PHARMACOLOGY

REVIEW
General Principles of
Pharmacology
1. Types of pharmacodynamic drug-
receptor interaction
Agonist - activates receptor
Antagonist - binds to prevent activation
• Competitive antagonist - can be overcome by
increasing the concentration of agonist, reversible
• Irreversible antagonist - cannot be overcome by
increasing agonist concentration
Partial agonist - activates receptors at a lesser extent
when alone and decreases the effect of full agonists
Inverse agonist - binds to the inactive state of
receptor and decreases constitutive activity
2. Differentiate first order from second
order elimination
First-Order Elimination
• rate of elimination proportional to the concentration
• concentration in plasma decreases exponentially with time
• have a characteristic half-life of elimination that is constant regardless of the
amount
• most drugs in clinical use

B. Zero-Order Elimination
• rate of elimination is constant regardless of concentration
• occurs with drugs that saturate their elimination mechanisms
• decrease in a linear fashion over time
• ethanol (over most of its plasma concentration range) and of phenytoin and
aspirin at high therapeutic or toxic concentrations
3. Effects of Ph on the permeability of
drugs
Bases are ionized/polar/water-soluble/less lipid
soluble/less permeable to tissues/ when protonated/
mixed in more acidic environments

Acids are not ionized hence less water soluble/more lipid

soluble when they are protonated

Ex. Overdose of Basic drug, manage by making the urine

more acidic to protonate the drug, making it less lipid
soluble, hence less able to cross thru kidney membranes
back into the body
Principles of
Therapeutics
4. Drug interactions involving CYP450
inducers
ETHEL ETHANOL
CYP450 BARBIE BARBITURATES
&
INDUCER PHI-PHI PHENYTOIN
Faster
metabolism/elimination
of certain drugs REFUSES RIFAMPICIN
GREASY GRISEOFULVIN
CARB CARBAMEZEPINE
SHAKES ST. JOHN’S WORT
SMOKING
 5. Drug interactions involving CYP450
inhibitors
G GRAPEFRUIT
R RITONAVIR
CYP450 A AMIODARONE

IN- V
E
VALPROIC ACID
ERYTHROMYCIN
Of the
HIBITOR S
I
SULFONAMIDES
ISONIAZID
Slowe C CIMETIDINE
K KETOCONAZOLE
metabolism/elimination
of certain drugs
Queen QUINIDINE
6. Effects of Acetylation
Polymorphism
Toxic effects
• INH – peripheral neuropathy
• Procainamide or hydralazine – lupus
• Sulfasalazine – hemolytic anemia
• Environmental benzidine – urinary bladder Ca
Prescription Writing
7. Types of Deviant Prescriptions
• Violative Prescriptions
• Generic name not written/not legible, brand name legible or brand name
indicated with “no substitution” phrase
• Consequence: Not filled. Retained and reported to DOH

• Erroneous Prescriptions
• Brand name precedes generic name. Generic name in parenthesis. Brand name
not in parenthesis
• Filled but Retained and reported

• Impossible Prescriptions
• Only generic name written but not legible
• Generic name does not correspond to brand name
• Both generic and brand names not legible
• Drug prescribed not registered by BFAD
• Consequence: Not filled. Retained and reported to DOH
Principles of Clinical
Research and Statistical
Analysis
8. Types of Observational Studies
Cross-Sectional Studies - Exposure status and disease
status are measured at one point in time (or over a short
period)

Cohort Studies – People healthy/free of the

outcome/disease are classified according to presence of
risk factor, then followed until development of disease

Case-control - Persons with a particular disease (the

cases) and persons without it (the controls) are selected
Proportions of cases and controls who have been
exposed are compared
Effect measures
• Prevalence ratio – used in cross-sectional
• Risk ratio – used in cohort
• Odds ratio – used in case-control
• Efficacy – used in experimental
Stage Purpose Time and cost Outcome

Clinical trial in I (few volunteers) – 3 – 10 yrs; Filing of NDA

humans safety/dosage, PK ~100 M$
II (hundreds) –
safety/effectiveness
III (thousands) – verify
effectiveness/ safety long
term
Respiratory Drugs
11. Strategies of Asthma Therapy
• Acute bronchospasm must be treated promptly and
effectively with bronchodilators (“reliever” drugs) - Beta2
agonists, muscarinic antagonists, and theophylline and its
derivatives are available for this indication.
• Long-term preventive treatment requires control of the
inflammatory process in the airways (“controller” drugs).
• The most important anti-inflammatory drugs in the
treatment of chronic asthma are the corticosteroids.
• Long-acting β2 agonists can improve the response to
corticosteroids. Anti-IgE antibodies also appear promising
for chronic therapy.
• leukotriene antagonists have effects on both
bronchoconstriction and inflammation but are used only for
prophylaxis
12. Toxicities of anti-asthmatic
drugs
13-15. Effects of anti-asthmatic drugs
Gastrointestinal Drugs
16. Effects of Drugs for Acid-
Peptic Disease
17. Regimen for H-pylori
eradication
• Chronic infection with H pylori is present in most
patients with recurrent non-NSAID-induced peptic
ulcers.
• One regimen of choice consists of:
• proton pump inhibitor
• clarithromycin
• amoxicillin (or metronidazole if with penicillin allergy)
18. Describe the antacids
• Antacids differ in their absorption and effects on
stool consistency
• Magnesium hydroxide (Mg[OH]2) and aluminum
hydroxide (Al[OH]3)
• Neither is significantly absorbed from the bowel
• Magnesium hydroxide has a strong laxative effect
• Aluminum hydroxide has a constipating action
• Calcium carbonate and sodium bicarbonate are
also weak bases, but they differ from aluminum
and magnesium hydroxides in being absorbed from
the gut.
19. Sites of action of Acetylcholine
Transmitter at:
• all autonomic ganglia
• between parasympathetic postganglionic neurons
and their effector cells
• postganglionic sympathetic neurons to the
thermoregulatory sweat glands
• somatic (voluntary) skeletal muscle neuromuscular
junction
20. Synthesis
and storage of
Norepinephrine
21. Role of ANS in aqueous humor
balance
Ciliary muscle
accommodation
• Primarily by
muscarinic
receptors
innervated by
the PANS
Ciliary epithelium
• β receptors have
a permissive
effect on
aqueous humor
secretion
22. Clinical uses of antimuscarinic drugs

Organ Drugs Applications

CNS Benztropine, To treat the

Trihexyphenidyl, manifestations of
Biperiden Parkinson’s disease

Scopolamine To prevent or reduce

motion sickness

Eye Atropine, Homotropine, To produce mydriasis

Cyclopentolate, and cycloplegia
Tropicamide
 23. Describe depolarizing
neuromuscular blockers
Depolarizing neuromuscular blockers
• These are nicotinic agonists, not antagonists
• Only succinylcholine is used clinically
• Causes flaccid paralysis, but unlike non-
depolarizing agents, there is initial
fasciculation and sometimes post-op pain
• Hydrolyzed by pseudocholinesterase with a
half life a few minutes
24. Describe Cholinesterase
regenerators
• Not receptor antagonists, but chemical antagonists
• Contain an oxime group, which binds avidly to
phosphorus in organophosphate insecticides,
displacing the insecticide and regenerating
cholinesterase
• Pralidoxime is currently used in the ER for
organophosphate poisoning, such as parathion
25. Clinical uses of propranolol
• Antihypertensive
• Migraine prophylaxis
• Familial tremor, other types of tremor, “stage
fright”
• Thyroid storm, thyrotoxicosis
26. Selectivity of beta blockers

Memory Aid
“OLOL Family”
From A – M are 1-selective except
Carteolol & Labetalol
The rest are non-selective
27. Receptor selectivity of direct acting
cholinergic agonists
Drug Action Pharmacokinetic features
Direct Acting
Acetylcholine B Rapidly hydrolyzed by
cholinesterase (ChE)
Duration 5-30 sec
Bethanechol M Resistant to ChE
Carbachol B Duration 30min – 2hrs
Pilocarpine M Not an ester, good lipid solubility
Duration 30min – 2hrs
Nicotine N Like pilocarpine
Duration 1 – 6hrs
Legend: M – muscarinic N – Nicotinic B - both
Analgesic Drugs
28. Toxicity of Aspirin
• Toxicity
• Aspirin
• GI disturbances and increased risk of bleeding
• Asthma, tinnitus, vertigo, hyperventialtion, respiratory
alkalosis,
• Very high doses – metabolic acidosis, dehydration,
hyperthermia, collapse, coma, death
• Children – increased risk of Reye’s syndrome (hepatic fatty
degeneration and encephalopathy)
29. Clinical Uses of Opioids
Analgesia • Treatment of moderate to severe pain
(codeine, hydrocodone, tramadol)
• Morphine and fentalyl have been given
transdermally
Cough • Oral codeine and dextromethorpahn are
suppression useful
Diarrhea • Oral diphenoxylate and loperamide
Management of • Parenteral morphine is useful due to its
pulmonary hemodynamic actions and calming effects
edema
Anesthesia • Used for pre-operative medication and
intraoerative adjuncts in balanced anesthesia
(morphine, fentanyl)
Opioid • Methadone and buprenorphone (long-acting)
dependence are used in management
30. Other clinical uses of DMARDS
31. Describe acetaminophen
• The mechanism of analgesic action of
acetaminophen is unclear.
• The drug is only a weak COX-1 and COX-2 inhibitor
in peripheral
• tissues, which accounts for its lack of anti-
inflammatory
• effect. Evidence suggests that acetaminophen may
inhibit a third
• enzyme, COX-3, in the CNS
32. Comparison of effectiveness
and adverse effects of NSAIDs
The other older nonselective NSAIDs (ibuprofen,
indomethacin, many others) vary primarily in their potency,
analgesic and anti-inflammatory effectiveness, and duration
of action.

Ibuprofen and naproxen have moderate effectiveness;

indomethacin has greater anti-inflammatory effectiveness;
and ketorolac has greater analgesic effectiveness.

Celecoxib was the first member of a newer NSAID subgroup,

the cyclooxygenase-2 (COX-2)-selective inhibitors, which were
developed in an attempt to lessen the gastrointestinal toxicity
associated with COX inhibition while preserving efficacy
33.Mode of action of anti-gout
agents
Dermatologic Agents
34. Pharmacodynamics of
Tretinoin
In addition to treating acne, tretinoin improves
photodamaged human skin

Epidermal effects include increased epidermal and

granular layer thickness, decreased melanocytic activity,
and increased secretion of a glycosaminoglycan-like
substance into the intercellular space

In the dermis, blood vessel vasodilation and angiogenesis

and increased papillary dermal collagen synthesis have
been documented.
35. Management of pruritus
• Inflammatory disorders such as atopic dermatitis,
contact dermatitis, and lichen simplex chronicus -
topical glucocorticoids and oral doses of sedating
antihistamines
• Antihistamines are useful in histamine-induced pruritus
and in other pruritic disorders in which the sedating
effects of these drugs facilitate sleep and reduce
scratching at night
• Cholestasis-associated pruritus may respond to
cholestyramine, ursodeoxycholic acid, ondansetron, or
rifampin
• The pruritus of uremia is treated most effectively with
UVB radiation
Psychopharmacology
36. Mode of action of
BENZODIAZEPINES
• BZ receptors form part of a GABA-A
receptor Cl ion channel
macromolecular complex
• BZ increase frequency of Cl ion
channel opening
37. Describe Buspirone
• Buspirone
• selective anxiolytic, minimal CNS depressant effects and
no anticonvulsant or muscle relaxant properties
• interacts with the 5-HT1A as a partial agonist
• slow onset of action (>1 week)
• used in generalized anxiety disorder, less effective in
panic disorders
• tolerance minimal, little withdrawal symptoms
38. Identify the CNS effects of ethanol
corresponding to its blood concentration
CNS •Major effects are sedation, loss of
inhibition, impaired judgment, slurred
speech and ataxia
39. Describe the toxicities associated
with halogenated anesthetics
Toxicity •Halothane – postoperative hepatitis (rare0
•Methoxyflurane – renal insufficiency due to
its metabolite (flurorid)
•Prolonged NO - megalopblastic anemia
•Halogenated agents – malignant
hyperthermia
–Uncontrolled release of calcium by
sarcoplasmic reticulum of skeletal
muscle
–Treated with dantrolene and
management of hyperthermia and
cardiovascular instability
40. Pharmacologic
strategies for
parkinsonism
41. Pharmacologic strategies for
Schizophrenia
• Traditional drugs like haloperidol are effective for
positive symptoms like hallucinations but not
effective for negative symptoms of schizophrenia
(eg, emotional blunting and social withdrawal)
• Olanzapine, Risperidone and Sertindole – improve
negative symptoms
• Clozapine – most effective for patients refractory to
other drugs but associated with agranulocytosis
42. Clinical manifestations of
Serotonin Syndrome
• Serotonin syndrome is a group of symptoms that
may occur following use of certain serotonergic
medications or drugs
• Symptoms include high body temperature,
agitation, increased reflexes, tremor, sweating,
dilated pupils, and diarrhea
• Body temperature can increase to greater than 41.1
°C
• Complications may include seizures and extensive
muscle breakdown.
Substance of Abuse
43. Describe Marijuana
• Active component is tetrahydrocannabinol
• Intoxication: Increased heart rate and blood
pressure, injected conjunctiva, dry mouth,
bronchodilation and hunger
44. Describe withdrawal symptoms
from sedative hypnotics
• The most important signs of withdrawal are from
excessive CNS stimulation including anxiety, tremor,
nausea and vomiting, delirium and hallucinations
45. Management of Opioid abuse
• Overdose is managed with intravenous naloxone
and ventilatory support
• Treatment of withdrawal– replacement of the illicit
drug with a pharmacologically equivalent agent (eg,
methadone) followed by slow dose reduction
Fluid and blood
replacement
46. Describe colloid solutions
• Contain proteins, or other high weight
molecules, which tend to remain in the
intravascular space for extended periods of time.
• Physically opposite of crystalloids. Will not
dissolve in water. Will not pass through
semipermeable membranes.
• Rarely used prehospital due to expense and
short shelf-life.
Examples: Plasmanate®, Salt-poor albumin,
Dextran®, Hetastarch
47. Describe Crystalloid Solutions
• Created by dissolving crystals (i.e.: salts and
sugars) in water
• Lower osmotic pressure than colloids
• Will equilibrate faster than colloids
• Fluid of choice in prehospital IV therapy
• 2/3 of infused crystalloid solution will leave the
vascular space within 1 hour (3 ml of crystalloid
solution is needed to replace 1 ml of blood)
Examples: Lactated Ringer’s solution, normal
saline, glucose solutions in water
48. Describe Lactated Ringer’s
solution
Lactated Ringer’s
• Lactate converted to HCO3 in the liver
• Minimal effects on normal body fluid composition
and p-H
• Most closely resembles the electrolyte composition
of normal blood serum
• No calories
Antiseptics and
Disinfectants
49. Describe glutaraldehyde
• Used as a disinfectant and sterilant, in particular for
low-temperature disinfection and sterilization of
endoscopes and surgical equipment
• MoA: strong association with the outer layers of
bacterial cells, specifically with unprotonated
amines on the cell surface leading to inhibitory
action on transport and on enzyme systems
50. Describe alcohol as a
disinfectant
• Isopropyl alcohol is slightly more efficacious against
bacteria, ethyl alcohol is more potent against
viruses
• Isopropyl alcohol has greater lipophilic properties and is
less active against hydrophilic viruses
• Antimicrobial activity is optimal in the 60 to 90%
range
• MoA: Membrane damage and rapid denaturation
of proteins, with subsequent interference with
metabolism and cell lysis
Thyroid and Anti-thyroid
Drugs
51. Describe Thioamides
Thioamides – Methimazole and Propylthiouracil
- Sulfur containing; inhibit thyroid hormone synthesis by
blocking peroxidase reactions, tyrosine iodination and DIT-
MIT coupling
- PTU (less extent methimazole) inhibit peripheral conversion
T4 to T3
- Preformed thyroid hormone not acted upon, hence need for
3-4 wk for full effect
- Methimazole preferred due to OD dosing
- PTU preferred in pregnancy due to less ability to cross
placenta, even to breast milk
- A/E: Skin rash (common), vasculitis, agranulocytosis,
hypoprothrombinemia, liver dysfunction
52. Drugs that block peripheral
conversion of T4 to T3
53. Describe Lugol’s solution
Iodide Salts and Iodine (Lugol’s solution)
- Inhibit tyrosine iodination and thyroid hormone release
- Decrease vascularity of hyperplastic thyroid gland
- Onset is rapid, within 2-7 days
- Effects transient, thyroid gland escapes from block after
weeks of treatment
- Used for thyroid storm and prepare for surgical
resection
- A/E: rash, drug fever, metallic taste, bleeding disorders,
anaphylactic reactions
Insulin, Oral
Hypoglycemic Agents,
and Corticosteroids
54. Describe the toxicity of
thiazolindiones
TOXICITIES
When used alone, hypoglycemia is extremely rare
Causes fluid retention (mild anemia, edema, risk of heart failure)
Rosiglitazone – risk of myocardial infarction
Pioglitazone – risk of bladder cancer
Troglitazone (original thiazolindione) – removed due to
hepatotoxicity, hence still requiring liver function monitoring
even in new agents
Bone fractures in females
CYP450 inducer (affects particularly oral contraceptives and
cyclosporine)
55. Describe Metformin
METFORMIN

MECHANISM
- AMP stimulated protein kinase
- Reduce both postprandial and fasting glucose
- Inhibit hepatic and renal gluconeogenesis
- Stimulates glucose uptake and glycolysis
- Reduces glucose absorption in GIT, and glucagon
- In cases of insulin resistance, there is reduction of endogenous
insulin production from enhanced insulin sensitivity (insulin
sparing effect) hence NO WEIGHT GAIN – first choice in
overweight cases of DM 2
- Restore fertility in those with PCOS
56. Effects of Insulin
secretagogues

- Rapid onset and short duration of action applicable

for postprandial use
TOXICITIES
- High potency (glyburide and glipizide) can cause
hypoglycemia
- Older agents (tolbutamide and chlorpropamide)
affected by drugs that compete for protein binding
- Weight gain
57. Describe Gliflozin
• Inhibits Sodium Glucose Transport Protein 2 (SGLT-
2) hence inhibits glucose reabsorption in the
kidneys
• Empagliflozin – highest specificity to SGLT-2
inhibition and the only oral medicine for T2DM that
has been shown to reduce risk of cardiovascular
death
58. Describe the relative anti-
inflammatory potency of
glucocorticoids
59. Describe the mode of action
of steroids

• Enters cells and bind to cytosolic receptors that

transport the steroid into the nucleus
• Steroid-receptor complex bind to Glucocorticoid
Response Elements or Mineralocorticoid Specific
Elements to alter gene expression
• This explains the relative delay of onset and longer
duration of action compared to other drugs with
different receptor sites
60. Describe the immunosuppressive
effects of glucocorticoids
IMMUNOSUPPRESSIVE EFFECTS
- Inhibition of cell-mediated immunologic functions,
particularly lymphocytes (hence important in tx of
hematologic cancers)
- DO NOT interfere with development of normal
acquired immunity
- Delay rejections in organ transplants
Autacoids and
Antagonists
61. Describe the effects of H1
blockers
• H1 blockers are competitive pharmacologic antagonists
at the H1 receptor

• Structure closely resembles that of muscarinic blockers

and α-adrenoceptor blockers
• Sedation is common, especially with diphenhydramine
and promethazine
• Antimuscarinic effects such as dry mouth and blurred
vision occur with some first generation drugs in some
patients.
• Alpha-adrenoceptor blockade, which is significant with
phenothiazine derivatives such as promethazine, may
cause orthostatic hypotension.
62. Describe the clinical uses of
serotonin antagonists
• Ketanserin is used as an antihypertensive drug outside
the United States
• Ketanserin, cyproheptadine, and phenoxybenzamine
may be of value in the treatment of carcinoid tumor, a
neoplasm that secretes large amounts of serotonin
(and peptides) and causes diarrhea,
bronchoconstriction, and flushing.
• Ondansetron and its congeners are extremely useful in
the control of vomiting associated with cancer
chemotherapy and postoperative vomiting
• Alosetron is used in the treatment of women with
irritable bowel syndrome associated with diarrhea.
63. Describe the effects of ergot
alkaloids
Vessels
• Ergot alkaloids can produce marked and prolonged α-receptor-mediated vasoconstriction.
Ergotamine is the prototype
• Because they are partial agonists, the drugs may also block the α-agonist effects of
sympathomimetics, and ergotamine can cause epinephrine reversal.

Uterus
• Ergot alkaloids produce powerful contraction in this tissue, especially near term. Ergonovine is
the prototype

Brain
• Hallucinations may be prominent with the naturally occurring ergots and with lysergic acid
diethylamide (LSD), a semisynthetic prototypical hallucinogenic ergot derivative, but are
uncommon with the therapeutic ergot derivatives. Although LSD is a potent 5-HT2 blocker in
peripheral tissues, its actions in the CNS are thought to be due to agonist actions at dopamine
receptors.
• Bromocriptine and pergolide are among the most potent semisynthetic ergot derivatives. They
act as dopamine D2 receptors in the pituitary and in the basal ganglia
Drugs for Hypertension
and Heart Failure
64. Describe the
compensatory
response to
antihypertensive
drugs
65. Describe the effects of Central
Nervous System Active agents
• Alpha2-selective agonists (eg, clonidine, methyldopa)
cause a decrease in sympathetic outflow by activation
of α2 receptors in the CNS.
• Clonidine and methyldopa reduce blood pressure by
reducing cardiac output, vascular resistance, or both.
• Sudden discontinuation of clonidine causes rebound
hypertension, which may be severe
• Methyldopa occasionally causes hematologic
immunotoxicity
• Both drugs may cause sedation
66. Describe the mechanism of
action of vasodilators
67. Describe the effects of
diuretics
68. Differentiate dihydropyridine and
non-dihyropyridine Ca channel
blockers
Dihyropyridines: Nifedipine, amlodipine, felodipine,
isradipine
• Greater vasodilator than cardio-depressant effects

Non-dihyropyridines: Verapamil and Diltiazem

• Moderate vascular effect with strong cardiac effect
69. Describe the use of diuretics
in congestive heart failure
• Diuretics are the first-line therapy for both systolic
and diastolic failure and are used in heart failure
• Furosemide - immediate reduction of the
pulmonary congestion and severe edema
associated with acute heart failure and for
moderate or severe chronic failure
• Thiazides - sufficient for mild chronic failure
• Spironolactone and eplerenone (aldosterone
antagonist diuretics) - significant long-term benefits
and can reduce mortality in chronic failure.
70. Describe the effects of Digoxin
• Inhibition of Na+/K+ ATPase of the cell membrane by
digitalis is considered to be the primary biochemical
mechanism of action
• Inhibition of Na+/K+ ATPase results in a small increase
in intracellular sodium
• The increased sodium alters the driving force for
sodium-calcium exchange by the exchanger, NCX, so
that less calcium is removed from the cell.
• The increased intracellular calcium is stored in the
sarcoplasmic reticulum and upon release increases
contractile force.
Drugs for Acute Myocardial
Infarction and Ischemic
Heart Disease
71. Discuss the mode of action of
novel anti-anginal drugs
Increase the efficiency of oxygen utilization by
shifting the energy substrate preference of the heart
from fatty acids to glucose - ranolazine and
trimetazidine

Selectively reduces heart rate with no other

detectable hemodynamic effects by inhibition of the
sinoatrial pacemaker current - Ivabradine
72. Discuss the toxicity of nitrates
and nitrites
• The most common toxic effects of nitrates are the
responses evoked by vasodilation. These include
tachycardia (from the baroreceptor reflex),
orthostatic hypotension (a direct extension of the
venodilator effect), and throbbing headache from
meningeal artery vasodilation

• Nitrites are of significant toxicologic importance

because they cause methemoglobinemia at high
blood concentrations
73. Describe the interaction of
nitrates with drugs for erectile
dysfunction
• Sildenafil and other drugs for erectile dysfunction -
inhibit a phosphodiesterase isoform (PDE5) that
metabolizes cGMP
• Increased cGMP in erectile smooth muscle relaxes it,
allowing for greater inflow of blood and more effective
and prolonged erection
• This effect also occurs in vascular smooth muscle.
• Combination of nitrates (through increased production
of cGMP) and a PDE5 inhibitor (through decreased
breakdown of cGMP) causes a synergistic relaxation of
vascular smooth muscle
• Dangerous hypotension and inadequate perfusion of
critical organs
74. Discuss the therapeutic
strategies for angina
• The nitrates, calcium blockers, and β blockers all
reduce the
• oxygen requirement in atherosclerotic angina.
Nitrates and calcium
• channel blockers (but not β blockers) can also
increase oxygen
• delivery by reducing spasm in vasospastic angina.
75. Discuss the use of B-blockers
in angina
• Beta blockers are used only for prophylactic
therapy of angina; they are of no value in an acute
attack
• They are effective in preventing exercise-induced
angina but are ineffective against the vasospastic
form
• The combination of β blockers and nitrates is useful
because the adverse undesirable compensatory
effects evoked by the nitrates (tachycardia and
increased cardiac force) are prevented or reduced
by β blockade
Drugs for Hyperlipidemia
76. Describe the clinical use of
HMG-CoA inhibitors
• Statins can reduce LDL cholesterol levels dramatically
• Large clinical trials have shown that they reduce the
risk of coronary events and mortality in patients with
ischemic heart disease, and they also reduce the risk of
ischemic stroke.
• Rosuvastatin, atorvastatin, and simvastatin have
greater maximal efficacy than the other HMG-CoA
reductase inhibitors.
• These drugs also reduce triglycerides and increase HDL
cholesterol in patients with triglycerides levels that are higher
than 250 mg/dL and with reduced HDL cholesterol levels
• Fluvastatin has less maximal efficacy than the other
drugs in this group
77. Describe the toxicities of bile acid-binding
resins (cholestyramine, colestipol,
colesevelam)
• Adverse effects from resins include bloating,
constipation, and an unpleasant gritty taste.
Absorption of vitamins (eg, vitamin K, dietary
folates) and drugs (eg, thiazide diuretics, warfarin,
pravastatin, fluvastatin) is impaired by the resins.
78. Discuss the primary hyperlipoproteinemias
and their drug treatment
Anti-arrhythmic Drugs
79. Enumerate the class of anti-
arrhythmic agents
1. Sodium channel blockers
2. Beta-adrenoceptor blockers
3. Potassium channel blockers
4. Calcium channel blockers
80. Describe amiodarone
• Amiodarone is useful in most types of arrhythmias and
is considered the most efficacious of all antiarrhythmic
drugs
• It blocks sodium, calcium, and potassium channels and
β adrenoceptors.
• Causes microcrystalline deposits in the cornea and skin,
thyroid dysfunction (hyper- or hypothyroidism),
paresthesias, tremor, and pulmonary fibrosis.
• Amiodarone rarely causes new arrhythmias, perhaps
because it blocks calcium channels and β receptors as
well as sodium and potassium channels
81. Describe Group 1 anti-
arrhythmic drugs
• All group 1 drugs slow conduction in ischemic and
depolarized cells and slow or abolish abnormal
pacemakers wherever these processes depend on
sodium channels
• The most selective agents (those in group 1B) have
significant effects on sodium channels in ischemic
tissue, but negligible effects on channels in normal
cells.
• In contrast, less selective group 1 drugs (groups 1A
and 1C) cause some reduction of INa even in
normal cells.
82. Describe Group 3
antiarrhythmics
• Dofetilide and ibutilide are typical group 3 drugs.
• Sotalol is a chiral compound (ie, it has 2 optical
isomers).
• One isomer is an effective β blocker, and both isomers
contribute to the antiarrhythmic action.
• The clinical preparation contains both isomers.
• Amiodarone is usually classified as a group 3 drug
because it blocks the same K channels and markedly
prolongs AP duration as well as blocking sodium
channels
• The hallmark of group 3 drugs is prolongation of the AP
duration
Anti-microbial drugs
83. Discuss the wide spectrum
penicillinase-susceptible drugs
Ampicillin and amoxicillin
• Clinical uses include indications similar to penicillin G as well as infections resulting from
enterococci, Listeria monocytogenes, Escherichia coli, Proteus mirabilis, Haemophilus
influenzae, and Moraxella catarrhalis
• When used in combination with inhibitors of penicillinases (eg, clavulanic acid), their
antibacterial activity is often enhanced.
• In enterococcal and listerial infections, ampicillin is synergistic with aminoglycosides.

Piperacillin and ticarcillin

• have activity against several gram-negative rods, including Pseudomonas, Enterobacter,
and in some cases Klebsiella species.
• Most drugs in this subgroup have synergistic actions when used with aminoglycosides
against such organisms.
• Piperacillin and ticarcillin are susceptible to penicillinases and are often used in
combination with penicillinase inhibitors (eg, tazobactam and clavulanic acid) to enhance
their activity.
84. Discuss the effects of protein
synthesis inhibitors
85. Discuss the aminoglycosides
86. Discuss the fluorquinolones
87. Discuss the effects of the Anti-
TB drugs
88. Discuss the mode of action of
antifungal agents
89. Discuss the drugs used for
malaria
90. Discuss the anti-helminthic
drugs
Toxicology
91. Describe the toxic syndrome
of antimuscarinic drugs
92. Describe the toxic syndrome
of opioids
93. Discuss the antidotes
94. Discuss the toxic features of
poisons
Hematinics
95. Discuss the clinical use of iron
preparations
• Prevention or treatment of iron deficiency anemia
is the only indication for iron administration
• Dietary ferrous iron supplementation: ferrous
sulfate, ferrous gluconate, or ferrous fumarate
• Parenteral iron preparations: iron dextran, sodium
ferric gluconate complex, and iron sucrose.
• Iron should not be given in hemolytic anemia
because iron stores are elevated, not depressed, in
this type of anemia.
96. Discuss the myeloid growth
factors
• G-CSF (filgrastim): Stimulates G-CSF receptors
expressed on mature neutrophils and their progenitors
• GM-CSF (sargramostim): myeloid growth factor that
acts through a distinct GM-CSF receptor to stimulate
proliferation and differentiation of early and late
granulocytic progenitor cells, and erythroid and
megakaryocyte progenitors.
• Plerixafor: antagonist of CXCR4 receptor used in
combination with G-CSF for mobilization of peripheral
blood cells prior to autologous transplantation in
patients with multiple myeloma or non-Hodgkin’s
lymphoma
Cancer Chemotherapy
and Immunotherapy
97. Discuss the targets of anti-
cancer drugs in the cell cycle
98. Discuss the rescue therapy for
anti-cancer drugs
• High doses of methotrexate may be given for 36–48 h to
cells of the gastrointestinal tract and bone marrow and
terminated before severe toxicity occurs.
• Leucovorin, a form of tetrahydrofolate that is accumulated more
readily by normal than by neoplastic cells, is then administered.
• This results in rescue of the normal cells because leucovorin
bypasses the dihydrofolate reductase step in folic acid synthesis.
• Mercaptoethanesulfonate (mesna) “traps” acrolein
released from cyclophosphamide and thus reduces the
incidence of hemorrhagic cystitis.
• Dexrazoxane inhibits free radical formation and affords
protection against the cardiac toxicity of anthracyclines (eg,
doxorubicin).
99. Discuss the monoclonal
antibodies
100. Discuss the
immunosuppressive agents