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- Toxic effects of tricyclic antidepressants (TCA) are result of the following 4 pharmacologic properties:
1. Inhibition of norepinephrine & serotonin reuptake --> resultant seizure
2. Anticholinergic activity --> resultant altered mental status, tachycardia, mydriasis, ileus
3. Direct alpha-adrenergic blockade --> resultant hypotension
4. Cardiac myocyte sodium channel blockade --> resultant widened QRS
- A QRS interval greater than 100 milliseconds has ~30% chance of developing seizures and ~15% chance of developing a life-threatening cardiac arrhythmia.
- A QRS interval greater than 160 milliseconds increases the chance of ventricular arrhythmias to greater than 50%.
- Clinical pearl: A very wide complex ventricular rhythm, concomitant hypotension and/or seizure disorder is suspicious for toxic ingestion and standard ACLS algorithm will not suffice, treatment must address the underlying culprit (i.e. TCA --> Tx. fluids, vasopressors, sodium bicarbonate, and intravenous lipid emulsion).
References
Kerr GW, McGuffie AC, Wilkie S. Tricyclic antidepressant overdose: a review. Emerg Med J. Jul 2001;18(4):236-41.