Pharmacotherapeutic stature of doxazosin and its role in coronary risk reduction

Abstract

In hypertension the primary pathophysiologic abnormality is a generalized increase in the peripheral vascular resistance as a result of concentric narrowing of the systemic arterioles, as a result of alpha 1-receptor stimulation. Such stimulation is attenuated by the selective alpha 1-inhibitor doxazosin. The pharmacologic attributes of doxazosin are translated into direct relaxation of the peripheral arteriolar resistance vessels and venous capacitance system, particularly those with a high alpha-adrenoceptor population. The direct effects of such vascular dilatation are immediately beneficial to the heart in reducing systemic and pulmonary vascular pressures that reduce left ventricular wall stress and myocardial oxygen consumption. In clinical studies doxazosin has been found to have a plasma half-life of 19 to 22 hours, of which a single daily dose is sufficient to control hypertension. The antiatherogenic changes in the blood lipid profile resulting from long-term treatment with doxazosin can also be expected to advance its primary prevention potential in hypertensive patients, which is in marked contrast to the potentially disadvantageous changes in the blood lipid profile that follow treatment with beta-blockers and thiazide diuretics. The therapeutic efficacy of doxazosin has been confirmed, irrespective of hypertension severity, age and race of the patient, or the presence of renal impairment or diabetes mellitus. Its side-effect profile is not substantially different from that of placebo or other antihypertensive drug treatment. Given its unique actions regarding antihypertensive efficacy, together with favorable effects on blood lipids, doxazosin probably holds more promise for the prevention of precocious coronary heart disease in hypertensive patients than any other currently available antihypertensive agent.