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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