Explain hypertensive drugs its classification its duration of action onset of actio. Uses containdicstion
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Antihypertensive Drugs: Classification, Mechanism, Onset/Duration, Uses & Contraindications
OVERVIEW: Pharmacologic Classification
Antihypertensive drugs are grouped into the following major classes:
| # | Class | Subclasses / Examples |
|---|---|---|
| 1 | Diuretics | Thiazides, Loop diuretics, Potassium-sparing |
| 2 | Beta-Blockers (β-blockers) | Non-selective, β1-selective, Mixed α/β-blockers |
| 3 | Calcium Channel Blockers (CCBs) | Dihydropyridines, Non-dihydropyridines (benzothiazepines, diphenylalkylamines) |
| 4 | ACE Inhibitors (ACEi) | Sulfhydryl (captopril), Carboxyl (enalapril, lisinopril), Phosphinyl (fosinopril) |
| 5 | Angiotensin Receptor Blockers (ARBs) | Biphenyl tetrazoles, Non-biphenyl tetrazoles |
| 6 | Alpha-Blockers (α1-blockers) | Prazosin, Doxazosin, Terazosin |
| 7 | Alpha-Beta Blockers | Labetalol, Carvedilol |
| 8 | Centrally Acting Agents | Clonidine (α2-agonist), Methyldopa |
| 9 | Direct Vasodilators | Hydralazine, Minoxidil, Sodium nitroprusside |
| 10 | Renin Inhibitors | Aliskiren |
| 11 | Aldosterone Antagonists | Spironolactone, Eplerenone |
1. DIURETICS
A. Thiazide Diuretics
Examples: Hydrochlorothiazide (HCTZ), Chlorthalidone, Indapamide, Metolazone
| Property | Details |
|---|---|
| Mechanism | Block Na/Cl reabsorption in the distal convoluted tubule → reduce plasma volume → lower cardiac output → long-term: reduce peripheral vascular resistance |
| Onset | 1-2 hours (oral) |
| Peak Effect | 3-6 hours |
| Duration | HCTZ: 6-12 h; Chlorthalidone: 24-72 h (long-acting) |
| Uses | First-line for hypertension; heart failure; nephrolithiasis (calcium stones - HCTZ reduces urinary Ca); osteoporosis |
| Contraindications | Gout (raises uric acid); hypokalemia; anuria; severe renal failure (GFR <30 mL/min, except metolazone); sulfonamide allergy |
| Key ADR | Hypokalemia, hyperuricemia, hyperglycemia, hypercalcemia, hyponatremia |
B. Loop Diuretics
Examples: Furosemide, Torsemide, Bumetanide, Ethacrynic acid
| Property | Details |
|---|---|
| Mechanism | Block Na-K-2Cl cotransporter in the thick ascending limb of loop of Henle |
| Onset | Oral: 30-60 min; IV: 5 min |
| Duration | Furosemide IV: 2 h; Oral: 4-6 h; Torsemide: 6-8 h |
| Uses | Hypertension with heart failure or renal failure (GFR <30); pulmonary edema; hypercalcemia |
| Contraindications | Anuria; sulfonamide allergy (furosemide); dehydration; hypokalemia |
| Key ADR | Hypokalemia, hypocalcemia, hypomagnesemia, ototoxicity (ethacrynic acid highest risk), hyperuricemia |
C. Potassium-Sparing Diuretics
Examples: Spironolactone, Eplerenone, Amiloride, Triamterene
| Property | Details |
|---|---|
| Mechanism | Spironolactone/Eplerenone: aldosterone receptor antagonists; Amiloride/Triamterene: block epithelial Na channels in collecting duct |
| Onset | Spironolactone: 2-3 days (slow); Amiloride: 2-4 hours |
| Duration | Spironolactone: 48-72 h; Amiloride: 24 h |
| Uses | Resistant hypertension (spironolactone); heart failure; primary hyperaldosteronism; used to prevent K+ loss with thiazides/loop diuretics |
| Contraindications | Hyperkalemia; severe renal failure; concurrent use of ACEi/ARBs (risk of life-threatening hyperkalemia); Addison disease |
2. BETA-BLOCKERS (β-Adrenoceptor Blockers)
Examples:
- Non-selective: Propranolol, Nadolol, Timolol
- β1-selective (cardioselective): Metoprolol, Atenolol, Bisoprolol, Nebivolol
- With ISA (intrinsic sympathomimetic activity): Pindolol, Acebutolol
| Property | Details |
|---|---|
| Mechanism | Decrease cardiac output (↓ HR and contractility); reduce renin release from kidneys → ↓ angiotensin II and aldosterone; decrease CNS sympathetic outflow. Nebivolol also causes NO-mediated vasodilation |
| Onset | Oral: 1-2 h; IV (propranolol): 2-5 min |
| Duration | Propranolol: 3-6 h; Atenolol: 12-24 h; Bisoprolol: 12-24 h; Nadolol: 17-24 h |
| Uses | Hypertension + coronary artery disease; post-MI; heart failure (bisoprolol, metoprolol, carvedilol); tachyarrhythmias; hyperthyroidism; migraine prophylaxis; portal hypertension; anxiety |
| Contraindications | Asthma/COPD (non-selective β-blockers absolutely; cardioselective with caution); bradycardia; 2nd/3rd degree AV block; cardiogenic shock; Raynaud's disease; abrupt withdrawal (rebound); uncontrolled HF |
| Key ADR | Bradycardia, bronchospasm, fatigue, sexual dysfunction, cold extremities, masking hypoglycemia in diabetics |
3. CALCIUM CHANNEL BLOCKERS (CCBs)
A. Dihydropyridines (DHP) - Vascular Selective
Examples: Amlodipine, Nifedipine, Felodipine, Nicardipine, Clevidipine
| Property | Details |
|---|---|
| Mechanism | Block L-type voltage-gated Ca²+ channels in vascular smooth muscle → vasodilation → reduced peripheral resistance |
| Onset | Nifedipine IR: 20 min; Amlodipine: 6-12 h (slow onset) |
| Duration | Nifedipine SR: 12-24 h; Amlodipine: 24-36 h (longest, once-daily) |
| Uses | Hypertension; angina; Raynaud's phenomenon; elderly patients; isolated systolic hypertension |
| Contraindications | Cardiogenic shock; aortic stenosis (severe, for some agents); pregnancy (nifedipine is used in gestational HT though) |
| Key ADR | Peripheral edema (ankle), reflex tachycardia (especially short-acting nifedipine), flushing, headache, gingival hyperplasia |
B. Non-Dihydropyridines - Cardiac Selective
Examples: Verapamil (diphenylalkylamine), Diltiazem (benzothiazepine)
| Property | Details |
|---|---|
| Mechanism | Block L-type Ca²+ channels in both cardiac and vascular smooth muscle → slow SA node discharge, slow AV conduction, decrease contractility |
| Onset | Verapamil IV: 3-5 min; Oral: 1-2 h |
| Duration | Verapamil SR: 12-24 h; Diltiazem SR: 12-24 h |
| Uses | Hypertension + SVT/atrial fibrillation; angina; hypertrophic cardiomyopathy |
| Contraindications | Heart failure with reduced EF; bradycardia; 2nd/3rd degree AV block; sick sinus syndrome; combined use with β-blockers (high risk of AV block/asystole); WPW syndrome (verapamil) |
4. ACE INHIBITORS (ACEi)
Examples:
- Sulfhydryl: Captopril
- Carboxyl: Enalapril, Lisinopril, Ramipril, Perindopril, Quinapril, Benazepril
- Phosphinyl: Fosinopril
| Property | Details |
|---|---|
| Mechanism | Inhibit ACE (kinase II) → block conversion of Ang I → Ang II → reduce vasoconstriction, aldosterone secretion, ADH release, and sympathetic activation; also inhibit bradykinin breakdown → accumulation → vasodilation |
| Onset | Captopril: 15-30 min (fastest); Enalapril: 1-4 h; Lisinopril: 1 h |
| Peak Effect | Captopril: 1-1.5 h; Enalapril: 4-8 h; Lisinopril: 6-8 h |
| Duration | Captopril: 6-12 h (TID); Enalapril: 12-24 h; Lisinopril: 24 h (OD); Ramipril: 24 h |
| Uses | Hypertension; heart failure; post-MI (reduce remodeling); diabetic nephropathy (proteinuria reduction); CKD with proteinuria; left ventricular dysfunction |
| Contraindications | Bilateral renal artery stenosis (critical - can cause acute renal failure); Pregnancy (teratogenic - fetopathic effect in 2nd/3rd trimester); History of angioedema; Hyperkalemia; Combined with ARBs (dual blockade - risk of AK/hyperkalemia) |
| Key ADR | Dry persistent cough (bradykinin accumulation - most common reason for switching to ARB), angioedema, first-dose hypotension, hyperkalemia, fetopathy |
5. ANGIOTENSIN RECEPTOR BLOCKERS (ARBs)
Examples: Losartan, Valsartan, Irbesartan, Candesartan, Olmesartan, Telmisartan, Azilsartan
| Property | Details |
|---|---|
| Mechanism | Block AT1 receptor (angiotensin II type 1) selectively → same hemodynamic benefits as ACEi but WITHOUT bradykinin accumulation (no cough, less angioedema) |
| Onset | Losartan: 1-3 h; Valsartan: 2 h; Telmisartan: 1-2 h |
| Duration | Losartan: 6-9 h (active metabolite extends to 24 h); Telmisartan: 24 h (longest half-life ~24 h); Valsartan: 6-12 h |
| Uses | Same as ACEi; preferred when ACEi-induced cough is intolerable; heart failure; diabetic nephropathy; post-MI; hypertension in stroke prevention |
| Contraindications | Same as ACEi: bilateral renal artery stenosis, pregnancy, hyperkalemia; cannot combine with ACEi (ONTARGET trial showed no benefit and increased harm) |
| Key ADR | Similar to ACEi but NO cough; rare angioedema; hyperkalemia; renal impairment |
6. ALPHA-1 BLOCKERS (α1-Adrenergic Antagonists)
Examples: Prazosin, Doxazosin, Terazosin
| Property | Details |
|---|---|
| Mechanism | Competitive blockade of α1-adrenoceptors → relaxation of arterial and venous smooth muscle → reduced peripheral vascular resistance |
| Onset | Prazosin: 0.5-1 h |
| Duration | Prazosin: 4-6 h (TID); Doxazosin: 18-36 h (OD); Terazosin: 12-18 h |
| Uses | Resistant hypertension; benign prostatic hyperplasia (BPH); pheochromocytoma (phenoxybenzamine - non-selective); Raynaud's disease |
| Contraindications | Heart failure (not shown to improve outcomes); patients prone to orthostatic hypotension; not first-line for hypertension alone |
| Key ADR | First-dose syncope/orthostatic hypotension (classic), reflex tachycardia, nasal congestion, salt and water retention |
7. ALPHA-BETA BLOCKERS
Examples: Labetalol, Carvedilol
| Property | Details |
|---|---|
| Mechanism | Block α1, β1, and β2 receptors → vasodilation + reduced cardiac output |
| Onset | Labetalol IV: 2-5 min; Oral: 20 min-2 h |
| Duration | Labetalol: 8-12 h |
| Uses | Hypertensive emergencies (labetalol IV); gestational hypertension/preeclampsia; heart failure (carvedilol); post-MI |
| Contraindications | Asthma; severe bradycardia; AV block; decompensated heart failure |
8. CENTRALLY ACTING AGENTS
A. Clonidine (α2-Agonist)
| Property | Details |
|---|---|
| Mechanism | Activates central α2-receptors in the brainstem (nucleus tractus solitarius) → inhibits sympathetic vasomotor center → reduces sympathetic outflow → lowers BP and HR |
| Onset | Oral: 30-60 min; Transdermal patch: 2-3 days |
| Duration | Oral: 6-8 h; Transdermal: 7 days |
| Uses | Resistant hypertension; hypertension in renal disease (doesn't reduce GFR); ADHD; opioid withdrawal; menopausal flushing |
| Contraindications | Sick sinus syndrome; AV block; depression; avoid abrupt discontinuation |
| Key ADR | Sedation, dry mouth, constipation, rebound hypertension on abrupt withdrawal (classic) |
B. Methyldopa
| Property | Details |
|---|---|
| Mechanism | Converted to α-methylnorepinephrine → central α2-agonist activity |
| Onset | 4-6 h |
| Duration | 12-24 h |
| Uses | Drug of choice for hypertension in pregnancy; resistant hypertension |
| Contraindications | Active liver disease; pheochromocytoma; concurrent MAO inhibitor use |
| Key ADR | Sedation, positive Coombs test (hemolytic anemia), hepatotoxicity, drug-induced lupus |
9. DIRECT VASODILATORS
A. Hydralazine
| Property | Details |
|---|---|
| Mechanism | Directly relaxes arterial smooth muscle (arteriolar) by opening K+ channels → reduces afterload |
| Onset | Oral: 20-30 min; IV: 10-20 min |
| Duration | 3-8 h |
| Uses | Hypertension in pregnancy (2nd line after methyldopa); hypertensive emergencies (IV); heart failure (combined with isosorbide dinitrate in African Americans) |
| Contraindications | Coronary artery disease; aortic dissection (causes reflex tachycardia - worsens dissection); mitral valve rheumatic heart disease |
| Key ADR | Reflex tachycardia, fluid retention, lupus-like syndrome (SLE-like - with doses >200 mg/day), sodium retention |
B. Sodium Nitroprusside
| Property | Details |
|---|---|
| Mechanism | Releases NO → activates guanylate cyclase → relaxes both arterial and venous smooth muscle |
| Onset | Seconds (30-60 sec) - fastest of all antihypertensives |
| Duration | 1-10 min (requires continuous IV infusion) |
| Uses | Hypertensive emergencies (aortic dissection, hypertensive encephalopathy); acute HF; controlled hypotension in surgery |
| Contraindications | Hepatic/renal failure (cyanide and thiocyanate toxicity risk); compensatory hypertension; Leber optic atrophy |
| Key ADR | Cyanide toxicity (accumulates in renal failure); thiocyanate toxicity; hypotension |
C. Minoxidil
| Property | Details |
|---|---|
| Mechanism | Activates K+ channels → hyperpolarization → relaxes arterial smooth muscle |
| Onset | 30 min - 2 h |
| Duration | 24-72 h |
| Uses | Severe/refractory hypertension; also topical for alopecia |
| Contraindications | Pheochromocytoma; acute MI |
| Key ADR | Hypertrichosis (hair growth - basis for Rogaine), fluid retention, reflex tachycardia, pericardial effusion |
10. RENIN INHIBITOR
Aliskiren
| Property | Details |
|---|---|
| Mechanism | Direct renin inhibitor → blocks the rate-limiting step of the RAAS → decreases Ang I, Ang II, and aldosterone |
| Onset | 1-3 h |
| Duration | 24 h (OD) |
| Uses | Hypertension (used alone or in combination) |
| Contraindications | Pregnancy; combined with ACEi or ARBs in diabetic patients (ALTITUDE trial - increased renal adverse events, hyperkalemia, hypotension); renal artery stenosis |
QUICK REFERENCE: Onset & Duration Summary
| Drug | Onset | Duration | Frequency |
|---|---|---|---|
| Sodium nitroprusside IV | 30 sec | 1-10 min | Continuous drip |
| Labetalol IV | 2-5 min | 3-6 h | Bolus/infusion |
| Captopril | 15-30 min | 6-12 h | TID |
| Hydralazine IV | 10-20 min | 3-8 h | q4-6h |
| Clonidine oral | 30-60 min | 6-8 h | BID-TID |
| Propranolol | 1-2 h | 3-6 h | BID-TID |
| Enalapril | 1-4 h | 12-24 h | OD-BID |
| Nifedipine SR | 1-2 h | 12-24 h | OD-BID |
| Lisinopril | 1 h | 24 h | OD |
| Atenolol | 1-2 h | 12-24 h | OD-BID |
| Amlodipine | 6-12 h | 24-36 h | OD |
| Chlorthalidone | 2-3 h | 24-72 h | OD |
| Telmisartan | 1-2 h | 24 h | OD |
| Spironolactone | 2-3 days | 48-72 h | OD-BID |
| Methyldopa | 4-6 h | 12-24 h | BID-TID |
| Minoxidil | 30 min-2 h | 24-72 h | OD-BID |
COMPELLING INDICATIONS - Which Drug for Which Condition?
| Condition | Preferred Agents |
|---|---|
| Heart failure (reduced EF) | ACEi/ARBs, β-blockers (carvedilol, bisoprolol), diuretics, aldosterone antagonists |
| Post-MI | ACEi, β-blockers |
| Diabetic nephropathy | ACEi or ARBs (reduce proteinuria) |
| Pregnancy | Methyldopa, Labetalol, Hydralazine, Nifedipine |
| Hypertensive emergency | Sodium nitroprusside, Labetalol IV, Nicardipine IV, Clevidipine |
| BPH + hypertension | Alpha-blockers (doxazosin) |
| Hypertension + angina | CCBs, β-blockers |
| Raynaud's phenomenon | Amlodipine (DHP-CCBs) - α-blockers contraindicated with β-blockers |
| Afro-Caribbean patients | CCBs and thiazides preferred; ACEi/ARBs less effective alone |
| Atrial fibrillation | Non-DHP CCBs (verapamil, diltiazem), β-blockers |
| Isolated systolic hypertension (elderly) | Thiazides, long-acting DHP-CCBs (amlodipine) |
KEY ABSOLUTE CONTRAINDICATIONS AT A GLANCE
| Drug Class | Absolute Contraindication |
|---|---|
| ACEi / ARBs | Pregnancy, bilateral renal artery stenosis, prior angioedema (ACEi) |
| Non-selective β-blockers | Asthma, COPD, AV block, cardiogenic shock |
| Non-DHP CCBs | Heart failure (reduced EF), AV block, sick sinus syndrome |
| Thiazides | Gout (relative), severe renal failure |
| Aldosterone antagonists | Hyperkalemia, severe renal failure |
| Clonidine | Do not stop abruptly (rebound crisis) |
| Hydralazine | Aortic dissection, lupus |
| Nitroprusside | Hepatic/renal failure (cyanide toxicity) |
Sources: Lippincott Illustrated Reviews Pharmacology, 7th Edition; Brenner and Rector's The Kidney, 2-Volume Set; Goldman-Cecil Medicine; Katzung's Basic and Clinical Pharmacology, 16th Edition
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