Reading File
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Finding Sources
Reading File
Reading File
I now have excellent content. Let me compile a comprehensive answer for all four questions.
Pharmacology Exam Answers
Q1. Classify Anti-Tubercular Drugs + Mechanism of Action & Adverse Effects of Isoniazid
Classification of Anti-Tubercular Drugs
First-Line Drugs (RIPES):
| Drug | Type |
|---|---|
| Rifampicin (R) | Bactericidal |
| Isoniazid (I/H) | Bactericidal |
| Pyrazinamide (P/Z) | Bactericidal |
| Ethambutol (E) | Bacteriostatic |
| Streptomycin (S) | Bactericidal |
Second-Line Drugs:
- Fluoroquinolones: Levofloxacin, Moxifloxacin
- Injectable agents: Amikacin, Kanamycin, Capreomycin
- Others: Ethionamide, Prothionamide, Cycloserine, Para-aminosalicylic acid (PAS)
- Newer agents: Bedaquiline, Linezolid, Pretomanid, Delamanid
Mechanism of Action of Isoniazid
Isoniazid (INH) is a prodrug activated by the mycobacterial KatG catalase-peroxidase enzyme. Once activated, it couples with NADH to form an isonicotinic acyl-NADH complex that:
- Inhibits InhA (enoyl-ACP reductase / ketoenoyl-reductase), blocking fatty acid synthase II
- This prevents mycolic acid synthesis - mycolic acids are essential long-chain fatty acids that form the mycobacterial cell wall
- KatG activation also releases free radicals including nitric oxide, which have direct antimycobacterial activity
The result is disruption of cell wall integrity, leading to bactericidal action (especially against actively dividing bacilli).
Resistance arises from mutations in katG (loss of activation) or inhA (target mutation).
Adverse Effects of Isoniazid
| Adverse Effect | Mechanism/Notes |
|---|---|
| Peripheral neuropathy | Most common - INH competes with pyridoxine (B6) for enzyme binding; prevented by supplementing pyridoxine 25-50 mg/day |
| Hepatotoxicity | Most serious - INH is acetylated by NAT2 to acetylhydrazine, a hepatotoxic metabolite; risk higher in slow acetylators, elderly, alcoholics |
| Drug-induced lupus (SLE-like) | Rare; more in slow acetylators |
| CNS effects | Seizures, psychosis, optic neuritis - due to pyridoxine deficiency |
| Hypersensitivity reactions | Rash, fever, agranulocytosis |
| Pellagra-like symptoms | Interferes with niacin metabolism |
Harrison's Principles of Internal Medicine 22E - INH is given with pyridoxine 25-50 mg daily to prevent drug-related peripheral neuropathy.
Q2. Six Important Antihypertensive Drugs + Rationale for Hydrochlorothiazide with Losartan
Six Important Antihypertensive Drug Classes
| # | Drug/Class | Example |
|---|---|---|
| 1 | Thiazide diuretics | Hydrochlorothiazide (HCTZ) |
| 2 | ACE inhibitors | Enalapril, Ramipril |
| 3 | Angiotensin Receptor Blockers (ARBs) | Losartan, Telmisartan |
| 4 | Calcium channel blockers | Amlodipine, Nifedipine |
| 5 | Beta-blockers | Atenolol, Metoprolol |
| 6 | Centrally acting agents | Clonidine, Methyldopa |
Rationale for Combining HCTZ with Losartan
Complementary mechanisms:
- Losartan (ARB): Blocks AT1 receptors, preventing angiotensin II from causing vasoconstriction and aldosterone release. This reduces peripheral vascular resistance and decreases sodium/water retention.
- HCTZ (Thiazide diuretic): Inhibits Na⁺/Cl⁻ cotransporter in the distal convoluted tubule, promoting sodium and water excretion, reducing blood volume.
Why the combination works better:
- Additive/synergistic BP lowering via two independent mechanisms
- HCTZ-induced volume depletion activates the Renin-Angiotensin-Aldosterone System (RAAS); Losartan blocks this compensatory RAAS activation, preventing the reflex BP rise that limits thiazide efficacy alone
- HCTZ causes hypokalemia (by stimulating aldosterone via RAAS); Losartan blocks aldosterone release, mitigating this potassium loss - the combination is K⁺-neutral
- Fixed-dose combination improves patient compliance
This combination (Losartan 50 mg + HCTZ 12.5 mg, trade name Hyzaar) is a first-line option in JNC/WHO guidelines for hypertension.
Q3. Anti-Cough Preparations + Why Dextromethorphan is Preferred for Dry Cough
Anti-Cough (Antitussive) Preparations
Centrally acting:
- Dextromethorphan (non-opioid)
- Codeine (opioid)
- Noscapine
Peripherally acting:
- Benzonatate (local anesthetic - numbs stretch receptors)
- Levodropropizine
Demulcents/Expectorants (for productive cough):
- Guaifenesin, Ambroxol, Bromhexine
Why Dextromethorphan is Preferred Over Other Antitussives for Dry Cough
| Feature | Dextromethorphan | Codeine |
|---|---|---|
| Mechanism | NMDA receptor antagonist + sigma opioid receptor agonist; suppresses cough center in medulla | Opioid µ-receptor agonist |
| Addiction potential | None / very low | High (opioid dependence) |
| Respiratory depression | No, even at antitussive doses | Yes, dose-dependent |
| Sedation | Minimal | Significant |
| Analgesic effect | None | Present (unnecessary for cough) |
| Constipation | No | Yes |
| OTC availability | Yes | Prescription-only |
| Efficacy in dry cough | Equal to codeine | Equal, but more side effects |
Key point: For dry (non-productive) cough, suppression of the cough reflex is the goal. Dextromethorphan achieves this without opioid adverse effects, making it safer, especially in children and outpatient settings. It is the D-isomer of levorphanol and lacks opioid analgesic or euphoric activity at standard doses.
Q4. Rationale for Drug Use
(a) Salbutamol (Albuterol) in Bronchial Asthma
Mechanism:
Salbutamol is a selective short-acting β₂-adrenergic agonist (SABA). It binds β₂ receptors on bronchial smooth muscle, activating adenylyl cyclase → increased cAMP → protein kinase A activation → phosphorylation of myosin light chain kinase → smooth muscle relaxation → bronchodilation.
Rationale for use in asthma:
- Asthma involves bronchoconstriction from airway inflammation and smooth muscle hyper-reactivity
- Salbutamol directly reverses this bronchoconstriction within 5 minutes of inhalation
- Inhaled route delivers drug directly to the airway - maximum local effect, minimum systemic side effects
- Also inhibits mast cell mediator release (secondary effect)
- Used as a rescue bronchodilator for acute episodes in all asthma severity levels
Goodman & Gilman's lists albuterol/salbutamol as the standard inhaled bronchodilator for asthma, COPD, and exercise-induced bronchospasm.
(b) Glyceryl Trinitrate (GTN / Nitroglycerin) in Angina Pectoris
Mechanism:
GTN is an organic nitrate that is converted to nitric oxide (NO) in vascular smooth muscle. NO activates soluble guanylate cyclase → increases cGMP → activates protein kinase G → dephosphorylates myosin → vascular smooth muscle relaxation and vasodilation.
Rationale for use in angina:
| Effect | Benefit |
|---|---|
| Venodilation (veins >> arteries) | Reduces venous return (preload) → decreases cardiac filling pressure and wall tension → reduces myocardial O₂ demand |
| Coronary vasodilation | Dilates large coronary vessels and collaterals → improves O₂ supply to ischemic myocardium |
| Arterial vasodilation | Reduces afterload (at higher doses) → further reduces myocardial work |
| First choice for vasospastic angina | Directly relieves coronary vasospasm |
Sublingual GTN acts within 1-3 minutes, making it ideal for acute angina relief. It is also the first-line drug for all angina types (exertional, vasospastic, unstable).
Adverse effects: Headache (most common, due to meningeal vessel dilation), dizziness, postural hypotension, reflex tachycardia. Tolerance develops after >16 hours of continuous use - a nitrate-free interval of >8 hours is required.
Goodman & Gilman's Pharmacological Basis of Therapeutics - GTN causes NO-mediated vasodilation of large (venous > arterial) vessels with preferential preload reduction.
This is a shared conversation. Sign in to Orris to start your own chat.