DOXAZOSIN - AN UPDATE OF ITS CLINICAL-PHARMACOLOGY AND THERAPEUTIC APPLICATIONS IN HYPERTENSION AND BENIGN PROSTATIC HYPERPLASIA

Doxrazosin is a long-acting alpha(1)-adrenoceptor antagonist structurally related to prazosin and terazosin. Its antihypertensive effect is produced by a reduction in the smooth muscle tone of peripheral vascular beds resulting in a decrease in total peripheral resistance without significant effect on cardiac output or heart rate. In benign prostatic hyperplasia, doxazosin's effect of relieving bladder outflow obstruction is produced through a reduction in prostatic tone mediated via alpha(1)-adrenoceptor blockade. In most comparative trials doxazosin has proven to be equally effective as the comparator drug in treatment of mild to moderate hypertension. It has been used in a variety of patient populations including the elderly, Blacks, smokers, and patients with concomitant disease states such as renal dysfunction, hypercholesterolaemia, non-insulin dependent diabetes in mellitus (NIDDM) and respiration disease. Doxazosin has also been used successfully in combination with beta-adrenoceptor antagonists, diuretics, calcium channel antagonists and angiotensin-converting enzyme inhibitors in patients with hypertension that is uncontrolled with monotherapy. Doxazosin has a beneficial effect on some of the risk factors associated with coronary heart disease including elevated serum lipid levels, impaired glucose metabolism, insulin resistance and left ventricular hypertrophy. Modest decreases in total cholesterol, low density lipoprotein cholesterol and triglycerides are seen with doxazosin therapy while small increases in high density lipoprotein cholesterol and the high density lipoprotein cholesterol/total cholesterol ratio are consistently reported. Some studies have report an improvement in glucose tolerance although this effect has been more consistently seen in nondiabetic patients than in patients with NIDDM. Additionally, doxazosin produces a similar reduction in left ventricular hypertrophy to other antihypertensive agents. Modelling-based calculations suggest that doxazosin significantly reduces the risk of developing coronary heart disease in patients with mild to moderate hypertension, although this remains to be confirmed in long term prospective studies. Doxazosin appears to be a promising agent in the treatment of urinary symptoms associated with benign prostatic hyperplasia. Similar to other alpha(1)-adrenoceptor antagonists, doxazosin treatment produces increases in peak and mean urinary flow rates and improves other objective and symptomatic measures. In acute and long term studies, doxazosin has an incidence of adverse effects and withdrawal rates similar to other alpha(1)-adrenoceptor antagonists and other classes of antihypertensive agents. The most commonly reported adverse effects are dizziness, headache, fatigue/malaise and somnolence. Of most concern is the possibility of first-dose postural effects such as syncope; however, the risk of this appears to be minimal with careful dosage titration.