Premium
α‐Receptor function changes after the first dose of prazosin
Author(s) -
Bahr Christer,
Lindström Björn,
Seideman Peter
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.124
Subject(s) - prazosin , phenylephrine , blood pressure , pharmacology , medicine , antagonism , dosing , endocrinology , antagonist , chemistry , receptor
The effect of oral prazosin on blood pressure and antagonism of phenylephrine‐induced blood pressure increase was investigated in six healthy subjects during a dosing interval after the first dose and 3 days after the first dose of the drug. Prazosin lowered standing blood pressure more after the first dose than after the same dose 3 days later, despite similar plasma levels. Blood pressure decrease correlated with plasma prazosin levels during the elimination phase at the first dose, but not after 3 days of therapy. The phenylephrine log dose‐response curves shifted to the right after prazosin, which indicates α‐receptor antagonism of the drug. On day 4, the phenylephrine curve before prazosin dose shifted to the right of the pretreatment curve on day 1, despite very low prazosin plasma levels. On day 4 after prazosin dosing the phenylephrine dose‐response curves were shifted to the left of that on day 1. Our data indicate tolerance to prazosin effect on blood pressure and to phenylephrine agonism after 3 days dosing. Our data suggest that this might be due to de sensitization of α 1 ‐adrenoceptors with differential effects of agonists and antagonists. Clinical Pharmacology and Therapeutics (1982) 32, 41–47; doi: 10.1038/clpt.1982.124