Morphine may moderately raise serum levels of esmolol, butthis is unlikely to be clinically important. The fatal doses of morphine and propranolol are markedly reduced by concurrent usein animals, but clinical relevance of this in man is uncertain.
Clinical evidence,mechanism, importance and management
In a study in 10 healthy men a 3mg injection of morphine sulfate increased steady-state levels of a 300 microgram/kg per minute infusion of esmolol, given over 4 hours. However, increases were only statistically significant in 2 of subjects (increase of 46%), and were considered to be of no clinical importance. The pharmacokinetics of morphine were unchanged (See reference number 1).
Studies in animals have shown that median fatal dose of propranolol was reduced two to sevenfold by morphine in mice(See reference number 2) and median lethal dose of morphine was reduced fifteen to sixteenfold by propranolol in rats.(See reference number 3) The same interaction has also been seen in dogs (See reference number 3). There do not appear to be any published reports of synergistic toxicity involving morphine and propranolol, so clinical relevance of this is uncertain.
Lowenthal DT,Porter RS, Saris SD, Bies CM, Slegowski MB, Staudacher A. Clinical pharmacology, pharmacodynamics and interactions with esmolol. Am J Cardiol (1985) 56, 14Fâ18F.
Murmann W,Almirante L, Saccani-Guelfi M. Effects of hexobarbitone, ether, morphine, andurethane upon the acute toxicity of propranolol and D-(-)-INPEA. J Pharm Pharmacol (1966) 18, 692â4.
Davis WM,Hatoum NS. Possible toxic interaction of propranolol and narcotic analgesics.Drug Intell Clin Pharm (1981) 15, 290â1.