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 structura lly related to prazosin and terazosin. Its antihypertensive effect is produced by a reduction in the smooth muscle tone of peripheral vascul ar beds resulting in a decrease in total peripheral resistance without significant effect on cardiac output or heart rate. In benign prostat ic hyperplasia, doxazosin's effect of relieving bladder outflow obstru ction is produced through a reduction in prostatic tone mediated via a lpha(1)-adrenoceptor blockade. In most comparative trials doxazosin ha s proven to be equally effective as the comparator drug in treatment o f mild to moderate hypertension. It has been used in a variety of pati ent populations including the elderly, Blacks, smokers, and patients w ith concomitant disease states such as renal dysfunction, hypercholest erolaemia, non-insulin dependent diabetes in mellitus (NIDDM) and resp iration disease. Doxazosin has also been used successfully in combinat ion with beta-adrenoceptor antagonists, diuretics, calcium channel ant agonists and angiotensin-converting enzyme inhibitors in patients with hypertension that is uncontrolled with monotherapy. Doxazosin has a b eneficial 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. Modes t decreases in total cholesterol, low density lipoprotein cholesterol and triglycerides are seen with doxazosin therapy while small increase s in high density lipoprotein cholesterol and the high density lipopro tein cholesterol/total cholesterol ratio are consistently reported. So me studies have report an improvement in glucose tolerance although th is effect has been more consistently seen in nondiabetic patients than in patients with NIDDM. Additionally, doxazosin produces a similar re duction in left ventricular hypertrophy to other antihypertensive agen ts. 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 pros tatic 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 a nd withdrawal rates similar to other alpha(1)-adrenoceptor antagonists and other classes of antihypertensive agents. The most commonly repor ted adverse effects are dizziness, headache, fatigue/malaise and somno lence. Of most concern is the possibility of first-dose postural effec ts such as syncope; however, the risk of this appears to be minimal wi th careful dosage titration.