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Antihypertensive drugs
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Classify antihypertensive drugs
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Classification of Antihypertensive Drugs
Antihypertensive drugs are classified based on their principal site or mechanism of action. All act at one or more of four anatomic control sites: the CNS, peripheral neurons, the heart, or blood vessels/kidneys.
1. Diuretics
Lower BP primarily by depleting body sodium, reducing blood volume and cardiac output; after 6-8 weeks, peripheral vascular resistance also falls.
| Subclass | Examples |
|---|---|
| Thiazides | Hydrochlorothiazide, Chlorthalidone, Indapamide |
| Loop diuretics | Furosemide, Bumetanide |
| Potassium-sparing | Spironolactone, Eplerenone, Amiloride, Triamterene |
First-line agents for most patients with uncomplicated hypertension.
2. Renin-Angiotensin-Aldosterone System (RAAS) Blockers
Block the RAAS to reduce peripheral vascular resistance and blood volume.
| Subclass | Examples |
|---|---|
| ACE Inhibitors (ACEIs) | Captopril, Enalapril, Lisinopril, Ramipril, Benazepril |
| Angiotensin Receptor Blockers (ARBs) | Losartan, Valsartan, Irbesartan, Olmesartan |
| Direct Renin Inhibitors | Aliskiren |
| Mineralocorticoid Receptor Antagonists | Spironolactone, Eplerenone (also diuretics) |
ACEIs and ARBs are preferred in patients with diabetes, CKD, or heart failure.
3. Calcium Channel Blockers (CCBs)
Block voltage-gated L-type Ca²+ channels, reducing smooth muscle contraction and vascular resistance.
| Subclass | Examples | Primary Effect |
|---|---|---|
| Dihydropyridines | Amlodipine, Nifedipine, Felodipine, Nicardipine | Vasodilation (peripheral) |
| Non-dihydropyridines | Verapamil (phenylalkylamine), Diltiazem (benzothiazepine) | Also reduce heart rate/contractility |
4. Sympathoplegic (Sympatholytic) Agents
Lower BP by reducing peripheral vascular resistance, inhibiting cardiac function, and increasing venous pooling.
A. Beta-Blockers (β-blockers)
Reduce cardiac output by blocking β₁-adrenoceptors.
| Type | Examples |
|---|---|
| Non-selective (β₁ + β₂) | Propranolol, Nadolol, Pindolol |
| Cardioselective (β₁) | Atenolol, Metoprolol, Bisoprolol, Betaxolol, Esmolol |
| Combined α + β blockade | Labetalol, Carvedilol |
| β₁ blocker + NO release | Nebivolol |
B. Alpha-Blockers (α-blockers)
Block α₁-adrenoceptors → vasodilation.
| Type | Examples |
|---|---|
| Selective α₁-blockers | Prazosin, Doxazosin, Terazosin |
| Non-selective α-blockers | Phentolamine, Phenoxybenzamine (used in pheochromocytoma) |
C. Centrally Acting Agents (Central Sympatholytics)
Reduce central sympathetic outflow.
| Drug | Mechanism |
|---|---|
| Clonidine, Methyldopa | Stimulate central α₂ receptors / imidazoline receptors → reduced sympathetic tone |
| Moxonidine | Selective imidazoline I₁ receptor agonist |
D. Ganglionic Blockers
- Mecamylamine, Trimethaphan (largely obsolete)
E. Adrenergic Neuron Blockers
- Reserpine (depletes norepinephrine stores), Guanethidine (largely obsolete)
5. Direct Vasodilators
Directly relax vascular smooth muscle, reducing peripheral resistance.
| Drug | Site of Action | Notes |
|---|---|---|
| Hydralazine | Arterioles | Oral; used in pregnancy (safe) |
| Minoxidil | Arterioles (K⁺ channel opener) | Severe/resistant HTN |
| Sodium Nitroprusside | Arterioles + veins | IV only; hypertensive emergencies |
| Fenoldopam | Dopamine D₁ receptors | IV; renal-protective in emergencies |
| Diazoxide | Arterioles (K⁺ channel opener) | IV; hypertensive emergencies |
Summary Diagram
Blood pressure = Cardiac Output x Peripheral Vascular Resistance
Reduce Cardiac Output: → Beta-blockers, Diuretics
Reduce Peripheral Resistance: → CCBs, Alpha-blockers, Direct vasodilators
Reduce Blood Volume: → Diuretics, ACEIs, ARBs
Reduce Sympathetic Drive: → Central agents, Ganglionic blockers
Key First-Line Agents (per current guidelines): Thiazide diuretics, ACE inhibitors, ARBs, and CCBs.
Sources: Katzung's Basic & Clinical Pharmacology, 16th Ed., p. 271-273 | Lippincott Illustrated Reviews: Pharmacology, p. 287-293
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