Comparison of pharmacokinetics and pharmacodynamics of adrenoceptor agonists and antagonists as antihypertensive agents.

Central and peripheral alpha-adrenoceptors play an important role in cardiovascular regulation, and selective alpha 1-adrenoceptor antagonists and alpha 2-adrenoceptor agonists have an established place in the therapy of hypertension. Prazosin is a selective alpha 1-antagonist that is both effective in lowering blood pressure and well tolerated. However, the more recently developed alpha 1-antagonists doxazosin and terazosin offer the advantage of having longer half-lives, allowing once daily administration. Clonidine is a centrally acting alpha 2-agonist whose clinical use has often been limited by the dose dependent side effects of dry mouth and sedation, and the belief that it should be given three times per day. However, recent studies have shown that it has substantial antihypertensive efficacy with minimal side effects at low doses, and that half-life is long enough to allow twice daily administration. An improved understanding of the pharmacodynamics and pharmacokinetics of drugs acting on alpha-adrenoceptors allows a more rational approach to their clinical application.