Module 10.2 - Cyclic Antidepressant Toxicity - Podcast

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This educational content provides a comprehensive understanding of Cyclic Antidepressant toxicity, a critical area in clinical toxicology.
The Danger of CAs: Cyclic Antidepressants, including tricyclics and variants like tetracyclic maprotiline, are highly relevant xenobiotics, primarily known for their low therapeutic index. Even mild increases in plasma concentration can lead to severe toxicity, and CAs remain among the leading xenobiotics associated with fatalities reported to poison control centers.
Mechanism and Presentation: The primary mechanism contributing to patient mortality is sodium channel blockade in the myocardium, resulting in life-threatening cardiotoxicity. The most frequent life threat is refractory hypotension. Diagnosis relies heavily on the ECG, where QRS widening ( 100 msec) and right-axis deviation of the terminal 40 msec (terminal R wave in aVR 3 mm) are critical indicators of severe toxicity and increased risk for seizures and dysrhythmias. Central Nervous System (CNS) toxicity often includes generalized seizures (about 10% of overdoses).
Management Cornerstone: Effective management hinges on rapid stabilization. Because CAs are highly lipophilic and have a large volume of distribution, enhanced elimination techniques (e.g., hemodialysis) are ineffective. The mainstay therapy for wide-complex dysrhythmias and conduction delays is serum alkalinization and sodium loading using hypertonic sodium bicarbonate. This intervention counteracts sodium channel blockade and reduces free drug concentration by targeting a serum pH of 7.50–7.55.
Antidysrhythmics & Adjuncts: For refractory ventricular dysrhythmias persisting despite bicarbonate, lidocaine is the second agent of choice. Magnesium sulfate (at least 2g IV) is critical for managing Torsades de Pointes, a dysrhythmia seen more commonly with therapeutic doses than with acute overdoses. Vasopressors like norepinephrine are preferred for refractory hypotension. Conversely, Class Ia Ic antiarrhythmics, Phenytoin, Flumazenil, and Physostigmine are absolutely contraindicated as they worsen cardiotoxicity or precipitate seizures. Intravenous Lipid Emulsion (ILE) is reserved as a third-line option for refractory cardiac arrest, but should not delay bicarbonate administration. (1983 characters)