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• W2895337229 abstract "SESSION TITLE: Medical Student/Resident Pharmacotherapeutics SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Loperamide is a frequently used over-the-counter antidiarrheal medication thought to have very low abuse potential. In previously reported cases, toxic levels of medication have led to respiratory failure due to central nervous system depression. We describe a fatal case of repeated intoxication and overdose leading to cardiac arrest secondary to prolongation of QRS and QTc. CASE PRESENTATION: A 25-year-old man with a history of opiate abuse was found unresponsive and was subsequently intubated and placed on mechanical ventilation. He reportedly took over 100 tablets of loperamide per day (2mg/tablet). EKG revealed severe sinus bradycardia within a rate of 30 bpm, and a prolonged QRS (184) and QTc (640). In addition to infusion of isoproterenol and sodium bicarbonate, a transvenous pacer was used for overdrive pacing. The patient improved clinically after three days and was discharged with psychiatric follow-up. Three months later, he presented after being found unresponsive again with a bottle of loperamide by his side. Quantitative testing detected 147 ng/mL of loperamide. The patient went into ventricular tachycardia arrest, and despite prolonged aggressive resuscitation efforts, he expired. DISCUSSION: Loperamide use as an opioid substitute has been increasing among patients. The myocardial opioid receptors are Gi/Go-coupled in comparison to the Gs-coupled B1 and B2 receptors. Thus, stimulation of opioid receptors results in negative inotropic and chronotropic effects that can produce profound bradycardia. The therapeutic range of loperamide is <2 ng/mL. At concentrations of 15.7 μg/L to 20.5 ng/mL, loperamide blocks myocardial potassium channels resulting in QTc prolongation and at levels 114 to 141 ng/mL it blocks myocardial sodium channels leading to QRS prolongation (1). Co-administration of loperamide with inhibitors of CYP2C8 or CYP3A4 (cimetidine or grapefruit juice) can result in significantly elevated plasma concentrations that prolongs the drug's elimination half-life. Treatment options include overdrive pacing, intravenous lipid emulsion, or extracorporeal membrane oxygenation, however mortality remains significantly high. CONCLUSIONS: Because of its opioid effects and easy accessibility, misuse and abuse of loperamide is on the rise in the US. With increasing regulations attempting to restrict access to opioids, the use of loperamide as an opioid substitute is likely to continue to rise. Since routine drug screens do not detect loperamide, physicians must have heightened awareness of the abuse potential and the life-threatening cardiotoxicity that can result. Kang J, et al. Proarrythmic mechanisms of the common anti-diarrheal medication loperamide: revelations from the opioid abuse epidemic. Reference #1: Naunyn Schmiedebergs Arch Pharmacol 2016;389:1133-37. DISCLOSURES: No relevant relationships by Adam Austin, source=Web Response No relevant relationships by Stacey Burns, source=Web Response No relevant relationships by Muhammad Imtiaz, source=Web Response No relevant relationships by Biplab Kumar Saha, source=Web Response" @default.
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• W2895337229 date "2018-10-01" @default.
• W2895337229 modified "2023-10-16" @default.
• W2895337229 title "LOPERAMIDE CAN KILL: A RISING TREND AMIDST THE OPIOID EPIDEMIC" @default.
• W2895337229 doi "https://doi.org/10.1016/j.chest.2018.08.752" @default.
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