Tricyclic antidepressants are believed to act by centrally blocking the reuptake of norepinephrine (noradrenaline) and/or 5-hydroxytryptamine (serotonin, 5-HT). In addition, they block the parasympathetic nervous system (anticholinergic action) and the peripheral reuptake of norepinephrine. Their effect on the heart is similar to that of the class Ia antiarrhythmic agents (membrane-stabilizing or quinidine-like effect) at low doses, which in overdose is highly toxic to the heart and is the main mechanism responsible for a fatal outcome. Deaths from tricyclic antidepressant overdose are due to the negative inotropic effect resulting in profound hypotension and electromechanical dissociation, or the proarrhythmic effect, causing intraventricular conduction delays leading to ventricular arrhythmias ( Pentel and Benowitz
Fig. 1 Mechanisms of the cardiac toxicity of tricyclic antidepressants: EMD, electromechanical dissociation.
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