Clonidine interaction in amitriptyline poisoning.
The effect of clonidine on amitriptyline-induced cardiotoxicity was investigated in an experimental rat mode. A continuous infusion of amitriptyline (30 mg/kg/h) was given until the animal died, usually within 2 hours. Fifteen minutes after starting the amitriptyline infusion, 50 micrograms/kg of clonidine was given intravenously over five minutes. This led to an increase in blood pressure and left ventricular end-diastolic pressure. There was no significant change in cardiac contractility. Heart rate decreased. These changes can be explained by an increase in afterload due to peripheral vasoconstriction. No signs of reduced sympathetic outflow were seen on the ECG. The peripheral effects of clonidine dominated over the central effects, which may be due to a competitive inhibition of amitriptyline at central noradrenergic sites. An increased afterload pushes the heart towards failure and increases mortality. In this model, clonidine did not reverse amitriptyline-induced cardiovascular toxicity. It may even be potentially harmful if used to treat tricyclic antidepressant poisoning.
Knudsen
K
K
Department of Anesthesia and Intensive Care, University of Gothenburg, Sahlgren's Hospital, Sweden.
Ricksten
S E
SE
Heath
A
A
D000639:Amitriptyline / Q000037:antagonists & inhibitors* / Q000506:poisoning; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000639:Amitriptyline; D003000:Clonidine