Action of beta-adrenoceptor blockers on liver function of rats.
Three nonselective beta-adrenoceptor blockers, propranolol, cloranolol and talinolol, were examined in male rats. The amount and function of polysubstrate monooxygenase, serum bilirubin and carbohydrate metabolism were investigated. Doses producing a 25% reduction in heart beat/min were given orally. The effect of a single dose was compared to that of a 12-day treatment period. Propranolol in a single dose did not influence hepatic parameters. The 12-day treatment reduced the amount of cytochrome P-450 (cP-450) and prolonged hexobarbital biotransformation time. Cloranolol decreased cP-450, prolonged hexobarbital anaesthesia and inhibited aminopyrine-N-demethylation (AND) even in a single dose. No further impairment occurred with continued treatment. A single dose of talinolol led to cP-450 loss and inhibited cP-450 dependent liver functions. This inhibition progressed with continued treatment. High bilirubin levels were measured. Both cloranolol and talinolol elicited an initial rapid hyperglycaemia with normal liver glycogen content. At the end of the treatment blood glucose and liver glycogen values were normal. The reversible hyperglycemic reaction shows the necessity of controlling glucose tolerance. When talinolol is administered liver function parameters should be checked in appropriate time intervals.
Kulcsár-Gergely
J
J
Department of Pharmacology, Medical University, Debrecen, Hungary.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006591:Hexobarbital / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008111:Liver Function Tests; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D008112:Liver Glycogen; D011412:Propanolamines; C011550:talinolol; D003577:Cytochrome P-450 Enzyme System; D011433:Propranolol; D006591:Hexobarbital; C025725:tobanum