENT & REGULATION
Sale and use of drugs are regulated in almost all countries by governmental agencies.
In the United States, regulation is by the Food and Drug Administration (FDA).
 NATURE/SOURCES OF DRUGS
SOURCES OF DRUG
Natural Synthetic Semisynthetic
Animals Plants Microorganisms Aspirin Ampicillin

Minerals
Sulfonamide from penicillin
Pethidine
Insulin Digoxin Penicillin Procaine
MgSO4
(pancreatic -cells) (Digitalis purpura) (P chrysogenum) (Laxative)
Heparin Quinine Streptomycin Mg trisilicate
(Liver extract) (Cinchona bark) (S. griseus) (Antacid)
Vitamin B12 Atropine Chloramphenicol
(Liver) (Atropa belladonna) (S. venezuelae)
ADH
(hypothalamus)
 FORMS OF DRUGS
FORMS OF DRUG
SOLID LIQUID GASES
1. Tablets—Paracetamol 1. Injections—Benzyl penicillin Nitric Oxide

2. Capsules—Ampicillin 2. Mixtures—Potassium chloride
3. Powders—Dusting antiseptic powder 3. Solution—Eyedrop
4. Pressary—Antifungals 4. Suspension—Antacid
5. Suppository—Analgesics. 5. Emulsion—Cod liver oil
6. Lotions—After shave lotions
7. Enema—Barium enema
 NOMENCLATURE OF DRUGS
NOMENCLATURE OF DRUG
Official name or
Chemical Name Proprietary name Generic Name
nonproprietary name
Name chosen by the official Forms or class or genus in

Describes the chemistry of a Name chosen by the firm
bodies & used by which the drug in question
drug manufacturing or marketing
pharmacopias falls
EXAMPLE:
 Chemical name: 7 chloro 1,3 dihydro—1 methyl 5 phenyl 2H, 1,4 benzodiazepine—2.
 Official name: Diazepam
 Proprietary name: Valium
 Generic name: Benzodiazepine
 DRUGS CLASSIFICATION
A drug class is group of medications having similar chemical structures, mechanism of action and mode of action.
1. Prototypic/First-in-Class/Novel Drug: An individual drug that represents a drug class
2. Me-too Drugs: Drugs similar to prototypic drugs having same mechanism of action with:
 Faster onset of action
 Improved selectivity
 Increased potency
 Longer duration of action
 Less toxicity

24
 DRUGS DEVELOPMENT
ANIMAL TESTING (PRE-CLINICAL)

One basis of two things evaluated:
1. Function of proposed use: Topical usage drugs require less testing than one for chronic systemic administration.
2. Urgency: Anticancer or anti-HIV drugs require less testing than one for life threatening diseases.
TEST DETERMINATION PERFORMANCE EXAMPLES
 All pharmacologic effects Effects on CVS, GIT, Respiration, Hepatic,
Pharmacological profile
 Graded & quantal dose response data Renal, Endocrine and CNS intestinal
Acute dose that is lethal Usually two species (1
Determine the no-effect dose and the
Acute toxicity in approximately 50% rodent, 1 non-rodent),
maximum tolerated dose.
animals. two routes.
The longer the duration of expected clinical
Three doses, two use, the longer the subacute test.
Subacute toxicity
species for 2-4 weeks. 2 weeks - 3 months of testing may be
 Biochemical effects
required before clinical trials.
 Physiologic effects
Rodent & at least one Required when drug is intended to be used in
Chronic toxicity nonrodent species for ≥ humans for prolonged periods.
6 months. Usually run concurrently with clinical trials.
Effects on: Two species, (one
Teratogenic/
 Mating behavior rodent & rabbits) during
Reproductive Toxicity
early pregnancy
Teratogenesis is induction  Reproduction Examples: thalidomide, isotretinoin, valproic
(organogenesis take
of development defects in  Parturition acid, ethanol, glucocorticoids, warfarin,
place) and by later
somatic tissues of fetus  Progeny lithium, and androgens.
(examining fetuses or
(exposure to chemical,  Birth defects neonates for
infection, or radiation).  Postnatal development abnormalities).
Mutagenic Toxicity Test effects on genetic stability and mutations in:
Mutagenesis is induction of 1. Sallmonella bacteria in culture (Ames test): Aflatoxin, cancer
changes in genetic material  Genetic stability drugs, and agents binding to DNA give this test positive
of animals of any age and  Mutations 2. Mammalian cells in culture
therefore induction of 3. Mice (Dominant lethal test): Clastogenicity in mice & exposure
heritable abnormalities. is before mating
Required when drug is intended to be used in
humans for prolonged periods.
Carcinogenic Toxicity
Examples: coal tar, aflatoxin,
Carcinogenesis is the  Gross pathology
Two years, two species. dimethylnitrosamine and other nitrosamines,
induction of malignant  Histologic pathology.
urethane, vinyl chloride, and polycyclic
characteristics in cells.
aromatic hydrocarbons in tobacco smoke (eg,
benzo[a]pyrene) and other tobacco products
REPRODUCTIVE SAFETY (FDA RATINGS)

D
A B C X
CATEGORY (teratogenic but
(very safe) (safe) (may be safe) (teratogenic)
used when serious)
+
Animals - +/- +/0 +
+
Humans - -/0 0 +

25
CLINICAL TESTING & MARKETING
PRECLINICAL PHASE 1 PHASE 2 PHASE 3 PHASE 4
~ 20-100 healthy
volunteers ~ 100- 200 patients Post marketing
2 different animal
(Exception: Cancer & (most drugs failed ~ 1000-6000 patients surveillance (after FDA
species
toxic drugs to target here) approval)
patients)
Effectiveness (check in
 Safety  Safety Confirm effectiveness &
monitored patients) Common as wells as
 Efficacy  Dosage common side effects
with placebo in single rare side effects
 Biological Activity  Pharmacokinetics or double blind check
(double blind check)
ORPHAN DRUGS
 An orphan drug is a drug for a rare disease (one affecting < 200,000 people in the United States).
 Study of such agents has often been neglected because profits from the sales of an effective agent for an uncommon ailment
might not pay the costs of development.
 Some countries bestow certain commercial advantages on companies that develop drugs for uncommon diseases

26
2
AUTONOMIC NERVOUS SYSTEM
PHARMACOLOGY
DESCRIPTION PAGE NO
INTRODUCTION TO AUTONOMIC PHARMACOLOGY 27
PARASYMPATHOMIMETICS 28
ANTICHOLINERGIC DRUGS 29
SYMPATHOMIMETICS 31
ADRENERGIC BLOCKERS 33
DRUGS USED IN GLAUCOMA 33

27
INTRODUCTION TO AUTONOMIC PHARMACOLOGY
CLASSIFICATION OF CHOLINERGIC RECEPTORS
Mnemonic Location G Protein Mechanism
M1 Nadia Nerve Endings Gq IP3, DAG cascade
+
cAMP, K channels
M2 Have Heart Gi
activate
Effector Cells: Smooth Muscle, Glands,
M3 Effective Gq IP3, DAG cascade
Endothelium
+
cAMP, K channels
M4 Gi
CNS CNS activate
M5 Gq IP3, DAG cascade
NN Nerve Ganglia + +
- Na /K depolarizing current
NM NeuroMuscular Junction
Anything that comes under parasympathetic control and not from M1 (Increased gastric secretions) and M2 (Heart
depression effects) will come under M3. Most of the functions are reverse of sympathetic control!
CLASSIFICATION OF ADRENERGIC RECEPTORS
Mnemonic Location G Protein Mechanism
1 England Effector Cells: Smooth Muscle, Glands Gq IP3, DAG cascade
2 Never Nerve Endings Gi cAMP
1 Have Heart, JG apparatus
2 Some Smooth Muscle, Liver, Heart
Gs cAMP
3 Apology Adipocytes
D1 and D5 Brain, Smooth Muscles of Renal Vasculature
D2 D3 and D4 Brain, Smooth Muscles, CVS Gi cAMP
 1-receptors are further classified to 1A, 1B & 1D while 2-receptors are into 2A, 2B & 2C.
 1-receptors follow BIG FISH BIG EYE theory! Imagine a Fish made of rope with a big Eye. And you pulled
rope and the Fish became smaller i.e. 1 has big eye (mydriasis) and other things generally constricted or
contracted.
 2-receptors resemble a fish bigger than 1-receptors. She was playing but some batameez betas (
receptors) start fighting with her. At the end, she won by eating the batameez betas but left some poop. So
what happens is 2-receptors have functions of opposing Batmez Betas. Poop represents platelets
aggregation.
 1, 2 and 3 receptors resemble heart and kidney; relaxing wings of butterfly; triglyceride molecule
respectively.
INNERVATIONS OF ORGAN SYSTEMS (Most by both SANS and PANS except)

 Only SANS supply; Save Blood Save Human (Sweat Glands, Blood Vessels, Spleen, Hair Follicles)
 Only PANS supply; Punjab Group of Colleges (Pancreatic Glands, Gastric Glands, Ciliary Muscle)
DRUGS MNEMONICS
Cholinergic Transmission: Hepatitis Virus B = Hemicholinium, Vesamicol, Botulinum
Adrenergic Transmission: MRGA (‫)رماغ‬ = Me-tyros-ine, Re-serp-ine, Gua-nethid-ine, Amphetam-ine
CT (‫)ٹک‬ = Cocaine, TCA
ERECTION & EJACULATION: (Point & Shoot) i.e. PANS & SANS

28
PARASYMPATHOMIMETICS
Parasympatho-
mimetics
Indirect Acting
Direct Acting
(AChE Inhibitors)
Muscuranic Intermediate acting Short acting Long acting

Both Receptors Nicotinic
cabamates alcohols organophosphates
Bethanechol Neostigmine Parathion

Nicotine
Acetylcholine Methacholine Physostigmine Malathion
Varinicline Edrophonium
Carbachol Pilocarpine Pyridostigmine Sarin, Tubin
Succinylcholine
Muscarine Ambonemium Metrifonate
Lobeline
 WHY NEOSTIGMINE IS PREFERRED OVER PHYSOSTIGMINE IN TREATMENT OF

MYASTHENIA GRAVIS?
Neostigmine has quaternary nitrogen; hence, it is more polar and cannot cross BBB to enter CNS, but cross the
placenta. Physostigmine is lipid soluble and can cross BBB to enter CNS.
 DIFFERENCE BETWEEN PARATHION AND MALATHION
FEATURE PARATHION MALATHION
Clinical Use Insecticide Insecticide + Scabicide
Duration Days to Weeks Days
Metabolized to inactive
Pharmacokinetics Lipid Soluble
form in mammals & birds
Danger High Less

29
ANTICHOLINERGIC DRUGS
Antiparkinsonims
& Dystonia when
Antimotion L-dopa is
CNS Sickness unresponsive
(Scopolamine) (Benztropine,
Biperiden,
Trihexiphenidyl)
Atropine (72h),
Eye
Homatropine (24h)
(Mydriasis,
Cyclopentolate (12h),
Cycloplegia)
Tropicamide (4h)
Bronchi Ipratropium,
(Asthma, Tiotropium,
COPD) Aclidiunum
Anti-
muscuranics
Non Selective M1 Selective
Gut (Dicycloamine, (Pirenzepine,
Glycopyrrolate) Telenzepine)
M3 Selective
(Tolterodine,
Bladder Non Selective Festerodine,
(Urinary (Oxybutynin, Propiverine,
Anticholinergic Urgency) Trospium) Darifenancin,
Drugs Solifenancin)
Intoxication of
AChE Atropine
inhibitors
Hexamethonium
Ganglion
Mecamylamine
Blockers
Parasympatho Trimethaphan
-lytics
Anti-
nicotinics Nondepolarizing
Pan-curonium
Tubo-curarine
NMJ Depolarizing Ve-curonium
Blockers Succinylcholine Cis-atra-curium
Ro-curonium
Atra-curium
AChE Miva-curium
Oximes Pralidoxime
Regenerators
 TREATMENT OF ORGANOPHOSPHATE POISONING
1. Stabilize the patient vitally ABC.

2. Contaminated clothes should be removed and exposed skin should be washed with Na2CO3 solution.
3. Atropine 2 mg is given IM or IV at once and repeated every 15 min till mydriasis, tachycardia and dry mouth occurs.
4. Specific cholinesterase reactivator, Pralidoxime 1 gm in 100 ml normal saline or 5% glucose is given by IV infusion
and repeated as indicated by patient’s condition. It should be given as early as possible in order to be effective.
5. Artificial respiration with positive pressure device may be needed.
6. Airway should be kept clear as there is bronchoconstriction and excessive bronchial secretion. Endotracheal
intubation or tracheostomy with suction may be required.
7. Diazepam may be needed for convulsions.

30
 ATROPINE EFFECTS IN ORDER OF INCREASING DOSE
1. Decreased secretions (salivary, bronchiolar, sweat)
2. Mydriasis and cycloplegia
3. Hyperthermia (with vasodilation)
4. Tachycardia
5. Sedation
6. Urinary retention & constipation
7. Behavioral: excitation & hallucinations

31
SYMPATHOMIMETICS
Sympathomimetics
Direct Acting Indirect Acting Both
Reuptake
 &  Agonists  Agonists  Agonists Releasers
Inhibitors Ephedrine
Epinephrine Amphetamine
Nonselective Nonselective Cocaine
(,) Methamphetamine
Oxymetazoline Isoproterenol TCA
Norepinephrine Tyramine
(, except 2)
Dopamine (D1,,
except 2) 1 selective 1 selective
Phenylephrine Dobutamine
Tetrahydrozoline
Midodrine
2 selective
SHORT ACTING
2 selective Albuterol
Clonidine Metaproterenol
Methyldopa Terbutaline
Apraclonidine Ritrodrine
Brimonidine LONG ACTING
Salmeterol
Formoterol
Indacaterol
Vilanterol
Olodaterol
 SYMPATHOMIMETIC EFFECTS ON CVS

32
 WHY NOR EPINEPHRINE IS NOT USED IN ANAPHYLACTIC SHOCK?
Epinephrine and norepinephrine are very similar neurotransmitters and hormones. While epinephrine has slightly more
of an effect on your heart, norepinephrine has more of an effect on your blood vessels.
 WHY DOPAMINE IS GIVEN IV ONLY?

Since the half-life of dopamine in plasma is short—approximately one minute in adults, two minutes in newborn babies
and up to five minutes in preterm babies—it is usually given as a continuous intravenous drip rather than a single
injection.
 USES OF CLONIDINE IN DIABETIC DIARRHEA
Activate uninnervated 2 receptors and cause water and salt absorption in GIT that relieves diarrhea

33
ADRENERGIC ANTAGONISTS
Adrenergic Antagonists
&
 Blockers  Blockers
Blockers
Labetolol 1 selective 2 selective Nonselective 1 selective 2 selective

Nonselective Parazosin Propranolol Acebutolol
Carvedilol Yohimbine Butoxamine
Doxazosin Rauwolscine Betaxolol Nebivolol
Terazosin Nadolol Esmolol
Reversible & Irreversible & Silodosin Pindolol Metoprolol
Short Acting Long Acting Tamsulosin Timolol Atenolol
Sotalol Bisoprolol
Phentolamine Phenoxybenzamine
DRUGS USED IN GLAUCOMA

Drugs for Glaucoma
(All are qiven in TOPICAL DROPS except the highlighted)
Decrease Secretion of Removal of Water from

Increased Aqeuous Outflow
Aqueous Humour Eye
 Agonists Carbonic
 Blockers 2 selective Cholinomimetic (uveoscleral Anhydrase Osmotic
Prostaglandins
Agonists s (Contraction) veins) Inhibitors Agents
(HCO3 lack)
Pilocarpine Latanoprost Mannitol

Timolol Apraclonidine Epinephrine Bimatoprost Acetazolamide
Betaxolol Brimonidine Physostigmine (IV) for acute
Unoprost (ORAL)
(GEL) closed angle
Travoprost
Dorzolamide
Brinzolamide

34
3
AUTOCOIDS & NSAIDS PHARMACOLOGY
DESCRIPTION PAGE NO
AUTOCOIDS 35
EICOSANOID AGONISTS & ANTAGONISTS 36
NSAIDS, DMARDS & ANTI-GOUT DRUGS 37

35
AUTOCOIDS
Drugs for Unit 16
Histamine Antagonists Serotonin Ergot Alkaloids
H1 Antagonists H2 Antagonists Serotonin Agonists Serotonin Antagonists Vessels

Ergotamine
1st Generation 5-HT1 Agonist 5-HT2 Antagonist

Cimetidine Suma-triptan
Diphenhydramine Famotidine Ketanserin Uterus
Dimenhydrinate Riza-triptan Cycloheptadine Ergonovine
Ranitidine Frova-triptan
Doxylamine Nizatidine Phenoxybenzamine
Promethazine Almo-triptan
Cyclizine Ele-triptan
Zolmi-triptan Brain
Chlorpheniramine Lysergic Acid
Nara-triptan 5-HT3 Antagonist
Ondan-steron Diethylamide (LSA)
Grani-steron Bromocriptine
2nd Generation Dola-steron Pergolide
5-HT2 Agonist Cabergoline
Cetirizine Locaserin Palono-steron
Fexofenadine Alo-steron Methylsergide
Fenfluramine
Loratadine Dex-fenfluramine
Des-loratadine
5-HT4 Agonist
Tegaserod
 HISTAMINE METABOLISM  SEROTONIN METABOLISM
DAO
HCl secretion in stomach

Inflammation
Strong Vasodilation (due to NO release)
Thepeuratic Value (none)
Allergy
Mast Cells (production)
IgE
Neurotransmitter or Narrow Airways (Bronchoconstriction)
E (x)

36
EICOSANOID AGONISTS & ANTAGONISTS
Eicosanoids
Agonists Antagonists
COX Inhibitors Phospholipase

Straight Chain Cyclic LT Antagonists
(NSAIDS) A2 Inhibitors
Leukotrienes Thromboxane LOX Inhibitor Non-Selective Corticosteroids

LTB4 TXA4 Zileuton Reversible
LTC4 Ibuprofen
LTD4 Indomethacin
Prostacyclin LT2 Receptor Naproxen
PGI2 Inhibitor Piroxicam
Epo-prostenol Monte-lukast
Tre-prostinil Zafir-lukast
Non-Selective
Irreversible
Prostaglandins Aspirin
PGE1
Miso-prostol
Al-prostadil
PGE2 Selective COX2
Dino-prostone Inhibitor
PGF2 Cele-coxib
Latano-prost Rafe-coxib
Bimato-prost Valde-coxib
Uno-prost Meloxicam
Travo-prost

37
NSAIDS, DMARDS & ANTI-GOUT DRUGS
Drugs
Anti-inflammtory Gout Drugs

Analgesic Drug
drugs
COX Inhibitors Acet-amino-phen Acute Chronic

DMARDS
(NSAIDS) Phenacetin
Cytotoxic NSAIDS
Non-Selective Microtuble
Methotrexate Indomethacin
Reversible Assembly Inhibitor
Phenylbutazone
Ibuprofen Col-chi-cine
Indomethacin
Naproxen Interfere T-Cell
Piroxicam Cyclosporine Glucocorticoids
Chloroquine Uricosurics
Abatacept Probenecid
Leflunomide Sulfinpyrazole
Non-Selective Sulfasalazine
Irreversible Col-chi-cine in low
Aspirin doses
Xanthine Oxidase
Interfere B-Cell Inhibitors
Belimumab Allopurinol
Selective COX2 Rituximab Febuxostat
Inhibitor
Cele-coxib
Rafe-coxib
Valde-coxib Interfere
Meloxicam Macrophages
Gold Compounds
Gold Sodium
Thiomalate
Aurothioglucose
Auranofin
Anti-TNF Drugs
Etanercept
Infliximab
Golimumab
Adalimumab
***Biological DMARDS
 PHARMACOLOGICAL EFFECTS OF ASPIRIN

MAJOR URIC ACID
DOSE ACID & ELECTROLYTE BALANCE
EFFECT ELIMINATION
Low:
Antiplatelet
(300 mg/d) ↓ tubular secretion →
Moderate: Analgesic + hyperuricemia
(300-2400 mg/d) Antipyretic
Mild uncoupling of oxi. Phosphorylation → ↑ respiration →↓ pCO2→
–
High: Anti- ↓ tubular reabsorption respiratory alkalosis → renal compensation →↑ HCO3 elimination
(2400-4000 mg/d) inflammatory → uricosuria →compensated respiratory alkalosis (pH = normal, ↓ HCO3−,
↓ pCO2)
Inhibits respiratory center →↓ respiration→↑pCO2→ respiratory
acidosis (↓ pH, ↓ HCO3–, normalization of pCO2) plus inhibition of
Krebs cycle and severe uncoupling of oxi. phosphorylation (↓ ATP)
→metabolic acidosis, hyperthermia, and hypokalemia
TOXICITY MANAGEMENT
Toxic Dose 1. No specific antidote.
2. Gastric lavage ( activated charcoal)
3. Ventilatory support
4. Symptomatic management of acid-base/ electrolyte
imbalance, & hyperthermia & dehydration.
5. Urine volume & its alkalinization facilitate salicylate renal
elimination. (zero-order elimination)

38
 SELECTIVE COX-2 INHIBITORS vs
 NSAIDS vs ASPIRIN
NSAIDS
1. Analgesia: ketorolac > ibuprofen/naproxen > ASA
2. Gastrointestinal irritation: < ASA 1. Less gastrointestinal toxicity
3. Minimal effects on acid-base balance 2. Less antiplatelet action
4. No effects on uric acid elimination 3. Not effective as an antiinflammatory agent.
5. Allergy: common, possible cross-hypersensitivity with ASA 4. Exert prothrombotic effects via inhibition of endothelial cell
6. Renal: chronic use may cause nephritis, nephritic syndrome, function (MI and strokes).
acute failure (via ↓ formation of PGE2 and PGI2, which 5. Increased risk of Arterial Thrombosis
normally maintain GFR and RBF)
 ACETAMINOPHEN IS PREFERRED OVER
 ACETAMINOPHEN vs ASPIRIN
ASPIRIN
1. Renal Disease
1. No antiplatelet effect
2. Duodenal Ulcer
2. No implication in Reye Syndrome
3. Viral Infections
3. No effects on uric acid
4. Aspirin Allergies
4. Low GUT distress
5. Bleeding Disorder
5. Not bronchospastic
6. Late Pregnancy

39
4
RESPIRATORY PHARMACOLOGY
0.5 SEQ + 2 MCQs = 5.5 Marks
GASTROINTESTINAL PHARMACOLOGY
DESCRIPTION PAGE NO
DRUGS FOR ASTHMA & COPD 40
DRUGS FOR GASTROINTESTINAL DISORDERS 41

40
DRUGS FOR ASTHMA
Drugs for Asthma
ACUTE ASTHMA CHRONIC ASTHMA BOTH

[Bronchodilators (Relievers)] (Controllers) (Leukotriene Antagonists)
Sympathomimetics Anti-inflammtory LOX Inhibitors

SHORT ACTING  2 AGONISTS Bronchodilators
Drugs Zileuton
(SABA)
Albuterol
Metaproterenol
Sympathomimetics Corticosteroids
Terbutaline INHALED (ICS) Receptor Inhibitors
Ritrodrine LONG ACTING  2 Montelukast
AGONISTS (LABA) Mo-methasone
NON SELECTIVE DIRECT Flutica-sone Zafirlukast
Salmeterol
Epinephrine Formoterol Dexa-methasone
Isoproterenol Beclo-methasone
Olodaterol
DIRECT/INDIRECT Flun-solide
Ephedrine Bude-sonide
SYSTEMIC
Prednisone
Prednilosone
Antimuscuranics Hydrocotisone
Ipratropium (Short Acting)
Anti-IgE Antibodies
Methyl-xanthines Omalizumab
Theophylline
Aminophylline
Release Inhibitors
Cromolyn
Nedocromil
***Porphylaxis of Asthma
 MANAGEMENT OF ASTHMA
Bronchoconstrictive Results of peak flow or Quick relief of
Classification Long-term control
episodes spirometry Symptoms
Intermittent < 2 days per week No daily medication
> 2 days per week, not Near normal*
Mild persistent Low-dose ICS
daily
Moderate Low-dose ICS + LABA OR SABA
Daily 60% to 80% of normal
persistent Medium-dose ICS
Severe Medium-dose ICS + LABA OR
Continual < 60% of normal
persistent High-dose ICS + LABA
 DRUGS FOR COPD
Drugs for COPD
Bronchodilators Anti-inflammtory Drugs
Sympathomimetics Antimuscuranics Methyl-xanthines Corticosteroids

SHORT ACTING  2 Ipratropium Rof-lumi-last INHALED (ICS)
AGONISTS (SABA) Tiotropium Mo-methasone
Albuterol Aclidinum Flutica-sone
Metaproterenol Beclo-methasone
Terbutaline Bude-sonide
Ritrodrine
LONG ACTING  2 AGONISTS
(LABA)
Salmeterol
Formoterol
Indacaterol
Vilanterol
Olodaterol

41
DRUGS FOR GASTROINTESTINAL DISORDERS
1. Antacids: Mg(OH)2 ; Al(OH)3
2. H2 Blockers: Cimetidine; Famotidine; Ranitidine; Nizatidine
ACID PEPTIC 3. Proton Pump Inhibitors: Ome-prazole; Panto-prazole; Rabe-prazole;
DISEASE Dex-lanso-parazole; Lanso-prazole; Es-ome-prazole
4. Mucosal Protective Agents: Sucralfate; Misoprostol; Colloid Bismuth
5. Antibiotics: Amoxicillin, Metronidazole, Clarithromycin
PROKINETIC 1. D2 Blockers: Metoclopramide; Domperidone

AGENTS 2. Macrolides: Erythromycin
(MOTILITY) 3. Cholinomimetics: Neostigmine
1. Bulk Forming: Psyllium, Methylcellulose, Polycarbophil

2. Osmotic: MgO, Mg(OH)2, Sorbitol, Lactulose, Mg citrate, Na3PO4,
Polyethylene glycol
LAXATIVES/
3. Stool Softening/Lubricating/Surfactants: Docusate, Glycerin, Mineral oil
PURGATIVES
4. Stimulant: Aloe, Bisacodyl, Cascara, Castor oil, Senna
5. Chloride Channel Activator: Lubiprostone, Linaclotide (cGMP)
6. Opioid Antagonists: Methylnaltrexone, Alvimopan
1. Opoid Agonists: Loperamide; Diphenoxylate

ANTI-
2. Colloid Bismuth Compounds: Subsalicylate; Citrate
DIARRHEALS
3. Adsorbents: Kaolin + Pectin
1. 5-HT3 Blockers: Alo-setron

IRRITABLE
Drugs for GIT 2. Anticholinergics: Dicycloamines, Hyoscyamine
BOWEL
Disorders 3. Chloride Channel Activators: Lubiprostone
SYNDROME
4. 5-HT4 Agonist: Tegaserod
1. Antimuscuranics: Scopolamine, Phenothiazines

2. Corticosteroids: Dexamethasone
3. Cannabinoids: Dronabinol; Nabilone
ANTIEMETICS 4. D2 Blockers: Phenothiazines; Metoclopramide
5. 5-HT3 Blockers; Ondan-steron; Grani-steron; Dola-steron; Palono-steron
6. H1 Blockers: Diphenhydramine, Dimenhydrinate, Cyclizine
7. NK1 Blockers: Apre-pitant, Netu-pitant, Rowa-pitant
1. Aminosalicylates (5-ASA): Me-salamine, Pentasa, Asacol, Lialda, Rowasa,

Canasa
2. AZO Compounds: Bal-salazide, Ol-salazine, Sulfa-salazine
INFLAMMATORY 3. Glucocorticoids: Budesonide
BOWEL DISEASE 4. Immunosuppressive Antimetabolites: 6-Mercaptopurine, Azathioprine,
Methotrexate
5. Anti-TNF Drugs: Infliximab, Golimumab, Adalimumab
6. B-Cell Intregrin Blocker: Natalizumab
PANCREATIC Pancrelipase
SUPPLEMENTS Pancreatin
BILE ACID
Ursodiol
THERAPY

42
5
CARDIOVASCULAR, DIURETIC & BLOOD
PHARMACOLOGY
DESCRIPTION PAGE NO
ANTIHYPERTENSIVE DRUGS 43
ANTIANGINAL DRUGS 44
HEART FAILURE DRUGS 45
ANTIARRHYTHMIC DRUGS 48
DIURETICS 50
DRUGS USED IN CYTOPENIAS/ ANEMIAS 51
DRUGS USED IN COAGULATION 52
ANTIHYPERLIPIDEMICS 53

43
ANTI-HYPERTENSIVE DRUGS
Anti-Hypertension Drugs
Diuretics Angiotension
Sympathoplegics Vasodilators Renin Antagonist
(Blood Volume ) Antagonists
Thiazide Diuretics Baroreceptor Calcium Channel ACE Inhibitors Aliskiren

(mild-moderate Sensitizing Agents Blockers Capto-pril
hypertension) (SANS, Heart Dihydropyridines Benaze-pril
Hydro-choloro- Vagal tone) Felo-dipine Lisino-pril
thiazide Veratrum Alkaloids Isra-dipine Enala-pril
Chlorothiazide (Natural) Nicar-dipine
Metolazone Nisol-dipine
Chlorthalidone Nife-dipine ARBs
CNS Acting (2 Amlo-dipine Cande-sartan
Agonists) Verapa-mil Lo-sartan
Loop Diuretics
(severe (CO, TPR) Dilti-azem Irbe-sartan
Clonidine Val-sartan
hypertension)
Furosemide Methyldopa
NO Releasers
Bumetanide Hydrala-zine
Torsemide Ganglion Blockers Nitroprusside
Ethacrynic Acid Hexamethonium
Mecamylamine
Postassium Channel HYPERTENSION DRUG
Trimethaphan
Openers
Minoxidil Sulfate STRATEGY:
Postganglionic Diazoxide 1. TPR
Neuron Blockers
2. CO
Reserpine D1 Agonist
Guanethidine Fenoldopam 3. Body Fluid Volume
Guanadrel COMPENSATORY RESPONSE:
MAO inhibitors 1. Reflex Tachycardia (SANS) - Baroreceptors
2. Edema (Renin)
Adrenoceptor
Blockers
1 Blockers
(TPR)
Para-zosin
Doxa-zosin
Tera-zosin
 Blockers
(CO, TPR)
Propranolol
 1 Blockers
(CO, TPR)
Atenolol
Nebivolol
Esmolol
Metoprolol
Acebutalol
/ Blockers
(CO, TPR)
Labetolol
Carvedilol
 COMBINATION OF DRUGS IN CO-MORBID  LOSARTAN IS PREFERRED OVER

DISEASES CAPTOPRIL?
INDICATION It has lower incidence of cough i.e. by inhibiting
(Hypertension +) DRUG(S)
kininase II (which normally prevents degradation of
Angina -blockers, CCBs histamine).
Diabetes, Chronic Kidney Disease ACEI, ARBs, CCBs (-dipines)
 DOES CCBs AFFECT SKELETAL
Heart failure ACEIs, ARBs, -blockers
Post-MI -blockers MUSCLE?
BPH -blockers No, as contraction in skeletal muscles is mediated by
2+
Ca release from sarcoplasmic reticulum and CCBs
Dyslipidemias -blockers, CCBs, ACEIs/ARBs 2+
affects L- type Ca channel located in plasma
Pregnancy (Chronic Hypertension) Methyldopa/ Labetolol membranes of smooth and cardiac muscles most
Pregnancy (Preeclampsia) Hydralazine/Labetolol effectively.

44
ANTI-ANGINAL DRUGS
Anti-Anginal Drugs
Vasodilators Cardiac Depressents Others
Nitrates Calcium Channel Blockers -Blockers pFOX Inhibitors

Ranolazine
Trimetazidine
Ultrashort Acting Dihydropyridines (Oral) Non-Selective  Blockers
(Inhalational) Felo-dipine Propranolol
Amyl nitrite Isra-dipine Selective HR
Nicar-dipine Ivabradine
Nisol-dipine
Nife-dipine 1 Blockers
Short Acting (Sublingual) Amlo-dipine
Nitroglycerin Atenolol
Isosorbide dinitrate Nebivolol
Esmolol
Verapa-mil (Oral & Metoprolol
Parenteral) Acebutalol
Intermediate Acting (Oral)
Nitroglycerin
Isosorbide dinitrate ERECTILE DYSFUNCTION
Isosorbide mononitrate
Pentaerythritol tetranitrate Dilti-azem (Oral & Nitrates + “-afils”
Parenteral) i. Silden-afil
ii. Tadal-afil
Long Acting (Transdermal) iii. Varden-afil
Nitroglycerin
 TREATMENT STRATEGIES FOR ANGINA

TYPE OF
TREATMENT STRATEGY COMPENSATORY
ANGINA
Atherosclerotic/ Oxygen Requirement by TPR, CO or Both
Stable/ Classic  Coronary Blood Flow From action of nitrates:
Angina/ Angina of Acute Attack: Nitrates + Rest (Repeat in recurrence); Nifedipine can also be given 1. Reflex Tachycardia
Effort Prophylaxis: CCBs, -blockers
(SANS) –
Vasospastic/ Rest/ Oxygen Delivery by reversing vasospasm
Baroreceptors
Variant/  Coronary Blood Flow
Prinzmetal’s Nitrates 2.  Heart Force
Angina Prophylaxis: CCBs
Unstable/
Crescendo I/V nitrates (nitroglycerin) given
Angina/ Acute Definite: Myocardial Revascularization (Coronary Artery Bypass Grafting CABG, -
Coronary Percutaneous Transluminal Coronary Angioplasty PTCA)
Syndrome
 TREATMENT OF CYANIDE POISONING
TREATMENT 1
(3 step procedure)
1. Immediate inhalation of amyl nitrite & IV administration of sodium nitrite promotes formation of MetHb, which binds CN−
ions, forming cyanoMetHb which prevents inhibitory action of CN− (complex IV of ETC)
2. CyanoMetHb is reconverted to MetHb by treatment with IV sodium thiosulfate, forming MetHB and the less toxic thiocyanate
ion (SCN−) excreted by kidney.
3. MetHb is converted to OxyHb with methylene blue.
TREATMENT 2
Hydroxocobalamin (preferred now)

45
HEART FAILURE DRUGS (A: ACUTE; C: CHRONIC)
Heart Failure Drugs
Positive Inotropic Drugs Vasodilators Miscellanous drugs for CHF
Cardiac Glycosides (CHF) Loop Diuretics (AHF +

Digoxin NO Releasers (AHF)
Nitroprusside CHF)
Digitoxin (long duration) Furosemide
Nitroglycerin
Bumetanide
Torsemide
-Agonists (AHF) Ethacrynic Acid
Dobutamine NO Releasers (CHF)
Dopamine Nitrates
Hydralazine Thiazide Diuretics (CHF)
Hydrochloro-thiazide
Chlorothiazide
PDE Inhibitors/Bipyridines Metolazone
(AHF) Chlorthalidone
Milrinone ADH
Theophylline
Antagonists
Coni-vaptan ACE Inhibitors (CHF)
Capto-pril
Tol-vaptan Benaze-pril
Enala-pril
Lisino-pril
ARBs (CHF)
Irbe-sartan
Cande-sartan
Lo-sartan
Val-sartan
Natriuretic Peptide (AHF)

Ne-siri-tide
-Blockers (CHF)
Bisoprolol
Carvedilol
Metoprolol
Nebivolol
K+ Sparing Diuretics (CHF)

Spironolactone
Eplerenone
** Yellow Highlighted for AHF

** Blue Highlighted for both AHF & CHF
HEART FAILURE DRUGS STRATEGY

1. Preload (Blood Volume x Venous Tone)
a. Blood Volume by Diuretics, ACEIs, ARBs
b. Venous Tone by Venodilators
2. Afterload (TPR or BP) by ACEIs, ARBs, -blockers ,
Arteriodilators
3. Contractility by Positive Inotropic Drugs
4. Remodeling of Heart Muscles by ACEIs, ARBs, -blockers,
K+ sparing diuretics

46
 DIGOXIN MECHANISM OF ACTION & EFFECTS
Digoxin
Direct Effect Indirect Effect
Cardiac Na/K ATPase Inhibit Neuronal Na/K ATPase Inhibit
Intracellular Na & K  PANS Activity
NCX Exchanger (stops)

Atria AV Node
Intracellar Ca (not removed)
ERP ; Conduction Velocity ERP ; Conduction Velocity
 Heart Force/ Contractility
(Positive Inotropy) Negligible Effects on ECG PR Interval
( Ventricle ERP)  Heart Rate (Negative
 QT Interval Chronotropy)
T-wave inversion
ST-segment depression
CO, EF
Remodelling   SANS Tone

 ESS (Vasodilation)
 EDS  Preload
 Afterload
 Heart Rate (Negative Chronotropy)
 TYPES OF HEART FAILURE & TREATMENT

47
 HEART FAILURE DIFFERENCES

48
ANTI-ARRHYTHMIC DRUGS
Anti-Arrhythmic Drugs
Group 1 Group 2 Group 3 Group 4 Group 5

INa Blockers -Blockers IK Blockers L-type ICa Misc.
Propranolol Prolong AP Blockers Adenosine
Metoprolol Sota-lol Verapamil Potassium
Group 1B Timolol Ibu-tilide Diltiazem Magnesium
Group 1A Group 1C Esmolol Amio-darone
Prolong AP Shorten AP Dofe-tilide Ranolazine
Fast Kinetics No effect on AP Sota-lol Amio-darone Ivabradine
Moderate Kinetics Slow Kinetics Amio-darone
Procain-amide Lidoca-ine Drone-darone
Mexilet-ine Flecain-ide
Disopyr-amide
Quini-dine Phenytoin
Amio-darone
***Sotalol Effect: IK blocker > -blocker
***Amiodarone Effect: IK blocker > INa blocker > -blocker > ICa blocker
 PROPERTIES OF PROTOTYPIC ANTI-ARRHYTHMIC DRUGS (PM: PACE MAKER)
INa Block ER Period - ICa PR QRS QT PM
Group Drug AP
Normal Ischemic Normal Ischemic Block Block Interval Duration Interval Activity
Procaineamide -
1A Disopyramide  + +++   + + /   
Quinidine -
Lidocaine
1B
Mexiletine
 - +++   - - - - -/ 
1C Flecainide - + +++ -  - -   - 
Propranolol
2
Esmolol
- - +   +++ -  - - 
3, 1A, Amiodarone
2, 4
 + +++   + +    
Dronedarone
Ibutilide
3
Dofetilide
 - -  ? - - - -  -
3, 2 Sotalol  - -   +++ -  -  
Verapamil
4
Diltiazem
- - + -  + +++  - - 
5 Adenosine - - - - - + +  - - -
 ANTI-ARRHYTHMIC DRUGS THERAPY

49
 CLINICAL USES OF ANTI-ARRHYTHMIC DRUGS

50
DIURETICS
Diuretics
Drugs that modify salt Drugs that modify water

excretion excretion
PCT TAL DCT CCT Osmotic ADH Agonists ADH

Diuretics Desmo- Antagonists
Mannitol pressin Coni-vaptan
Carbonic Loop Thiazides K+ Sparing Glycerin Tol-vaptan
Anhydrase Diuretics Diuretics Vaso-pressin
Diuretics Isosorbide Demeclocylcine
Inhibitors Furosemide Hydrochloro- Spironolactone Urea Lithium
Aceta-zolamide Torsemide thiazide Eplerenone
Dor-zolamide Bumetanide Chlorothiazide Amiloride
Brin-zolamide Ethacrynic Acid Metolazone Triamterene
Chlorthalidone
SGLT2 Inhibitors
Can-agliflozin
Dap-agliflozin
Emp-agliflozin
Ipr-agliflozin
 ACIDOSIS & ALKALOSIS
 HYPOKALEMIA & METABOLIC ALKALOSIS

51
DRUGS USED IN CYTOPENIAS/ ANEMIAS
Cytopenia Drugs
Erythrocyte factors Granulocyte Factors Platelet Factors
Erythropoiesis- Myeloid Growth

Iron Vitamins Megakaryocyte
Stimulating Agents Factors
Growth Factors
(ESAs) - (IV/SC) (Subcutaneous)
Iron Preparations Vitamin B12 1-3 x per week G-CSF Agonist IL-11 Agonist
Oral (Parenteral) Epoetin alfa Fil-grastim Oprelvekin (SC)
Ferrous sulfate Cyano-cobalamin Peg-fil-grastim
Ferrous gluconate Hydro-cobalamin Leno-grastim
Ferrous fumarate
Parenteral Thrombopoietin
Iron dextran Weekly
Darb-epoetin alfa Agonists
Iron sucrose Vitamin B9 (Oral) GM-CSF Agonist Romiplostim (SC)
Ferumoxytol Folic Acid (Folacin) Sargramostim Eltrombopag (Oral)
Sodium Ferric
Gluconate Complex
1-2 x per month
Methoxy polyethylene CXCR4 Antagonist
glycol-epoetin beta Plerixafor
Iron Chelators
Defera-sirox (Oral)
Defer-xamine
(Parenteral)

52
DRUGS USED IN COAGULATION DISORDERS
Coagulation Drugs
Anticlotting Drugs Drugs that facilitate clotting
Anticoagulants Thrombolytics (IV) Antiplatelets Reversal Agents

Vitamin K1
(Phytonadione)
Protamine
Heparins (Parenteral) t-PA derivatives COX Inhibitor (oral)
Unfractioned heparin (selective for fibrin- Aspirin
LMW heparins bound plasminogen) Other NSAIDs Clotting Factors
Dalte-parin Recombinants Factor VIII
Enoxa-parin Al-teplase Plasma and Human
Tinza-parin Modified Purified Clotting Factors
Fonda-parinux Re-teplase GP IIa/IIIb Inhibitor (P) Desmopressin
Tenec-teplase Abc-iximibab
Eptifibatide
Direct Factor X Inhibitors Tirofiban
(P/O) Antiplasmin Agents
IV Recombinant Streptokinase Aminocaproic Acid
Lepi-rudin (non-selective) Tranexamic Acid
IV Modified ADP Receptor
Desi-rudin Antagonist (oral)
Bevali-rudin Clopidogrel
Arga-troban Prausugrel
Oral Ticlopidine
Dabi-gatran Ticagrelor
Direct Thrombin Adenosine Uptake &

Inhibitors (Oral) PDE3 Inhibitors (oral)
Api-xaban Dipyridamole
Edo-xaban Cilostazol
Rivaro-xaban
Coumadin Anticoagulant
(Oral)
Warfarin
 DIFFERENCE BETWEEN LMW HEPARINS & HMW HEPARINS
Feature HMWH LMWH
Molecular Weight 15000-20000 Daltons 2000-6000 Daltons
Bioavailability Low High (90%)
Half Life Short (Dose dependent) Long (Dose independent)
Mode of Action Inactivates both factor IIa & Xa Inactivates only Xa
Anticoagulant Effect More effective Less Effective
Monitoring By aPTT Not required (given once/twice a day)
Protamine Reversal More Effective Partially Effective
Heparin Induced Thrombocytopenia More risk Less risk
Osteroporosis More risk Less risk
Excretion Less reliable More reliable

53
ANTIHYPERLIPIDEMICS
Antihyperlipidemics
Bile Acid Binding Sterol Absoprtion Homozygous

HMG-CoA Fibrates Niacin
Resins Inhibitor Familial
Reductase
Hypercholestr-
Inhibitors(Statins)
emia
Gemfibrozil Colestipol Ezetimibe
Fenofibrate Cholestyramine
Pra-vastatin Colesevelam Lomitapide
Sim-vastatin Mipomersen
Lo-vastatin
Ceri-vastatin
Rosu-vastatin
Ator-vastatin
Flu-vastatin

54
6
ANTIFUNGAL, ANTIVIRAL &
ANTICANCER PHARMACOLOGY
DESCRIPTION PAGE NO
ANTIFUNGAL DRUGS 55
ANTIVIRAL DRUGS 56
ANTICANCER DRUGS 57

55
ANTI-FUNGAL DRUGS
Anti-Fungal Drugs
Alter cell membrane Disrupt microtubule

Block -glucan synthesis Block nucleic acid
permeability (ergosterol) functions + Inhibit synthesis
synthesis
of nucleic acids
Azoles Echinocandins Antimetabolite

Imid-azole (2 Nitrogens) Griseofulvin
Caspo-fungin Flu-cytosine/
Ketocon-azole Mica-fungin 5-Fluorocytosine (5FC)
Micon-azole Anidula-fungin
Clotrim-azole
Tri-azoles (3 Nitrogens)
Flucon-azole
Itracon-azole
Voricon-azole
Posacon-azole
Amphipathic Polyenes
Amphotericin B
Nystatin
Terbinafine
 SPECTRUM OF AZOLES
Cutaneous Subcutaneous Systemic Opportunistic
Name Spectrum
Mycoses Mycoses Mycoses Mycoses
Ketoconazole +
Miconazole > Ketokonzaole Dermatophytes Candida (CMC)
Clotrimazole > Ketokonzaole
Coccidioides Candida
Fluconazole ++ Dermatophytes
Blastomyces Cryptococcus
Coccidioides
Sporothrix Histoplasma Cryptococcus
Itraconazole +++ Dermatophytes
Chromomycosis Blastomyces Aspergillus
Paracoccidioides
Candida
Voriconazole +++
Aspergillus
Candida
Posaconazole ++++ Aspergillus
Rizopus

56
ANTIVIRAL DRUGS
Anti-Viral Drugs
Anti-Herpes Drugs Anti-HIV Drugs Anti-Influenza Drugs Drugs for Hepatitis
HSV, VZV NRTIs Influenza A HBV

Acy-clovir Zido-vudine* Oselta-mivir IFN-
Val-acy-clovir Sta-vudine* Zana-mivir Lami-vudine
Penci-clovir Lami-vudine* A-mantadine Telbi-vudine
Famci-clovir Abaca-vir* Ri-mantadine Ade-fovir
Docosanol Tenofo-vir Teno-fovir
Cidofovir Didanosine* Entecavir
Foscarnet Emtri-citabine*
Idox-uridine Zal-citabine
Influenza B
Trifl-uridine Oselta-mivir
Vidarabine Zana-mivir HCV
IFN-
Sofosbu-vir
CMV Riba-virin
Ganci-clovir NNRTIs Bocepre-vir
Val-ganci-clovir Dela-vird-ine
Cidofovir Nevirap-ine*
Foscarnet Etravir-ine
Vidarabine Efa-virenz
Fomivirsen
Protease Inhibitors
Indi-navir*
Saqui-navir*
Ataza-navir
Daru-navir
Tipra-navir
Nelfi-navir*
Rito-navir*
Fosampre-navir
Entry Inhibitors
CCR5 Antagonist:
Maraviroc
Fusion Inhibitor:
Enfuvirtide
Integrase Inhibitors:
Raltegraver
*Anti-retroviral drugs used in pregnancy

57
ANTICANCER DRUGS
Anti-Cancer
Drugs
Hormonal
Alkylating Agents Antimetabolites Natural Product Antitumour
Misc. Anticancer
Anticancer Drugs Antiboides
Drugs
Nitrogen Mustards Folic Acid Vinca Alkaloids Anthracyclines TK Inhibitors Glucocorticoids

Chlorambucil Antagonist Vin-blastine Doxo-rubicin Ima-tinib Prednisone
Cyclophosphamide Methotrexate Vin-cristine Dauno-rubicin Dasa-tinib
Mechlorethamine Vin-orelbine Ida-rubicin Nilo-tinib
Epi-rubicin Bosu-tinib GH Inhibitors
Nitrosoureas Purine Mito-xantrone Suni-tinib
Podophyllotoxins Tamoxifen
Car-mustine Antagonists Pazopa-nib Toremifene
Lo-mustine Mercaptopurine Eto-poside Sorafe-nib
Teni-poside Flutamide
Thioguanine Bleo-mycin
Mito-mycin
Platinum Analogs Growth Factor
Cis-platin Camptothecins GnRH Analogs
Pyrimidine Receptor Leuprolide
Carbo-platin Antagonists Topo-tecan Inhibitors
Oxai-platin Irino-tecan Gose-relin
Fluorouracil Trastuzu-mab Nafa-relin
Cytarabine Cetuxi-mab
Gemcitabine Pantiumu-mab
Alkyl Sulfonates Taxanes Gefi-tinib
Bu-sulfan Pacli-taxil Erlo-tinib Aromatase
Doce-taxil Inhibitors
Anas-trozole
Le-trozole
Others VEGF Inhibitors
Pro-carbazine Bevaci-zumab
Da-carbazine Ziv-aflibercept
Others
Rituximab
Proteosome Asparaginase
Inhibitors Interferons
Borte-zomib
Carfil-zomib
*Green Highlighted are CCS (Cell Cycle Specific) Drugs

58
7
ANTI-MYCOBACTERIAL & PARASITIC
PHARMACOLOGY
DESCRIPTION PAGE NO
ANTIPROTOZOAL DRUGS 59
ANTIHELMINTHIC DRUGS 60
ANTIMYCOBACTERIAL DRUGS 61

59
ANTI-PROTOZOAL DRUGS
Anti-Protozoal Drugs
for Intestinal & Urogneital Protozoans
Amebiasis Giardiasis Cryptosporidiosis Trichomoniasis
Tissue Amebicides (act Luminal Amebicides Metronidazole Paromomycin Metronidazole

on GIT wall & Liver) (act on GIT wall) Tinidazole Nitazoxanide Tinidazole
Metronidazole Diloxanide furoate
Tinidazole Iodoquinol
Chloroquine Paromomycin
Emetines
Anti-Protozoal Drugs
for Blood & Tissue Protozoans
Malaria Toxoplasmosis Pneumocystis Pneumonia Trypanosomiasis Leishmaniasis
Tissue TMP-SMZ TMP-SMZ American type Visceral type

Schizonticides (kill Antifolates Pentamidine (Chagas Disease) Pentamidine
schizonts in liver) (Pyrimethamine + Atovaquone Nifurtimox Paromomycin
Prima-quine Clindamycin + Primaquine + Clindamycin Miltefosine
Folinic Acid) Trimetrextae + Leucovorin
Trimethoprim + Dapsone African type
Blood Suramin Cutaneous type
Schizonticides (kill Pentamidine Metrodinazole
schizonts in RBCs) Melarsoprol Fluconazole
Chloro-quine Eflornithine
Meflo-quine Nifurtimox
Qui-nine
Artemisi-nins Mucocutaneous type
(Artesunate, Amphotericin B
Artemether,
Dihydro-artemisinin)
All types
Sodium
Sporonticides stibogluconate
(prevent sporogony)
Antifolates
(Sulfonamide,
Proguanil,
Pyrimethamine)
Other Malarial Drugs

Doxycycline
Atovaquone
Halofantrine
Amodiaquine
Lumefantrine
 DRUG REGIMEN IN TREATMENT OF MALARIA

DESCRIPTION DRUG
All Plasmodium species
Chloroquine
(except Chloroquine-resistant P. falciparum)
Mefloquine
Quinine + Doxycycline
Quinine + Clindamycin
Chloroquine-resistant P. falciparum
Artemisinins + Lumefantrine
Artemisinins + Amodiaquine
Fansidar (Primethamine + Sulfadoxine)
Prevention of relapses in case of P. vivax & P. ovale only Primaquine
Prevention of malaria (Prophylaxis) in Chloroquine-sensitive geographic areas Chloroquine
Malarone (Atovaquone + Proguanil)
Prevention of malaria (Prophylaxis) in Chloroquine-resistant geographic areas
Mefloquine
Doxycycline
Prevention of malaria in pregnancy
Mefloquine

60
ANTI-HELMINTHIC DRUGS
Anti-Helminthic Drugs
Nematodes Trematodes Cestodes

(roundworms) (flukes) (tapeworms)
All Roundworms All Flukes Beef/Pork/Fish Tapeworm

Albendazole Praziquantel Praziquantel
Niclosamide
Intestinal Roundworms Sheep Liver Fluke

(except Strongyloides) Bithional Pork Larval Tapeworm
Mebendazole Triclabendazole Praziquantel
Albendazole
Tissue Roundworms Large Intestinal Fluke

(Wuchereria, Loa) Praziquantel Dog Tapeworm
Diethylcarbamazine Niclosamide Albendazole
Strongyloides, Larva Migrans S.haematoblium

Thiabendazole Metrifonate
Ivermectin (+ Onchocerca)
Ascaris S. mansoni
Piperazine Oxamniquine
Pyrantel pamoate (+ Hookworm)

61
ANTI-MYCOBACTERIAL DRUGS
Anti-Mycobacterial Drugs
Atypical Mycobacterial
Tuberculosis Drugs Leprosy Drugs
Infection Drugs
First Line Drugs Alternative/ 2nd Line Drugs Sulfones M. Avium Intracellulare
Isonazid Amikacin (Dapsone, Acedapsone) Drugs
Rifamycins Ciprofloxacin Clofa-zimine Clarithromycin/
(Rifampin, Rifabutin, Ofloxacin Rifampin Azithromycin
Rifapentine) Ethionamide Ethambutol
Ethambutol p-Aminosalicyclic Acid (PAS) Rifabutin
Pyrazinamide Caspreomycin
Streptomycin Cycloserine
Other Atypical
Mycobacterium Drugs
First Line Anti-TB Drugs
Amikacin
Cephlosporins
Fluoroquinolones
Macrolides
Tetracyclines

62
8
ANTI-BACTERIAL PHARMACOLOGY
DESCRIPTION PAGE NO
GENERAL CONSIDERATIONS 63
CELL WALL SYNTHESIS INHIBITORS 65
PROTEIN SYNTHESIS INHIBITORS & AMINOGLYCOSIDES 68
ANTIFOLATE DRUGS & FLUOROQUINOLONES 71

63
GENERAL CONSIDERATIONS
 BASIS OF CLASSIFICATION OF ANTIMICROBIAL AGENTS
A. NATURE
 Antimicrobials are of two types:
 -cidal drugs = kills
 Beta-Lactams (Cell wall synthesis Inhibitors)
 Vancomycin & relatives
 Fluoroquinolones
 Aminoglycosides
 Cotrimoxazole
 Streptogramins
 -static drugs = inhibit growth
 All other then –cidal drugs
 Usage
 Immunocompetent person = Both types
 Immunocompromised person = Only – cidal drugs
B. TYPE OF MICRORGANISMS
C. CHEMICAL STRUCTURE
D. SOURCE
 Antibiotics
 Non-antibiotic
E. MECHANISM OF ACTION
 DIFFERENT PATTERNS OF ANTIMICROBIAL ACTION

FEATURE TYPE – I = CDK TYPE – II = TDK TYPE – III = Both CDK & TDK
Pattern of Concentration dependent with Time dependent with prolonged
Time dependent with minimal PAE
Activity prolonged PAE PAE
PK/PD AUC/MIC
T > MIC AUC/MIC
Parameter Cmax/MIC
Goal of therapy Maximize concentration Maximize duration of exposure Maximize amount of drug
More frequent (Multiple Small
Dosing Less frequent (Single High Dose) Depends
Doses)
Aminoglycosides Beta Lactams Macrolides
Examples
Flouroquinilones Vancomycin Tetracycline
 MIC: Minimal Inhibitory Concentration:

An estimate of the drug sensitivity of pathognes for comparison with anticipated levels in blood or tissue
 PAE: Post Antibiotic Effect:
Antibacterial effect that persists after drug concentration falls below the MIC
 AUC: Area Under Curve

64
 GRAPHS FOR PATTERNS OF ANTIMICROBIAL ACTION
 GENERAL MECHANISMS OF RESISTANCE TO ANTIMICROBIAL ACTION

65
CELL WALL SYNTHESIS INHIBITORS
Cell Wall Synthesis
Inhibitors
Beta Lactams Others
Pencillins Cephalosporins** Others Glycoproteins

Vanco-mycin
Teico-planin
Wider Spectrum  Narrow Spectrum Wider Spectrum Mono-bactam Tela-vancin
Narrow Spectrum Beta Lactamase Actreo-nam
Inhibitors**
1st Generation 2nd Generation Lipoproteins
(Gm +ve) (Gm -ve > +ve) Carba-penems Dapto-mycin
Pencillinase Extended Cefazolin (P) Cefaclor (O) Mero-penem
Susceptible Spectrum Cefalexin (O) Cefamandol (O) Erta-penem
Penicillin G Ampi-cillin Cefotetan (P) Dori-penem Peptide
Cefadroxil (O) Bacitracin
Penicillin V Amoxi-cillin Cefoxitin (P) Imi-penem
Cefuroxime (O/P)
Pencillinase Anti-pseudomonal Antimetabolite
Beta Lactamase Inhibitors
Resistant Pipera-cillin 3rd Generation Inhibitors
Methi-cillin Ticar-cillin (Gm +ve & -ve) Fosfo-mycin
Clavu-lanic Acid Cyclo-serine
Naf-cillin Cefoperazone (P) Sul-bactam
Oxa-cillin Cefotaxime (P) Tazo-bactam
Dicl-oxa-cillin Cefixime (O)
Ceftazidime (P)
Ceftizoxime (P)
Ceftriaxone (P)
4th Generation
(Gm -ve)
Cefepime (P)
Cefpirome (P)
5th Generation
(MRSA)
Ceftaroline (P)
** Extended & Antipseudomonal spectrum of Pencillins + Carbapenems = Stable to Pencillinases
st nd
** All cephalosporins can cross BBB except 1 generation, 2 generation, Cefoperazone & Cefixime.
 SPECTRUM OF PENICILLIN
DRUG GRAM + COCCI GRAM - COCCI GRAM + RODS GRAM - RODS SPIROCHETES
NARROW SPECTRUM
 Bacillus anthracis
Pencillinase  Streptococcus pyogenes  Neisseria  Treponema
A  Clostridium
 Streptococcus viridians
Susceptible
Penicillin G  Streptococcus
gonorrhoeae
 Neisseria
perfringens
 Corynebacterium
 pallidum
 Leptospira
Penicillin V pneumoniae A interrogans
meningitidis diphtheriae
Pencillinase
Resistant
Methi-cillin
Naf-cillin
 Staphylococci
B
   
Oxa-cillin
BROAD SPECTRUM
Extended  S. pyogenes  Escherichia coli
Spectrum   S. viridians C  Haemophilus
 N. gonorrhoeae  Listeria
Beta Lactamase
Inhibitors


S. pneumonia
Staphylococci
B  N. meningitidis
C monocytogenes
infuenzae
 Proteus mirabilis

Ampi-cillin
Amoxi-cillin  Enterococci  Salmonella typhi
 E. coli
Anti-
 H. infuenzae
pseudomonal 
 P. mirabilis
Beta Lactamase
Inhibitors
Less potent than prototypes  Pseudomonas
aeruginosa

Pipera-cillin
Ticar-cillin  Klebsiella
 Enterobacter
A. Non-penicillinase-producing.
B. Not effective against methicillin-resistant staphylococcal infections (MRSA). Only MSSA
C. Penicillinase producing.

66
 SPECTRUM OF CEPHALOSPORINS
DRUG GRAM + COCCI GRAM - COCCI GRAM + RODS GRAM - RODS OTHERS
NARROW SPECTRUM
 Streptococcus
st pyogenes
1 Generation  Streptococcus  Escherichia coli
(Gm +ve)  Proteus mirabilis
Cefazolin
Cefalexin
(anerobes)
 PRSP
A
B
   Klebsiella 
Cefadroxil  MSSA
 Staphylococcus
epidermidis
BROAD SPECTRUM
nd
2 Generation  E. coli
(Gm -ve > +ve)  S. pyogenes
 Neisseria  Haemophilus  Bacteroides
Cefaclor  Streptococcus
Cefamandol
Cefotetan
(anerobes)
 PRSP
A 
gonorrhoeae
Moraxella  infuenzae
 P. mirabilis
fragilis
(anaerobe)- Cefo
B catarrhalis  Klebsiella drugs
Cefoxitin  MSSA
Cefuroxime  Enterobacter
rd
3 Generation  E. coli
(Gm +ve & -ve)  S. pyogenes  H. infuenzae
Cefoperazone  P. mirabilis  Bacteroides
 Streptococcus  N. gonorrhoeae –
 Klebsiella
Cefotaxime
Cefixime
(anerobes)
 PRSP
A
Cefixime,
Ceftriaxone
  Enterobacter
fragilis
(anaerobe)-
Ceftazidime B  Serratia Ceftizoxime
 MSSA
Ceftizoxime  Pseudomonas
Ceftriaxone aeruginosa
th
4 Generation/
Anti-
pseudomonal  Combines the gram (+) activity of 1st generation with gram (-) activity of 3rd generation cephalosporins.
(Gm -ve)  Used in P. aeruginosa mainly
Cefepime
Cefpirome
th
5 Generation
(MRSA)
Ceftaroline (P)
 MRSA
C
   
A. PRSP: Pencillin resistant pneumococci
B. MSSA: Methicillin suspectible staphylococci
C. MRSA: Methicillin resistant staphylococci
 SPECTRUM OF OTHER BETA LACTAMS
 Klebsiella
Monobactam
Aztreonam     Serratia
 Pseudomonas

Pathogens inside &
outside enteric tract
 Salmonella
 Escherichia coli
Pathogens outside
enteric tract  Bacteroides
Carbapenems  Neisseria  Listeria  Klebsiella fragilis
Mero-penem  Streptococci B monocytogenes  Serratia (anaerobe)
C A gonorrhoeae
Erta-penem  MSSA  Clostridium sp.  Enterobacter  Fusobacterium
 Neisseria
Dori-penem  Enterococci B  Gardnerella  Proteus (anaerobe)
Imi-penem meningitidis vaginalis  Providencia  Actinomyces
 Pseudomonas  Nocardia
Respiratory Tract
 H. influenzae
Others
 Acinetobacter sp.
 Citrobacter sp.
Beta Lactamase
Inhibitors
 Good inhibitors of Plasmid encoded beta-lactamases i.e. Streptococci, Gonococci, E. coli, H. influenza
Clavu-lanic Acid
 Bad inhibitors of Chromosome encoded beta-lactamases i.e. Serratia, Enterobacter , Pseudomonas
Sul-bactam
tazo-bactam
A. MSSA: Methicillin suspectible staphylococci
B. Penicillinase producing strains
C. Not effective against P. auruginosa and Acinetobacter spp.

67
 SPECTRUM OF OTHER AGENTS
 Listeria
 Streptococci
Glycoproteins monocytogenes
 PRSP
 Clostridium difficle
Vanco-mycin
Teico-planin


MSSA/ MRSA
S. epidermidis
 (Orally)   Actinomyces
Tela-vancin  Clostridium sp.
 Enterococci
 Coryneabacterium
 Streptococci
 PRSP
 MSSA/ MRSA
Lipoprotein
Dapto-mycin


S. epidermidis
Enterococci
  Coryneabacterium  
A
 VRE
B C
 VISA /VRSA
Beta Lactamase
Inhibitors
 Good inhibitors of Plasmid encoded beta-lactamases i.e. Streptococci, Gonococci, E. coli, H. influenza
Clavu-lanic Acid
 Bad inhibitors of Chromosome encoded beta-lactamases i.e. Serratia, Enterobacter , Pseudomonas
Sul-bactam
tazo-bactam
A. VRE: Vancomycin resistant enterococci
B. VISA: Vancomycin intermediate staphylococci aureus
C. VRSA: Vancomycin resistant staphylococci aureus

68
PROTEIN SYNTHESIS INHIBITORS & AMINOGLYCOSIDES
Protein Synthesis
Inhibitors
Inhibitors of 30S Inhibitors of 50S

Subunit Subunit
Broad Spectrum Broad Spectrum Moderate Spectrum Narrow Spectrum
Tetracyclins Macrolides Lincosamides

Chloramphenicol
Tetra-cycline Azi-thro-mycin Clindamycin
Doxy-cycline Clari-thro-mycin
Mino-cycline Ery-thro-mycin
Demeclo-cycline Streptogramins
Quinupristin-dalfopristin
Ketolides
Teli-thro-mycin
Glycylcycline Oxazolidinone
Tige-cycline Linezolid
Aminoglycosides
Genta-micin
Tobra-mycin
Amika-cin
Strepto-mycin
Neo-mycin
Netil-micin
Kana-mycin
Spectino-mycin
 MECHANISM OF ACTIONS
MECHANISM OF
DRUG CLASS EFFECT
ACTION
Blocks functioning of
initiation complex
Aminoglycosides Bactericidal
and causes
misreading of mRNA
Blocks tRNA binding
Tetracyclines Bacteriostatic
to ribosome
Blocks
peptidyltransferase
Chloramphenicol Both*
i.e. transpeptidation
blocked
Macrolides Bacteriostatic
Telithromycin Blocks translocation Both*
Clindamycin Bacteriostatic
Blocks early step in
Linezolid Both*
ribosome formation
Causes premature
Streptogramins release of peptide Both*
chain
*Primarily bacteriostatic but can be bacteriocidal depending on dose.

69
 SPECTRUM OF AMINOGLYCOSIDES
DRUG CLASS ORGANISMS/USES Route
E. coli
Enterobacter
Aerobic Gram Negative Rods
Klebsiella
(causing UTI or Sepsis) IV
Genta-micin th Serratia
Ref: Levinson Microbiology 15 Ed. Page 145
Tobra-mycin Proteus
Amika-cin Pseudomonas
H. influenzae
Aerobic Gram Negative Rods M. catarrhalis IV
Shigella
Aerobic Gram Negative Rods
Aminoglycosides + Pseudomonas (pneumonia) IV
(causing UTI or Sepsis)
Cell Wall Synthesis
Gram Positive Cocci Enterococci (carditis) IV
Inhibitors
Gram Positive Rods Listeria IV
Strepto-mycin + Aerobic Gram Negative Rods F. tularensis (tularemia)
IV
Cell Wall Synthesis (associated with animal sources) Yersenia pestis (plague)
Inhibitors Acid Fast Rods Mycobacterium tuberculosis IM
Amika-cin + Multidrug Resistant Strain of
Cell Wall Synthesis Acid Fast Rods Mycobacterium tuberculosis IM
Inhibitors resistant to Streptomycin
Neo-mycin
Topical/
Kana-mycin - Eliminate bowel flora
Oral
Genta-micin
Netil-micin - Infections resistant to other AGs IV
Gonorrhea in patients allergic to
Spectino-mycin - IM
beta-lactams
 SPECTRUM OF OTHER PROTEIN SYNTHESIS INHIBITORS
 Chlamydiae
 Rrickettsiae
Chloramphenicol  Streptococcus  Neisseria  Salmonella
pneumoniae meningitidis   H. influenzae


Spirochetes
Anaerobes (Bacteroides
fragilis)
Doxycycline
 Bacillus  Mycoplasma
Tetracyclines  Brucella sp.
anthracis  Chlamydiae
Tetra-cycline (T)  Streptococcus  Neisseria  Vibrio cholerae
 Clostridium  Rickettsiae
Doxy-cycline pneumoniae meningitides  Yersinia pestis
perfringens  Spirochetes
Mino-cycline (M)  MSSA (M)  Helicobacter
Demeclo-cycline  Clostridium  Borrelia burgdorferi
pylori (T)
tetani  Leptospira interrogans
 Treponema pallidum
Extended
 MRSA Extended
spectrum gram
 VRE spectrum gram
Glycylcycline
Tige-cycline  Multidrug
resistant
negative beta
lactamase  negative beta
lactamase
 Acinetobacter
producing
streptococci producing bacteria
bacteria
 Spirochetes (A)
 Bordetella  Treponema pallidum
pertussis  Chlamydia (A)
 Campylobacter
 C. pneumoniae
Macrolides  Neisseria  Clostridum jejuni
 Streptococcus  C. psittaci
Azi-thro-mycin (A) gonorrhoeae difficile (F)  H. infuenzae
pneumonia  C. trachomatis
Clari-thro-mycin (C) (A)  Coryne- (A)
 Streptococcus  Mycoplasma (A)
Ery-thro-mycin (E)  Moraxella bacterium  Helicobacter
Fidaxo-micin (F)
pyogenes
catarrhalis (A) diphtheria (E) pylori (C)  M. pneumonia
 Ureaplasma urealyticum
 Legionella
pneumophila  Other
(A)  Mycobacterium avium
complex (C)
Ketolide  Same as macrolides
Teli-thro-mycin  Also effective against multidrug resistant organisms and macrolide resistant organisms
  Anaerobes (Bacteroides
Lincosamides
Clindamycin 
Streptococci
MRSA    fragilis)
 PRSP
Streptogramins  MRSA
Quinupristin-
dalfopristin


VRSA
VRE (only E.
   
faecium)

70
 PRSP  Coryne-
 MRSA bacterium sp.
  Listeria
Oxazolidinone
Linezolid 
MRSE
VRSA  monocytogenes   Mycobacterium tuberculosis
 VRE  Clostridium
 Streptococci perfringens

71
ANTIFOLATES & FLUOROQUINOLONES
Drugs Interfering Folic
Acid Synthesis
Antifolates Fluoroquinolones
(DNA Gyrase/
Toposisomerase IV
Inhibitors)
Dihydro-pteroate
Synthase Inhibitors
(Sulfonamides)
SHORT ACTING (Oral) Narrow Spectrum Wider Spectrum
Sulfis-oxazole
Sulfa-acetamide
Sulfa-diazine
INTERMEDIATE 1st Generation 2nd Generation 3rd Generation
ACTING (Oral) Nor-floxacin Cipro-floxacin (Respiratory)
Sulfameth-oxazole O-floxacin Gemi-floxacin
LONG ACTING (Oral) Moxi-floxacin
Sulfa-doxine Levo-floxacin
Sulfa-salazine
TOPICAL
Mafenide
Silver Sulfa-diazine
Dihydro-folate
Reductase Inhibitor
Trimethoprim
Combination
Co-trim-oxazole
(TMP-SMZ)
 SPECTRUM OF DRUGS
DRUG GRAM + COCCI GRAM - COCCI GRAM + RODS GRAM - RODS OTHER ORGANISM
 E. coli
 H. infuenzae PARASITES
 Listeria
  P. jirovecii
Co-trim-oxazole  S. aureus  monocytogenes

Legionella
P. mirabilis  Toxoplasmosis
 S. typhi gondii
 Shigella
 E. coli
 H. infuenzae
 Legionella
 P. mirabilis
Fluoroquinolones  S. pneumoniae   Bacillus anthracis 

Shigella
P. aeruginosa
 M. tuberculosis
 Serratia
 Klebsiella
 Enterobacter

72
9
ENDOCRINE PHARMACOLOGY
DESCRIPTION PAGE NO
HYPOTHALAMIC & PITUITARY HORMONES 73
THYROID HORMONES 74
CORTICOSTEROIDS HORMONES 75
GONADAL HORMONES 76
PANCREATIC HORMONES 77
DRUGS AFFECTING BONE MINERAL HOMEOSTASIS 78

73
HYPOTHALAMIC & PITUITARY HORMONES
Hypothalamic & Pituitary
Hormones
Hypothalamus Anterior Pituitary Posterior Pituitary
GnRH Analogs GH Agonists Oxytocin Agonist

Leu-prolide Somatotropin Oxytocin
Gonado-relin Mecasermin
Gose-relin
Buse-relin
Hist-relin
Nafa-relin Oxytocin Antagonist
Tripto-relin GH Antagonists Atosiban
Peg-visomant
Somatostatin Analogs
Oct-reotide
Lan-reotide
GnRH Antagonist D2 receptor Agonist Vasopressin Agonist
Aba-relix Bromo-criptine Vasopressin (V1, V2)
Gani-relix Desmopressin (V2)
Cetro-relix
Dega-relix
GT: FSH Analogs
Follitropin alfa Vasopressin Antagonist
Follitropin beta Coni-vaptan (V1a, V2)
Uro-follitropin Tol-vaptan (V2)
Menotropin
GT: LH Analogs
hCG
CG alfa
Lutropin
Menotropin
Prolactin Antagonist/
Dopamine Agonist
Bromociptine
Cabergoline
Pergolide

74
THYROID HORMONES
Thyroid Hormones
Hypo-thyroidism Hyper-thyroidism
Thyroid Preparations Thioamides Iodide

Levo-thyroxine (T4) Methi-mazole Lugol's Solution
Lio-thyronine (T3) Propyl-thiouracil (PTU) Potassium Iodide (KI)
Radioactive Iodine (I131)
Anion Inhibitors Radiocontrast Media

Thiocyanate (SCN) Oral Dia-trizoate
Perchlorate (CLO4) IV Iohexol
Beta Blockers Antiayyhythmic

Propanolol Amiodarone

75
CORTICOSTEROID HORMONES
Corticosteroid Hormones
Glucocorticoid Agonists Mineralocorticoid Agonists Receptor Antagonists Synthesis Inhibitors

Cortisol Aldo-sterone Mife-pristone (GC) Ketoconazole
Beta-methasone Deoxy-cortisterone Spironolactone (MC) Aminoglutethimide
Beclo-methasone Fludro-cortisone Eplerenone (MC) Metyrapone
Bude-sonide
Dexa-methasone
Predni-sone
Triamci-nolone

76
GONADAL HORMONES
Ovarian Hormones
Estrogens Progestins
Agonists Antagonists Agonists Antagonists

Estradiol Progesterone Mifepristone (RU 486) in
Ethinyl estradiol combination with PGE
Estradiol cypionate analog Misoprostol
Estrone
Diethyl-stil-bestrol SERMS
Mestranol Tamo-xifen
Tore-mifene Synthetic Progestins
Ralo-xifene Medroxy-progesterone acetate
Bazedo-xifene Megestrol acetate
Clo-miphene
Full Receptor Antagonist Older 19-Nortestosterone

Fulve-strant Compounds
L-Nor-gestrel
Nor-ethindrone
Synthesis (Aromatase)
Inhibitors
Anas-trozole Newer 19-Nortestosterone
Le-trozole Compounds
Exemestane Nor-gestimate
Nor-elgestromin
Deso-gestrel
Etono-gestrel
GnRH Agonists
Leu-prolide
Spironolactone Derivatives
Dor-spirenone
GnRH Antagonists
Gani-relix
Cetro-relix
Androgen Hormones
Testosterone
Receptor Antagonist
Oral Androgens Fl-utamide
Fluoxy-me-sterone Bical-utamide
Methyl-testosterone Nil-utamide
Spironolactone
Esters
Testosterone cypionate 5 -reductase Inhibitors
Fin-asteride
Dut-asteride
Anabolic Steroids
Ox-androlone GnRH Agonists
N-androlone Leu-prolide
GnRH Antagonists
Aba-relix
Dega-relix
Synthesis Inhibitors
Ketoconazole

77
PANCREATIC HORMONES
Pancreatic Hormones
Antidiabetics Hyperglycemics
Insulin Non-Insulin Glucagon
Rapid Acting Insulin Secretagogues

Lispro 1st Gen-Sulfonylureas
Aspart Tolaz-amide
Glulisine Tolbut-amide
Inhaled Regular Chlorprop-amide
Acetohex-amide
2nd Gen-Sulfonylureas
Gli-piz-ide
Gli-mepir-ide
Short Acting Gly-bur-ide
Regular Insulin Meglitinide Analogs
Repa-glinide
Nate-glinide
Intermediate Acting
NPH
Biguanides
Metformin
Long Acting
Detemir Thiazolidinediones
Glargine Rosi-glitazone
Pio-glitazone
-glucosidase Inhibitors
A-carbose
Miglitol
Incretin Based Drugs

GLP-1 Agonists
Exenatide
Lira-glutide
Albi-glutide
Dula-glutide
DPP-4 Antagonists
Sita-gliptin
Saxa-gliptin
Lina-gliptin
Alo-gliptin
Vilda-gliptin
Amylin Analogs
Pramlintide
SGLT2 Inhibitors
Cana-gliflozin
Dapa-gliflozin

78
DRUGS AFFECTING BONE MINERAL HOMEOSTASIS
Bone Homeostasis Regulators
Hormonal Non-hormonal
PTH Biphosphonates
Teri-paratide Alen-dronate
Eti-dronate
Rise-dronate
Iban-dronate
Pami-dronate
Vitamin D Analogs
Tilu-dronate
Chole-calciferol
Zole-dronate
Ergo-calciferol
Calcitriol
Doxer-calciferol
Pari-calcitol
Calci-potriene RANKL Inhibitor
Deno-sumab
Calcitonin
Calcimimetics
Cina-calcet
SERM
Ralo-xifene Misc.
Gallium Nitrate
Thiazide Diuretics
Plicamycin
Glucocorticoids Mithramycin
Furosemide
Fluoride
Strontium Ranelate
Sevelamer

79
 10 
CENTRAL NERVOUS SYSTEM
PHARMACOLOGY
DESCRIPTION PAGE NO
SEDATIVE HYPNOTICS 80
ALCOHOLS 81
ANTISEIZURE/ANTIEPILEPTIC DRUGS 82
GENERAL ANESTHETICS 83
LOCAL ANESTHETICS 84
SKELETAL MUSCLE RELAXANTS 85
DRUGS FOR MOVEMENT DISORDER 86
ANTIPSYCHOTIC & BIPOLAR DRUGS 87
ANTIDEPRESSANTS 89
OPIODS ANALGESICS & ANTAGONISTS 90
DRUGS OF ABUSE 92

80
SEDATIVE HYPNOTICS
Sedative Hypnotics
Benzo-dia-zepines
Benzo-dia-zepines Barbiturates Misc.
Antagonist
Short Acting (3-8 hours) Fluma-zenil Ultra Short Acting Newer Hypnotics (BZ1)
Oxa-zepam (20 minutes) Zolpi-dem
Tria-zolam Thio-pental Zalep-lon
Eszopic-lone
Intermediate Acting Short Acting (3-8 hrs)

(8-20 hrs) Pento-barbital Melatonin Agonists
Alpra-zolam Seco-barbital Ra-melteon
Clona-zepam Amo-barbital Tasi-melteon
Esta-zolam Buta-barbital
Lora-zepam
Tema-zepam
5-HT1A Agonist
Long Acting Bu-spirone
(1-2 days)
Long Acting (1-3 days) Pheno-barbital
Clorazepate
Chlordiazepoxide Orexin Antagonist
Dia-zepam Suvo-rexant
Flura-zepam
 CLINICAL INDICATIONS OF BARBITURATES

NAME OF DRUG CLINICAL INDICATIONS
Alpra-zolam Anxiety (Panic, Phobias)
Clona-zepam Anxiety, Bipolar disorder, Seizures disorder
Dia-zepam Anxiety, Anesthesia IV, Muscle Relaxation, Status epilepticus, Withdrawal states
Lora-zepam Anxiety, Status epilepticus
Chlordiazepoxide Withdrawal states
Mida-zolam Anesthesia IV
Flura-zepam
Esta-zolam
Tria-zolam Sleep disorders
Tema-zepam
Oxa-zepam
 DIFFERENCE BETWEEN BENZODIAZEPINES & BARBITURATES
FEATURE BENZODIAZEPINES BARBITURATES
Potentiate GABA Prolong GABA activity
Mode of Action ↑ the frequency of Cl− channel opening ↑ duration of Cl− channel opening
Have no GABA mimetic activity Have GABA mimetic activity at high doses
Act through BZ receptors Do not act through BZ receptors
Receptors
These receptors are part of GABAA complex Have their own binding sites on GABAA complex
Dependence
Less High
Liability
Half lives 2-4 hours 4-60 hours
Antagonism By Fluma-zenil No

81
ALCOHOLS
Alcohols
Alcohol Withdrawal Alcohol Dependency Methanol & Ethylene

Agonists
Drugs Drugs Glycol Poisoning Drugs
Ethanol Benzodiazepines Opioid Antagonist Alcohol Dehydrogenase

Methanol (Wood Alcohol) Diazepam Nal-trexone Inhibitor
Ethylene Glycol Chlordiazepoxide Fome-pizole
NMDA Antagonist
Vitamin Acamprosate Alcohol
Thiamine Ethanol
Aldehyde
Dehydrogenase Inhibitor
Disulfiram

82
ANTISEIZURE/ANTIEPILEPTIC DRUGS
Antiseizure Drugs
(Clinical Uses)
Tonic-Clonic (Grand Absence (Petit Mal)

Partial Seizures Myoclonic Seizures Status Epilepticus
Mal) Seizures Seizures
Drug of Choice Drug of Choice Drug of Choice Drug of Choice Short Acting
Phenytoin Phenytoin Ethosuximide Valproate Diazepam (IV)
Fos-phenytoin Fos-phenytoin Valproate Lorazepam (IV)
Carbama-zepine Carbama-zepine Phenobarbital (child)
Ox-carba-zepine Ox-carba-zepine
Valproate Lamotrigine Back up &
Back up & Adjunctives
Adjunctives Felbamate Long Acting
Clona-zepam Clona-zepam Phenytoin
Drug of Choice Back up & Lamotrigine Lamotrigine Fos-phenytoin
(infants) Adjunctives Levetiracetam Levetiracetam
Phenobarbital Gabapentin Zonisamide Topiramate
Primidone Felbamate Zonisamide
Pregabalin
Phenobarbital OTHER USES:
Topiramate
Back up & 1. Manic Phase of Bipolar Disorder: Valproate
Adjunctives Valproate
2. Migraine: Phenytoin, Topiramate
Gabapentin
Lamotrigine 3. Neuropathic pain: Gabapentin, Pregabalin
Levetiracetam 4. Neuralgia (trigeminal): Carbamazepine, Oxcarbazepine
Topiramate 5. Bipolar disorders: Carbamazepine, Lamotrigine
Zonisamide
Mechanism of Actions
of Anti-seizure Drugs
Sodium Channel Calcium Channel Glutamate Receptor

GABA Related Targets
Blockade Blockade (T type) Blockade
Therapuetic Doses GABAA Receptor Agonist Etho-suximide Phenobarbital

Phenytoin Benzodiazepines Valproate Topiramate
Topiramate (increase frequency of Cl- Gabapentin Felbamate
Car bama-zepine channel opening) Topiramate
Lamo-trigine Dia-zepam Pregabalin
Zonis-amide Clona-zepam
Lora-zepam
Barbiturates
(increase duration of Cl-
High Doses channel opening)
Pheno-barbital Phenobarbital
Valproate
GABA Transaminase Inhibitor

Vigabatrin
Valproate
GABA Reuptake Inhibitor

Tiagabine
GABA Analog
Gabapentin
GABA Facilitators
Felbamate
Topiramate
Valproate

83
GENERAL ANESTHETICS
General Anesthetics
Inhaled Anesthetics Intravenous Anesthetics
Gas Volatile Liquid GABAA Receptor Glutamate NMDA Opoid Receptor 2 Agonist
Nitrous Oxide Halogenated Inhibition Facilitators Blockers Agonists Dex-mede-
(N2O) Hydrocarbons BENZODIAZEPINES Ketamine Fenta-nyl tomidine
Des-flurane Midazolam Al-fenta-nil
Sevo-flurane BARBITURATES Remi-fenta-nil
Iso-flurane Thio-pental Morphine
En-flurane Thio-amylal
Halothane Metho-hexital
Methoxy-flurane IMIDAZOLE
Ethomidate
PHENOLS
Propofol
Fos-propofol
 DIFFERENCE BETWEEN NITROUS OXIDE & HALOTHANE

FEATURE HALOTHANE NITROUS OXIDE
Potency High Low
Induction Slow Rapid
Recovery Slow Rapid
Blood Gas Coefficient 2.30 0.47
MAC 0.75% > 100%
Metabolism > 40% None
Arrhythmia Increased risk None
Hepatotoxic Increased risk (not in children) None
DOC in children Rapid onset and recovery
Therapeutic Actions
Good for asthmatic bronchodilation Good analgesia
 MERITS & DEMERITS OF HALOTHANE
MERITS DEMERITS
Potent Hypotension and Bradycardia
Less irritant Arrhythmiogenic
Smooth and rapid induction Hepatotoxic
Smooth and rapid recovery Shivering during recovery
Non inflammable Not an analgesic
Bronchodilator Variable muscle relaxation

84
LOCAL ANESTHETICS
Local Anesthetics
Amides (2 i's) Esters (1 i)
Medium Acting Long Acting Surface Acting Short Acting Long Acting
Arti-caine Bu-piva-caine Benzo-caine Pro-caine Tetra-caine
Lido-caine Levo-bu-piva-caine Co-caine
Prilo-caine Me-piva-caine
Ro-piva-caine

85
SKELETAL MUSCLE RELAXANTS
Skeletal Muscle Relaxants
Neuromuscular Blockers Spasmolytic Drugs
Depolarizing Acute Use Others

Non-Depolarizing Chronic Use Botulinum Toxin
Succinylcholine Cyclo-benz-apine
Meta-xalone Gabapentin
Metho-carbamol Pregablin
CNS Action Orphenadrine
Rapid Acting
Atra-curium (Spinal Cord)
Cis-atra-curium Baclofen
Diazepam
Tizanidine
Intermediate
Acting
Miva-curium Muscle Action
Ro-curonium Dantrolene
Ve-curonium
Long Acting
Doxa-curium
Pan-curonium
Tubo-curarine

86
DRUGS FOR MOVEMENT DISORDERS
Drugs for Movement
Disorders
Parkisonism Physiological
Huntington's Touretter's Drug Induced Restless Legs
(Paralysis & Essential Wilson's Disease
Disease Syndrome Dyskinesias Syndrome
Agitans) Tremor
Drug of Choice -Blockers Amine D2 Antagonists Benzotropine Pencillamine Dopamine

Levodopa  Propran-olol Depletors Haloperidol Diphenhydramine Tri-entine Agonists
Carbidopa Metopr-olol Reserpine Pimozide Tetrathiomolybdate Ropinirole
Tetrabenazine Pramipexole
Dopamine Antiseizure 2 Agonist
Agonists Drugs D2 Clonidine Opoid
D2 AGONIST Gabapentin Antagonists Analgesics
Apo-morphine Topiramatee Haloperidol
Ropinirole Primidone Perphenazine Benzodiazepine
Bromocriptine Clonazepam Benzodiazepine
D3 AGONIST Others Atypical
Pramipexole Botulinum Antipsychotic Antiseizure Antisezure
Toxin Olanzapine Drugs Drugs
MAOB Inhibitors Carbamazepine Gabapentin
Rasa-giline
Sele-giline
Atypical
Antipsychotic
COMT Molindone
Inhibitors
Tol-capone
Enta-capone
Antimuscuranic
Benzotropine
Biperiden
Orphenadrine
Others
Amantadine
Increase Dopamine Function

Increase Dopamine
Decrease ACh Function
 FUNCTIONAL CIRCUITRY BETWEEN CORTEX, BASAL GANGLIA AND THALAMUS
In Parkinson’s disease, there is

degeneration of pars compacta
of substantia nigra, leading to
overactivity in indirect pathway
(red) and increased
glutamatergic activity by
subthalamic nucleus.

87
ANTIPSYCHOTIC & BIPOLAR DRUGS
Antipsychotic &
Bipolar Drugs
Antipsychotics
Bipolar Drugs
(Neuroleptics)
Classic Drugs Newer Drugs Classic Drug Newer Drugs

(D2 receptor (5HT2 receptor
affinity) affinity)
Lithium Acute Mania
Phenothiazines Thioxanthenes Butyrophenonones Aripipr-azole Olanz-apine
PROPYLAMINE Thiothixene Haloperidol Cloz-apine Queti-apine
SIDE-CHAIN Lox-apine Valproate
Chlorprom-azine Olanz-apine Acute Mania 
PIPERIDINE Queti-apine Prophylaxis
SIDE-CHAIN Molin-done Carbama-zepine
Thiorid-azine Risperi-done Clona-zepam
PIPERAZINE Ziprasi-done Lamo-trigine
SIDE-CHAIN
Trifluoper-azine
Fluphen-azine
Prochlorper-azine
Perphen-azine
**Sedation & anti-cholinergic effects decreases from top to bottom subclasses.

** Extrapyramidal effects increases from top to bottom subclasses.
** Extrapyramidal effects are maximum in this class of drugs.
** Least sedating of newer antipsychotics.
 ANTIPSYCHOTICS ADVERSE EFFECTS

88
 DIFFERENCE BETWEEN TYPICAL & ATYPICAL ANTIPSYCHOTICS
FEATURE TYPICAL ANTIPSYCHOTICS ATYPICAL ANTIPSYCHOTICS
Receptor Affinity D2 > 5-HT2 5-HT2 > D2
Schizophrenia Symptoms  Positive Symptoms  Positive & Negative Symptoms
Extrapyramidal Side Effects  tendency (maximum in Haloperidol)  tendency
Tardive Dyskinesias High risk Low risk
Metabolic Disturbances None May produce
Agranulocytosis None May produce (Cloz-apine)
QT Interval Prolongation None May produce (Queti-apine & Ziprasi-done)
Withdrawal Symptoms Less High
 TYPES OF PSYCHIATRIC ILLNESS

89
ANTIDEPRESSANTS
Antidepressants
TCAs SSRIs Heterocyclics MAO Inhibitors
Ami-triptyline Fluo-xetine SNRIs MAOA & MAOB Inhibitor

Clo-mipramine Paro-xetine Levo-milna-cipran Phenel-zine
I-mipramine Fluvo-xamine Dulo-xetine Tranyl-cy-promine
Ser-traline Venla-faxine
Citalo-pram Des-venla-faxine
Es-citalo-pram
MAOB Inhibitor
5-HT2A Antagonists Sele-giline
Nef-azodone
Tr-azodone
Others
Amoxa-pine
Mirtaze-pine
Bu-pro-pion
Ma-pro-tiline
 ANTIDEPRESSANTS ADVERSE EFFECTS
 ADVANTAGES OF SSRIs OVER TCAs

1.  Sedation
2. Not interfere with cognitive and anticholinergic effects
3. No postural hypotension (Suitable for elders)
4. Wide safety margin
5. Better patient acceptability
6. Preferred for porphylaxis of recurrent depression.
7. Additional use in NEUROSIS psychiatric illnesses

90
OPIOID ANALGESICS & ANTAGONISTS
Opioid Drugs
Agonists Mixed Agonist-Antagonists Antagonists Others
Full Agonists  Agonist &  Antagonist Older Agents Antitussives

Fentanyl Butor-phanol (Crosses BBB) Codeine
Morphine Nal-buphine Nalo-xone Dextro-meth-orphan
Oxy-morphone Penta-zocine Nalme-fene
Hydro-morphone Naltre-xone
Methadone
Meperidine  Agonist &  Antagonist
Heroin Newer Agents/
Bupre-norphine Antidiarrheals
Levor-phanol
Loper-amide (Antidiarrheal) (Do not cross BBB)
Diphenoxylate (Antidiarrheal) Methyl-naltre-xone
 Agonist & 5-HT Reuptake Alvimopan
Inhibitor
Tramadol
Partial Agonists
Codeine
Oxy-codone  Agonist & NE Reuptake
Hydro-codone Inhibitor
Tapentadol
Weak Agonists
Prop-oxy-phene
Overdose reversed by Naxolone

Overdose cannot be reversed by Naxolone
 OPIOID RECEPTORS
RECEPTOR FUNCTIONS ENDOGENOUS OPIOID PEPTIDE AFFINITY
Supraspinal and spinal analgesia
Respiratory inhibition
Hormone modulation
μ (mu) Endorphins > enkephalins > dynorphins
Neurotransmitter release
Sedation
Slowed GIT transit
Hormone modulation
δ (delta) Enkephalins > endorphins = dynorphins
Neurotransmitter release
Tolerance development
Sedation
κ (kappa) Dynorphins > > endorphins = enkephalins
Slowed GIT transit
Psychotomimetic effects
 PHARMACOLOGICAL & ADVERSE EFFECTS OF OPIOIDS
ACUTE EFFECTS (BAD AMERICANS Hormones Imbalanced)
1. Bradycardias & hypotension
2. Analgesia (treatment of moderate to severe pain)
3. Dependence
4. Anorexia (poor appetite)
5. Miosis (characteristic of all opioids except meperidine)
6. Euphoria (state of excitement)
7. Respiratory depression
8. Increase smooth muscles activity (characteristic of all opioids except meperidine)
 Biliary tract constriction  Biliary Colic
  Ureteral & bladder sphincter tone
  Uretrine tone  Prolongation of labor
9. Constipation (atidiarrheal agents)
10. Antitussive (suppression of cough reflex by inhibiting respiratory centres with decrease response to CO 2 challenge)
11. Nausea and vomiting (activate chemoreceptor trigger zone)
12. Sedation and mental clouding (at higher doses)
13. Hormones Imbalanced
  Release of ADH & Prolactin
  Release of LH
 Exaggerate response in adrenal insufficiency & hypothyroidism

91
CHRONIC EFFECTS (TD)
1. Tolerance
2. Dependance  Abstinence Syndrome  GLARY De CMH (Gooseflesh, Lacrimation, Anxiety, Rhinorrhea, Yawning,
Diarrhea, Chills, Muscle aches, Hostility)
 ADVERSE EFFECTS OF OPIOIDS
(MORPHINE)
1. Miosis
2. Out of it i.e Sedation
3. Respiratory depression
4. Pneumonia (aspiration)
5. Hypotension
6. Infrequent urination
7. Nausea
8. Emesis

92
DRUGS OF ABUSE
Drugs of Abuse
Sedative- Opioid CNS

Hallucinogens Marijuana Inhalants Steroids
Hypnotics Analgesics Stimulants
Benzodiazepine Fentanyl Caffeine Phencyclidine Tetrahydro- Anesthetics

Barbiturates Morphine Nicotine LSD cannabinol Industrial Solvents
Ethanol Meperidine Cocaine Mescaline Cannabidiol Organic Nitrates
Heroin Amphetamines Psilocybin Cannabinol
Codeine
Oxy-codone
 MECHANISMS OF ACTION OF DRUGS OF ABUSE

93
 11 
DRUGS OF CHOICE
DESCRIPTION PAGE NO
AUTONOMIC NERVOUS SYSTEM PHARMACOLOGY 94
AUTOCOIDS & NSAIDS PHARMACOLOGY 95
RESPIRATORY PHARMACOLOGY 96
GASTROINTESTINAL PHARMACOLOGY 97
CARDIOVASCULAR PHARMACOLOGY 98
RENAL PHARMACOLOGY 99
BLOOD PHARMACOLOGY 100
ANTIFUNGAL PHARMACOLOGY 101
ANTIVIRAL PHARMACOLOGY 102
ANTI-MYCOBACTERIAL PHARMACOLOGY 103
PARASITIC PHARMACOLOGY 104
ANTIBACTERIAL PHARMACOLOGY 105
ENDOCRINE PHARMACOLOGY 107
CENTRAL NERVOUS SYSTEM PHARMACOLOGY 108

94
AUTONOMIC NERVOUS SYSTEM PHARMACOLOGY
CONDITION DRUG OF CHOICE

Mushroom poisoning
– Early (Inocybe sp.) Atropine
– Delayed (Amanita sp.) Thioctic acid
Glaucoma
– Open angle Latanoprost
– Angle closure Acetazolamide
Myasthenia gravis
– Diagnosis Edrophonium
– Treatment Neostigmine/pyridostigmine
Belladona poisoning Physostigmine
Atropine poisoning Physostigmine
Dhatura poisoning Physostigmine
Alzhiemer’s dementia Donepezil/Rivastigmine/Gallantamine
Cobra bite Anti-venom
Anticholinesterase poisoning
– Organophosphate Atropine
– Carbamate Atropine
Colicky pain Anticholinergics like hyoscine/dicyclomine
Bronchial asthma Salbutamol
Refraction testing
– In adults Tropicamide
– In children Atropine
Fundoscopy Phenylephrine
Uveitis
– Iridocyclitis Atropine + steroids
– Posterior uveitis Steroids
– Panuveitis Steroids
Bradycardia Atropine
Atrioventricular block Atropine
Drug induced Parkinsonism Anticholinergics like benzhexol
Shock
– Cardiogenic Nor-adrenaline or dopamine
– with oligourea Dopamine
– Anaphylactic Adrenaline
– Distributive Nor-adrenaline or phenylephrine
– Septic Broad spectrum antimicrobials
– Shock due to adrenal insufficiency Corticosteroids
– Hypovolumic Fluids (crystalloids)
– Secondary Prazosin (α-blockers)
Postural hypotension Fludrocortisone
Attention deficit hyperkinetic disorder Methylphenidate
Narcolepsy Modafinil or armodafinil
Pheochromocytoma
– Before surgery Phenoxybenzamine
– Long term CCBs like nifedipine or nicardipine extended release
Cheese reaction Phentolamine or tolazoline
Rebound hypertension due to clonidine withdrawl Phentolamine or tolazoline
Raynaud’s phenomenon CCBs like nifedipine ER or amlodipine
Essential tremors Propanolol
Akathisia Propanolol
Hypertrophic obstructive cardiomyopathy Propanolol
Beta blocker poisoning Glucagon
Benign hyperplasia of prostate
– Without hypertension Tamsulosin
– With hypertension Prazosin or doxazosin
Performance anxiety Propanolol

95
AUTOCOIDS PHARMACOLOGY

Migraine
– Acute-mild to modrate NSAIDs
– Acute-severe Sumatriptan
– Prophylaxis Propanolol
Abortion < 7 weeks Mifepristone + misoprostol
Induction of labour Oxytocin
Post-partum hemorrhage Oxytocin
Cervical priming Misoprostol
NSAID-induced peptic ulcer Proton pump inhibitors
Open angle glaucoma Latanoprost
To maintain patency of ductus arteriosus Alprostadil
Treatment of patent ductus arteriosus (PDA) Indomethacin
Bartter syndrome Indomethacin
Pulmonary hypertension Oral diltiazem or amlodipine or nifedipine
Erectile dysfunction Sildenafil
Rheumatoid arthritis
– Pain relief NSAIDs
– Bridge therapy Corticosteroids
– DMARD Methotrexate
Flushing due to nicotinic acid Aspirin
Prophylaxis of MI and stroke Aspirin
Acetaminophen (Paracetamol) poisoning N-Acetyl cysteine
Anaphylactic shock Adrenaline
Acute mediterranean fever Colchicine
Cancer chemotherapy induced vomiting 5HT3 antagonists like ondansetron
Cisplatin induced vomiting
– Early Ondansetron
– Delayed Aprepitant
Gout
– Acute NSAIDs except aspirin
– Refractory acute Colchicine
– Chronic Allopurinol
– Chronic (in patient allergic to allopurinol) Febuxostat
Hyperuricemia secondary to anticancer drugs Allopurinol

96
RESPIRATORY PHARMACOLOGY

Bronchial Asthma
– Acute attack Salbutamol
– Acute attack in pregnancy Salbutamol
– Acute attack during labour Ipratropium
– Acute attack in patients on beta blocker therapy Ipratropium
– Prophylaxis Corticosteroids
Exercise-induced asthma
Aspirin-induced asthma

97
GASTROINTESTINAL PHARMACOLOGY

Peptic ulcer
– Gastric ulcer Proton pump inhibitors (PPI)
– Duodenal ulcer PPI
– Stress ulcer PPI
– NSAID-induced PPI
– H. pylori associated Lansoprazole + Amoxycillin + Clarithromycin
– Zollinger Ellison syndrome PPI
– Gastro Esophageal Reflux Disease PPI
Vomiting
– Chemotherapy induced 5-HT3 antagonists like palonosetron
– Levo-dopa induced Domperidone
– Migraine associated Metoclopramide
– Drug or disease associated Metoclopramide
– Post-operative Ondansetron
– Radiation induced Ondansetron
– Cisplatin induced
* Early 5-HT3 antagonists
* Delayed Aprepitant
– Prophylaxis of motion sickness Hyoscine
– Pregnancy (Morning sickness) Doxylamine + Pyridoxine
Opioid induced constipation Methyl naltrexone
Diarrhea in carcinoid syndrome Octreotide
To prevent dehydration in diarrhea ORS
Crohn’s disease Corticosteroids
Ulcerative colitis 5-ASA derivatives
Hepatic encephalopathy Lactulose

98
CARDIOVASCULAR PHARMACOLOGY

Diabetic nephropathy ACE inhibitors or ARBs
Scleroderma hypertensive crisis Captopril
Congestive heart failure
– Decompensated Dobutamine
– Compensated ACEI/ARB
Hypertrophic obstructive cardiomyopathy Propanolol
Angina pectoris
– Acute attack Sublingual nitroglycerine
– Prophylaxis Oral/transdermal nitrates
Esophageal spasm Nitroglycerine
Cyanide poisoning Hydroxocobalamin/amyl nitrite
Raynaud's phenomenon Nifedipine ER or amlodipine
Myocardial infarction
– Pain relief Sublingual nitroglycerine ↓ Morphine
– Prophylaxis Aspirin
– Thrombolytic for STEMI Reteplase or alteplase
Hypertension Thiazides
– With BHP Prazosin
– With diabetes mellitus ACE inhibitors
– With ischemic heart disease (angina) Beta blockers
– With chronic kidney disease ACE inhibitors
– In pregnancy Labetalol
Acute severe digitalis toxicity Digibind
Hypertensive emergencies Nicardipine + Esmolol
– In cheese reaction Phentolamine
– in clonidine withdrawl Phentolamine
– In aortic dissection Nitroprusside + esmolol
– In Pregnancy Labetalol
Hyperlipidemia
– Type IIa and IIb Statins
– Type III (hypertriglyceridemia) Fibrates
– Type IV Statins
– Secondary to diabetes or nephrotic syndrome Statins
Supraventricular tachycardia
– Narrow QRS complex Verapamil or beta blockers
– Wide complex Flecainide
– WPW syndrome Flecainide
Paroxysmal supraventricular tachycardia (PSVT)
– Acute treatment Adenosine
– Prophylaxis Verapamil
Ventricular tachycardia Lignocaine
– Digitalis induced Lignocaine
Long QT syndrome (Torsades' de pointes) Magnesium

99
RENAL PHARMACOLOGY

Edema
– Due to CHF Furosemide
– Due to renal disease or nephrotic syndrome Furosemide
– Pulmonary edema Furosemide
– Cerebral edema Mannitol
– Edema due to cirrhosis Spironolactone
Diabetes insipidus
– Central Desmopressin
– Nephrogenic Thiazides
– Lithium-induced Amiloride
Recurrent calcium stones in kidney due to hypercalciurea Thiazides
Acute congestive glaucoma Acetazolamide
Acute mountain sickness Acetazolamide
Nocturnal enuresis Desmopressin
SIADH Fluid restriction + Hypertonic saline +
Furosemide

100
BLOOD PHARMACOLOGY

Anemia
– Iron deficiency anemia Ferrous sulphate
– Megaloblastic anemia
* Folate deficiency Folic acid
* B12 deficiency Vitamin B12
* Pernicious anemia Vitamin B12
* Chemotherapy induced anemia Erythropoietin
– Anemia due to chronic kidney disease Erythropoietin
Iron poisoning
– Acute Desferrioxamine
– Chronic Deferipirone
Cyanide poisoning Hydroxocobalamin/Amyl nitrite
Deep vein thrombosis
– Prophylaxis Warfarin
– Initiation of therapy LMW heparin + warfarin
– With severe chronic kidney disease Unfractionated heparin
Pulmonary embolism
– Stable patient LMW heparin
– Unstable patient Thrombolytics (Reteplase)
Chronic Atrial fibrillation
– Prophylaxis Dabigatran or Rivaroxaban or Apixaban
– In mechanical prosthetic valves Warfarin
– Advanced kidney disease Warfarin
– Mitral stenosis Warfarin
Myocardial Infarction
– Acute STEMI Thrombolytics (Reteplase)
– Prophylaxis Aspirin
Heparin overdose Protamine
Warfarin overdose Vitamin K
Bleeding due to overdose of anticoagulants Fresh frozen plasma
(heparins or warfarin)
Fibrinolytic overdose Tranexamic acid or Epsilon Amino Caproic Acid
Chemotherapy induced leukopenia Sargramostim
Chemotherapy induced thrombocytopenia Oprelvekin
Immune thrombocytopenic purpura Corticosteroids
Heparin induced thrombocytopenia Argatroban

101
ANTIFUNGAL PHARMACOLOGY

Candida albicans Fluconazole
Candida glabrata Caspofungin
Candida krusei Caspofungin
Candida endocarditis Amphotericin B (AMB)
Histoplasmosis
– Meningeal AMB
– Non-meningeal Itraconazole
Coccidioidomycosis AMB
Para-coccidioidomycosis Itraconazole (For severe cases: AMB)
Sporotrichosis Itraconazole
Blastomycosis
– Mild and Non-CNS Itraconazole
– Severe or CNS AMB
Penicillium marneffei Itraconazole (For severe cases: AMB)
Chromoblastomycosis Itraconazole
Mycetoma
– Eumycetoma Itraconazole
– Actinomycetoma Itraconazole
Cryptococcal meningitis
– Induction AMB (for 2 weeks)
– Maintenance Fluconazole (for further 8 weeks)
Aspergillosis
– Invasive Voriconazole
– Allergic broncho-pulmonary (AMBA) Prednisolone + Itraconazole/Voriconazole
Mucormycosis AMB (Posaconazole should be given after disease has stabilized)
Pseudoallescheria boydii Voriconazole
Fusarium Voriconazole
Exserohilum AMB
Febrile neutropenia
– Treatment Voriconazole
– Prophylaxis Fluconazole

102
ANTIVIRAL PHARMACOLOGY

Herpes simplex
– Keratitis Topical vidarabine/Trifluridine
– Neonatal Acyclovir
– Encephalitis Acyclovir
– Dissemnated Acyclovir
– Esophagitis Acyclovir
– Genital Acyclovir
– Bell’s Palsy Prednisolone
Varicella Acyclovir
Herpes zoster
– Acute Valacyclovir
– Post herpetic neuralgia Gabapentin
Epstein Barr virus Symptomatic (no antiviral)
Cytomegalo virus
– Retinitis Ganciclovir
– Post-transplant
* Mild Valganciclovir
* Severe Ganciclovir
Measels Ribavirin (Indication: Severe pneumonitis)
Prion disease Flupirtine (cognitive decline but does not stop mortality)
Viral hemorrhagic fever
– Lassa virus Ribavirin
– Rift Valley fever Ribavirin
– Congo crimean hemorrhage fever Ribavirin
– Hantaan virus Ribavirin
Respiratory syncytial virus
– High risk patient, acute Ribavirin (aerosolized)
– Prophylaxis (infants) Palivizumab
Influenza virus
– Seasonal influenza Oseltamivir
– Avian influenza (including bird flu) Oseltamivir
– Oseltamivir-resistant influenza Zanamivir
Human immunodeficiency virus (HIV)
– Treatment Zidovudine + Lamivudine + Nevirapine
– Post-exposure prophylaxis Zidovudine + Lamivudine ± Atazanavir

103
ANTIMYCOBACTERIAL PHARMACOLOGY

Tuberculosis
– Latent TB Infection (Chemoprophylaxis) Daily INH for 9 months
– Category 1 (New or previously untreated cases) 2HRZE + 4HR
– Category 2 (Previously treated cases; relapses 2HRZES + HRZE + 5HRE
and treatment defaults)
– Treatment failure and special cases:
a. Resistance (or intolerance) to H 6 RZE + Q (for extensive disease)
b. Resistance (or intolerance) to R 12 HZEQ + S (for extensive disease)
c. Intolerance to Z 2 HRE + 7 HR
d. MDR TB (resistance to H + R) HRZE
e. Extensive drug resistance (XDR) HRZE
Leprosy
– Multibacillary (x 12 months) Rifampicin (600mg) once monthly supervised
Clofazimine 300mg once monthly supervised
Dapsone 100 mg OD
Clofazimine 50mg OD
– Paucibacillary (x 6 months) Rifampicin 600 mg once monthly supervised
Dapsone 100 mg OD
– Type 1 Lepra reaction Corticosteroids
– Type 2 Lepra reaction Corticosteroids
M. avium intracellulare Azithromycin + Ethambutol ± Rifabutin
M. kansasii Isoniazid + Rifampicin ± Ethambutol
M. fortuitum chelonei Cefoxitin + clarithromycin
(Q: Fluoroquinolone, H: Isoniazid, R: Rifampicin, Z: Pyrazinamide, E: Ethambutol, S: Streptomycin)

104
PARASITIC PHARMACOLOGY

ANTI-PROTOZOAN
Ameobiasis
– Asymptomatic intestinal Diloxanide furoate
– Mild, moderate and severe intestinal Metronidazole + diloxanide
– Extra-intestinal (hepatic abcess) Metronidazole + diloxanide
– Primary ameobic meningo-encephalitis (Naegleria fowleri) AMB
– Acanthameoba keratitis Topical propamidine isethionate
Coccidiosis Nitazoxanide/Paromomycin
– Cryptosporidiosis
– Isoporiasis Cotrimoxazole
– Cyclosporiasis Cotrimoxazole
– Microsporidiosis Albendazole
– Sacrocytosis No treatment
– Trypanosomiasis
– East African sleeping sickness
* Early haemo lymphatic stage Suramin
* Late CNS stage Melarsoprol
– South-American (Chagas disease) Benznidazole (alternative is nifurtimox)
ANTI-HEMINTHICS
Flukes
– Fasciola Triclabendazole
– Schistosoma Praziquantal
– Clonorchis Praziquantal
– Opisthorchis Praziquantal
– Paragonimus Praziquantal
– Fasciolopsis Praziquantal
Tapeworms
– Taenia solium Praziquantal
– T. saginata Praziquantal
– D. latum Praziquantal
– H. nana Praziquantal
– Echinococcus Albendazole
– Neurocysticercosis Albendazole
Nematodes
– Ascaris Albendazole
– Trichuris Albendazole
– Ancylostoma Albendazole
– Necator Albendazole
– Enterobius Albendazole
– Trichinella Albendazole
– Cutaneous larva migrans Albendazole
– Visceral lara migrans Albendazole
– Dracunculus (Guinea worm) Metronidazole
Filarial worm
– W. bancrofti Di Ethyl Carbamezine (DEC)
– B. malayi Di Ethyl Carbamezine (DEC)
– B. timori Di Ethyl Carbamezine (DEC)
– Loa loa Di Ethyl Carbamezine (DEC)
– Onchocerca volvolus Ivermectin
Strongyloides stercoralis Ivermectin

105
ANTIBACTERIAL PHARMACOLOGY

GRAM-POSITIVE COCCI
Streptococcus
1
• S. pneumoniae Penicillin G
1
• Hemolytic, groups A, B, C, G Penicillin G
1, 2
• S. viridans Penicillin G
Staphylococcus
1
• Non penicillinase producing Penicillin G
• Penicillinase producing Penicillinase resistant penicillin (cloxa, oxa, naf or
dicloxacillin)
• Methicillin resistant (MRSA) Vancomycin
• Coagulase negative Vancomycin
ENTEROCOCCUS
3
• faecalis Ampiillin
3
• faecium Vancomycin
GRAM-POSITIVE BACILLI
• Actinomyces Penicillin G
• Bacillus
– Anthracis Ciprofloxacin or Doxycycline
– Cereus and others Penicillin G
• Clostridium Pencillin G
4
• Corynebacterium Erythromycin
5
• Listeria Ampicillin
GRAM-NEGATIVE COCCI
• Neisseria
– meningitides Penicillin G
– gonorrhea Ceftriaxone + Azithromycin/Doxycycline
• Moraxella Fluoroquinolones
GRAM-NEGATIVE BACILLI
• Campylobacter Macrolides
• Legionella Macrolides
• Bordetella Macrolides
• Brucella Doxycyline + Rifampicin
• Acinetobacter Carbapenems
• Hemophilus
– Serious infections like meningitis Ceftriaxone
– Respiratory infections, otitis Cotrimoxazole
– Ducreyi (chancroid) Azithromycin
• Prevotella Clindamycin
• Bacteroides Metronidazole
• Pseudomonas Anti-Pseudomonal β-lactam (piperacillin or ceftazidime
or cefepime or imipenem) + Gentamicin
• Burkholderia
– mallei (glanders) Streptomycin + Tetracycline
– pseudomallei (melioidosis) Ceftazidime
• Helicobacter pylori Clarithromycin + Amoxycillin + Proton pump inhibitor
• Enterobactericiae
– Salmonella Ceftriaxone
6
– E. coli sepsis Ceftriaxone
7
– Klebsiella Ceftriaxone
8
– Proteus vulgaris Ceftriaxone
– Enterobacter Carbapenems
– Serratia Carbapenems
– Shigella Fluoroquinolones
– Yersinia Streptomycin + tetracycline
SPIROCHETES
• Treponema
– pallidum (syphilis) Penicillin G
– pertenue (yaws) Penicillin G

106
• Leptospira Penicillin G
• Borrelia
– burgdorferi (Lyme’s) Doxycycline
– recurrentis (Relapsing fever) Doxycycline
CHLAMYDIAE
• C. psittaci Doxycycline
• C. trachomatis Doxycycline
• C. pneumoniae Doxycycline
RICKETTSIAE
• R. prowazekii (Epidemic typhus) Doxycycline
• R. typhi (Endemic typhus) Doxycycline
• Orientia tsutsugamushi (scrub typhus) Doxycycline
• R. rickettssi (Rocky mounted spotted fever) Doxycycline
• R. akari (Rickettsial pox) Doxycycline
• Rickettsia fever Doxycycline
• Ehrlichia Doxycycline
• Coxiella burnetii (Q fever) Doxycycline
MYCOPLASMA Azithromycin
NOCARDIA Cotrimoxazole
1. Oral penicillin V can be used for mild cases
2. Addition of gentamicin decreases the duration of treatment
3. Gentamicin is added for meningitis or endocarditis
4. For C. jeikium, vancomycin is drug of choice
5. Gentamicin is added for first few days
6. For UTI by E.coli, nitrofurantion or fosfomycin are used
7. For ESBL producing strains, carbapenems are drug of choice
8. For P. mirabilis, ampicillin is drug of choice

107
ENDOCRINE PHARMACOLOGY

Infantile spasms ACTH
Hypothyroidism Levo-thyroxine
Myxedema coma Levo-thyroxine
Hyperthyroidism Carbimazole or methimazole
– In lactation Propylthiouracil
– In 1st trimester of pregnancy Prophylthiouracil
– In 2nd and 3rd trimester of pregnancy Carbimazole or methimazole
– Graves' opthalmopathy Methylprednisolone
Thyroid storm Propanolol (life saving)+ Iodides
Diabetes mellitus
Type 1 (IDDM) Insulin
Type 2 (NIDDM) Metformin
– In obese Metformin
– Uncontrolled Insulin
– Pregnancy Insulin
– To tide over stress Insulin
Diabetic ketoacidosis Insulin (Regular)
Post prandial hyperglycemia Nateglinide
Acute hyperkalemia Calcium gluconate
Beta blocker poisoning Glucagon
Hypoglycemia Glucose (oral or i.v.)
Adrenal insufficiency
– Acute Hydrocortisone
– Chronic (Addison's disease) Hydrocortisone
Erectile dysfunction Sildenafil
Contraceptive
– Newly married Combined oral contraceptives
– In lactation Mini pills
– Emergency contraceptive Levonorgestrel
Anovulatory infertility Clomiphene
Osteoporosis
– Post menopausal Alendronate
– Steroid-induced Alendronate
– In women with risk factors for breast cancer Raloxifene
Hypercalcemia of malignancy Bisphosphonates
Paget's disease of bone Bisphosphonates
Tetany Calcium
Induction of labour Oxytocin
Post partum hemorrhage Oxytocin
Acromegaly Cabergoline
Esophageal varices Terlipressin (if not available, octreotide)
Hyperprolactinemia Cabergoline
Androgenital alopecia Finasteride
Dysfunctional uterine bleeding
– Light bleeding Medroxyprogesterone acetate
– Heavy bleeding Combined oral contraceptives
– Intractable bleeding Leuprolide
Endometriosis Combined oral contraceptives
Ectopic pregnancy Methotrexate

108
CENTRAL NERVOUS SYSTEM PHARMACOLOGY

Alcohol dependence
– Withdrawl symptoms (including seizures) Benzodiazepines like chlordiazepoxide or diazepam
– Maintenance therapy Chlordiazepoxide
– To prevent craving Naltrexone
Methanol poisoning Fomepizole
Ethylene glycol poisoning Fomepizole
Anxiety disorders
– Performance anxiety Propanolol
– Generalized anxiety disorder (GAD)
* Acute attacks Benzodiazepines
* Sustained treatment Antidepressants (venlafaxine/duloxetine)
– Panic disorder
* Acute panic attacks Benzodiazepines
* Sustained treatment SSRI (Sertraline)
Insomnia Zolpidem
Benzodiazepine poisoning Flumazenil
Epilepsy/seizure disorders
– Grand mal (GTCS) Valproate
– Petit mal (Absence) Valproate
– Focal Carbamazepine/Oxcarbazepine
– Myoclonic Valproate
– Atonic Valproate
– Infantile spasms
* Without tuberous sclerosis (TS) ACTH
* With TS Vigabatrin
– Febrile seizures Diazepam
– Status epilepticus Lorazepam
– Eclamptic seizures Magnesium sulphate
– Epilepsy in pregnancy Lamotrigine/Topiramate/levetiracetam
– Lennox-Gastaut syndrome Valproate/Rufinamide/Clonazepam
Neuropathic pain
– Trigeminal neuralgia Carbamazepine
– Post-herpetic neuralgia Pregabalin or gabapentin
– Diabetic neuropathic pain Pregabalin or gabapentin
Parkinsonism
– Early Pramipexole/Ropinirole
– Late Pramipexole/Ropinirole
– Drug induced Anticholinergics (Benzhexol)
Levo-dopa induced
– Vomiting Domperidone
– Psychosis Atypical antipsychotics (olanzapine)
Schizophrenia Olanzapine
– In non-compliant patients Risperidone LAI (long acting injection)
– Refractory Clozapine
Manic disorder
– Acute mania Benzodiazepines/Antipsychotics (olanzapine) + lithium
– Prophylaxis of mania Lithium
– Bipolar disorder Lithium
– Rapid cyclers Valproate
Gille de la Tourette syndrome 1. Haloperidol (FDA-approved)
2. Clonidine/Guanafacine (off label)
Relapsing remitting multiple sclerosis Beta-interferon
Huntington’s disease Tetrabenazine
Wilson disease Zinc
Depression SSRI
– Mild to moderate SSRI (Fluoxetine)
– Severe SNRI (Venlafaxine)
Neurotic disorders
– Obsessive compulsive disorder SSRI (Fluoxetine)
– Post-traumatic stress disorder SSRI (Sertraline)

109
– Bulimia SSRI (Fluoxetine)
– Phobia SSRI (Sertraline)
– Impulse-control disorders SSRI (Fluoxetine)
Attention deficit hyperkinetic disorder Methylphenidate
Nocturnal enuresis Desmopressin
Severe (cancer) pain Opioids (morpine)
Opioid poisoning
– Acute Naloxone
– Maintenance Naltrexone
Opioid de-addiction
– Maintenance therapy Methadone
– To prevent relapse Naltrexone
– To treat withdrawl symptoms Beta blockers/clonidine
Alzhiemer’s dementia Donepezil
Amyotrophic lateral sclerosis Riluzole
Extrapyramidal symptoms
– Acute muscular dystonias Benzhexol
– Parkinsonism Benzhexol
– Akathisia Propanolol
– Neurolept malignant syndrome Dantrolene
– Tardive dyskinesia No treatment (benzodiazepines may help)
Restless leg syndrome Pramipexole
Neurolept analgesia Droperidol + Fentanyl
Neurolept anaesthesia Droperidol + Fentanyl + Nitrous Oxide
GA for internal version Halothane
GA for asthma
– Inducing agent Ketamine
– Inhalational Halothane
GA to produce controlled hypotension Isoflurane
GA for cardiac surgery
– Inducing agent Etomidate
– Inhalational Isoflurane
GA for neurosurgery Isoflurane
Day care surgery Propofol
Total Intravenous Anaesthesia Propofol
GA for malignant hyperthermia Propofol
GA in patients with shock Ketamine
LA in patients with malignant hyperthermia Procaine
Intravenous Regional Anaesthesia (IVRA; Bier’s Prilocaine
block)
Malignant hyperthermia Dantrolene
Malignant Neuroleptic Syndrome Danrolene
MR in patients with asthma Vecuronium
MR in liver and kidney disease Atracurium or Cis-atracurium
MR for endotracheal intubation Succinylcholine
 GA : General Anaesthetic
 LA : Local Anaesthetic
 MR : Muscle Relexant

110

Pharmacology & Therapeutics Supplements: Ali Raza Chaudary (N67)

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Pharmacology & Therapeutics Supplements: Ali Raza Chaudary (N67)

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PHARMACOLOGY &

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

1. Area of Absorptive Surface (directly proportional) e.g. intestine > stomach

2. Degree of Ionization (inversely proportional) By Henderson-Hasselbalch Equation

ALI RAZA CHAUDARY (N67)

Topical Enteral Parenteral Others

ROUTE PATTERN ADVANTAGES DISADVANTAGES

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

 > Sublingual / Parenteral

2. Solubility of the drug:  Liver (major site)

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

3. Effect on Half Life:

SITES EFFECTS ADVANTAGES

ALI RAZA CHAUDARY (N67)

FEATURE PHASE I REACTIONS PHASE II REACTIONS

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

Metabolism of acetaminophen (Ac) to harmless conjugates or to toxic metabolites.

ADVERSE DRUG EFFECTS

Unpredictable Effects Predictable Effects

Cummulation Teratogeni- Carcinogeni-

ALI RAZA CHAUDARY (N67)

 Clearance of a drug that is very effectively extracted by an organ is often flow-limited.

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

1. For drugs to be removed by renal route only

2. For drugs to be removed 50% by renal route and 50% by liver

3. Shortcut for measuring CLCr directly by Cockcroft Gault Equation

4. Shortcut for measuring GFR directly by MDRD Equation

ALI RAZA CHAUDARY (N67)

FEATURE TYPE-I TYPE-II TYPE-III TYPE-IV

 DIFFERENCE BETWEEN INERT BINDING SITE & RECEPTOR SITE

ALI RAZA CHAUDARY (N67)

 DIFFERENCE BETWEEN DOSE CURVE GRAPHS

ALI RAZA CHAUDARY (N67)

 THERAPEUTIC INDEX (TI)

 It estimates the safety of the drug.

 PHARMACOLOGICAL DRUG INTERACTIONS

Pharmacokinetic Pharmacodynamic Additive Synergestic Potentiation Tachyphylactic Antagonism

Absorption Receptor Pharma-

Distribution Non-receptor Physiological

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

Natural Synthetic Semisynthetic

Animals Plants Microorganisms Aspirin Ampicillin

SOLID LIQUID GASES

1. Tablets—Paracetamol 1. Injections—Benzyl penicillin Nitric Oxide

Name chosen by the official Forms or class or genus in

ALI RAZA CHAUDARY (N67)

ANIMAL TESTING (PRE-CLINICAL)

REPRODUCTIVE SAFETY (FDA RATINGS)

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

ALI RAZA CHAUDARY (N67)

INNERVATIONS OF ORGAN SYSTEMS (Most by both SANS and PANS except)

ALI RAZA CHAUDARY (N67)