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.
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Definition
Absorption is the passage of a drug from its site of administration into the bloodstream; bioavailability is the fraction reaching systemic circulation unchanged.
Mechanisms of Absorption
- Passive diffusion (commonest)
- Facilitated diffusion
- Active transport
- Pinocytosis
Factors Affecting Absorption
- Lipid solubility, ionisation (pH)
- Molecular size
- Route of administration
- Blood flow, surface area
- Formulation (dissolution rate)
Bioavailability
- IV route — 100% by definition
- Oral — reduced by first-pass metabolism
Drug crosses membranes into blood; oral drugs lose some to first-pass metabolism. Route Bioavailability Intravenous 100% Oral Variable (first-pass) Sublingual High (bypasses liver) Applied
- Bioequivalence of generic drugs
- Sublingual nitrates in angina
🔑KEY POINTS TO REMEMBER- Absorption mainly by passive diffusion (lipid-soluble, unionised).
- Bioavailability = fraction reaching circulation unchanged.
- IV = 100%; oral reduced by first-pass metabolism.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Distribution is the reversible movement of a drug from blood into tissues and body compartments.
Factors Affecting Distribution
- Lipid solubility
- Plasma protein binding (albumin)
- Blood flow to the organ
- Tissue binding
- Barriers (blood-brain, placental)
Volume of Distribution (Vd)
- Vd = dose / plasma concentration
- Low Vd — confined to plasma
- High Vd — extensive tissue distribution
Only free drug leaves the blood to reach and act on tissues. Feature Effect ↑ Protein binding ↓ free drug ↑ Lipid solubility ↑ distribution High Vd Tissue-bound Applied
- Displacement interactions (warfarin)
- Blood-brain barrier limits CNS entry
🔑KEY POINTS TO REMEMBER- Only free (unbound) drug distributes and acts.
- Vd = dose / plasma concentration.
- Barriers: blood-brain, placental.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Drug metabolism (biotransformation) is the enzymatic conversion of drugs into more polar metabolites for excretion, mainly in the liver.
Phase I Reactions
- Oxidation, reduction, hydrolysis
- By cytochrome P450 enzymes
- Product may be active or inactive
Phase II Reactions
- Conjugation (glucuronidation, sulphation, acetylation)
- Makes drug water-soluble
- Almost always inactivates
Consequences
- Active drug → inactive metabolite
- Prodrug → active drug
- Occasionally → toxic metabolite
Two phases convert lipid-soluble drugs into excretable water-soluble forms. Phase Reaction Result I Oxidation (CYP450) Polar metabolite II Conjugation Water-soluble Applied
- Prodrugs (enalapril, levodopa)
- Paracetamol → toxic metabolite in overdose
🔑KEY POINTS TO REMEMBER- Phase I: oxidation/reduction/hydrolysis (CYP450).
- Phase II: conjugation → water-soluble, inactive.
- Prodrugs are activated by metabolism.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Excretion is the removal of drug from the body; clearance is the volume of plasma cleared of drug per unit time.
Routes of Excretion
- Renal — main route (filtration, secretion, reabsorption)
- Biliary (enterohepatic circulation)
- Lungs (volatile agents)
- Milk, sweat, saliva
Clearance & Half-Life
- Clearance = rate of elimination / plasma concentration
- Half-life (t½) = time for concentration to halve
- Steady state in ~4–5 half-lives
Kidneys filter and secrete drug; reabsorption depends on urine pH. Route Example Renal Most drugs Biliary Rifampicin Lungs Anaesthetic gases Applied
- Dose reduction in renal failure
- Urine alkalinisation in aspirin overdose
🔑KEY POINTS TO REMEMBER- Renal excretion = main route (filtration, secretion, reabsorption).
- Clearance = plasma volume cleared per unit time.
- Steady state in 4–5 half-lives.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Routes of drug administration are the paths by which a drug is given, broadly enteral, parenteral and topical.
Enteral
- Oral — convenient, safest (first-pass loss)
- Sublingual — rapid, bypasses liver
- Rectal — partial first-pass bypass
Parenteral
- Intravenous — immediate, 100% bioavailability
- Intramuscular, subcutaneous — slower absorption
- Intrathecal, intradermal
Topical / Others
- Skin, eye, inhalation, transdermal patch
Routes divide into enteral (via gut) and parenteral (bypassing gut). Route Onset Note IV Immediate 100% available Oral Slow First-pass Sublingual Rapid Bypasses liver Applied
- Emergency → IV route
- Sublingual nitroglycerin in angina
🔑KEY POINTS TO REMEMBER- Enteral (oral, sublingual, rectal) vs parenteral (IV, IM, SC).
- IV = immediate, 100% bioavailable.
- Sublingual bypasses first-pass metabolism.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Bioavailability is the fraction of an administered dose that reaches the systemic circulation in unchanged (active) form.
Features
- IV route = 100% (reference standard)
- Oral route — reduced by incomplete absorption and first-pass metabolism
- Expressed as a percentage
Factors Affecting It
- First-pass metabolism
- Drug formulation, food
- Gut motility, disease
Bioavailability measures how much of the dose actually reaches the blood. Route Bioavailability IV 100% Oral Variable Sublingual High Applied
- Bioequivalence testing of generics
- Dose adjustment when switching routes
🔑KEY POINTS TO REMEMBER- Bioavailability = fraction reaching circulation unchanged.
- IV = 100%; oral reduced by first-pass.
- Basis of bioequivalence testing.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
First-pass metabolism is the metabolism of an orally administered drug by the gut wall and liver before it reaches systemic circulation.
Mechanism
- Drug absorbed from gut → portal vein → liver
- Metabolised before reaching circulation
- ↓ Bioavailability
Drugs with High First-Pass
- Propranolol, morphine, lignocaine
- Nitroglycerin, testosterone
Oral drugs pass through the liver first, where much may be destroyed. Route First-pass Oral Yes Sublingual Bypassed IV Bypassed Applied
- Sublingual / IV routes bypass it
- Explains high oral doses of propranolol
🔑KEY POINTS TO REMEMBER- First-pass = gut/liver metabolism before circulation.
- ↓ oral bioavailability (propranolol, morphine, lignocaine).
- Bypassed by sublingual, IV, rectal (partly).
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Enzyme induction is increased synthesis of drug-metabolising enzymes; enzyme inhibition is their reduced activity — both cause drug interactions.
Enzyme Inducers
- ↑ Metabolism → ↓ drug effect
- Slow onset (days–weeks)
- Rifampicin, phenytoin, carbamazepine, phenobarbitone, chronic alcohol
Enzyme Inhibitors
- ↓ Metabolism → ↑ drug effect / toxicity
- Rapid onset
- Erythromycin, ketoconazole, cimetidine, ciprofloxacin
Inducers speed drug breakdown; inhibitors slow it and risk toxicity. Type Effect Example Inducer ↓ drug level Rifampicin Inhibitor ↑ drug level Erythromycin Applied
- Rifampicin → oral contraceptive failure
- Warfarin interactions
🔑KEY POINTS TO REMEMBER- Inducers (rifampicin, phenytoin) → ↑ metabolism, ↓ effect.
- Inhibitors (erythromycin, cimetidine) → ↑ levels, toxicity.
- Major cause of drug interactions.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Plasma protein binding is the reversible binding of drugs to plasma proteins, mainly albumin, forming an inactive reservoir.
Features
- Acidic drugs → albumin; basic drugs → α1-acid glycoprotein
- Bound drug is inactive (cannot cross membranes)
- Only free drug is active and excretable
- Acts as a drug reservoir (prolongs action)
Bound drug is stored and inactive; only the free fraction works. Fraction Status Bound Inactive, reservoir Free Active, excreted Applied
- Displacement interaction (aspirin + warfarin)
- Hypoalbuminaemia → ↑ free drug → toxicity
🔑KEY POINTS TO REMEMBER- Drugs bind albumin reversibly (acidic drugs).
- Bound = inactive reservoir; free = active.
- Displacement / low albumin → toxicity.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
First-order kinetics eliminates a constant fraction of drug per unit time; zero-order kinetics eliminates a constant amount.
First-Order
- Constant fraction eliminated
- Rate ∝ plasma concentration
- Constant half-life
- Most drugs at therapeutic doses
Zero-Order (saturation)
- Constant amount eliminated
- Enzymes saturated
- Half-life varies with dose
- Alcohol, phenytoin, aspirin (high dose), theophylline
Most drugs clear proportionally; saturated systems clear a fixed amount. Feature First-order Zero-order Eliminated Fraction Amount Half-life Constant Varies Example Most drugs Alcohol, phenytoin Applied
- Phenytoin toxicity on small dose increase
- Alcohol elimination is constant
🔑KEY POINTS TO REMEMBER- First-order = constant fraction; constant half-life.
- Zero-order = constant amount (saturated enzymes).
- Zero-order: alcohol, phenytoin, high-dose aspirin.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
The apparent volume of distribution (Vd) is the theoretical volume in which the total amount of drug would need to be distributed to give the observed plasma concentration.
Formula & Interpretation
- Vd = total amount of drug in body / plasma concentration
- Low Vd — confined to plasma (heparin, warfarin)
- High Vd — extensive tissue binding (digoxin, chloroquine)
Factors
- Lipid solubility, protein binding, tissue binding
Vd is a calculated volume showing how widely a drug spreads into tissues. Vd Meaning Example Low In plasma Heparin High In tissues Digoxin Applied
- Guides loading-dose calculation
- High Vd → dialysis ineffective
🔑KEY POINTS TO REMEMBER- Vd = amount in body / plasma concentration.
- Low Vd = plasma-confined; high Vd = tissue-bound.
- Used to calculate the loading dose.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Plasma half-life (t½) is the time for plasma drug concentration to fall by half; steady state is when the rate in equals the rate out.
Half-Life
- t½ = 0.693 × Vd / clearance
- Determines dosing frequency
- ~4–5 half-lives to eliminate a drug
Steady State
- Reached in ~4–5 half-lives of repeated dosing
- Rate of administration = rate of elimination
- Loading dose reaches it faster
With regular dosing, levels plateau after about five half-lives. Concept Time Steady state 4–5 t½ Elimination 4–5 t½ Applied
- Loading dose for rapid effect
- Dose interval based on half-life
🔑KEY POINTS TO REMEMBER- t½ = 0.693 × Vd / clearance.
- Steady state in 4–5 half-lives.
- Loading dose achieves it faster.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.