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

Central and peripheral α-adrenoceptors play an important role in cardiovascular regulation, and selective α₁-adrenoceptor antagonists and α₂-adrenoceptor agonists have an established place in the therapy of hypertension. Prazosin is a selective α₁-antagonist that is both effective in lowering blood pressure and well tolerated. However, the more recently developed α₁-antagonists doxazosin and terazosin offer the advantage of having longer half-lives, allowing once daily administration. Clonidine is a centrally acting α₂-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 α-adrenoceptors allows a more rational approach to their clinical application.