{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:57:07Z","timestamp":1791435427310,"version":"4.3.3"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Loperamide is a synthetic opioid commonly used as an antidiarrheal due to its activation of u-opioid receptors in the myenteric plexus. In therapeutic doses, it inhibits peristalsis and has anti-secretory and anti-motility effects, until metabolized by intestinal and hepatic CYP3A4 and CYP2C8 into inactive metabolites. Furthermore, loperamide also inhibits L-type voltage-gated calcium (Ca2+) channels, increases action potential duration, and can induce arrhythmias and even cardiotoxicity, particularly when taken in extremely high doses. Thus, the aim of this study was to perform an integrative review of the available evidence in the recent literature on the cardiac risks of acute and chronic use of loperamide. In electrocardiogram (ECG) analysis, the most common finding was QTc prolongation in 27 cases, followed by QRS prolongation, first-degree atrioventricular (AV) block, torsades de pointes, ventricular tachycardia, and right bundle branch block. As for the symptoms encountered, syncope, weakness, palpitations, lightheadedness, shortness of breath, nausea, vomiting, bradycardia, and cardiac arrest were the most common. Loperamide can inhibit hERG voltage-gated potassium (K+) channels (Kv11.1), leading to the prolongation of repolarization, QTc interval prolongation, and increased risk of torsades de pointes. In addition, loperamide can inhibit voltage-gated sodium (Na+) channels (Nav1.5), impairing electrical cardiac conduction and potentiating QRS interval widening. Therefore, QTc prolongation, torsades de pointes, and other ECG alterations are of particular concern regarding loperamide toxicity, particularly when overdosed.<\/jats:p>","DOI":"10.3390\/jcdd9120431","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T04:40:09Z","timestamp":1670215209000},"page":"431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Risk of Cardiac Lesion with Chronic and Acute Use of Loperamide\u2014An Integrative Review"],"prefix":"10.3390","volume":"9","author":[{"given":"Bruna Cremonezi","family":"Lammoglia","sequence":"first","affiliation":[{"name":"School of Medicine, Universidade Santo Amaro (UNISA), S\u00e3o Paulo 04829-300, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Hasselmann","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidade Santo Amaro (UNISA), S\u00e3o Paulo 04829-300, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5839-1265","authenticated-orcid":false,"given":"Marcelo","family":"Pires-Oliveira","sequence":"additional","affiliation":[{"name":"School of Medicine, Uni\u00e3o Metropolitana de Educa\u00e7\u00e3o e Cultura, Lauro de Freitas 42700-000, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Antonio","family":"Duarte Nicolau","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Universidade Federal do Delta do Parna\u00edba (UFDPar), Parna\u00edba 64202-020, PI, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-3382","authenticated-orcid":false,"given":"Jand Venes","family":"Rolim Medeiros","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Universidade Federal do Delta do Parna\u00edba (UFDPar), Parna\u00edba 64202-020, PI, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Sabia Tallo","sequence":"additional","affiliation":[{"name":"Department of Urgency and Emergency Care, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murched","family":"Omar Taha","sequence":"additional","affiliation":[{"name":"Department of Surgery, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rildo","family":"Yamaguti Lima","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidade Santo Amaro (UNISA), S\u00e3o Paulo 04829-300, SP, Brazil"},{"name":"Postgraduate Program in Cardiology, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afonso","family":"Caricati-Neto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7913-0585","authenticated-orcid":false,"given":"Francisco Sandro","family":"Menezes-Rodrigues","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidade Santo Amaro (UNISA), S\u00e3o Paulo 04829-300, SP, Brazil"},{"name":"Postgraduate Program in Cardiology, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","first-page":"e6936","article-title":"Cardiac Arrhythmia Secondary to Loperamide Abuse and Toxicity","volume":"12","author":"Ali","year":"2020","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ehjcr\/ytz150","article-title":"Loperamide Overdose Causing Torsades de Pointes and Requiring Impella Temporary Mechanical Support: A Case Report","volume":"3","author":"Cicci","year":"2019","journal-title":"Eur. 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