Other Antihypertensives

Beyond the first-line drugs (diuretics, ACE-I/ARBs, calcium-channel blockers, beta-blockers), several other classes lower blood pressure by different routes — used as add-ons, for resistant hypertension, or specific situations. Four groups matter here, and each is best remembered by its distinctive adverse effect.

Alpha-1 blockers (the -osin drugs), central alpha-2 agonists (clonidine, methyldopa), and direct vasodilators (hydralazine, minoxidil, nitroprusside) each relax vessels or reduce sympathetic drive in their own way. The direct renin inhibitor aliskiren blocks the renin–angiotensin system at its first step.

Alpha-1 blockers (prazosin, doxazosin, terazosin — -osin) block alpha-1 receptors on blood vessels, relaxing them to lower BP; they also relax the prostate/bladder neck, so doxazosin and terazosin double as BPH treatment. Their signature danger is the "first-dose phenomenon" — severe orthostatic hypotension and syncope after the first dose — so the first dose is given at bedtime and started low. Doxazosin and terazosin labels add that the same syncope can follow a dose increase or restarting after a break of several days.

Central alpha-2 agonists (clonidine, methyldopa) work in the brainstem, stimulating alpha-2 receptors that reduce sympathetic outflow — lowering heart rate and BP. Their catch is rebound hypertension: stopping clonidine abruptly removes the brake and causes a dangerous BP surge, so it must be tapered. (Methyldopa is safe in pregnancy — a preferred option there alongside labetalol and long-acting nifedipine, though some sources rank it second-line.) Methyldopa has its own immune and hepatic catch: on prolonged therapy 10–20% of patients develop a positive direct Coombs test, which rarely progresses to hemolytic anemia, and fever, abnormal liver tests or jaundice can signal drug-induced liver injury — either one means stopping it for good.

Direct vasodilators relax arterial smooth muscle powerfully. Because the sudden BP drop triggers a reflex sympathetic response, they cause reflex tachycardia and fluid retention (often co-prescribed with a beta-blocker and diuretic). Hydralazine can cause a drug-induced lupus-like syndrome (fever, joint pain, rash — reversible on stopping). Minoxidil causes hypertrichosis — fine body hair grows longer and darker in about 80% of patients, without virilism — and its topical form treats hair loss.

Sodium nitroprusside is a potent IV vasodilator for hypertensive emergencies — but it is metabolized to cyanide, so prolonged/high-rate infusion risks cyanide toxicity (metabolic acidosis, altered mental status); it is light-protected, titrated, and time-limited.

Aliskiren is a direct renin inhibitor (the -kiren stem): it lowers plasma renin activity and stops renin converting angiotensinogen to angiotensin I. With ACE inhibitors and ARBs, renin activity climbs once angiotensin II no longer feeds back; with aliskiren the extra renin cannot act, so renin activity, angiotensin I and angiotensin II all fall.

Because it works on the same system as ACE inhibitors and ARBs, it shares their hazards: a boxed fetal-toxicity warning (stop as soon as pregnancy is detected), angioedema, hyperkalemia and renal impairment. It must not be combined with an ACE inhibitor or ARB in a patient with diabetes, and that combination is generally avoided. It is poorly absorbed (bioavailability about 2.5%) and high-fat meals cut absorption substantially, so it is taken the same way relative to meals every day.