Verapamil. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension.

Although verapamil is a well-established treatment for angina, cardiac arrhythmias and cardiomyopathies, this review reflects current interest in calcium antagonists as anti-hypertensive agents by focusing on the role of verapamil in hypertension. Verapamil is a phenylalkylamine derivative which antagonises calcium influx through the slow channels of vascular smooth muscle and cardiac cell membranes. By reducing intracellular free calcium concentrations, verapamil causes coronary and peripheral vasodilation and depresses myocardial contractility and electrical activity in the atrioventricular and sinoatrial nodes. Verapamil is well suited for the management of essential hypertension since it produces generalised systemic vasodilation resulting in a marked reduction in systemic vascular resistance and, consequently, blood pressure. Evidence from clinical studies supports the role of oral verapamil as an effective and well-tolerated first-line treatment for the management of patients with mild to moderate essential hypertension. Clinical studies have shown that verapamil is more effective the higher the pretreatment blood pressure and some authors have found a more pronounced antihypertensive effect in older patients or in patients with low plasma renin activity. Sustained release verapamil formulations are available for oral administration which, as a single daily dose, are as effective in lowering blood pressure over 24 hours as equivalent doses of conventional verapamil formulations given 3 times daily. As a first-line antihypertensive agent, oral verapamil is equivalent to several other calcium antagonists, beta-blockers, diuretics, angiotensin-converting enzyme (ACE) inhibitors and other vasodilators, and is not associated with many of the common adverse effects of these treatments. Verapamil may be preferred as an alternative first-line antihypertensive treatment to diuretics in elderly patients because it has similar efficacy in these patients without causing the adverse effects commonly linked with diuretic treatment. Furthermore, because verapamil does not cause bronchoconstriction, it may be used in preference to beta-blockers in patients with asthma or chronic obstructive airway disease. Reflex tachycardia, orthostatic hypotension or development of tolerance is not evident following verapamil administration. As a second- or third-line treatment for patients refractory to established antihypertensive regimens, verapamil produces marked blood pressure reductions when combined with diuretics and/or ACE inhibitors, beta-blockers and vasodilators such as prazosin.(ABSTRACT TRUNCATED AT 400 WORDS)