USMLE (United States Medical Licensing Examination) Step 1 Practice Exam

What is the effect of Tricyclic Antidepressants (TCAs) on cardiac Na+ channels leading to QT and QRS prolongation and arrhythmias?

1. Activation

2. Blockage

3. Sensitization

4. Inhibition

The correct answer is: Blockage

Tricyclic Antidepressants (TCAs) primarily exert their effect by blocking the reuptake of norepinephrine and serotonin, but they also have a significant influence on cardiac sodium (Na+) channels. The blockage of these channels leads to a slowing of conduction in the cardiac tissue, which contributes to both QT and QRS interval prolongation on the electrocardiogram. When sodium channels are blocked, the depolarization phase of the cardiac action potential is altered, resulting in delayed conduction through the heart. Prolongation of the QRS complex indicates that there is a delay in ventricular depolarization, which can predispose patients to serious arrhythmias, such as tachycardia or even ventricular fibrillation. The QT interval may be prolonged as well, increasing the risk of torsades de pointes, a specific type of life-threatening arrhythmia. This understanding emphasizes the cardiotoxic potential of TCAs, particularly in overdose situations, where the effects on sodium channels can lead to significant cardiovascular instability.