The effect of increasing amitriptyline doses on cardiomyocytes’ electrophysiology – simulation study
Author:
Tylutki Zofia,Jornil Jakob,Polak Sebastian
Abstract
AbstractOverdoses of tricyclic antidepressants may lead to arrhythmia. The aim of the study was to simulate the effect of increasing concentrations of amitriptyline (AMI) and its metabolite, nortriptyline, on the action potential of human ventricular cell.Simulations were performed in Cardiac Safety Simulator platform with the use of the O’Hara-Rudy model. Input data included literature-derived, drug-specific IC50 values for IThe values of simulated endpoints (APD50, APD90, triangulation, and ΔAPD90) increase with drug concentrations. ΔAPD90 was statistically significant for doses up from 1000 mg. EADs were observed after administration of 10,000-mg AMI.The consequences of various doses of AMI on the single cardiac myocytes were simulated in our study. Repolarization abnormalities were not expected for the therapeutic doses. EADs may be observed for very high doses of AMI.
Publisher
Walter de Gruyter GmbH
Subject
Health Informatics,Biochemistry, Genetics and Molecular Biology (miscellaneous),Medicine (miscellaneous),General Computer Science
Reference42 articles.
1. antidepressant poisoning;Thanacoody;Rev,2005
2. de Cross - national epidemiology of DSM - IV major depressive episode;Bromet;BMC Medicine,2011
3. of amitriptyline overdose in emergency;Güloğlu;Analysis medicine Emerg Med J,2011
4. World Federation of Societies of Biological guidelines for biological treatment of unipolar depressive disorders Part Update on the acute and continuation treatment of unipolar depressive disorders;Bauer;Psychiatry World Biol Psychiatry,2013
5. Simulation of the undiseased human cardiac ventricular action potential : model formulation and experimental validation;Hara;Biol,2011