Đánh giá lâm sàng: Độc tính của Loperamid

Được đăng tải trên tạp chí: Toxicology/Review Article, tập 70

Ngày xuất bản: Ngày 13 tháng 5 năm 2017

Đồng tác giả: Peter E. Wu, MD, MSc

David N. Juurlink, MD, Tiến sĩ

Tóm tắt

Loperamide là một loại thuốc gây nghiện opioid không cần kê đơn được sử dụng rộng rãi để điều trị tiêu chảy. Mặc dù nó tương đối an toàn ở liều điều trị, các báo cáo ngày càng mô tả nhiều về việc sử dụng sai cách và lạm dụng nó ở liều rất cao để gây hưng phấn hoặc làm giảm các triệu chứng của hội chứng cai opioid. Nhiễm độc loperamide đe dọa tính mạng có thể là kết quả của hội chứng lâm sàng tương đối mới về ngộ độc tim do loperamide. Những bệnh nhân này thường trẻ và có thể có biểu hiện ngừng tim hoặc ngất tái phát không được báo trước, kết hợp với các bất thường về điện tâm đồ, bao gồm kéo dài khoảng QT rõ rệt, giãn khoảng QRS và rối loạn nhịp thất. Các đặc điểm của độc tính opioid thông thường cũng có thể có. Các phương pháp điều trị chính bao gồm trợ tim và chăm sóc hỗ trợ, mặc dù những bệnh nhân được chọn có thể phải gây tăng nhịp tim, tiêm lipid nhũ tương hoá trong tĩnh mạch hoặc trao đổi oxy qua màng ngoài cơ thể. Ở những bệnh nhân sống sót sau ngộ độc loperamide, nên cân nhắc điều trị chứng rối loạn cơ bản do sử dụng opioid nếu có.

DOI: https://doi.org/10.1016/j.annemergmed.2017.04.008

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Tài liệu tham khảo

1. DEA Office of Diversion Control. DEA Orange Book Lists of Scheduling Actions. US Dept of Justice, 2016 (Available at:) http://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf (Accessed June 12, 2016)
2. Loperamide dependence and abuse. BMJ Case Rep. 2015; http://dx.doi.org/10.1136/bcr-2015-209705
3. Surveillance of loperamide ingestions: an analysis of 216 poison center reports. J Toxicol Clin Toxicol. 1997; 35: 11-19
4. Abuse potential of loperamide. Clin Pharmacol Ther. 1980; 28: 812-819
5. Dependence liability of two antidiarrheals, nufenoxole and loperamide. Clin Pharmacol Ther. 1980; 27: 659-664
6. Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose. J Anal Toxicol. 2005; 29: 750-754
7. “I just wanted to tell you that loperamide will work”: a web-based study of extra-medical use of loperamide. Drug Alcohol Depend. 2013; 130: 241-244
8. Human pharmacokinetics and comparative bioavailability of loperamide hydrochloride. J Clin Pharmacol. 1979; 19: 211-218
9. Distribution of loperamide in the intestinal wall. Biochem Pharamcol. 1979; 28: 1433-1434
10. Antisecretory effect of loperamide in colon epithelial cells by inhibition of basolateral K+ conductance.
11.  Loperamide: blockade of calcium channels as a mechanism for antidiarrheal effects. J Pharmacol Exp Ther. 1984; 231: 628-632
12. Loperamide: a review of its pharmacological properties and therapeutic efficacy in diarrhoea. Drugs. 1978; 15: 33-52
13. Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004; 60: 575-581
14. Loperamide. J Pain Symptom Manage. 2011; 42: 319-323
15. DrugBank. Loperamide. 2005. Available at: http://www.drugbank.ca/drugs/DB00836. Accessed June 13, 2016.
16. LC-MS determination and bioavailability study of loperamide hydrochloride after oral administration of loperamide capsules in human volunteers. J Pharm Biomed Anal. 2004; 36: 421-427
17. Loperamide toxicokinetics: serum concentrations in the overdose setting. Clin Toxicol. 2015; 53: 495-496
18. Loperamide and P-glycoprotein inhibition: assessment of the clinical relevance. J Pharm Pharmacol. 2010; 62: 401-412
19. Effects of ABCB1 multidrug resistance transporter gene mutations on disposition and central nervous effects of loperamide in healthy volunteers. Pharmacogenetics. 2003; 13: 651-660
20. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest. 1996; 97: 2517-2524
21. Itraconazole, gemfibrozil and their combination markedly raise the plasma concentrations of loperamide. Eur J Clin Pharamcol. 2006; 62: 463-472
22. Ritonavir increases loperamide plasma concentrations without evidence for P-glycoprotein involvement. Clin Pharmacol Ther. 2001; 70: 405-414
23. Increased drug delivery to the brain by P-glycoprotein inhibition. Clin Pharmacol Ther. 2000; 68: 231-237
24. Effects of HM30181, a P-glycoprotein inhibitor, on the pharmacokinetics and pharmacodynamics of loperamide in healthy volunteers. Br J Clin Pharmacol. 2014; 78: 556-564
25. Tariquidar, a selective P-glycoprotein inhibitor, does not potentiate loperamide’s opioid brain effects in humans despite full inhibition of lymphocyte P-glycoprotein. Anesthesiology. 2008; 109: 1092-1099
26. Pharmacokinetics of single ascending doses of the P-glycoprotein inhibitor tariquidar in healthy subjects. Pharmacology. 2013; 91: 12-19
27. On the relationship between block of the cardiac Na+ channel and drug-induced prolongation of the QRS complex. Br J Pharmacol. 2011; 164: 260-273
28. Proarrythmic mechanisms of the common anti-diarrheal medication loperamide: revelations from the opioid abuse epidemic. Naunyn Schmiedebergs Arch Pharmacol. 2016; 389: 1133-1137
29. Potent inhibition of hERG channels by the over-the-counter antidiarrheal agent loperamide. J Am Coll Cardiol EP. 2016; 2: 784-789
30. Epidemiologic trends in loperamide abuse and misuse. Ann Emerg Med. 2017; 69: 73-78
31. Bluelight. Loperamide (Imodium) megathread: we have now lost at least 2 of our own from Lope. 2007. Available at: http://www.bluelight.org/vb/threads/296086-Loperamide-(Immodium)-Megathread-We-have-now-lost-at-least-2-of-our-own-from-Lope. Updated March 2014. Accessed June 12, 2016.
32. Drugs Forum. Loperamide: the secret opioid. 2012. Available at: https://drugs-forum.com/forum/showthread.php?t=185004. Accessed June 12, 2016.
33. Erowid. Absolutely awesome! Loperamide 2008. Available at: https://www.erowid.org/experiences/exp.php?ID=66159. Accessed June 12, 2016.
34. Piperine a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther. 2002; 302: 645-650
35. Drugs Forum. Loperamide report. 2012. Available at: https://drugs-forum.com/forum/showthread.php?t=175644. Accessed June 13, 2016.
36. Loperamide-induced torsades de pointes: a case series. J Med Toxicol. 2017; 13: 3-46
37. Adverse event detection using the FDA post-marketing drug safety surveillance system: cardiotoxicity associated with loperamide abuse and misuse. J Am Pharm Assoc. 2017; 57: 563-567
38. Unexpected serious cardiac arrhythmias in the setting of loperamide abuse. R I Med J. 2017; 100: 33-36
39. Loperamide metabolite-induced cardiomyopathy and QTc prolongation. Clin Toxicol. 2017; http://dx.doi.org/10.1080/15563650.2017
40. Torsades de pointes with high-dose loperamide. J Electrocardiol. 2017; http://dx.doi.org/10.1016/j.jelectrocard.2017.01.011
41. High-dose loperamide abuse-associated ventricular arrhythmias. Heart Rhythm Case Rep. 2016; 2: 232-236
42. Ventricular dysrhythmias from loperamide misuse. J Emerg Med. 2016; 50: 508-509
43. Loperamide induced life threatening ventricular arrhythmia. Case Rep Cardiol. 2016; http://dx.doi.org/10.1155/2016/5040176
44. Electrocardiographic abnormalities, malignant ventricular arrhythmias and cardiomyopathy associated with loperamide abuse. J Cardiovasc Electrophysiol. 2016; 27: 1230-1233
45. Loperamide abuse associated with cardiac dysrhythmia and death. Ann Emerg Med. 2017; 69: 83-86
46. Not your regular high: cardiac dysrhythmias caused by loperamide. Clin Toxicol. 2016; 54: 454-458
47. Mukarram O, Hindi Y, Catalasan G, et al. Loperamide induced torsades de pointes: a case report and review of the literature. Case Rep Med. http://dx.doi.org/10.1155/2016/4061980.
48. The long QT teaser: loperamide abuse. Am J Med. 2015; 128: 1083-1086
49. Ventricular tachycardia associated with high-dose chronic loperamide use. Pharmacotherapy. 2015; 35: 234-238
50. Torsade de pointes associated with high-dose loperamide ingestion. J Innov Cardiac Rhythm Manage. 2015; 6: 1897-1899
51. Cardiac conduction disturbance after loperamide abuse. Clin Toxicol. 2014; 52: 952-957
52. Loperamide-related deaths in North Carolina. J Anal Toxicol. 2016; 40: 677-686
53. Poor man’s methadone: a case report of loperamide toxicity. Am J Forensic Med Pathol. 2015; 36: 268-270
54. Liquid chromatography–tandem mass spectrometry determination of loperamide and its main metabolite desmethylloperamide in biological specimens and application to forensic cases. J Chromatogr B Analyt Technol Biomed Life Sci. 2004; 811: 31-36
55. Activated charcoal for acute overdose: a reappraisal. Br J Clin Pharmacol. 2016; 81: 482-487
56. Loperamide overdose managed by naloxone. Lancet. 1980; 1: 1413
57. Loperamide toxicity in a child after a single dose. Br Med J (Clin Res Ed). 1987; 294: 1383
58. American College of Medical Toxicology. ACMT position statement: interim guidance for the use of lipid resuscitation therapy. J Med Toxicol. 2011; 7: 81-82
59. Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity. Clin Toxicol. 2016; 54: 194-221
60. A review of emergency cardiopulmonary bypass for severe poisoning by cardiotoxic drugs. J Med Toxicol. 2013; 9: 54-60
61. Burpenorphine treatment for hospitalized, opioid-dependent patients: a randomized clinical trial. JAMA Intern Med. 2014; 174: 1369-1376

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