Pharmacology
MBBS Pharmacology — high-yield long questions and short notes from K.D. Tripathi, covering general pharmacology, autonomic and cardiovascular drugs, CNS, autacoids, chemotherapy, endocrine and more, written to the marks with mechanisms, classification, clinical uses, adverse effects and pearls.
12chapters144questions99High-Yield
Definition
Pharmacodynamics is the study of what the drug does to the body; most drugs act through receptors to produce their effect.
Mechanisms of Drug Action
- Receptor-mediated (commonest)
- Enzyme inhibition (aspirin → COX)
- Ion channels (calcium blockers)
- Transporters / pumps (omeprazole)
- Physical / chemical action (antacids)
Receptor Types
- Ion-channel — fast (nicotinic)
- G-protein-coupled — second messengers
- Enzyme-linked — insulin receptor
- Nuclear — steroids (slow, gene effect)
Drug binds a receptor, triggering signalling that produces the effect. Receptor Speed Example Ion-channel Milliseconds Nicotinic G-protein Seconds Adrenergic Nuclear Hours Steroid Applied
- Receptor selectivity → fewer side effects
- Drug design targets receptors
🔑KEY POINTS TO REMEMBER- Drugs act via receptors, enzymes, ion channels, transporters.
- Receptors: ion-channel, G-protein, enzyme-linked, nuclear.
- Nuclear receptors act slowest (gene transcription).
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
The dose–response relationship describes how effect varies with dose; agonists activate receptors and antagonists block them.
Dose–Response Curve
- Sigmoid curve (log dose vs response)
- Potency — dose needed for an effect (ED50)
- Efficacy — maximum effect achievable (Emax)
Agonists
- Full agonist — maximal response
- Partial agonist — submaximal response
- Inverse agonist — opposite effect
Antagonists
- Competitive — reversible, surmountable
- Non-competitive — irreversible
- Physiological, chemical antagonism
Agonists switch receptors on; antagonists prevent activation. Term Meaning Potency Dose needed (ED50) Efficacy Maximum effect Affinity Binding strength Applied
- Partial agonists (buprenorphine)
- Antagonists reverse overdose (naloxone)
🔑KEY POINTS TO REMEMBER- Potency = dose needed; efficacy = maximum effect.
- Agonists activate (full, partial, inverse).
- Antagonists block (competitive vs non-competitive).
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
The therapeutic index (TI) is the ratio of the toxic dose to the effective dose — a measure of a drug’s safety margin.
Definition & Formula
- TI = TD50 / ED50 (animal); LD50 / ED50
- High TI — safe drug (penicillin)
- Low TI — narrow margin (digoxin, lithium, warfarin, phenytoin)
Drug Safety Measures
- Therapeutic drug monitoring for narrow-TI drugs
- Individualised dosing
- Watch for interactions
The wider the gap between effective and toxic dose, the safer the drug. Drug Therapeutic index Penicillin High (safe) Digoxin, lithium Low (narrow) Warfarin Low Applied
- Serum monitoring of digoxin, lithium, phenytoin
- Narrow TI → toxicity risk
🔑KEY POINTS TO REMEMBER- TI = TD50 / ED50 (safety margin).
- High TI = safe; low TI = digoxin, lithium, warfarin, phenytoin.
- Narrow-TI drugs need therapeutic monitoring.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
An adverse drug reaction (ADR) is any harmful, unintended response to a drug at normal therapeutic doses.
Classification
- Type A (augmented) — dose-related, predictable (bleeding with warfarin)
- Type B (bizarre) — unpredictable, not dose-related (allergy)
- Type C (chronic), D (delayed), E (end-of-use)
Types of Reactions
- Side effects, toxic effects
- Idiosyncrasy, allergy
- Teratogenicity, carcinogenicity
- Drug dependence, withdrawal
ADRs split into predictable dose-related and unpredictable bizarre types. Type Feature Example A Dose-related Warfarin bleeding B Unpredictable Penicillin allergy D Delayed Teratogenicity Applied
- Pharmacovigilance reporting
- Thalidomide (teratogenicity)
🔑KEY POINTS TO REMEMBER- ADR = harmful unintended response at therapeutic dose.
- Type A = dose-related/predictable; Type B = unpredictable.
- Monitored by pharmacovigilance.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Factors modifying drug action are patient and drug variables that alter the response to a given dose.
Patient Factors
- Age — neonates, elderly (↓ metabolism/excretion)
- Body weight — dose per kg
- Sex, pregnancy, lactation
- Genetics — pharmacogenetics
- Disease — liver, kidney failure
Drug Factors
- Route, dose, formulation
- Drug interactions
- Tolerance, cumulation
The same dose produces different effects depending on the patient. Factor Effect Elderly ↓ dose needed Liver disease ↓ metabolism Renal failure ↓ excretion Applied
- Dose adjustment in renal/hepatic failure
- Paediatric dosing by weight
🔑KEY POINTS TO REMEMBER- Patient factors: age, weight, genetics, disease, pregnancy.
- Drug factors: route, dose, interactions, tolerance.
- Adjust dose in liver/kidney failure and extremes of age.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
An agonist binds a receptor and activates it; an antagonist binds but produces no effect, blocking the agonist.
Agonist
- Has affinity + intrinsic activity
- Produces a response
- Full, partial or inverse
Antagonist
- Has affinity but no intrinsic activity
- Blocks agonist action
- Competitive or non-competitive
Both bind the receptor, but only the agonist activates it. Feature Agonist Antagonist Affinity Yes Yes Intrinsic activity Yes No Effect Response Blocks Applied
- Adrenaline (agonist); propranolol (antagonist)
- Naloxone reverses morphine
🔑KEY POINTS TO REMEMBER- Agonist = affinity + intrinsic activity → response.
- Antagonist = affinity only → blocks agonist.
- Naloxone antagonises morphine.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
The therapeutic index is the ratio of the dose producing toxicity to the dose producing the desired effect — a measure of drug safety.
Formula
- TI = TD50 / ED50 (or LD50 / ED50)
- Higher ratio = safer drug
- Therapeutic window = safe concentration range
Examples
- High TI — penicillin, paracetamol (usual doses)
- Low TI — digoxin, lithium, phenytoin, warfarin
A large gap between effective and toxic doses means a safe drug. TI Meaning High Wide safety margin Low Narrow — monitor levels Applied
- Therapeutic drug monitoring (digoxin, lithium)
🔑KEY POINTS TO REMEMBER- TI = TD50 / ED50.
- High TI = safe; low TI = digoxin, lithium, phenytoin.
- Low TI needs drug-level monitoring.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Competitive antagonism is reversible blockade at the same receptor site; non-competitive antagonism is irreversible or at a different site.
Competitive
- Binds the same (active) site
- Reversible, surmountable by ↑ agonist
- Shifts dose-response curve right; Emax unchanged
- E.g. atropine vs acetylcholine
Non-Competitive
- Binds a different site or binds irreversibly
- Not surmountable
- ↓ Emax (maximum response)
- E.g. phenoxybenzamine
Extra agonist overcomes competitive but not non-competitive blockade. Feature Competitive Non-competitive Reversible Yes No / different site Emax Unchanged Reduced Curve Right shift Flattened Applied
- Atropine (competitive)
- Phenoxybenzamine (non-competitive)
🔑KEY POINTS TO REMEMBER- Competitive: same site, surmountable, Emax unchanged.
- Non-competitive: not surmountable, ↓ Emax.
- Atropine vs phenoxybenzamine.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Drug allergy is an immunologically mediated adverse reaction to a drug, unrelated to its dose or pharmacological action.
Types (Gell & Coombs)
- Type I — immediate, IgE (anaphylaxis, urticaria)
- Type II — cytotoxic (haemolysis)
- Type III — immune complex (serum sickness)
- Type IV — delayed, cell-mediated (contact dermatitis)
Features
- Not dose-related (Type B ADR)
- Needs prior sensitisation
- Common drugs: penicillin, sulphonamides
Previous exposure primes the immune system to react on re-exposure. Type Mechanism Example I IgE Anaphylaxis II Cytotoxic Haemolysis IV T cell Contact dermatitis Applied
- Penicillin anaphylaxis → adrenaline
- Always take drug-allergy history
🔑KEY POINTS TO REMEMBER- Drug allergy = immune-mediated, not dose-related.
- Types I–IV (Gell & Coombs); Type I = anaphylaxis.
- Penicillin the classic culprit; treat with adrenaline.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Tolerance is a gradual decrease in response to a drug on repeated use; tachyphylaxis is rapid tolerance developing within minutes to hours.
Tolerance
- Develops slowly (days–weeks)
- Needs ↑ dose for the same effect
- E.g. opioids, barbiturates, alcohol
- Cross-tolerance between related drugs
Tachyphylaxis
- Rapid (minutes–hours)
- Due to depletion of mediator or receptor desensitisation
- E.g. ephedrine, nitrates
Both reduce response; they differ in how fast they develop. Feature Tolerance Tachyphylaxis Onset Slow Rapid Example Opioids Ephedrine Applied
- Nitrate-free interval prevents tolerance
- Opioid dose escalation
🔑KEY POINTS TO REMEMBER- Tolerance = slow ↓ response (opioids, alcohol).
- Tachyphylaxis = rapid ↓ response (ephedrine, nitrates).
- Nitrate-free interval prevents nitrate tolerance.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
G-protein-coupled receptors (GPCRs) are seven-transmembrane receptors that signal through G proteins and second messengers.
Structure & Mechanism
- Seven transmembrane domains
- Agonist binds → G protein activated
- G protein → effector enzyme
- Second messenger → cellular response
Second Messengers
- cAMP (via adenylyl cyclase)
- IP3 / DAG (via phospholipase C)
- Calcium, cGMP
The receptor activates a G protein, which generates second messengers. G protein Effect Gs ↑ cAMP Gi ↓ cAMP Gq ↑ IP3 / DAG Applied
- β-adrenergic (Gs → ↑ cAMP)
- Most drug targets are GPCRs
🔑KEY POINTS TO REMEMBER- GPCR = 7-transmembrane receptor signalling via G proteins.
- Second messengers: cAMP, IP3/DAG, calcium.
- Gs ↑ cAMP, Gi ↓ cAMP, Gq ↑ IP3.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Pharmacogenetics is the study of genetically determined variation in drug response.
Examples
- Slow / fast acetylators — isoniazid (neuropathy in slow)
- G6PD deficiency — haemolysis with primaquine
- Pseudocholinesterase deficiency — prolonged succinylcholine apnoea
- Malignant hyperthermia (halothane)
Inherited enzyme differences change how patients handle the same drug. Variation Consequence Slow acetylator Isoniazid neuropathy G6PD deficiency Haemolysis Pseudocholinesterase Prolonged apnoea Applied
- Basis of personalised medicine
- Explains unpredictable reactions
🔑KEY POINTS TO REMEMBER- Pharmacogenetics = genetic variation in drug response.
- Slow acetylators, G6PD deficiency, pseudocholinesterase deficiency.
- Basis of personalised medicine.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.