Direct-acting vasodilators.

KEY POINTS AND PRACTICAL RECOMMENDATIONS: •  Hydralazine and minoxidil act by dilating resistance arterioles, thus reducing peripheral resistance, with no dilating effect on the venous side of the circulation. •  There is a baroreflex-mediated venoconstriction, resulting in an increase in venous return to the heart, along with a direct catecholamine-mediated positive inotropic and chronotropic stimulation of the heart. •  Hydralazine therapy is usually combined with a sympathetic inhibitor to prevent expression of this reflex, as well as with a diuretic agent to prevent sodium retention caused by reduction in renal perfusion pressure. •  Hydralazine is indicated in the long-term therapy of essential hypertension, in the short-term therapy of pregnancy-induced hypertension and eclampsia, and in the therapy of hypertensive crisis. •  Adverse effects include the anticipated tachycardia, fluid retention, and headache, caused by the vasodilation, especially in the early days of therapy, but may frequently be prevented by the concomitant use of a β-blocker. •  As with other drugs that are N-acetylated, there is a low risk of lupus-like syndrome with high doses and long-term use. •  Because of the severity of adverse effects with minoxidil, its usage is limited to persons with severe hypertension unresponsive to other treatments. •  Hirsutism, a common side effect of minoxidil, is particularly bothersome in women and reverses in a few months after discontinuation. •  Sodium nitroprusside is used in the intensive care setting to lower pressure in hypertensive crisis or to treat severe left ventricular failure, particularly valuable when elevated pressure or severe left ventricular failure threatens the patient's survival. •  Although nitrates have not achieved widespread use as antihypertensive agents, they are effective in producing sustained blood pressure (BP) reductions when added to other antihypertensive regimens.