Studies on the clinical pharmacology of prazosin. I: Cardiovascular, catecholamine and endocrine changes following a single dose.

Clinical pharmacology of prazosin: further discussion [letter]

“…As to the neuroendocrine effects of the drug, we reported no changes in prolactin (PRL) and growth hormone (GH) levels following acute (Barbieri, Caldera et al, 1980) as well as chronic (Barbieri, Ferrari, Borzio, Piepoli & Caldara, 1980) prazosin treatment, in general agreement with the results of Rubin & Blaschke (1980), since the augmented GH concentration reported in this investigation, although significant, is of small magnitude and similar to that observed in our study. The observations concerning PRL appear very interesting.…”

“…These findings suggest that prazosin administration is not associated with an increased sympathetic outflow and therefore it has been concluded that this drug induces in man the same effects observed in rabbit pulmonary artery strips (Brogden, Heel, Speight & Avery, 1977). The results of the investigation by Rubin & Blaschke (1980) do not seem in keeping with such a view; nonetheless in this study prazosin administration induced in supine patients a fall in blood pressure but no significant changes either in HR or in PRA, although an increase in plasma noradrenaline was observed; only on standing, drug administration was associated with a dramatic decrease in blood pressure, together with evidence of sympathetic overactivity, i.e. increase in HR, PRA and noradrenaline levels.…”

“…The pharmacological properties of prazosin have been recently discussed by Rubin and Blaschke (1980). In their paper two points are of particular interest: the observations on the mechanism of action of prazosin and on its endocrinological effects.…”

Pharmacological tolerance to alpha 1-adrenergic receptor antagonism mediated by terazosin in humans.

“…However, one major problem with the clinical efficacy of a,-adrenergic receptor antagonists is that tolerance to the therapeutic effect develops during chronic drug administration, especially in congestive heart failure (9-13). Many mechanisms to account for toler-creased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system (19)(20)(21)(22)(23)(24), advancing disease (25,26), and altered production of vasodilator factors (27).…”

Lack of relationship between debrisoquine oxidation phenotype and the pharmacokinetics and first dose effect of prazosin.

“…This 'first-dose' phenomenon is dose-dependent but whether it is related to plasma drug or metabolite concentration is unclear (Rubin & Blaschke, 1980;Elliott et al, 1981). Prazosin undergoes extensive first pass oxidative metabolism primarily via 0-dealkylation to two metabolites which are less potent in hypotensive action than the parent compound (Taylor et al, 1977;Jaillon, 1980).…”