anti hypertensive drugs exam answer pharmacology
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I now have enough comprehensive content from Katzung's and Goldman-Cecil to write a thorough exam answer covering all major drug classes, mechanisms, uses, side effects, and contraindications. Let me compile this now.
Antihypertensive Drugs - Short Note (5-10 Marks)
Definition
Antihypertensive drugs are agents used to lower elevated blood pressure (hypertension = BP persistently >130/80 mmHg). All act by interfering with one or more of the four main regulatory sites: blood volume (renal), peripheral vascular resistance, cardiac output, or the renin-angiotensin-aldosterone system (RAAS).
Classification
Antihypertensive drugs are classified based on their site/mechanism of action into 5 major groups:
| Class | Examples |
|---|---|
| 1. Diuretics | Thiazides (HCTZ), Loop (furosemide), K-sparing (spironolactone) |
| 2. Renin-Angiotensin System (RAS) blockers | ACE inhibitors, ARBs, Direct renin inhibitors |
| 3. Calcium Channel Blockers (CCBs) | Amlodipine, nifedipine (dihydropyridines); Verapamil, diltiazem (non-DHP) |
| 4. Sympathoplegic agents (Adrenergic blockers) | Beta-blockers, alpha-blockers, central alpha-2 agonists, ganglionic blockers |
| 5. Direct Vasodilators | Hydralazine, minoxidil, nitroprusside |
1. Diuretics
Mechanism: Deplete body sodium stores - initially reduce blood volume and cardiac output; after 6-8 weeks, peripheral vascular resistance falls. Thiazides may also cause direct arterial vasodilation.
Uses:
- Thiazides (HCTZ, chlorthalidone) - first-line for mild-to-moderate hypertension
- Loop diuretics (furosemide) - hypertension with heart failure, renal insufficiency (GFR <30 mL/min)
- Aldosterone antagonists (spironolactone, eplerenone) - resistant hypertension, primary hyperaldosteronism
Side effects: Hypokalemia, hyperglycemia, hyperuricemia (gout), hyperlipidemia, sexual dysfunction (thiazides); ototoxicity (loop diuretics); gynecomastia, hyperkalemia (spironolactone)
Contraindications: Gout (thiazides), pregnancy (thiazides), severe renal failure (thiazides)
2. Renin-Angiotensin System Blockers
ACE Inhibitors (e.g., captopril, enalapril, lisinopril, ramipril)
Mechanism: Inhibit angiotensin-converting enzyme (ACE/kininase II), blocking:
- Conversion of angiotensin I to angiotensin II (vasoconstrictor)
- Degradation of bradykinin (vasodilator) - causes NO and prostacyclin release
Result: Reduced peripheral vascular resistance, no reflex tachycardia.
Uses:
- Hypertension (especially with diabetes, chronic kidney disease, or heart failure)
- Post-myocardial infarction; reduce incidence of new-onset diabetes
- Diabetic nephropathy - reduce proteinuria and slow renal disease progression
Side effects:
- Dry cough (10-20%) - due to bradykinin/substance P accumulation - most common reason for switching to ARB
- Angioedema (<1%) - more common in Black patients, women, elderly
- Hyperkalemia - especially with renal insufficiency, diabetes
- First-dose hypotension - in hypovolemic patients
- Acute renal failure - in bilateral renal artery stenosis
- Teratogenic - fetal renal agenesis, oligohydramnios (contraindicated in pregnancy)
- Captopril-specific: neutropenia, proteinuria, altered taste, skin rash
Contraindications: Pregnancy (all trimesters), bilateral renal artery stenosis, hyperkalemia, history of angioedema
Angiotensin Receptor Blockers / ARBs (e.g., losartan, valsartan, olmesartan, telmisartan, azilsartan)
Mechanism: Block AT1 receptors - more selective than ACE inhibitors (do not affect bradykinin metabolism). Allow angiotensin II to preferentially bind AT2 receptor (vasodilatory/antiproliferative).
Advantages over ACE inhibitors: No cough, rare angioedema; best-tolerated class overall
Uses: Same as ACE inhibitors; preferred when ACE inhibitor cough is intolerable. Valsartan + sacubitril (ARNI) for heart failure.
Side effects & contraindications: Similar to ACE inhibitors. Also teratogenic. Do NOT combine ACE inhibitor + ARB (increased renal injury, hyperkalemia).
Direct Renin Inhibitor - Aliskiren
Mechanism: Blocks conversion of pro-renin to renin - inhibits RAAS at its first step
Note: Not combined with ACE inhibitors or ARBs due to toxicity risk
3. Calcium Channel Blockers (CCBs)
Mechanism: Block L-type voltage-gated calcium channels in vascular smooth muscle and cardiac cells, causing:
- Vasodilation (reduction in peripheral vascular resistance)
- Non-dihydropyridines (verapamil, diltiazem): also reduce heart rate and cardiac contractility
Two subclasses:
| Feature | Dihydropyridines (amlodipine, nifedipine) | Non-dihydropyridines (verapamil, diltiazem) |
|---|---|---|
| Main effect | Vascular > cardiac | Cardiac = vascular |
| Reflex tachycardia | Yes (short-acting nifedipine) | No |
| Use in angina | Vasospastic angina | Stable angina, rate control |
| Use in arrhythmias | No | Yes (SVT, AF rate control) |
Uses:
- Hypertension (especially elderly, isolated systolic HTN, atherosclerotic angina)
- Amlodipine - long-acting, safe and effective first-line
- Raynaud phenomenon, subarachnoid hemorrhage (nimodipine)
Side effects: Peripheral edema (ankle), flushing, headache, reflex tachycardia (dihydropyridines); bradycardia, heart block, constipation (verapamil)
Contraindications: Verapamil/diltiazem contraindicated in heart failure with reduced EF, AV block, concurrent beta-blocker use (profound bradycardia risk)
4. Sympathoplegic (Adrenergic) Agents
Beta-Blockers (e.g., atenolol, metoprolol, propranolol, carvedilol)
Mechanism: Block beta-1 adrenoceptors - reduce heart rate, cardiac contractility, and renin release. Beta-2 blockade (non-selective agents) causes bronchoconstriction.
Uses: Hypertension with coronary artery disease, heart failure (carvedilol, metoprolol), post-MI, hyperthyroidism, migraine prophylaxis
Side effects: Bradycardia, heart block, bronchospasm, cold extremities, fatigue, masked hypoglycemia, impotence, dyslipidemia
Contraindications: Asthma/COPD (non-selective), decompensated heart failure (acute), AV block, Prinzmetal angina
Alpha-1 Blockers (prazosin, doxazosin, terazosin)
Mechanism: Block alpha-1 receptors on arterioles and veins - reduce peripheral resistance
Uses: Hypertension + benign prostatic hyperplasia (BPH). Pheochromocytoma (phenoxybenzamine)
Side effects: First-dose orthostatic hypotension (syncope), reflex tachycardia, sodium retention
Central Alpha-2 Agonists (methyldopa, clonidine)
Mechanism: Stimulate central alpha-2 receptors in the brainstem (nucleus tractus solitarius) - reduce sympathetic outflow, lower heart rate and peripheral resistance
Uses:
- Methyldopa: hypertension in pregnancy (drug of choice)
- Clonidine: hypertensive urgency (oral/transdermal), opioid withdrawal
Side effects: Sedation, dry mouth, bradycardia; clonidine withdrawal rebound hypertension; methyldopa - hemolytic anemia, hepatotoxicity, positive Coombs test
5. Direct Vasodilators
| Drug | Mechanism | Use | Key Side Effects |
|---|---|---|---|
| Hydralazine | Releases NO; dilates arterioles > veins | Pregnancy HTN (with methyldopa); severe HTN | Reflex tachycardia, fluid retention, lupus-like syndrome (SLE) at high doses |
| Minoxidil | Opens K+ channels in smooth muscle; potent arteriolar dilator | Severe/resistant HTN | Severe sodium retention, reflex tachycardia, hypertrichosis (hair growth) |
| Nitroprusside (IV) | Releases NO; dilates arteries AND veins | Hypertensive emergency | Cyanide/thiocyanate toxicity with prolonged use |
| Fenoldopam (IV) | Dopamine D1 agonist; renal vasodilation | Hypertensive emergency with renal insufficiency | Reflex tachycardia, increased intraocular pressure |
Because vasodilators cause reflex tachycardia and sodium retention, they are almost always combined with a beta-blocker (prevent tachycardia) and a diuretic (prevent fluid retention) - this is the basis for triple therapy. (Katzung, Basic & Clinical Pharmacology, 16th ed.)
Drug of Choice Summary (Exam Key Points)
| Situation | Preferred Agent |
|---|---|
| Hypertension + Diabetes / CKD / proteinuria | ACE inhibitor or ARB (first choice) |
| Hypertension + Heart failure (reduced EF) | ACE inhibitor/ARB + beta-blocker + diuretic |
| Hypertension in pregnancy | Methyldopa, labetalol, nifedipine (oral) |
| Hypertension + BPH | Alpha-1 blocker (doxazosin) |
| Hypertension + Angina | Beta-blocker or CCB |
| Isolated systolic HTN in elderly | Thiazide or long-acting CCB (amlodipine) |
| Hypertensive emergency | IV nitroprusside, IV labetalol, IV nicardipine |
| Hypertension + Pheochromocytoma | Alpha-blocker FIRST (phenoxybenzamine), then beta-blocker |
| Primary hyperaldosteronism | Spironolactone |
| Hypertension + Migraine | Beta-blocker (propranolol) |
| ACE inhibitor cough - switch to | ARB (losartan, valsartan) |
Combination Therapy Rationale
Most patients with moderate-severe hypertension need 2+ drugs. Common rational combinations:
- ACE inhibitor + Thiazide (complementary mechanisms, reduced K+ loss)
- CCB + ACE inhibitor (amlodipine/perindopril - reduces CCB-induced edema)
- Beta-blocker + Diuretic (but worsens metabolic effects)
- Avoid: ACE inhibitor + ARB (renal failure, hyperkalemia)
- Avoid: Verapamil + Beta-blocker (severe bradycardia/heart block)
One-Line Mnemonics
- ABCD approach: ACE inhibitor/ARB, Beta-blocker, CCB, Diuretic
- ACE inhibitor cough = BraKinetically mediated (bradykinin accumulation)
- Minoxidil = Massive hair growth + Massive fluid retention
- Clonidine = CLONO = CLose the brain (central alpha-2 agonist)
Sources: Katzung's Basic and Clinical Pharmacology, 16th Edition; Goldman-Cecil Medicine, International Edition
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