Although selective serotonin reuptake inhibitors are more popular, TCAs are still commonly prescribed in the treatment of enuresis, obsessive-compulsive disorder, and attention-deficit-hyperactivity disorders in children. These drugs are well-absorbed orally and are metabolized by the liver. TCA toxicity occurs by the following mechanisms: inhibiting nor- epinephrine and serotonin reuptake at the nerve terminals, creating anti- cholinergic blockade, directing α-adrenergic blockage, and blocking the cardiac myocytes fast sodium channels. The latter mechanism is a hallmark of TCA toxicity because it slows down phase zero of the action potential depolarization, and causes a widened QRS complex on the electrocardiogram (EKG).

Exposure to TCA dosages >5 mg/kg tend to be symptomatic and >15 mg/kg lethal. Early toxicity may present with signs and symptoms of anticholinergic toxidromes and central nervous system (CNS) involvement. The former include mydriasis, flushing, dry mouth, urinary incontinence, diminished bowel activity, hyperthermia, tachycardia; and the latter demonstrates mental status changes, confusion, hallucinations, and delirium. Mortality is attributed to cardiovascular collapse and CNS toxicity, including seizure and coma. CNS toxicity can be attributed partially to inhibition of the chloride ionophore on the γ-aminobutyric acid channel complex. In general, seizures are usually generalized and self-limited in nature. Signs of significant toxicity can be expected within 6 hours of ingestion.