Loperamide misuse and abuse

Miller, H.P.; Panahi, Ladan; Tapia, Daniel; Tran, Andrew; Bowman, John D.

doi:10.1016/j.japh.2016.12.079

Cited by 52 publications

(73 citation statements)

References 31 publications

(46 reference statements)

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“…First, they could make loperamide by prescription only, which would give the tightest control over availability and ensure that prescribers are aware of the patient's usage . The second option would be to move it behind the pharmacy counter with patients having to show a licensed pharmacist identification in order to purchase loperamide . This type of procedure is currently being done with pseudoephedrine through the Methamphetamine Epidemic Act of 2005.…”

Section: Reducing Loperamide Availabilitymentioning

confidence: 99%

Loperamide: A Readily Available but Dangerous Opioid Substitute

White

2019

The Journal of Clinical Pharma

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The antidiarrheal over‐the‐counter drug loperamide is increasingly being used to control opioid withdrawal or for opioid abuse. Taking many times above the normally recommended dose is dangerous with cardiovascular, respiratory, and neurological adverse events. Cytochrome P‐450 (CYP)2C8, CYP3A, and P‐glycoprotein inhibitors can increase the plasma and central nervous system concentrations and radically alter the risk profile of loperamide. Online forums suggest using over‐the‐counter metabolic enzyme blockers to enhance the effects. Public health options include switching over‐the‐counter loperamide to blister packs (the FDA‐preferred method), making loperamide only available by prescription, or moving the product behind the pharmacy counter. Although naloxone may ameliorate the neurological and respiratory adverse events, it is ineffective at reversing loperamide‐induced arrhythmias. Even magnesium might provide less efficacy in loperamide‐induced Torsade de Pointes necessitating the use of cardiac pacing and electrical cardioversion.

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Section: Reducing Loperamide Availabilitymentioning

confidence: 99%

Loperamide: A Readily Available but Dangerous Opioid Substitute

White

2019

The Journal of Clinical Pharma

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“…It also improves continence in patients with ileo‐anal pouches and reduces dehydration and malnutrition in ileostomized patients . Gastrointestinal symptoms (nausea and constipation), urinary retention, drowsiness, dizziness, and headache may occur at therapeutic doses …”

Section: Introductionmentioning

confidence: 99%

“…Different pharmacokinetic factors contribute to the lack of systemic and, particularly, central effects of loperamide . Firstly, its oral bioavailability is very low (<2%) due to extensive first‐pass hepatic metabolism and enterohepatic circulation (with substantial fecal excretion) .…”

Section: Introductionmentioning

confidence: 99%

“…Secondly, high doses may saturate the metabolic enzymes and/or the P‐glycoprotein efflux system . Thirdly, the combined use with other drugs which inhibit metabolic enzymes (CYP3A4 and CYP2C8) may increase plasma concentrations of loperamide and inhibitors of P‐glycoprotein may allow more loperamide to cross the blood‐brain barrier and cause central opioid effects …”

Section: Introductionmentioning

confidence: 99%

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

Vera

Girón

Martín-Fontelles

et al. 2019

Neurogastroenterology Motil

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Background Loperamide is a potent mu opioid receptor agonist available over the counter to treat diarrhea. Although at therapeutic doses loperamide is devoid of central effects, it may exert them if used at high doses or combined with drugs that increase its systemic and/or central bioavailability. Recently, public health and scientific interest on loperamide has increased due to a growing trend of misuse and abuse, and consequent reports on its toxicity. Our aim was to evaluate in the rat the effects of increasing loperamide doses, with increasing likelihood to induce central effects, on gastrointestinal motor function (including gastric dysmotility and nausea‐like behavior). Methods Male Wistar rats received an intraperitoneal injection of vehicle or loperamide (0.1, 1, or 10 mg kg−1). Three sets of experiments were performed to evaluate: (a) central effects (somatic nociceptive thresholds, immobility time, core temperature, spontaneous locomotor activity); (b) general gastrointestinal motility (serial X‐rays were taken 0‐8 hours after intragastric barium administration and analyzed semiquantitatively, morphometrically, and densitometrically); and (c) bedding intake (a rodent indirect marker of nausea). Animals from sets 1 and 3 were used to evaluate gastric dysmotility ex vivo at 2 and 4 hours after administration, respectively. Key Results Loperamide significantly induced antinociception, hypothermia, and hypolocomotion (but not catalepsy) at high doses and dose‐dependently reduced gastrointestinal motor function, with the intestine exhibiting higher sensitivity than the stomach. Whereas bedding intake occurred early and transiently, gastric dysmotility was much more persistent. Conclusions and inferences Our results suggest that loperamide‐induced nausea and gastric dysmotility might be temporally dissociated.

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“…Miller et al [2] published a comprehensive review this year, which I encourage the authors to go through in order to add to their report. They mention two interesting points regarding the epidemiology.…”

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confidence: 99%