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
Histamine is an autacoid released from mast cells mediating allergy and gastric secretion; antihistamines block its receptors.
Histamine Actions
- H1 — bronchoconstriction, vasodilation, itching, ↑ capillary permeability
- H2 — ↑ gastric acid secretion
- Triple response of Lewis (flush, flare, wheal)
H1 Antihistamines
- First generation — chlorpheniramine, promethazine (sedating)
- Second generation — cetirizine, loratadine, fexofenadine (non-sedating)
H2 Blockers
- Ranitidine, famotidine — ↓ gastric acid
Mast cells release histamine, which antihistamines block at H1 or H2. Receptor Effect Blocker H1 Allergy, itching Cetirizine H2 Gastric acid Ranitidine Applied
- Allergic rhinitis, urticaria
- Motion sickness (promethazine)
🔑KEY POINTS TO REMEMBER- H1 → allergy; H2 → gastric acid.
- First-generation sedating, second-generation non-sedating.
- Antihistamines do not reverse anaphylaxis (use adrenaline).
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
5-HT (serotonin) and prostaglandins are autacoids — locally acting mediators with wide physiological and pathological roles.
5-HT (Serotonin)
- From enterochromaffin cells, platelets, CNS neurons
- Actions: vasoconstriction, ↑ gut motility, platelet aggregation, mood
- Drugs: triptans (5-HT1 agonists), ondansetron (5-HT3 blocker)
Prostaglandins
- From arachidonic acid via cyclooxygenase (COX)
- Actions: inflammation, pain, fever, gastric protection, uterine contraction
- Drugs: misoprostol (PGE1), dinoprostone, latanoprost
Prostaglandins mediate inflammation but also protect the gastric mucosa. Autacoid Drug Use 5-HT1 Sumatriptan Migraine 5-HT3 Ondansetron Vomiting PGE1 Misoprostol Ulcer prevention Applied
- Ondansetron for chemotherapy-induced vomiting
- Misoprostol prevents NSAID ulcers
🔑KEY POINTS TO REMEMBER- 5-HT: vasoconstriction, gut motility, mood; triptans & ondansetron act on it.
- Prostaglandins from arachidonic acid via COX.
- PGs mediate inflammation and protect gastric mucosa.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
NSAIDs are drugs with analgesic, antipyretic and anti-inflammatory action, produced by inhibiting cyclooxygenase (COX).
Mechanism
- Inhibit COX → ↓ prostaglandin synthesis
- COX-1 — constitutive (gastric protection, platelets)
- COX-2 — inducible (inflammation)
Classification
- Non-selective — aspirin, ibuprofen, diclofenac, indomethacin
- Preferential COX-2 — nimesulide, meloxicam
- Selective COX-2 — celecoxib, etoricoxib
Uses
- Pain, fever, inflammation
- Rheumatoid arthritis, osteoarthritis
- Dysmenorrhoea
Blocking COX cuts prostaglandin production, easing pain and inflammation. Enzyme Role Effect of inhibition COX-1 Gastric protection Ulcers COX-2 Inflammation Anti-inflammatory Applied
- Adverse: peptic ulcer, renal impairment, bleeding
- COX-2 inhibitors → cardiovascular risk
🔑KEY POINTS TO REMEMBER- NSAIDs inhibit COX → ↓ prostaglandins.
- COX-1 (gastric protection) vs COX-2 (inflammation).
- Adverse: peptic ulcer, renal impairment; COX-2 → cardiovascular risk.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Aspirin is an irreversible COX inhibitor with antiplatelet action; paracetamol is an analgesic-antipyretic with little anti-inflammatory effect.
Aspirin
- Irreversibly acetylates COX
- Low dose (75–150 mg) — antiplatelet (↓ thromboxane)
- High dose — analgesic, anti-inflammatory
- Adverse: gastric ulcer, bleeding, Reye syndrome in children
Paracetamol
- Central COX inhibition
- Analgesic + antipyretic (weak anti-inflammatory)
- Safe in children, asthma, peptic ulcer
- Overdose → hepatotoxicity
Aspirin acts peripherally and irreversibly; paracetamol acts centrally. Feature Aspirin Paracetamol Anti-inflammatory Yes Minimal Antiplatelet Yes No Main toxicity Gastric, bleeding Liver Applied
- Low-dose aspirin in myocardial infarction, stroke prevention
- Avoid aspirin in children (Reye syndrome)
🔑KEY POINTS TO REMEMBER- Aspirin irreversibly inhibits COX; low dose = antiplatelet.
- Paracetamol = analgesic/antipyretic, minimal anti-inflammatory.
- Aspirin → Reye syndrome; paracetamol overdose → hepatotoxicity.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Antigout drugs treat acute attacks of gout or lower uric acid for long-term prevention.
Acute Attack
- NSAIDs — indomethacin, naproxen (first-line)
- Colchicine — inhibits neutrophil migration
- Corticosteroids (if others contraindicated)
Chronic (Prophylaxis)
- Allopurinol, febuxostat — ↓ uric acid synthesis (xanthine oxidase inhibitors)
- Probenecid — uricosuric (↑ excretion)
Principle
- Never start urate-lowering drugs during an acute attack
Acute attacks need anti-inflammatories; prevention needs urate-lowering. Phase Drug Action Acute Colchicine ↓ Neutrophils Chronic Allopurinol ↓ Uric acid synthesis Chronic Probenecid ↑ Excretion Applied
- Aspirin worsens gout (↓ urate excretion)
- Allopurinol may precipitate an acute attack initially
🔑KEY POINTS TO REMEMBER- Acute gout: NSAIDs, colchicine, steroids.
- Chronic: allopurinol/febuxostat (↓ synthesis), probenecid (↑ excretion).
- Do not start allopurinol during an acute attack.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
NSAIDs act by inhibiting cyclooxygenase; their adverse effects largely follow from loss of protective prostaglandins.
Mechanism
- Inhibit COX-1 and COX-2
- ↓ Prostaglandin synthesis
- → Analgesic, antipyretic, anti-inflammatory
Adverse Effects
- Gastrointestinal — gastritis, peptic ulcer, bleeding
- Renal — sodium retention, impairment
- Bleeding — antiplatelet effect
- Aspirin-induced asthma; Reye syndrome (aspirin)
Blocking COX-1 removes prostaglandin protection of stomach and kidney. System Adverse effect GI Peptic ulcer Renal Impairment Blood Bleeding Applied
- Give with proton-pump inhibitor if high risk
- Avoid in renal failure, peptic ulcer
🔑KEY POINTS TO REMEMBER- NSAIDs inhibit COX → ↓ prostaglandins.
- Adverse: peptic ulcer, renal impairment, bleeding.
- COX-1 inhibition causes gastric toxicity.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Paracetamol poisoning causes potentially fatal hepatotoxicity due to accumulation of the toxic metabolite NAPQI.
Mechanism
- Overdose saturates conjugation pathways
- Excess metabolised to NAPQI (toxic)
- Glutathione depleted → hepatocyte necrosis
Clinical Features & Treatment
- Early: nausea, vomiting (may be asymptomatic)
- 24–72 h: ↑ liver enzymes, jaundice → hepatic failure
- N-acetylcysteine — antidote (replenishes glutathione)
- Most effective within 8–10 hours
Once conjugation is overwhelmed, toxic NAPQI destroys liver cells. Feature Detail Toxic metabolite NAPQI Antidote N-acetylcysteine Best within 8–10 hours Applied
- Rumack-Matthew nomogram guides treatment
- Alcoholics at higher risk
🔑KEY POINTS TO REMEMBER- Paracetamol overdose → NAPQI → glutathione depletion → liver necrosis.
- Antidote: N-acetylcysteine (best within 8–10 h).
- Liver damage peaks at 24–72 hours.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Colchicine is an anti-inflammatory drug specific for acute gout, acting on neutrophils rather than on uric acid.
Mechanism
- Binds tubulin → inhibits microtubule formation
- ↓ Neutrophil migration and phagocytosis of urate crystals
- ↓ Inflammatory response
- Does not lower uric acid
Uses & Adverse Effects
- Acute gout (dramatic relief — diagnostic value)
- Prophylaxis when starting allopurinol
- Familial Mediterranean fever
- Adverse: diarrhoea, vomiting, abdominal pain, bone-marrow suppression
Stopping neutrophils reaching the joint quells the gouty inflammation. Feature Detail Target Tubulin / neutrophils Uric acid Unchanged Adverse Diarrhoea Applied
- Narrow therapeutic margin
- Diarrhoea limits the dose
🔑KEY POINTS TO REMEMBER- Colchicine binds tubulin → ↓ neutrophil migration.
- Relieves acute gout but does not lower uric acid.
- Dose limited by diarrhoea.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Allopurinol is a xanthine oxidase inhibitor that lowers uric acid production, used for long-term control of gout.
Mechanism
- Inhibits xanthine oxidase
- ↓ Conversion of hypoxanthine/xanthine → uric acid
- ↓ Serum and urinary uric acid
Uses & Adverse Effects
- Chronic gout (prophylaxis)
- Uric-acid stones
- Tumour lysis syndrome prevention
- Adverse: rash, hypersensitivity, may precipitate acute gout initially
Blocking xanthine oxidase cuts uric acid production at source. Feature Detail Target Xanthine oxidase Use Chronic gout Caution Not in acute attack Applied
- Cover initial period with colchicine/NSAID
- Interacts with azathioprine (↑ toxicity)
🔑KEY POINTS TO REMEMBER- Allopurinol inhibits xanthine oxidase → ↓ uric acid.
- For chronic gout prophylaxis, not acute attacks.
- Interacts with azathioprine; may trigger initial attack.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
H1 antihistamines are divided into first generation (sedating) and second generation (non-sedating) based on CNS penetration.
First Generation
- Cross the blood-brain barrier → sedation
- Anticholinergic effects (dry mouth, blurred vision)
- Antiemetic (useful in motion sickness)
- E.g. chlorpheniramine, promethazine, diphenhydramine
Second Generation
- Poor CNS penetration → non-sedating
- No anticholinergic effect, longer acting
- E.g. cetirizine, loratadine, fexofenadine
CNS penetration decides sedation and thus everyday usability. Feature First Second Sedation Yes No Anticholinergic Yes No Example Chlorpheniramine Cetirizine Applied
- Second generation preferred for daytime allergy
- First generation useful for motion sickness, at night
🔑KEY POINTS TO REMEMBER- First generation cross the blood-brain barrier → sedation, anticholinergic.
- Second generation are non-sedating and longer acting.
- Promethazine for motion sickness; cetirizine for daily allergy.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Leukotriene antagonists block the action or synthesis of leukotrienes, mediators of bronchoconstriction and inflammation in asthma.
Drugs & Mechanism
- Montelukast, zafirlukast — leukotriene-receptor antagonists
- Zileuton — 5-lipoxygenase inhibitor
- ↓ Bronchoconstriction, ↓ mucus, ↓ eosinophil recruitment
Uses
- Prophylaxis of bronchial asthma (oral)
- Aspirin-induced asthma
- Exercise-induced asthma
- Allergic rhinitis
Blocking leukotrienes prevents bronchoconstriction and airway inflammation. Drug Action Montelukast Receptor antagonist Zileuton ↓ Synthesis Applied
- Oral, once-daily — good compliance in children
- Prophylactic only (not for acute attack)
🔑KEY POINTS TO REMEMBER- Montelukast/zafirlukast block leukotriene receptors.
- Used for asthma prophylaxis, especially aspirin- and exercise-induced.
- Not effective in acute attacks.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.Definition
Triptans are selective 5-HT1B/1D agonists used for acute treatment of migraine.
Mechanism
- Agonist at 5-HT1B/1D receptors
- Cranial vasoconstriction (reverses vasodilation)
- ↓ Release of inflammatory neuropeptides
- Inhibit trigeminal nerve transmission
Uses & Cautions
- Acute migraine attack (not prophylaxis)
- Cluster headache
- Adverse: chest tightness, flushing, paraesthesia
- Contraindicated in coronary artery disease, uncontrolled hypertension
Triptans reverse the vasodilation and neurogenic inflammation of migraine. Feature Detail Example Sumatriptan Use Acute migraine Avoid in Coronary artery disease Applied
- Take early in the attack for best effect
- Prophylaxis uses propranolol, flunarizine, topiramate
🔑KEY POINTS TO REMEMBER- Triptans = 5-HT1B/1D agonists (sumatriptan).
- Cause cranial vasoconstriction → abort migraine.
- Contraindicated in coronary artery disease.
📚SOURCES: Essentials of Medical Pharmacology (K.D. Tripathi); Goodman & Gilman’s The Pharmacological Basis of Therapeutics; Katzung’s Basic & Clinical Pharmacology.