Doxazosin: a new alpha 1-adrenergic antagonist

Abstract

The physicochemical properties, pharmacology, pharmacokinetics, cardiovascular and metabolic effects, adverse effects, dosage, and administration of doxazosin are described, and comparative clinical studies of doxazosin therapy in patients with mild to moderate hypertension are reviewed. Doxazosin mesylate, an alpha 1-adrenoceptor antagonist, is rapidly absorbed after oral administration and undergoes extensive hepatic metabolism. The drug decreases blood pressure by reducing peripheral resistance. Maximum hypotensive effects occur four to eight hours after the dose. Doxazosin favorably affects serum lipids by increasing concentrations of high-density lipoprotein (HDL) cholesterol, increasing the HDL:total cholesterol ratio, and decreasing concentrations of low-density lipoprotein cholesterol, total cholesterol, and triglycerides. In comparative clinical trials, doxazosin lowered standing and supine systolic and diastolic blood pressures as effectively as other alpha-adrenoceptor antagonists, beta-adrenoceptor antagonists, diuretics, angiotensin-converting-enzyme inhibitors, and calcium-channel-blocking agents. The most frequently reported adverse effects are dizziness, headache, nausea, lethargy, and fatigue. Doxazosin may be used either alone or in combination with a beta-adrenoceptor inhibitor or a diuretic. Orthostatic hypotension after the first dose occurs infrequently and may be minimized by initiating therapy at a dosage of 1 mg/day. The dosage may be increased at two-week intervals as needed, and blood pressure should be closely monitored. Doxazosin has blood-pressure-lowering effects comparable to those of other alpha 1-adrenoceptor inhibitors and to those of antihypertensives in other drug classes.