Loperamide overdose-induced catatonia: potential role of brain opioid system and P-glycoprotein

Abstract

We speculate on a possible increase of loperamide's bioavailability after overdose owing to reduced expression and functioning of P-glycoprotein.

Loperamide misuse and abuse

“…26 The average number of case reports published per year increased by more than 10-fold in 2014 with an average of less than one case per year between 1985 and 2013 in comparison to 11 cases per year between 2014 and 2016. 13,[17][18][19]23, Gender and age Of all the loperamide-related case reports, males have accounted for the majority, making up 35 of the 54 cases reported from 1985 to 2016. Males had more reported loperamide toxicity cases than females did during 1985-2013 and 2014-2016.…”

“…22 Although loperamide predominantly acts peripherally, taking sufficiently high doses or taking concomitant medications that inhibit P-gp, CYP3A4, or CYP2C8 can result in toxic serum levels and central nervous system effects. 17,23 The most well-documented drug interaction with loperamide is the coadministration of a P-gp inhibitor, which has been shown to increase the serum loperamide concentration level by up to 3fold. 16 Examples of drugs that can lead to P-gp inhibition are corticosteroids, quinidine, methadone, ketoconazole, protease inhibitors, antineoplastic drugs, verapamil, and loperamide itself.…”

“…7,28 For QTc prolongation, intravenous isoproterenol, transcutaneous electrical pacing, and transvenous pacing have been used. 19,36,38 Reported toxicities categorized by organ system 13,[17][18][19]23,[27][28][29][30][31][32][33][34][35][36][37][38][39][40] Organ…”

Radiographic dose‐dependency study of loperamide effects on gastrointestinal motor function in the rat. Temporal relationship with nausea‐like behavior

“…Thus, only extremely high doses of loperamide might be able to induce catalepsy in laboratory animals. Interestingly, catalepsy occurs in catatonia, and, intriguingly, after excessive loperamide intake one patient developed severe catatonia that fully remitted with lorazepam …”

“…Interestingly, catalepsy occurs in catatonia, 45 and, intriguingly, after excessive loperamide intake one patient developed severe catatonia that fully remitted with lorazepam. 46 Intraperitoneal morphine-induced mild hypothermia in mice, 35 and, in the context of surgical pain management, persistent hypothermia after intrathecal morphine (generally associated with sweating and nausea) may occur. [47][48][49] In our study, changes in core temperature were mild and only occurred after Lop 10.…”