Loperamide Induced Life Threatening Ventricular Arrhythmia

Abstract

Loperamide is over-the-counter antidiarrheal agent acting on peripherally located μ opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100 mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200 mg of Loperamide daily for last two days before the cardiac arrest. We hypothesize that the patient's QTc prolongation and subsequent cardiac arrest are due to Loperamide toxicity. Patient experienced gradual resolution of tachyarrhythmia and gradual decrease in QTc interval during hospitalization which supports the evidence of causal relationship between Loperamide overdose and potentially fatal arrhythmias. It also provided the clue that patient may have congenital long QT syndrome which was unmasked by Loperamide causing ventricular arrhythmias. This case adds one more pearl in the literature to support that Loperamide overdose related cardiac toxicity does exist and it raises concerns over Loperamide abuse in the community.

Wide complex tachycardia and cardiomyopathy: What would you do?

“…Because of this, the FDA released a warning in 2016 regarding its potential for negative cardiac side effects . Since the earliest case reports in 2014, several case reports have since described the various cardiac manifestations induced by loperamide abuse . While the exact mechanisms are not completely understood, the various cardiac manifestations are suspected to be due to lopermide's effects primarily on hERG/Ikr potassium channel and cardiac sodium channels, which mimic the effect of Vaughan–Williams Class III and Class IA antiarrhythmic agents, respectively .…”

“…3 Since the earliest case reports in 2014, 1 several case reports have since described the various cardiac manifestations induced by loperamide abuse. [4][5][6][7][8][9][10] While the exact mechanisms are not completely understood, the various cardiac manifestations are suspected to be due to lopermide's effects primarily on hERG/Ikr potassium channel and cardiac sodium channels, which mimic the effect of Vaughan-Williams Class III and Class IA antiarrhythmic agents, respectively. 11,12 Patients with predominantly Class III manifestations exhibit the expected QT prolongation and torsades de pointes VT, whereas predominantly Class IA manifestations exhibit QRS widening due to delayed sodium channel upstroke and monomorphic ventricular tachycardia.…”

Ventricular fibrillation due to overdose of loperamide, the “poor man’s methadone”

“…It demonstrates structural similarities with methadone and terfenadine by having multiple phenyl rings. Therefore, it can be assumed that its QTc prolongation effect through a similar mechanism [10]. Prolonged QTc interval at supra-therapeutic doses can be explained by the blockade of the cardiac human ether-a-go-go (hERG) potassium channel.…”

Torsades de pointes induced by metoclopramide injection

“…10 In some literature and case reports explained that loperamide can cause a prolonged QT interval in high doses, in the case report obtained the dose that can cause elongation of QT interval is 25-200 mg, while the recommended maximal dose is 16 mg per day, overdose of loperamide ussually occur in opioid user. 11,12 This patient use a dose of 2 mg tid, so when compared to the literature, loperamide was less likely to be the cause TdP in this patient.…”