Overdose on specific substances - Tricyclic Antidepressants

Question 1

Explain the pathophysiology of TCA overdose.

Answer 1

Toxic symptoms arise from four major categories:
1) Inh. of serotonin/NE reuptake at nerve terminals -
2) Anticholinergic f(x)
3) Direct alpha-adrenergic blockade
4) Blockade of cardiomyocyte fast Na+ channels - like the class IA antiarrhythmics, decrease the sodium influx through the fast sodium channels and consequently decrease the slope of phase 0 –> prolonged QTc

Question 2

Explain the mechanism of TCA induced hypotension.

Answer 2

produces hypoTN by blocking alpha-adrenergic receptors in the peripheral vasculature

Question 3

Explain the ECG changes as a result of TCA overdose.

Answer 3

cardiomyocyte fast Na+ channels - like the class IA antiarrhythmics, decrease the sodium influx through the fast sodium channels and consequently decrease the slope of phase 0 –> prolonged QTc