Selective alpha1-adrenergic antagonists: Therapeutically relevant antihypertensive agents
1984; Elsevier BV; Volume: 53; Issue: 3 Linguagem: Inglês
10.1016/0002-9149(84)90829-4
ISSN1879-1913
Autores Tópico(s)Blood Pressure and Hypertension Studies
ResumoAlpha-adrenergic antagonists were the first substances to receive serious consideration as antihypertensive agents. However, their therapeutic potential in the management of essential hypertension was not realized until prazosin, a highly selective α1-adrenergic antagonist, became available. A number of analogs of prazosin have now been synthesized, as have several structurally distinct α1-adrenergic antagonists- Preliminary investigations suggest that these agents may also be clinically useful antihypertensive drugs. The α1 receptor of arteriolar smooth muscle is the predominant adrenergic subtype determining sympathetically mediated vascular tone. Therefore, its selective blockade by an agent such as prazosin is a relevant approach to the major pathophysiologic defect in hypertension: an elevation of peripheral vascular resistance. Because prazosin has little selectivity for the α2 receptor, the negative feedback control of norepinephrine release from sympathetic nerve terminals remains intact. This unique action of prazosin may explain why it effectively lowers arterial pressure without markedly increasing cardiac output, heart rate and plasma renin activity. An additional factor in the favorable therapeutic effects of this agent is its ability to induce a balanced reduction in both arteriolar and venous tone, with little change or even improvement in renal hemodynamics. The antihypertensive effects of prazosin, when used as a single agent, may be modest. However, it may be useful as initial as well as adjunctive therapy for the management of hypertension because of its high toxic to therapeutic ratio, coupled with a sustained reduction in arterial blood pressure, a low incidence of side effects, and a potentially favorable metabolic profile.
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