Clinical pharmacology of selective alpha blockers. Hemodynamics and effects on lipid levels

Selective alpha 1 antagonists decrease blood pressure by reducing elevated peripheral resistance and preserving normal cardiac reflexes. They have also been reported to usually decrease total cholesterol and low-density lipoprotein cholesterol levels, and, in some studies, to increase high-density lipoprotein cholesterol levels. Prazosin, a quinazoline derivative, is well tolerated and is not associated with chronic toxicity. Prazosin has been successfully used in the treatment of hypertension for more than 10 years. Its short plasma half-life requires twice-daily dosing. Although the hypotensive response to an initial dose of prazosin is usually greater than to subsequent doses during long-term therapy, the initial response is an accurate predictor of the hypotensive response in patients during long-term therapy. The vasodilatory action of prazosin is largely due to its blockade of vascular postjunctional alpha 1 receptors. The mechanism involved in its effect on lipid levels is currently under investigation and is an important consideration since hypercholesterolemia, as well as hypertension, is an independent risk factor for stroke and coronary heart disease. Reduction of blood pressure with conventional agents, such as beta blockers or diuretics, has not had the expected impact on coronary heart disease. However, since alpha 1 blockers may influence both hemodynamics and lipids, they warrant evaluation as first-line treatment of hypertension to confirm that they also have an effect on coronary heart disease.