Loperamide Abuse Research Articles

Loperamide abuse and overdose

Loperamide abuse and overdose

Cardiac Dysrhythmias Associated With Substitutive Use of Loperamide: A Systematic Review.

Recently, several deaths secondary to cardiac arrhythmias have been reported in association with substitutive use of loperamide. Therefore, we conducted a systematic review of all reported cases to overview the epidemiologic patterns and clinical outcomes to better elucidate loperamide-induced cardiac complications. Association between substitutive use of loperamide and cardiac arrhythmias. A comprehensive literature search was conducted across 6 databases using variety of keywords to identify all reports of cardiac side effects associated with loperamide abuse. Only original case reports of cardiac toxicity or cardiac arrhythmias after loperamide abuse or overuse were included. Data were extracted by 2 authors independently using a structured template from the selected reports. Quality assessment of the reports was performed by using a high-quality evaluation tool. Thirteen reports describing 19 cases were included in our review. Except for coronary artery spasm in one case, cardiac arrhythmias were the major reported cardiac adverse event. The average age of patients was 31 years with majority being men (79%). The most common presentation was syncope (63%). All cases were reported in US except for 1 case. Three patients were concomitantly taking cimetidine, which is known to cause inhibition of CYP3A4 and CYP2C8 leading to increased levels of loperamide. Thirteen of 19 patients were successfully treated and discharged in a stable condition. Our results indicate that measures such as restricting over-the-counter availability of loperamide and increasing awareness regarding loperamide's toxicity are imperative to prevent deaths associated with loperamide abuse.

Loperamide abuse

Loperamide abuse

Loperamide Abuse and Dependence: Clinical Features and Treatment Considerations

: Opioid use disorder and its associated mortality have become national epidemic problems. Different measures and regulations have been implemented to curb this trend, including stricter opioid prescribing practice. With the decreased access to prescription opioids, individuals with opioid use disorder have explored alternatives including loperamide, a peripheral opioid mu-receptor agonist. There are reports of increased loperamide misuse, dependence, and mortality rate in the past few years from poison control centers, medical examiners' offices, and clinical settings. Here, we report a case of loperamide use disorder, which led to the death of the patient. Associated clinical features and treatment of loperamide use disorder, including management of intoxication and withdrawal, and long-term maintenance therapy are discussed along with potential prescribing and sale regulations to manage this newly emerging substance use disorder.

Loperamide Abuse in a Soldier

Loperamide Abuse in a Soldier

Cardiac Toxicity Due to High-Dose Loperamide Therapy

Introduction: There has been a tragic increase in the adverse events seen with the use of loperamide owing to abuse by opiate addicted individuals. Loperamide is a peripherally acting Mμ-opioid agonist which binds receptors in the digestive tract slowing intestinal transit, and does not cross the blood-brain barrier at prescribed doses owing to an efflux transporter. However, when used at extremely high doses, euphoric effects similar to opiate use may occur as the drug overwhelms the efflux transporter, crossing the blood-brain barrier. Only two cases have been reported in the literature of the cardiac effects of loperamide overdose in IBD, although both individuals had a history of substance abuse, and the overdoses were attributed to its euphoric rather than anti-diarrheal effects. We present a case of a life-threatening EKG changes in the setting of excess loperamide use for its anti-diarrheal properties in the setting of IBD. CASE: Our patient is a 27 year-old Caucasian man with Crohn's disease and no history of substance abuse. He was managed in a step-up approach, eventually requiring adalimumab five years after diagnosis. He then developed obstructive symptoms requiring an ileocecectomy. He did well after surgery and resumed adalimumab. Unfortunately, the patient was lost to follow-up, and later revealed that he stopped adalimumab therapy because he felt well and did not want to continue this medication. Nineteen months later, he presented to the emergency room with pre-syncopal symptoms. He had markedly prolonged QT intervals and a wide QRS, resembling a sine wave at only 100 beats per minute with normal electrolytes. He underwent extensive evaluation and ultimately was diagnosed with an arrhythmia due to loperamide toxicity. He revealed that he had been ingesting 80-90mg of loperamide daily to help control his diarrhea after discontinuing adalimumab. On follow up his QT intervals and QRS improved after discontinuation of loperamide. DISCUSSION: This demonstrates one of the dangerous consequences of loperamide toxicity. Our case represents the first reported case of cardiac-related loperamide toxicity as a consequence of anti-diarrheal management in a patient with uncontrolled IBD. Typically this toxicity is seen in opioid addicted individuals; however, our case highlights the fact that providers must be cognizant of loperamide abuse in all settings.2063 Figure 1. The initial EKG showed a very wide QRS complex that fuses with QT, producing what looks like a sine wave. This is illustrated best by the red arrows. Given normal electrolytes, this is a result of loperamide toxicity and can predispose to torsades de pointes.

Loperamide abuse and overdose

Loperamide abuse and overdose

Cardiac electrophysiological effects of loperamide mimick clinical misuse and abuse outcome

Cardiac electrophysiological effects of loperamide mimick clinical misuse and abuse outcome

P4789Cardiac complications after loperamide abuse

P4789Cardiac complications after loperamide abuse

Loperamide abuse and overdose

Loperamide abuse and overdose

Brugada-Type Pattern on Electrocardiogram Associated with High-Dose Loperamide Abuse

BackgroundLoperamide has been increasing in popularity recently for its effects separate from treatment of diarrhea. In large doses or in combination with other agents, it can lead to desirable effects in the central nervous system. However, cardiotoxicity has been reported with its abuse. Case ReportA 49-year-old male who had been chronically abusing loperamide was found to have Brugada-like changes on his electrocardiogram (ECG). He had no other clinical symptoms associated with Brugada syndrome and did not have similar findings on previous ECGs. After abstaining from further loperamide use during hospitalization, this pattern slowly resolved without clinically significant dysrthymias. Why Should an Emergency Physician Be Aware of This?A patient with a history of loperamide abuse is at risk for cardiotoxicity. While other dysrhythmias are reported more commonly with loperamide abuse, Brugada-like ECG changes can occur and warrant appropriate consultation and prompt follow-up.

Molecular determinants of loperamide and N-desmethyl loperamide binding in the hERG cardiac K+ channel

Abuse of the common anti-diarrheal loperamide is associated with QT interval prolongation as well as development of the potentially fatal arrhythmia torsades de pointes. The mechanism underlying this cardiotoxicity is high affinity inhibition of the human ether-a-go-go-related gene (hERG) cardiac K+ channel. N-Desmethyl loperamide is the major metabolite of loperamide and is a close structural relative of the parent molecule. To date no information is available regarding the affinity of N-desmethyl loperamide for human cardiac ion channels. The effects of N-desmethyl loperamide on various cloned human cardiac ion channels including hERG, KvLQT1/mink and Nav1.5 were studied and compared to that of the parent. N-Desmethyl loperamide was a much weaker (7.5-fold) inhibitor of hERG compared to loperamide. However, given the higher plasma levels of the metabolite relative to the parent, it is likely that N-desmethyl loperamide can contribute, at least secondarily, to the cardiotoxicity observed with loperamide abuse. We used the recently solved cryo-EM structure of the hERG channel together with previously published inhibitors, to understand the basis of the interactions as well as the difference that a single methyl plays in the hERG channel blocking affinities of these two compounds.

Loperamide abuse

Loperamide abuse

Loperamide cardiotoxicity: "A Brief Review".

Loperamide is a popular antidiarrheal medication that has been used for many years. It is currently gaining more attention among healthcare professionals due to its increasing potential for side effects. At present, it is considered safe enough to be sold over the counter. In contrast with other opioid agonists, loperamide is a peripherally acting μ-receptor agonist exerting its effects mainly on the myenteric plexus of the gastrointestinal longitudinal muscle layer. It decreases peristalsis and fluid secretion resulting in longer gastrointestinal transit time. The bioavailability of the drug is extremely low. Moreover, it is actively excluded from the central nervous system; hence, it lacks the central effects of euphoria and analgesia at the recommended dosages. Loperamide abuse has been steadily increasing in the United States. Abusers typically ingest high doses in desire to achieve a satisfactory central nervous system drug penetration. This has made it a potential over the counter substitute for self-treating opioid withdrawal symptoms and achieving euphoric effects.

Seizur-Like Activity and Recurrent Cardiac Arrests in a Healthy 24-Year-Old: Loperamide Abuse; a Case Report and Literature Review

SESSION TITLE: Poisoning and Drug Overdose 2 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Loperamide is a relatively safe OTC anti-motility agent. However, at higher doses it can produce palliation for opiate withdrawal or even frank euphoria. We present an atypical case of loperamide toxicity with seizure like activity and recurrent cardiac arrests, treated successfully with Isoproterenol. CASE PRESENTATION: 24-year-old female transferred for seizure like activity. Her hospital stay was complicated with recurrent cardiac arrests, including pulseless electrical activity (n=1) and subsequently ventricular tachycardia (n=2) successfully resuscitated with standard ACLS protocol. Workup was remarkable for prolonged QTc at 645 milliseconds with no electrolyte imbalances, cardiac enzymes, negative CT brain, video electroencephalogram, and lumbar puncture. Coronary CT confirmed normal cardiac and coronary anatomy. Transthoracic echocardiogram revealed normal structure and function. Trial of IV Isoproterenol achieved normalization of QTc. DISCUSSION: Loperamide is a μ-opioid receptor agonist with poor oral bioavailability, limited GI absorption, and is metabolized by the liver. At super high doses, it is actively transported through the blood brain barrier via an efflux transporter. Our patient reported one year history of loperamide abuse and was treated successfully with isoproterenol infusion making ours the second case reported. The pro-arrhythmic mechanisms of loperamide induced dysrhythmia has been studied using cloned human cardiac sodium and potassium channels. Loperamide inhibits both the Nav1.5 sodium channel and especially the human ether-a-go-go-related gene potassium channel. This study attributed the QRS prolongation to the inhibition of the sodium channel and further devolution into Torsades to the potassium channel inhibition. CONCLUSIONS: Loperamide is increasingly abused for treatment of opioid withdrawal and euphoria. Because it is available without prescription, is not routinely tested for, and does not have a classic clinical presentation, diagnosis of loperamide overdose requires heightened clinical suspicion. Despite an FDA warning, loperamide abuse is on the rise. Therefore, general population and clinicians should be more attuned to the potential of cardiac toxicity, QTc prolongation, and death from loperamide abuse. Further studies need to be done focused on elucidating optimal treatment strategies and improved initial diagnostics. Reference #1: Swank, K et al. (2017). Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse. Journal of the American Pharmacists Association, Vol 10 Reference #2: Eggleston, W et al. (2016). Cardiac Dysrhythmias After Loperamide Abuse - New York 2008 - 2016. Morbidity and Mortality Weekly Report, Vol 65 Reference #3: Kang, J; Compton, D; Vas, R; Rampe, D (2016). Proarrhythmic mechanisms of the common anti-diarrheal medication loperamide; revalations from the opioid abuse epidemic. Naunyn-Schmiedeberg’s Archives of Pharmacology, Vol 389 DISCLOSURE: The following authors have nothing to disclose: Abhinav Mittal, Rahul Sangani, Monica Cerone, Robert Stansbury No Product/Research Disclosure Information

Quantification of Loperamide by Gas Chromatography Mass Spectrometry

Due to reported pharmacological activity similar to classical opioids at supratherapeutic concentrations, abuse of the anti-diarrheal medication loperamide (Imodium AD™) has become a target in the opioid epidemic. While this phenomenon is not new, published quantitative analytical methods use liquid chromatography tandem mass spectrometry. Described here is an 11 min method for quantification of loperamide in postmortem whole blood by gas chromatography mass spectrometry. Validation studies performed followed SWGTOX guidelines and included: accuracy, specificity, limit of detection (LOD), regression model analysis, stability, and matrix recovery enhancement and/or suppression. The accuracy study consisted of inter-day, intra-day, reproducibility and dilution integrity experiments. Inter-day and intra-day accuracy, precision and coefficient of variation (CV) were measured; normalized results were 1.05 ± 0.09 with 8.87% CV (n = 36) and 1.03 ± 0.09 with 8.53% CV (n = 27), respectively. Reproducibility was evaluated through standard addition with an observed CV of 10.84% (n = 10). Dilution integrity (2× and 4×) resulted in 0.94 ± 0.13 with a CV of 13.9% (n = 5). No interference was observed through analyses of the internal standard (loperamide-d6), endogenous compounds (10 blank matrices) or 60 commonly encountered analytes. The LOD/decision point was 100 ng/mL (CV 8.40%). A linear calibration model was established from 100 to 1,000 ng/mL. Stability was examined; observed analyte-to-internal standard response resulted in 6.59% CV. Recovery was determined for loperamide and loperamide-d6 (31% and 36%, respectively). Neither matrix suppression nor enhancement was observed with loperamide at 750 ng/mL and loperamide-d6 at 300 ng/mL (-6.5% and -4.2%); however, some suppression was exhibited at lower concentrations (-39.8%). The designed method was determined to be sufficient for the analysis of loperamide-related death cases in Alabama (n = 8) and offers postmortem toxicology laboratories an alternative approach that is both highly selective and specific.

Loperamide abuse and overdose

Loperamide abuse and overdose

Loperamide abuse

Loperamide abuse

Loperamide abuse.

Loperamide abuse.

Intentional Misuse and Abuse of Loperamide: A New Look at a Drug with “Low Abuse Potential”

BackgroundDespite its opioid properties, loperamide has long been thought to have low abuse potential due to its poor absorption from the gastrointestinal tract and limited potential to cross the blood–brain barrier. A recent patient reportedly taking loperamide to avoid heroin withdrawal symptoms, at doses approximately 100 times those recommended, directed our attention to this issue. Objectives1) Investigate number of cases of intentional loperamide abuse and misuse reported to poison centers between 2009 and 2015; 2) Compile reports of clinical effects of loperamide abuse; and 3) Search for evidence of increasing Internet interest in the central opioid effects of loperamide. MethodsFor the years 2009 thru 2015, we reviewed exposure calls related to misuse/abuse of loperamide in the Texas Poison Center Network's database and the National Poison Data System. We used Google trend analysis to detect evidence of increased Internet interest in the illicit use of loperamide. ResultsBetween 2009 and 2015, the number of misuse/abuse calls related to loperamide alone nearly doubled, with about one-third of cases occurring in teens and young adults in their 20s. Of particular concern are reports of significant cardiotoxic effects (∼18% of cases), including conduction defects and various dysrhythmias, sometimes leading to death. Google Trends analysis demonstrates an increasing number of searches for “loperamide high” and “loperamide withdrawal” beginning in 2011. ConclusionsLoperamide misuse/abuse seems to be on the rise. Given its propensity to induce conduction disturbances and dysrhythmias at very high doses, emergency physicians should be vigilant for this form of drug abuse.