The adverse effects of TCAs are largely predictable from their pharmacodynamic actions. These include (1) excessive sedation, lassitude, fatigue, and, occasionally, confusion; (2) sympathomimetic effects, including tachycardia, agitation, sweating, and insomnia; (3) atropine-like effects; (4) orthostatic hypotension, electrocardiogram (ECG) abnormalities, and cardiomyopathies; (5) tremor and paresthesias; and (6) weight gain. Overdosage with tricyclics is extremely hazardous, and the ingestion of as little as a 2-week supply has been lethal. Manifestations include (1) agitation, delirium, neuromuscular irritability, convulsions, and coma; (2) respiratory depression and circulatory collapse; (3) hyperpyrexia; and (4) cardiac conduction defects and severe arrhythmias. The "3 Cs"—coma, convulsions, and cardiotoxicity—are characteristic.
Tricyclic drug interactions (Table 30–2) include additive depression of the CNS with other central depressants, including ethanol, barbiturates, benzodiazepines, and opioids. Tricyclics may also cause reversal of the antihypertensive action of guanethidine by blocking its transport into sympathetic nerve endings. Less commonly, tricyclics may interfere with the antihypertensive actions of methylnorepinephrine (the active metabolite of methyldopa) and clonidine.