Tricyclic antidepressant poisoning : cardiovascular toxicity.
Tricyclic antidepressants remain a common cause of fatal drug poisoning as a result of their cardiovascular toxicity manifested by ECG abnormalities, arrhythmias and hypotension. Dosulepin and amitriptyline appear to be particularly toxic in overdose. The principal mechanism of toxicity is cardiac sodium channel blockade, which increases the duration of the cardiac action potential and refractory period and delays atrioventricular conduction. Electrocardiographic changes include prolongation of the PR, QRS and QT intervals, nonspecific ST segment and T wave changes, atrioventricular block, right axis deviation of the terminal 40 ms vector of the QRS complex in the frontal plane (T 40 ms axis) and the Brugada pattern (downsloping ST segment elevation in leads V1-V3 in association with right bundle branch block). Maximal changes in the QRS duration and the T 40 ms axis are usually present within 12 hours of ingestion but may take up to a week to resolve. Sinus tachycardia is the most common arrhythmia due to anticholinergic activity and inhibition of norepinephrine uptake by tricyclic antidepressants but bradyarrhythmias (due to atrioventricular block) and tachyarrhythmias (supraventricular and ventricular) may occur. Torsade de pointes occurs uncommonly. Hypotension results from a combination of reduced myocardial contractility and reduced systemic vascular resistance due to alpha-adrenergic blockade. Life-threatening arrhythmias and death due to tricyclic antidepressant poisoning usually occurs within 24 hours of ingestion. Rapid deterioration is common. Level of consciousness at presentation is the most sensitive clinical predictor of serious complications. Although a QRS duration >100 ms and a rightward T 40 ms axis appear to be better predictors of cardiovascular toxicity than the plasma tricyclic drug concentration, they have at best moderate sensitivity and specificity for predicting complications.
Thanacoody
H K Ruben
HK
Wolfson Unit of Clinical Pharmacology, School of Clinical and Laboratory Sciences, University of Newcastle, and National Poisons Information Service (Newcastle Centre), Newcastle upon Tyne, UK.
Thomas
Simon H L
SH
D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics / Q000506:poisoning*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D062787:Drug Overdose / Q000453:epidemiology; D006801:Humans; D011041:Poisoning / Q000453:epidemiology / Q000209:etiology*; D006113:United Kingdom / Q000453:epidemiology
D000929:Antidepressive Agents, Tricyclic