title: New alpha 1-adrenergic receptor antagonists for the treatment of hypertension: role of vascular alpha receptors in the control of peripheral resistance.
abstract: The pharmacology, clinical efficacy and safety of new alpha-adrenergic receptor antagonists for the treatment of hypertension was reviewed (Table XIV). Although all these agents block alpha 1 receptors, some of them have additional effects on histamine, serotonin, dopamine, and alpha 2 receptors. These other actions account for the differences in the side effect profiles observed, i.e., increased incidence of central nervous system side effects found with indoramin, ketanserin, and urapidil, as well as for some additional beneficial effects of ketanserin (i.e., antiplatelet aggregation activity). The magnitude of BP reduction observed with antagonists of alpha 1-adrenergic receptors is modest. In most studies, the degree of BP reduction is comparable to that of prazosin, but less than that achieved with thiazide diuretics, beta-receptor antagonists, or methyldopa. Studies on the comparative efficacy and safety of new alpha 1 antagonists with converting enzyme inhibitors or calcium-channel blockers are not available. In general, alpha 1 antagonists produce greater reductions in standing than in supine BP, an effect due to the venodilatory action of these drugs. New alpha 1 antagonists appear to have equal efficacy in black and white hypertensive individuals. Their comparative efficacy and safety in young vs elderly hypertensive individuals requires further investigation. No information about the possible development of tolerance during treatment with new alpha 1 blockers was encountered. The effects of alpha 1 antagonists on HR are variable and depend on how long after the oral dose the measurements were obtained. In most studies, no significant HR changes are noticed for readings obtained 24 hours post dose; whereas tachycardia has been observed at the time of peak hypotension. Since alpha 1 antagonist-induced tachycardia is most likely of reflex nature, i.e., mediated to an increase in sympathetic activity, the increased HR may be associated with increases in myocardial contractility and in myocardial oxygen consumption. Consequently, a 24-hour HR monitoring during treatment with alpha 1 antagonists should be required for evaluation of new agents. The hemodynamic, humoral, and hormonal effects of the newer alpha 1-receptor antagonists are comparable to those of prazosin. The most consistent finding is a reduction in total peripheral resistance associated with either no change or with only small increases in cardiac index. These agents have been shown either not to change or to increase renal blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D011942:Receptors, Adrenergic, alpha