Efficacy of antihypertensive drugs
Clonidine and other centrally acting α2-agonists (e.g., methyldopa, guanfacine) work by decreasing sympathetic outflow from the central nervous system; in small doses, this causes vasodilation and BP lowering. In larger doses, sedation, dry mouth, drowsiness, and other symptomatic adverse effects occur, which are presumably the reason clonidine was the least well-tolerated drug in the Department of Veterans Affairs monotherapy trial. Sudden discontinuation of short-acting α2-agonists causes rebound hypertension, which is best treated by reinstituting therapy. Clonidine is the only transdermal antihypertensive available in the United States.
Direct vasodilators (hydralazine, minoxidil) are typically used with a diuretic and β-blocker to counteract their tendency to cause sodium and fluid retention and reflex tachycardia. Accordingly, these drugs are typically used third-line or higher, as was hydralazine in ALLHAT. Hydralazine is typically limited to ≤300 mg/day because of the risk of drug-induced lupus, and it should be combined with a β-blocker to decrease reflex tachycardia; minoxidil causes hair growth that is not well tolerated by most women.