Loperamide as a Potential Drug of Abuse and Misuse: Fatal Overdoses at the Medical University of South Carolina.

Loperamide is an over-the-counter, µ-opioid receptor agonist commonly used as an antidiarrheal agent. Loperamide was thought to have minimal abuse potential due to its low bioavailability and limited central nervous system activity; however, there have been increasing reports of loperamide misuse in supratherapeutic doses to achieve euphoria and/or avoid opioid withdrawal. A literature review suggests a rise in loperamide abuse was inevitable, with substantial increases in reported cases over the last decade. Five fatal cases of toxic medication use where loperamide was listed as a primary or contributory cause of death were identified at the Medical University of South Carolina. The characteristic autopsy demographics and findings are described, and the mechanisms of abuse and toxicity of loperamide are reviewed. Loperamide overdoses are a growing concern from both a forensic and clinical standpoint, and the frequency of reported cases will likely increase as awareness grows within the medical and toxicological communities.

Loperamide-Induced Torsades de Pointes: A Case Series.

BACKGROUND: Loperamide is an over-the-counter, inexpensive, antidiarrheal opioid that can produce life-threatening toxicity at high concentrations. CASE REPORT 1: A 28-year-old man with a history of depression and substance abuse disorder (SUD) presented to the emergency department (ED) with shortness of breath and lightheadedness. He ingested large amounts of loperamide daily. The patient's initial electrocardiogram (ECG) demonstrated sinus rhythm, right axis deviation, undetectable PR interval, QRS 168 ms, and QTc 693 ms. He was administered intravenous sodium bicarbonate and magnesium sulfate and admitted to the intensive care unit, eventually developing Torsades de Pointes (TdP). He was given lidocaine and isoproterenol infusions, and an external pacemaker was placed. He was discharged in stable condition on hospital day (HD) 16. CASE REPORT 2: A 39-year-old woman with a history of hepatitis C, depression, and SUD was transported to the ED after reported seizure-like activity. The patient experienced TdP in the ED and admitted to ingesting large amount of loperamide daily. An ECG demonstrated sinus rhythm, right axis deviation, PR interval 208 ms, QRS interval 142 ms, and QTc 687 ms. She was administered intravenous magnesium, sodium bicarbonate, and isoproterenol. After intensive care unit admission, the patient experienced no further TdP and was discharged on HD 6. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should proceed with caution when treating patients with loperamide toxicity. Even in asymptomatic patients and drug discontinuance, obtain consultation with a medical toxicologist, promptly treat ECG abnormalities aggressively, and admit all patients for further monitoring.

Unexpected Serious Cardiac Arrhythmias in the Setting of Loperamide Abuse.

Loperamide (Imodium) is a non-prescription opioid receptor agonist available over-the-counter for the treatment of diarrhea. When ingested in excessive doses, loperamide can penetrate the blood-brain barrier and is reported to produce euphoria, central nervous system and respiratory depression, and cardiotoxicity. There is an emerging trend in its use among drug abusers for its euphoric effects or for self-treatment of opioid withdrawal. We report a case of ventricular dysrhythmias associated with loperamide abuse in a 28-year-old man who substituted loperamide for the opioids that he used to abuse. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp].

Loperamide metabolite-induced cardiomyopathy and QTc prolongation.

Loperamide is an over-the-counter, peripherally acting, µ-opioid receptor agonist used for the treatment of diarrhea. In recent times users have found that at higher doses, loperamide crosses the blood-brain barrier and reaches central µ-receptors in the brain, leading to central opiate effects including euphoria and respiratory depression. We report a case of a 37-year-old female who attempted suicide with over 200 loperamide tablets. During her overdose, her QTc was significantly prolonged at >600 ms. Our case aims to add to the growing body of literature describing life-threatening ventricular arrhythmias associated with loperamide toxicity and further suggests that a metabolite of loperamide, desmethylloperamide, may play a role in the pathogenesis.

Poor Man's Methadone: A Case Report of Loperamide Toxicity.

Loperamide, a common over-the-counter antidiarrheal drug and opioid derivative, is formulated to act upon intestinal opioid receptors. However, at high doses, loperamide crosses the blood-brain barrier and reaches central opioid receptors in the brain, leading to central opiate effects including euphoria and respiratory depression. We report the case of a young man found dead in his residence with a known history of drug abuse. At autopsy, the only significant findings were a distended bladder and bloody oral purge. Drug screening found nontoxic levels of alprazolam, fluoxetine, and marijuana metabolites. Liquid chromatography time-of-flight mass spectrometry found an unusual set of split isotope peaks consistent with chlorine. On the basis of autopsy and toxicological findings, loperamide toxicity was suspected because of its opioid properties and molecular formula containing chlorine. A sample of loperamide was analyzed by liquid chromatography time-of-flight mass spectrometry, resulting in a matching mass and retention time to the decedent's sample. Subsequently, quantitative testing detected 63 ng/mL of loperamide or more than 6 times of therapeutic peak concentration. Cause of death was determined as "toxic effects of loperamide with fluoxetine and alprazolam." Because of its opioid effects and easy accessibility, loperamide is known as "poor man's methadone" and may go undetected at medical and forensic drug screening.

Loperamide dependence and abuse.

Loperamide is a common over-the-counter antidiarrheal considered safe in a broad range of dosages and thought devoid of abuse potential. We describe the first case of a patient with loperamide dependence due to misuse of its opiate-like effects achieved by chronic massive oral ingestions. A 26-year-old man who was taking 800 mg of loperamide per day presented requesting detoxification referral. Loperamide has potential for euphoric effects and information on how to facilitate such effects is easily available. It is important for physicians to be aware of the potential for misuse of and dependence on loperamide, with symptoms mimicking opiate use.

Acute anticholinergic poisoning in children.

We report two cases of unintentional poisoning with anticholinergic agents. The first patient, a 7-year-old girl, was prescribed four different medications by a general practitioner for treatment of abdominal colic and diarrhoea. All drugs had anticholinergic properties. The second patient, a 16-month-old boy, ingested his mother's cyproheptadine tablets. Both children presented with central and peripheral symptoms and signs compatible with acute anticholinergic syndrome. They recovered spontaneously following intravenous fluid replacement and close observation. Gastric lavage was also performed on the boy. Poisoning with cholinergic antagonists in children is a potentially serious hazard in Hong Kong. It may be avoided by careful prescribing on the part of general practitioners and safe storage of all medicinal products in the home environment.

Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose.

We report a case involving a fatal intoxication with loperamide (Imodium). Loperamide is a synthetic opioid of the phenyl piperidine class used as an over-the-counter antidiarrheal. It exerts its effects through interaction with micro-opiate receptors in the intestine to reduce peristalsis. Loperamide lacks the typical euphoric opiate effects when administered at recommended doses. Both loperamide and its major metabolite, N-desmethylloperamide, were isolated by liquid-liquid extraction into n-butyl chloride from alkalinized samples. Extracts were analyzed by liquid chromatography-electrospray-mass spectrometry in selected-ion-monitoring mode. Rapid separation of the drug, metabolite, and internal standard (diphenoxylate) was achieved using a high-resolution C18 column with 1.8-microm particle diameter. The mobile phase consisted of 0.1% formic acid in deionized water (60%) and acetonitrile (40%) at a flow rate of 0.5 mL/min. Heart blood concentrations for loperamide and its metabolite were 1.2 mg/L and 3.3 mg/L, respectively. In contrast, reported peak plasma concentrations of loperamide after administration of recommended daily doses of 16 mg did not exceed 0.012 mg/L in controlled trials. Because the heart blood ethanol concentration was 0.08 g/dL, the medical examiner ruled that the cause of death was loperamide and ethanol intoxication, and the manner of death as undetermined.

[Relapse of Creosote poisoning: report of a case taking Seirogan tablets].

A thirty-eight year old man took about 180 tablets of Seirogan. He was unconscious and had dyspnea with dark brown urine on admission. He recovered gradually after initial treatment. Seirogan contains a phenolic component. Symptoms and signs of poisoning are unconsciousness, convulsion, digestive tract disorder, pulmonary edema, hepatic failure, renal failure, and miosis. Clinical features include dark brown urine. On day 7, he again showed signs of creosote poisoning: relapse of unconsciousness and dark colored urine. Plasma concentration of phenol determined on the day before the relapse was much higher than that expected from the half-life of blood phenol. It is reported that Creosote poisoning results in a decrease in the intestinal peristalsis, or paralytic ileus. We would like to emphasize that a relapse of Creosote poisoning may occur due to possible delayed absorption of the Seirogan tablets.

Surveillance of loperamide ingestions: an analysis of 216 poison center reports.

BACKGROUND: Loperamide was approved for nonprescription use in 1988. While efficacy is well documented, there are few data on loperamide overdose and management. METHODS: Eight poison centers participated in a prospective study enrolling 216 patients. RESULTS: Where the amount ingested was known, it ranged from 0.03 to 0.94 mg/kg. One- to 3-year-olds were involved in 57.9% of ingestions. Ingestion was unintentional in 182 cases (84.3%), including 59 patients with therapeutic errors (27.3% of all cases). Dispensing cup errors were implicated in 23 cases; 15 patients assumed the dispensing cup was the unit of measure. No symptoms developed in 63.0%; 27.8% had related symptoms. No related symptoms were life-threatening, and no fatalities occurred. The most frequent symptoms were drowsiness (15.7%), vomiting (4.2%), and abdominal pain or burning (3.7%). The frequency of related symptoms was compared in patients receiving the most frequently utilized decontamination modalities: ipecac alone, activated charcoal alone, lavage and activated charcoal, and ipecac and activated charcoal. Compared to the 112 patients who received no decontamination, only the ipecac-treated group demonstrated a significant reduction in the frequency of related symptoms; 13.9% of patients given ipecac alone (without other gastric decontamination) had related symptoms compared to 33.0% of patients who received no decontamination. Three patients received naloxone for CNS symptoms related to loperamide; two responded and the response of the third was unknown. CONCLUSION: Within the range of doses implicated in this study (up to 0.94 mg/kg), there were no life threatening clinical effects and no fatalities. Development of a management protocol is complicated by the absence of a predictable clinical response in each dose range. The data suggest that children over six months with single acute ingestions up to 0.4 mg/kg, and possibly higher, can be safely managed at home, without gastric decontamination.

Loperamide poisoning in the dog.

A retrospective study was conducted of 40 loperamide poisoning cases recorded at the Centre National d'Informations Toxicologiques Veterinaires. An apparent breed susceptibility of Collie dogs was observed. Neurologic disturbances (ataxia and prostration) were significant clinical findings. Treatment with naloxone resulted in rapid reversal of signs without sequelae.

[Reasec poisoning in childhood]. / Reasec mérgezések gyermekkorban.

Three cases of severe accidental poisoning with "Reasec" in infants and young children are reported. Patients' medical history, the clinical features and ways of antidote administration are described. In severe poisoning in addition to symptomatic intensive care administration of "Narcanti" in continuous infusion is recommended. The necessity of strict observation and ventilation facilities because of the potential respiratory failure is emphasised.

Paregoric intoxication with pulmonary edema in infancy.

This report describes a 3-week-old infant with paregoric intoxication and pulmonary edema. The pulmonary edema associated with opiod use is treatable even though the precise mechanism of its formation remains undefined. The report emphasizes that the medical rationale involved in the use of paregoric is unclear. The use of this preparation in pediatric patients should be abandoned in view of such serious complications.