title: Not your regular high: cardiac dysrhythmias caused by loperamide.
abstract: OBJECTIVE
  Loperamide, a non-prescription anti-diarrheal agent, is a peripheral mu-opioid receptor agonist that is excluded from the blood-brain barrier by p-glycoprotein at therapeutic doses. Overdoses of loperamide penetrate the central nervous system (CNS), leading to abuse. We report cardiac conduction abnormalities and dysrhythmias after ingestion of a recreational supra-therapeutic dose of loperamide confirmed with an elevated blood loperamide concentration.
  
  
  METHODS
  A 48-year-old woman with a history of alcohol and benzodiazepine abuse presented to the emergency department (ED) with somnolence, weakness and slurred speech. She was taking 20 to 40 tablets of 2 mg loperamide 1-2 times/day for weeks along with clonazepam and whiskey. Vital signs were: blood pressure (BP), 124/90 mmHg; heart rate (HR), 88/min; respiratory rate(RR), 20/min; T, 36.9 °C; O2 saturation 100% on room air (RA). Glucose was 6.4 mmol/L. Electrocardiogram (ECG) had a ventricular rate of 58/min, QRS 164 ms, QT 582 ms with no discernable p-waves. Lactate was 3.5 mmol/L and potassium was 6.2 mEq/L. Labs were notable for an anion gap of 20 mEq/L, ethanol of 3.9 mmol/L, creatinine of 2.3 mg/dL and loperamide concentration of 210 ng/mL (average therapeutic plasma concentration 1.2 ng/mL). She became hypotensive, but responded to fluids. Following treatment for hyperkalemia with calcium, insulin, dextrose, and hypertonic sodium bicarbonate a repeat ECG had a ventricular rate of 66/min, QRS 156 ms, and QT 576 ms. Magnesium was given and pacer pads were placed. During the infusion of magnesium, her BP fell to 92/58 mmHg with a HR of 54/min, RR 14/min, O2 saturation of 97% on RA so the infusion was stopped. The ECG after the magnesium infusion had a ventricular rate of 51/min, QRS of 134 ms, and QT 614 ms. In the ICU she had multiple runs of non-sustained ventricular tachycardia that did not require therapy. Over the next 48 h she improved and was transferred to a floor bed. On day four of hospitalization the patient left against medical advice. At that time, her ECG showed sinus tachycardia with a heart rate 114/min, QRS 82 ms, QT 334 ms.
  
  
  CONCLUSIONS
  Loperamide produces both QRS and QT prolongation at supra-therapeutic dosing. A blood loperamide concentration of 210 ng/mL is among the highest concentrations reported. Supra-therapeutic dosing of loperamide is promoted on multiple drug-use websites and online forums as a treatment for opioid withdrawal, as well as for euphoric effects. With the current epidemic of prescription opioid abuse, toxicity related to loperamide, an opioid agonist that is readily available without a prescription is occurring more frequently. It is important for clinicians to be aware of the potentially life-threatening toxicity related to loperamide abuse in order to provide proper diagnosis, management and patient education.
authors.affiliation: a Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine , NYU School of Medicine , New York , NY , USA ;
authors.forename: Rachel Sarah
authors.initials: RS
authors.lastname: Wightman
authors.affiliation: a Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine , NYU School of Medicine , New York , NY , USA ;
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hoffman
authors.affiliation: a Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine , NYU School of Medicine , New York , NY , USA ;|b St. John's University College of Pharmacy and Health Sciences , Department of Emergency Medicine, Division of Medical Toxicology , New York , NY , USA ;
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Howland
authors.affiliation: c Ronald O. Perelman Department of Emergency Medicine , NYU School of Medicine , New York , NY , USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Rice
authors.affiliation: a Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine , NYU School of Medicine , New York , NY , USA ;
authors.forename: Rana
authors.initials: R
authors.lastname: Biary
authors.affiliation: a Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine , NYU School of Medicine , New York , NY , USA ;
authors.forename: Daniel
authors.initials: D
authors.lastname: Lugassy
mesh_terms: D000437:Alcoholism / Q000150:complications; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000175:diagnosis; D001569:Benzodiazepines; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects / Q000503:physiopathology; D002998:Clonazepam / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose / Q000150:complications* / Q000175:diagnosis; D004562:Electrocardiography; D004636:Emergency Service, Hospital; D005260:Female; D005947:Glucose / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced / Q000188:drug therapy; D007328:Insulin / Q000627:therapeutic use; D008139:Loperamide / Q000097:blood / Q000506:poisoning*; D008274:Magnesium / Q000627:therapeutic use; D008875:Middle Aged; D056152:Respiratory Rate / Q000187:drug effects; D017693:Sodium Bicarbonate / Q000627:therapeutic use; D019966:Substance-Related Disorders / Q000188:drug therapy
chemical_list: D007328:Insulin; D001569:Benzodiazepines; D002998:Clonazepam; D008139:Loperamide; D017693:Sodium Bicarbonate; D008274:Magnesium; D005947:Glucose; D002118:Calcium
keywords: Drug abuse; dysrhythmia; loperamide