Loperamide Abuse/Misuse/Addiction and Cardiac Conduction Disturbances — Article Clearinghouse [UPDATED 2 Aug 2016]

loptabMad Margaret’s Loperamide Clearinghouse is here!

Below you will find medical articles published recently regarding loperamide abuse and its cardiac effects. I will add more as they are published (or as I discover them) so please stop back now and again for updates.

Most of these are citations only — they may only link to an abstract. You may order copies of the full papers from your local library. Medical professionals may download originals through their affiliated sources. I have ordered and read all of the full articles.

Publicly-available, web-based information is included with authors, source information, and a link to the original citation. Copyrights belong to original authors; no copyright by me is implied or claimed. These links and articles are provided for educational and public health purposes only.

Some additional related posts:

A few definitions that will help comprehension for our non-medical-personnel readers: QT/QTc, Ventricular TachycardiaTorsade de Pointes

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untitled

Bradycardia-induced Torsade de Pointes EKG strip resultant of Loperamide abuse.

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loptab3Loperamide-Induced Life-Threatening Ventricular Arrhythmia

Ankit Upadhyay, Vijaykumar Bodar, Mohammad Malekzadegan, Sharanjit Singh, William Frumkin, Aditya Mangla, and Kaushik Doshi
Jamaica Hospital Medical Center, Department of Medicine, Jamaica, NY 11418, USA

Abstract: Loperamide is over-the-counter antidiarrheal agent acting on peripherally located 𝜇 opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200mg of Loperamide daily for last two days before the cardiac arrest.We hypothesize that the patient’s QTc prolongation and subsequent cardiac arrest are due to Loperamide toxicity. Patient experienced gradual resolution of tachyarrhythmia and gradual decrease in QTc interval during hospitalization which supports the evidence of causal relationship between Loperamide overdose and potentially fatal arrhythmias. It also provided the clue that patient may have congenital long QT syndrome which was unmasked by Loperamide causing ventricular arrhythmias. This case adds one more pearl in the literature to support that Loperamide overdose related cardiac toxicity does exist and it raises concerns over Loperamide abuse in the community.

Hindawi Publishing Corporation
Case Reports in Cardiology
Volume 2016, Article ID 5040176, 3 pages

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loptab3Electrocardiographic Abnormalities, Malignant Ventricular Arrhythmias and Cardiomyopathy Associated with Loperamide Abuse

VAUGHN, P., SOLIK, M. M. K., BAGGA, S. and J. PADANILAM, B.
St. Vincent Medical Group, Indianapolis, IN

Abstract: A 20-year-old man presented with recurrent syncope and abnormal ECG. His evaluation revealed a prolonged QT interval > 600 ms, witnessed Torsades de Pointes (TdP) and dilated cardiomyopathy. At his initial admission, an ICD was implanted and atrial pacing at 80 beats per minute suppressed ventricular arrhythmias.  The patient was readmitted with device infection and recurrent TdP leading to intubation. This led to the discovery of a hitherto unrevealed loperamide abuse and his cardiac arrhythmias and LV dysfunction were determined to be related to large doses of loperamide. Following abstinence, his ejection fraction and ECG returned to normal.

Journal of Cardiac Electrophysiology
27 July 2016 Accepted Author Manuscript. doi:10.1111/jce.13052

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loptab3Loperamide-related Deaths in North Carolina

Sandra C. Bishop-Freeman, Marc S. Feaster, Jennifer Beal, Alison Miller, Robert L. Hargrove, Justin O. Brower and Ruth E. Winecker
North Carolina Office of the Chief Medical Examiner, Raleigh, NC 27607, USA

Abstract: Loperamide (Imodium®) has been accepted as a safe, effective, over-the-counter anti-diarrheal drug with low potential for abuse. It is a synthetic opioid that lacks central nervous system activity at prescribed doses, rendering it ineffective for abuse. Since 2012, however, the North Carolina Office of the Chief Medical Examiner has seen cases involving loperamide at supratherapeutic levels that indicate abuse. The recommended dose associated with loperamide should not exceed 16 mg per day, although users seeking an opioid-like high reportedly take it in excess of 100 mg per dose. When taken as directed, the laboratory organic base extraction screening method with gas chromatography-mass spectrometry/nitrogen phosphorus detector lacks the sensitivity to detect loperamide. When taken in excess, the screening method identifies loperamide followed by a separate technique to confirm and quantify the drug by liquid chromatography-tandem mass spectrometry. Of the 21 cases involving loperamide, the pathologist implicated the drug as either additive or primary to the cause of death in 19 cases. The mean and median peripheral blood concentrations for the drug overdose cases were 0.27 and 0.23 mg/L, respectively. Furthermore, an extensive review of the pharmacology associated with loperamide and its interaction with P-glycoprotein will be examined as it relates to the mechanism of toxicity.

Journal of Analytical Toxicology
doi: 10.1093/jat/bkw069; First published online: July 29, 2016

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loptab3Conduction Disturbances and Ventricular Arrhythmias Associated with High-Dose Loperamide

Galen Leung, Diana Altshuler, Ronald Goldenberg, David Fridman and Eugene Yuriditsky
New York University School of Medicine, New York, USA

Abstract: Although loperamide has been widely used for the treatment of diarrhea, there is growing popularity over its abuse potential in alleviating opioid-withdrawal symptoms and achieving euphoria. Toxic levels of loperamide have been associated with life-threatening ventricular tachyarrhythmias and cardiac arrest. We report a case of high-dose loperamide ingestion in a patient presenting initially with unstable bradycardia followed by episodes of polymorphic ventricular tachycardia, and an unmasked Brugada ECG pattern. This is the first such report of the Brugada pattern being unmasked on ECG with loperamide ingestion. The patient stabilized with supportive care without the need for inotropic support. We discuss potential mechanisms of toxicity leading to conduction abnormalities and provide a literature review of all published cases of loperamide toxicity to describe proposed treatment options. Recognition of the abuse potential and hazards of this over-the-counter anti-diarrheal therapy will alert the clinician of associated toxidromes and management strategies.

Journal of Clinical Toxicology
doi 10.4172/2161-0495.1000309; First published online: June 30, 2016

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loptab3Poster Session: Life-threatening Arrhythmias Associated with Loperamide and Cimetidine Abuse

Charles W. O’Connell 1, 2; Amir A. Schricker 3; Aaron B. Schneir 1; Imir G. Metushi 4; Ulrika Birgersdotter-Green 3;  Alicia B. Minns 1,2
1. Division of Medical Toxicology, Department of Emergency Medicine, UCSD
2. Department of Emergency Medicine, VA San Diego
3. Division of Cardiovascular Medicine, UCSD
4. Center for Advanced Laboratory Medicine, UCSD

Conclusions: Loperamide, taken chronically and and in high doses, can cause life- threatening cardiac conduction dysfunction and ventricular arrhythmias. The effects can be seen many days after discontinuation. Isoproterenol used to increase heart rate may be a useful medicinal modality to limit arrhythmogenic effects in the setting of loperamide overdose.

2016 American College of Medical Toxicology
ACMT Annual Scientific Meeting
Bench to Bedside: Neurologic and Metabolic Toxins
March 18-20, 2016
SOURCE

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loptab3Cimetidine/loperamide overdose and abuse; Various toxicities: case report

Authors presently unknown.

Reactions Weekly, June 2016, Volume 1605, Issue 1, pp 49-49

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loptab3Loperamide Abuse Associated With Cardiac Dysrhythmia and Death

William Eggleston, PharmD a; Kenneth H. Clark, MD b; Jeanna M. Marraffa, PharmD, DABAT c
a Upstate New York Poison Center, Syracuse, NY;
b Onondaga County Office of the Medical Examiner, Syracuse, NY;
c Department of Emergency Medicine, SUNY Upstate Medical University Hospital, Syracuse, NY

Abstract: Loperamide is an over-the-counter antidiarrheal with μ-opioid agonist activity. Central nervous system opioid effects are not observed after therapeutic oral dosing because of poor bioavailability and minimal central nervous system penetration. However, central nervous system opioid effects do occur after supratherapeutic oral doses. Recently, oral loperamide abuse as an opioid substitute has been increasing among patients attempting to self-treat their opioid addiction. Ventricular dysrhythmias and prolongation of the QRS duration and QTc interval have been reported after oral loperamide abuse. We describe 2 fatalities in the setting of significantly elevated loperamide concentrations.

© 2016 American College of Emergency Physicians        doi:10.1016/j.annemergmed.2016.03.047; Available online 29 April 2016

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loptab3Not your regular high: Cardiac dysrhythmias caused by loperamide

DOI: 10.3109/15563650.2016.1159310 Rachel Sarah Wightmana*, Robert S Hoffmana, Mary Ann Howlandab, Brian Ricec, Rana Biarya & Daniel Lugassya

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; c Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York, NY, USA

Discussion: 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.

Clinical Toxicology, Volume 54, Issue 5, 2016, pages 454-458

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loptab3High-dose loperamide abuse–associated ventricular arrhythmias

Charles W. O’Connell, MD-1, Amir A. Schricker, MD-2, MS, Aaron B. Schneir, MD-1, Imir G. Metushi, PhD-3, Ulrika Birgersdotter-Green, MD-2, Alicia B. Minns, MD-1

1 Division of Medical Toxicology, Department of Emergency Medicine, University of California – San Diego, San Diego, California; 2 Division of Cardiovascular Medicine, University of California – San Diego, San Diego, California; 3 Center of Advanced Laboratory Medicine, University of California – San Diego, San Diego, California

Conclusion: This case details the very serious and potentially life-threatening cardiac dysrhythmias that are associated with both chronic and very high doses of loperamide. Loperamide may not be as innocuous as once thought, when purposefully abused in chronic, high quantities. Isoproterenol infusion was very successful in eliminating ventricular arrhythmias in this setting. Loperamide overdose should be considered, when case appropriate, as a potential cause in similar cases of significant cardiac syncope and cardiac conduction disturbances with prolonged QRS and QTc intervals. Given the ubiquity of loperamide and the epidemic of opioid abuse, this may represent a growing problem. The number of new cases warrants further investigation and physician provider awareness.

Heart Rhythm Case Reports
Published Online: March 07, 2016, Open Access DOI: http://dx.doi.org/10.1016/j.hrcr.2016.01.002

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loptab3An Additional Clinical Scenario of Risk for Loperamide Cardiac-Induced Toxicity
Gilberto Fabián Hurtado-Torres, MD, MEda Rosa Laura Sandoval-Munro, MDb

a Internal Medicine and Clinical Nutrition Department Hospital Central Dr Ignacio Morones Prieto/UASLPS an Luis Potosí, Mexico; b Faculty of Medicine University of San Luis Potosí San Luis Potosí, Mexico

Excerpt: Because the drug is available over the counter, unregulated use is frequent to control gastrointestinal symptoms, mainly diarrhea and unfortunately as an increasing nonillicit drug of abuse in opioid users. Another potential clinical condition with risk of loperamide electrophysiologic side effects derives from the wide use and proven utility of loperamide in the management of loop ileostomy and short bowel syndrome-associated diarrhea.

The American Journal of Medicine 04/2016; 129(4):e33. DOI: 10.1016/j.amjmed.2015.10.041

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loptab3Loperamide Induced Torsades de Pointes: A Case Report and Review of the Literature

O. Mukarram, 1; Y. Hindi, 1; G. Catalasan, 2; and J. Ward, 3

1 Department of Internal Medicine, Texas Tech University Health Sciences Center, Permian Basin, USA; 2 Department of Critical Care, Texas Tech University Health Sciences Center, Midland Memorial Hospital, Midland, TX, USA; 3 Department of Clinical Pharmacology, Medical Center Hospital, Odessa, TX, USA

Abstract: Abuse of over the counter drugs often gets overlooked by health care providers. Loperamide is one such over the counter drug that is often abused by drug addicts. We present here a case of a young male attaining euphoria from taking massive doses of loperamide. He developed Torsades de Pointes and subsequent cardiac arrest. We found similarities in the progression of myocardial electrical conduction abnormalities among loperamide and other previously known arrhythmogenic drugs. We intend to raise concern over the ease of availability of such drugs over the counter and increase the index of suspicion for over the counter drug abuse from our experience.

Case Reports in Medicine
Volume 2016 (2016), Article ID 4061980, 3 pageshttp://dx.doi.org/10.1155/2016/4061980

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loptab3Ventricular Dysrhythmias from Loperamide Misuse

Daniel R. Lasoff, MD Veterans’ Administration Medical Center, San Diego, California
Aaron Schneir, MD Department of Emergency Medicine, Division of Medical Toxicology, University of California, San Diego Health System, San Diego, California

Abstract: We would like to alert emergency physicians to the potential for cardiac dysrhythmias associated with the misuse of loperamide. Multiple websites and online forums have described using high doses of oral loperamide for recreational abuse and amelioration of opioid withdrawal (1). A burgeoning number of reports have detailed the potential for QRS width prolongation, QTc prolongation, ventricular dysrhythmias, and cardiac arrest with this practice (2–6). We recently were involved in the management of such a patient.

Journal of Emergency Medicine

March 2016, Volume 50, Issue 3, Pages 508–509

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loptab344. An unusual method of loperamide abuse leading to opiate withdrawal

Lauren M Graham, Joseph H Yanta
University of Pittsburgh Medical Center, Pittsburgh PA USA

Excerpt: Cessation of loperamide abuse can lead to withdrawal symptoms similar to those seen with other centrally acting opiates…. Conclusion: While usually considered safe, clinicians should be aware of the abuse-potential of loperamide when used in conjunction with CYP3A4 and p-glycoprotein modulators like grapefruit juice and cimetidine.

Abstracts from the 2015 Annual Meeting of the North American Congress of Clinical Toxicology (NACCT)

Clinical Toxicology (2015), 53, 639–777
Copyright © 2015 Informa Healthcare USA, Inc.
ISSN: 1556-3650 print / 1556-9519 online
DOI: 10.3109/15563650.2015.1071025

LINK

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loptab350. Buprenorphine induced acute precipitated withdrawal in the setting of loperamide abuse

William Eggleston2, Nicholas Nacca1, Jeanna M Marraffa1
1SUNY Upstate Medical University, Department of Emergency
Medicine, Syracuse NY USA, 2SUNY Upstate Medical University,
Upstate New York Poison Center, Syracuse NY USA

Conclusion: Loperamide abuse may be associated with a withdrawal syndrome in the setting of drug discontinuation. Use of buprenorphine in patients actively intoxicated with loperamide may cause rapid reversal of mu-receptor agonism and induce acute precipitated withdrawal.

Abstracts from the 2015 Annual Meeting of the North American Congress of Clinical Toxicology (NACCT)

Clinical Toxicology (2015), 53, 639–777
Copyright © 2015 Informa Healthcare USA, Inc.
ISSN: 1556-3650 print / 1556-9519 online
DOI: 10.3109/15563650.2015.1071025

LINK

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loptab3The Long QT Teaser: Loperamide Abuse

Evbu O. Enakpene, M.D., 1; Irbaz Bin Riaz, M.D., MM, 2; Farshad M. Shirazi, MS, M.D. PhD, 3; Yuval Raz, M.D., 4; Julia H. Indik, MD, PhD, 2
1 Sarver Heart Center, University Of Arizona Medical Center, Tucson, Arizona.

2 Sarver Heart Center, University Of Arizona Medical Center, Tucson, Arizona.
3 Center for Pharmacology, Toxicology Education & Research, University of Arizona College of Medicine Phoenix, Arizona; Arizona Poison & Drug Information Center, University of Arizona College of Pharmacy, Tucson, Arizona.
4 Division of Pulmonary and Critical Care Medicine, University of Arizona Medical Center.

The American Journal of Medicine
Accepted Date: 27 May 2015
doi: 10.1016/j.amjmed.2015.05.019.

Excerpt: “The source of a 25-year-old woman’s puzzling signs and symptoms could not be determined until a search of her home yielded the answer….Her ECG irregularities resolved within 1 week, and her pacing thresholds normalized. After she recovered, she finally admitted to chronic abuse of loperamide, which she had denied during previous hospitalizations. Although she had successfully completed a drug rehabilitation program in the past, she began using loperamide after learning about it from Internet sources and friends. Her care required an interdisciplinary approach, including psychosocial counseling and social services. Upon discharge, she was in good condition. Two months after discharge, the patient was readmitted in cardiopulmonary arrest after continued loperamide abuse. Despite being placed on percutaneous femoral venoarterial extracorporeal membrane oxygenation, she had no significant improvement. She died 18 hours after admission.”

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loptab3Loperamide toxicokinetics: serum concentrations in the overdose setting.

Eggleston W1, Nacca N, Marraffa JM.
Clin Toxicol (Phila). 2015 Mar 30:1-2. [Epub ahead of print]

Clinical Toxicology

Excerpt: “A web-based study published in 2013 suggested that loperamide was being abused to attenuate the symptoms of opioid withdrawal. Marraffa et al recently reported a case series of patients who presented with cardiac conduction disturbances
after loperamide abuse. This case series outlined the clinical course of 5 patients, 3 of whom experienced life-threatening arrhythmias. Isolated serum levels were reported in four of these patients. We report a subsequent hospitalization and pharmacokinetic
profile of one of the patients in the case series.”

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loptab3Reply to: “Torsade de Pointes Associated with High‐dose Loperamide Ingestion”

Jeanna M. Marraffa, PharmD, Dabat, Michael G Holland, MD, Michael J Hodgman, MD, Upstate Medical University, Syracuse, New York, NY
Accepted 
March 16, 2015.

Journal of Innovations in Cardiac Rhythm Management, 5 (2015), 1958

Excerpt: “These reports underscore the need for further investigation of the cardiac effects of high‐dose loperamide. Further research into the mechanism of both QRS widening and QTc prolongation is warranted. Clinicians need to consider loperamide abuse in otherwise healthy patients with syncope or ventricular arrhythmias, especially those with a history of drug abuse or opioid dependence.”

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loptab3CASE REPORT: Loperamide dependence and abuse
Ryan MacDonald1, Jason Heiner2, Joshua Villarreal3, Jared Strote2
1Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, Washington, USA ; 2Division of Emergency Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA; 3Department of Pharmacy, University of Washington Medical Center, Seattle, Washington, USA
Published 2 May 2015

BMJ Case Reports 2015; doi:10.1136/bcr-2015-209705

Excerpt: “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.”

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loptab3Ventricular Tachycardia Associated with High-Dose Chronic Loperamide Use

Hannah L. Spinner, 1,* Nick W. Lonardo, 1 Roja Mulamalla, 2 and Josef Stehlik 2
1 Department of Pharmacy, University of Utah Health Care, Salt Lake City, Utah;
2 Division of Cardiovascular Medicine, University of Utah Health Care, Salt Lake City, Utah

PHARMACOTHERAPY:  Article first published online: 3 FEB 2015 DOI: 10.1002/phar.1540

Conclusion: “Our report concurs with two previous observations that patients exposed to high doses of loperamide may be at an increased risk of ventricular dysrhythmias. Further studies are needed to confirm a causal relationship, but clinicians should be aware of possible cardiac adverse effects related to the overuse of loperamide.”

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loptab3Torsade de Pointes Associated with High-dose Loperamide Ingestion

1 LUCAS N. MARZEC, MD, 1,2 DAVID F. KATZ, MD, 1,2 PAMELA N. PETERSON, MD, MSPH, 1  LAUREN E. THOMPSON, MD, 3 MARK C. HAIGNEY, MD and 1,2 MORI J. KRANTZ, MD — 1 Cardiology Division, University of Colorado Hospital, Aurora, CO; 2 Cardiology Division, Denver Health Medical Center, Denver, CO; 3 Cardiology Division, Uniformed Services University, Bethesda, MD

THE JOURNAL OF INNOVATIONS IN CARDIAC RHYTHM MANAGEMENT:  January 2015, vol 6 (2015), pp 1897–1899

Conclusion: “We report a case of markedly prolonged QTc and recurrent TdP in a patient who ingested large doses of loperamide coincident with cimetidine in an attempt to simulate the euphoric effects associated with opioid abuse. This is a sentinel case, as ingestion of large doses of loperamide for self-treatment of opioid withdrawal and as a drug of abuse appears to be increasing through internet dissemination. This may represent a growing public health danger and warrants further investigation.”

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loptab3Cardiac conduction disturbance after loperamide abuse

J. M. Marraffa, M. G. Holland, R. W. Sullivan, B. W. Morgan, J. A. Oakes, T. J. Wiegand, and M. J. Hodgman. 1 Department of Emergency Medicine, Upstate Medical University, Syracuse NY, USA. 2 Department of Emergency Medicine, School of Medicine, Emory University, Atlanta, GA, USA. 3 Department of Emergency Medicine, URMC and Strong Memorial Hospital, Rochester NY, USA. 4 URMC and Strong Memorial Hospital, Ruth A. Lawrence Poison and Drug Information Center, Rochester, NY, USA

CLINICAL TOXICOLOGY: November 2014, Vol. 52, No. 9 , Pages 952-957

Conclusion: ‘This case series describes several patients with cardiac conduction abnormalities and life-threatening ventricular arrhythmias temporally related to loperamide abuse. With the recent efforts to restrict the diversion of prescription opioids, increasing abuse of loperamide as an opioid substitute may be seen. Toxicologists should be aware of these risks and we urge all clinicians to report such cases to FDA Medwatch®”

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loptab3Cardiac Conduction Disturbances Secondary to Chronic Abuse of Loperamide: An Initial Case Report

Audi J,1 Layher J,2 Morgan B.11 Georgia Poison Center and Emory University Department of Emergency Medicine. Atlanta, GA;2 Athens Regional Medical Center. Department of Cardiology. Athens, GA

Journal of Toxicology, CLINICAL TOXICOLOGY, Vol. 42, No. 5, pp. 713–826, 2004

Conclusion: “This is the first case report of an adult with cardiac conduction disturbances following chronic high-dose loperamide use. Negative toxicologic screens, cardiac studies and normal electrolytes, and resolution of cardiac abnormalities after loperamide cessation leaves no other plausible explanation for this presentation.”

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loptab3Syncope and Recurrent Polymorphic Ventricular Tachycardia Following Loperamide Misuse

Jeanna M Marraffa, Michael G Holland, Ross W Sullivan, Robert Seabury, Michael J Hodgman; Upstate Medical University, Syracuse NY USA

From “2013 Annual Meeting of the North American Congress of Clinical Toxicology”

Conclusion: “Massive loperamide abuse may result in QTc prolongation and subsequent recurrent ventricular arrhythmias.”

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loptab31274: Loperamide: The Unexpected Culprit

Pokhrel, Kiran; Rajbhandary, Arunima; Thapa, Jhapat

 Critical Care Medicine: December 2013 – Volume 41 – Issue 12 doi:10.1097/01.ccm.0000440506.29056.c1
Poster Session: Case Reports

Discussion and Conclusion: “Loperamide is not known to cause QTc prolongation but methadone, also an opioid, dose cause QTc prolongation. Loperamide is also structurally similar to Haloperidol which has potential to prolong QTc. To our knowledge there is no known cases of Loperamide induced VT-storm. A case series (n=216) of Loperamide overdose failed to reveal any cardiac toxicity but the maximum ingested dose was 0.94mg/kg which is much less than in our patient. Internet search reveals that Loperamide is popular among substance abusers to prevent opioid withdrawals and to produce euphoric effects. Hence, Loperamide needs to be further evaluated for cardiac toxicity at super high doses.”

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loptab31204: Ventricular Tachycardia Storm – Can It Be A Side Effect From Over the Counter Anti-Diarrheal?

Boppana, V Subbarao; Kahlon, Arundeep; Bhatta, Luna

Critical Care Medicine: December 2012 doi: 10.1097/01.ccm.0000425416.95852.ed
Poster: ABSTRACT Only

Excerpt: “The spectrum of side effects from high doses of loperamide is still unknown. Abrupt resolution of the VT, normalization of QT and lack of the need for an anti-arrhythmic after discontinuation of loperamide in our patient makes us believe a causal relationship, but the pathogenesis remains unclear.”

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loptab31.2 Loperamide Intoxication in the Pursuit of Opioid Effects: Report of Two Fatalities

J. Denton1, A. Youmans 1, V. Arangelovich 2
1 McLean County Coroner’s Office, Bloomington, IL; 2 Will County
Coroners Office, Joliet, IL

National Association of Medical Examiners
Abstracts of the 2013 Annual Meeting
October 12-15, 2013

Excerpt: “We present two deaths from loperamide intoxication from excess ingestion of loperamide pills, likely related to attempts at attaining euphoria. Thorough death investigation, autopsy, and additional toxicology testing studies were required to establish the cause of death.”

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loptab3Systems Pharmacology of Arrhythmias

Seth I. Berger, Avi Ma’ayan, and Ravi Iyengar* Department of Pharmacology and Systems Therapeutics and Systems Biology Center New York, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1215, New York, NY 10029, USA

Science Signaling; 3(118): ra30. doi:10.1126/scisignal.2000723

Excerpt: From P.10: “The identification of such potential signaling pathways provides initial insights. For example, two drugs, dasatinib and loperamide, used to treat different pathophysiologies, cancer and severe diarrhea can have QT prolongation as an adverse event and can be connected to the LQTS disease genes through the LQTS neighborhood (Fig. 5C). The paths can be short; for example, loperamide can be connected to KCNH2 through CALM1 (one step), and dasatinib can be connected to KCNQ1 through PRKACA and SRC (two steps), or more convoluted. Such a tracking exercise provides hypotheses about how these drugs might affect the QT interval and increase TdP risk, which can be used to design experiments in animal models or combined with whole genome information to identify “at-risk” patients.”

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loptab3Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose.

Sklerov J, Levine B, Moore KA, Allan C, Fowler D., Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, 1413 Research Blvd., Rockville, Maryland 20850, USA.

Journal of Analytical Toxicology, 2005 Oct;29(7):750-4.

Abstract: “We report a case involving a fatal intoxication with loperamide (Imodium).”

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loptab3Loperamide Induced Brugada Syndrome

Sheyman, D.O. | Robert Crake, D.O.; Ohio Valley Medical Center, Wheeling WV; Feb 2014

February 2014 — Poster Presentation

Conclusion: 
”Although rare, there have been reported cases of antihistamine, cocaine, and psychotropic drug induced Brugada Syndrome. Loperamide is another agent that could induce this syndrome. At present, there are no reported case studies that involve loperamide and Brugada Syndrome, however, because of the patients lack of family or personal history of cardiac problems we believe this may be the first case of loperamide induced Brugada Syndrome.”

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loptab3A Web-based Study of Extra-medical Use of Loperamide: “I just wanted to tell you that loperamide WILL WORK”:

Raminta Daniulaitytea, Robert Carlsona, Russel Falcka, Delroy Cameronb, Sujan Pererab, Lu Chenb, Amit Shethb; a Center for Interventions, Treatment, and Addictions Research (CITAR), Department of Community Health, Boonshoft School of Medicine, Wright State University, United States; b Ohio Center of Excellence in Knowledge-Enabled Computing (Kno.e.sis), Wright State University, United States1

Drug and Alcohol Dependence: LINK1: Poster session — LINK2: Published Paper
Accepted 3 November 2012. Available online 30 November 2012

Conclusions: “This study suggests that loperamide is being used extra-medically to self-treat opioid withdrawal symptoms. There is a growing demand among people who are opioid dependent for drugs to control withdrawal symptoms, and loperamide appears to fit that role. The study also highlights the potential of the Web as a “leading edge” data source in identifying emerging drug use practices.”

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loptab3Characterizing the abuse potential of loperamide via physiologically-based pharmacokinetic/pharmacodynamic modeling and simulation

Garrett Ainslie 1,2, Evan Kharasch 3, Gary Pollack 2, and Mary Paine 1,2

1 Curriculum in Toxicology University of North Carolina Chapel Hill NC United States
2 College of Pharmacy Washington State University Spokane WA United States
3 Dept of Anesthesiology Washington University St Louis MO United States

April 2014 The FASEB Journal vol. 28 no. 1 Supplement 1053.6

From the Abstract: “Increased restrictions on opioid prescribing may fuel alternate means of abuse. Anecdotal reports suggest abuse of the over-the-counter opioid loperamide when taken at supratherapeutic doses with CYP3A/P-gp inhibitors.”

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loptab3Loperamide overdose-induced catatonia: potential role of brain opioid system and P-glycoprotein

Enrica Di Rosa a1 and Antonio E. Di Rosa a2

a1 Department of Clinical and Experimental Medicine, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy
a2 Department of Neurosciences, University of Messina, via Consolare Valeria, 1, 98125, Messina, Italy

Acta Neuropsychiatrica / Volume 26 / Issue 01 / February 2014, pp 58-60

From the Abstract: “We describe the case of a 20-year-old man who presented with severe catatonia following excessive intake of loperamide…”

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Editing note: I decided, out of respect to the authors, to not include content without permission aside from a notable quote that summarizes the article. But if you follow the links, I assure you, you’ll find what you’re looking for. Originally published 03 Apr 14.

 

About madmargaret

Nursing student, Mac nerd, medical 'genius', recovering addict, singer, ex-actor, and all-around swell egg. Really!
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6 Responses to Loperamide Abuse/Misuse/Addiction and Cardiac Conduction Disturbances — Article Clearinghouse [UPDATED 2 Aug 2016]

  1. thebrog1 says:

    I finally found what I have been searching for. Finally the stark reality that I can in fact be addicted to loperamide. I’m so happy and grateful to have found someone that can relate to what I’m going through. I was actually searching for ways to increase my loperamide dosage , when I stumbled across your blog. I can say I won’t be increasing my dosage. I will be contacting my doctor first thing Monday morning to get the help I need to get through withdrawal. Just the idea of dying is enough for me. I’ve had my battles from opiates to suboxone to tramadol and now loperamide. Just when I thought I was doing ok I noticed my need to increase my dose of loperamide. I know it’s not going to be an easy road but I’m ready to start over.

    • madmargaret says:

      Good for you and best of luck in your detox. Print out some of these articles and take them with you to the doctor — just to be sure he/she takes you seriously. You can do it — and PLEASE keep in touch and let me know how you’re doing.

  2. halestorm12 says:

    Thank you so much for your continued research and updates on loperamide. It took me a year of anxiety, journaling, and Googling to finally deduce that my heart issues were stemming from the lope. I lost my job and nearly my mind. I had symptoms of congestive heart failure, at its worst obviously when I was taking over 100 pills a day, but still persisting as my dose got smaller and smaller. I took my last dose yesterday (13 pills) and I’m stopping there. The information you provided is exactly what I needed to keep me on the right track. Thank you so much.

    Also, I came across an article or two just yesterday that stated that loperamide may affect affect calcium channels in the heart, that would explain the arrhythmias. Just interesting.

    Hales

    • madmargaret says:

      Hi Hales — You’re very welcome, and I’m so glad it’s helping you. That’s what it’s there for. But you did all the work for yourself. I’m thrilled for you that you’ve been able to successfully taper down on the loperamide. It’s hard — and it sucks that you had to lose your job and experienced the heart issues too. Take comfort in the knowledge that most research indicates loperamide-induced cardiac arrthythmias resolve themselves once the loperamide is withdrawn. You’re very lucky (and smart) to bravely taper down by yourself before you landed in hospital. As long as you stay off the lope, you’ll do well.

      Regarding loperamide’s calcium channel blockade action, it was me who initially remarked on it as it’s proven in my extensive research (many more articles than are listed here). Further analysis is being performed on a much higher level than mine where they continue scrutinizing the data for publication. Stay tuned. Further published papers will be added, I’m sure. You heard it here first. 🙂

      Again, thank you for writing and please stay in touch Hales!

      MM

  3. tgill42 says:

    Thanks so much for this MM. There is precious little of any significance out there about lope addiction. You could be starting the most important conversation in many peoples lives. Thank you.

    I’ve only been doing this lope thing about a month, and it was only as a “tide me over” when I ran out of my monthly suboxone. Problem was, last month, when I also added in some methadone to that “tide me over” I put myself into the absolute worst precipitated WD’s. Now I’m terrified of doing it again. I have almost two months worth of subs in my medicine cabinet, simply because I’m afraid to switch back.

    I’ve been using the Walmart dose of 144 tabs a day. In your opinion, how long do I need to wait after my last dose of lope to switch over to subs. My usual sub dose is 16 mg day. Any advice would be greatly appreciated. And, FYI, I plan on staying on subs for life if need be. It’s saved me, and the way I see if is, if I was diabetic, I’d take insulin the rest of my life. I’m an addict and if I have to take subs the rest of my life to stay of opioids then I will.

    Anyways, any thoughts would be great. Thanks so much for all you’ve done already.

    Regards,
    tgill42

  4. madmargaret says:

    Hi — sorry it took me a bit to get back to you. Regarding subs, you have to be very well along in withdrawal, so based on half life reduction, I would say NO less than three days (a full 36 hours) from last dose. Longer if you can hold out. Any less time and you will likely end up in miserable, precipitated withdrawal. You also may not need 16mg to start!! That’s A LOT. Try a smaller dose first and go up from there only if you need to. Remember you are planning to go from a drug that barely crosses into the brain to one that does. Potential for wreaked havoc.

    I know you’ve pretty much made your mind up about this, but I honestly wish you would consider tapering off the lope instead of adding another opiate drug that will worsen your addiction. I was originally planning to go the sub route too (same reason as you) and the NP talked me out of it and I am VERY glad I didn’t. Comfort meds and time… it was rough and I never EVER want to go through it again, but at least I’m free now and getting my brain back more and more every day. That wouldn’t be happening if I switched to subs.

    Also, if you choose to go that way, don’t plan on staying on subs for life. Honestly, it’s a miserable existence. I’ve talked to so many people who wish they’d never even started taking it. Plan on reducing (tapering) the subs according to whatever your doctor recommends. Your brain will heal itself back to normal but it takes time. The subs are safer than lope, but they introduce a whole new level of issues.

    My best advice is for you to get a doctor (or find your own Square-Jawed NP) on your side who can help you through this and get clean for real. You’ll thank yourself later.

    My best wishes — and please keep in touch and let me know how and what you do!!

    MM

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