- Pharmshala

Anti-Hypertensive Drugs

The RAAS pathway and the full range of drug classes used to lower blood pressure: ACE inhibitors, ARBs, diuretics, calcium channel blockers, beta-blockers and more.

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Blood pressure and the RAAS

Blood pressure = cardiac output × systemic vascular resistance, so antihypertensive drugs work by lowering cardiac output, lowering vascular resistance, or reducing blood volume. A large share of drug classes act on the renin–angiotensin–aldosterone system (RAAS), the body’s main long-term blood-pressure-raising pathway.

Falling renal perfusion triggers renin release, generating angiotensin II via ACE; angiotensin II vasoconstricts directly and raises aldosterone, which retains salt and water.

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ACE inhibitors and ARBs

ACE inhibitors: e.g. enalapril, ramipril, captopril, lisinopril. Block angiotensin-converting enzyme, so angiotensin II and aldosterone fall. ACE also breaks down bradykinin, so inhibiting it lets bradykinin accumulate — this underlies the characteristic dry cough and the rare but serious risk of angioedema.
ARBs (angiotensin receptor blockers): e.g. losartan, valsartan, telmisartan. Block the AT₁ receptor directly, downstream of ACE, so bradykinin is not affected — no cough. Otherwise similar benefits to ACE inhibitors.
Shared cautions: Both classes can cause hyperkalaemia (less aldosterone → less K⁺ excretion) and are contraindicated in pregnancy (foetal renal damage) and in bilateral renal artery stenosis (can precipitate renal failure, since GFR in that setting depends on angiotensin-II-mediated efferent arteriolar constriction).

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Diuretics

Class	Examples	Site / mechanism	Key points
Thiazides	Hydrochlorothiazide, chlorthalidone	Distal convoluted tubule: block the Na⁺/Cl⁻ symporter	First-line for most hypertension; mild, steady effect; can cause hypokalaemia, hyperuricaemia, hyperglycaemia.
Loop diuretics	Furosemide, bumetanide	Thick ascending limb: block the Na⁺/K⁺/2Cl⁻ symporter	More powerful natriuresis; used for oedema/CHF more than routine hypertension; can cause hypokalaemia, ototoxicity at high dose.
Potassium-sparing diuretics	Spironolactone, eplerenone (aldosterone antagonists), amiloride	Collecting duct	Weak alone; used to counteract the potassium loss from thiazides/loop diuretics, or (spironolactone) for its own aldosterone-blocking benefit in CHF.

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Calcium channel blockers (CCBs)

CCBs block L-type (voltage-gated) calcium channels, reducing Ca²⁺ entry into smooth muscle and cardiac cells. Two chemical families behave differently:

Dihydropyridines

e.g. amlodipine, nifedipine. Act mainly on vascular smooth muscle → strong vasodilation, little direct cardiac effect. Used widely for hypertension. Ankle oedema is a common side effect (precapillary dilation raises capillary pressure).

Non-dihydropyridines

Verapamil (phenylalkylamine) and diltiazem (benzothiazepine). Act significantly on the heart too — negative inotropic and negative chronotropic/dromotropic (slow AV conduction). Useful for hypertension with a coexisting supraventricular arrhythmia, but should not be combined with beta-blockers (risk of heart block).

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Beta-blockers

Beta-blockers reduce heart rate and contractility (β₁ blockade in the heart) and reduce renin release from the kidney (β₁ blockade of the juxtaglomerular apparatus), lowering blood pressure over time. No longer first-line for uncomplicated hypertension, but still important when hypertension coexists with ischaemic heart disease, CHF, or certain arrhythmias.

Type	Examples	Notes
Non-selective (β₁ + β₂)	Propranolol	β₂ blockade can provoke bronchospasm — avoid in asthma/COPD.
β₁-selective (“cardioselective”)	Atenolol, metoprolol, bisoprolol	Safer in reactive airway disease, though selectivity is relative, not absolute.
Combined α/β-blockers	Carvedilol, labetalol	Added α₁ blockade gives extra vasodilation; carvedilol is used in CHF, labetalol in hypertensive emergencies of pregnancy.

Do not stop abruptly

Chronic beta-blockade upregulates (sensitises) beta receptors; abrupt withdrawal can cause rebound tachycardia, hypertension, and angina. Taper the dose instead.

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Other antihypertensive classes

α₁-blockers: e.g. prazosin, doxazosin. Block postsynaptic α₁ receptors on vascular smooth muscle → vasodilation. Useful when hypertension coexists with benign prostatic hyperplasia (also relax prostatic/bladder-neck smooth muscle). Can cause marked “first-dose” postural hypotension.
Central α₂-agonists: Clonidine, methyldopa. Stimulate α₂ autoreceptors in the brainstem, reducing sympathetic outflow. Methyldopa is a traditional choice in pregnancy. Clonidine must not be stopped abruptly (rebound hypertensive crisis).
Direct vasodilators: Hydralazine (arteriolar), sodium nitroprusside (arterial and venous, IV, used in hypertensive emergencies). Reflex tachycardia and fluid retention are common, usually paired with a beta-blocker and a diuretic.
Renin inhibitor: Aliskiren — blocks renin directly, the first and rate-limiting RAAS step. Less commonly used.