Tricyclic antidepressant poisoning : cardiovascular toxicity.

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.
Toxicological Reviews 01/2005; 24(3):205-14.
Source: PubMed


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.

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    • "This group of agents is characterized by effects on a broad range of receptor pathways that are implicated in both the therapeutic and adverse mechanisms of action. They may cause significant inhibition of central cholinergic neurotransmission, which results in a number of widespread autonomic features, including tachycardia.34 This is accompanied by impaired neuronal uptake of norepinephrine, which may worsen tachycardia. "
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    • "However, toxicity of amitriptyline has been observed during standard treatments, and frequently during suicidal or accidental overdosage. Tricyclic antidepressant overdosage has toxic effects over cardiovascular, autonomous nervous, and central nervous systems, and may result in cardiotoxicity, cardiac conduction delays, dysrhythmia, hypotension, altered mental status, and seizures (Thanacoody and Thomas, 2005; Kiyan et al., 2006). "

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