Парацетамол – и друг, и враг: что должен знать педиатр?

Захарова И.Н., Бережная И.В., Сугян Н.Г. Парацетамол – и друг, и враг: что должен знать педиатр? Клинический случай. Педиатрия. Consilium Medicum. 2024;3:223–229.
DOI: 10.26442/26586630.2024.3.202961

© ООО «КОНСИЛИУМ МЕДИКУМ», 2024 г.

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Zakharova IN, Berezhnaya IV, Sugian NG. Paracetamol is both a friend and a foe: What should a pediatrician know? A clinical case. Pediatrics. Consilium Medicum. 2024;3:223–229. DOI: 10.26442/26586630.2024.3.202961

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Аннотация

Одним из наиболее распространенных побочных эффектов, связанных с приемом лекарственных средств, является гепатотоксичность. Наиболее часто тяжелое лекарственное поражение печени вызывает ацетаминофен (парацетамол), поскольку относится к категории безрецептурных препаратов. Парацетамол – безопасное и эффективное средство у детей и подростков при применении в терапевтических дозах, но с другой стороны является наиболее распространенной причиной острой печеночной недостаточности у детей (21% случаев) и взрослых (40%) при передозировке. Клиническая картина токсического поражения печени зависит от прошедшего после приема парацетамола времени и его количества. Симптомы поражения печени не всегда очевидны, но могут стремительно развиться со 2 по 5-е сутки после отравления. В статье приведено клиническое наблюдение непреднамеренной передозировки парацетамола у девочки-подростка при несоблюдении дозы и режима приема.

Ключевые слова: лекарственное поражение печени, гепатотоксичность, парацетамол, передозировка парацетамола, ацетаминофен, отравление, дозосберегающий эффект

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One of the most common drug-related side effects is hepatotoxicity. The most common cause of severe drug-induced liver injury is acetaminophen (paracetamol), as it is an over-the-counter drug. Paracetamol is safe and effective in children and adolescents at therapeutic doses; however, it is the leading cause of acute liver failure in children (21% of cases) and adults (40%) with overdose. The clinical presentation of toxic liver damage depends on the time elapsed after taking paracetamol and its dose. Symptoms of liver damage are not always obvious but can develop rapidly from day 2 to day 5 after poisoning. The article presents a clinical case of an unintentional overdose of paracetamol in a teenage girl due to non-compliance with the dose and regimen.

Keywords: drug-induced liver injury, hepatotoxicity, paracetamol, acetaminophen, paracetamol overdose, poisoning, dose-sparing effect

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Список литературы

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DOI:10.1248/bpb.b19-00722
22. McGill MR, Jaeschke H. Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res. 2013;30(9):2174-87. DOI:10.1007/s11095-013-1007-6
23. Yoon E, Babar A, Choudhary M, et al. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update. J Clin Transl Hepatol. 2016;4(2):131-42. DOI:10.14218/JCTH.2015.00052
24. Jaeschke H, Williams CD, Ramachandran A, Bajt ML. Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int. 2012;32(1):8-20. DOI:10.1111/j.1478-3231.2011.02501.x
25. Hossen MS, Akter A, Azmal M, et al. Unveiling the molecular basis of paracetamol-induced hepatotoxicity: Interaction of N-acetyl-p-benzoquinone imine with mitochondrial succinate dehydrogenase. Biochem Biophys Rep. 2024;38:101727. DOI:10.1016/j.bbrep.2024.101727
26. Lee H, Yang X, Jin PR, et al. The Discovery of Gut Microbial Metabolites as Modulators of Host Susceptibility to Acetaminophen-Induced Hepatotoxicity. Drug Metab Dispos. 2024;52(8):754-64. DOI:10.1124/dmd.123.001541
27. Van der Marel CD, Anderson BJ, van Lingen RA, et al. Pharmacokinetics of paracetamol and metabolites in infants. Eur J Clin Pharmacol. 2003;59;243-51.
DOI:10.1007/s00228-003-0608-0
28. Guo W, Liu J, Sun J, et al. Butyrate alleviates oxidative stress and regulates NRF2 nuclear accumulation and H3K9/14 acetylation via GPR109A in bovine mammary and breast epithelial cells. Free Radical Biol Med. 2020;152:728-42.
29. Gamal W, Treskes P, Samuel K, et al. Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver. Sci Rep. 2017;7:37541. DOI:10.1038/srep37541
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34. Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014;60(4):1399-408. DOI:10.1002/hep.27317
35. Kesar V, Channen L, Masood U, et al. Liver Transplantation for Acute Liver Injury in Asians Is More Likely Due to Herbal and Dietary Supplements. Liver Transpl. 2022;28(2):188-99. DOI:10.1002/lt.26260
36. Захарова И.Н., Бережная И.В., Сугян Н.Г., и др. Лечение лихорадки при острых респираторных инфекциях верхних дыхательных путей у детей. Медицинский совет. 2022;16(1):88-95 [Zakharova IN, Berezhnaya IV, Sugyan NG, et al. Treatment of fever in acute upper respiratory tract infections in children. Medical Council. 2022;16(1):88-95 (in Russian)]. DOI:10.21518/2079-701X-2022-16-1-88-95

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1. Mulchandani R, Kakkar AK. Reporting of adverse drug reactions in India: A review of the current scenario, obstacles and possible solutions. Int J Risk Saf Med. 2019;30(1):33-44. DOI:10.3233/JRS-180025
2. Tantikul C, Dhana N, Jongjarearnprasert K, et al. The utility of the World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) system for the assessment of adverse drug reactions in hospitalized children. Asian Pac J Allergy Immunol. 2008;26(2-3):77-82.
3. Shukla AK, Jhaj R, Misra S, et al. Agreement between WHO-UMC causality scale and the Naranjo algorithm for causality assessment of adverse drug reactions. J Family Med Prim Care. 2021;10(9):3303-8. DOI:10.4103/jfmpc.jfmpc_831_21
4. Alomar MJ. Factors affecting the development of adverse drug reactions (Review article). Saudi Pharm J. 2014;22(2):83-94. DOI:10.1016/j.jsps.2013.02.003
5. Srisuriyachanchai W, Cox AR, Jarernsiripornkul N. Patients’ Identification, Management and Prevention of Adverse Drug Reactions: A Cross-Sectional Survey of Patients with Severe Adverse Drug Reactions. J Clin Med. 2024;13(14):4165. DOI:10.3390/jcm13144165
6. Mt M, Ss J, Plgc L, Tghk S. Prevalence, Characteristics and Factors Associated with Adverse Drug Reactions Among Hospitalized Patients. Hosp Pharm.
2024;59(4):489-97. DOI:10.1177/00185787241234217
7. Ivashkin VT, Baranovsky AYu, Raikhelson KL, et al. Drug-Induced Liver Injuries (Clinical Guidelines for Physicians). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(1):85-115 (in Russian). DOI:10.22416/1382-4376-2019-29-1-101-131
8. Bessone F, Hernandez N, Tagle M, et al. Drug-induced liver injury: A management position paper from the Latin American Association for Study of the liver. Ann Hepatol. 2021;24:100321. DOI:10.1016/j.aohep.2021.100321
9. Aithal G, Watkins PB, Andrade RJ, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011;89:806-15. DOI:10.1038/clpt.2011.58
10. Dijmărescu I, Guţă OM, Brezeanu LE, et al. Drug-Induced Hepatitis in Children: The Experience of a Single Center in Romania. Children (Basel). 2022;9(8):1136. DOI:10.3390/children9081136
11. Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther. 2013;37(1):3-17. DOI:10.1111/apt.12109
12. Ostapowicz G, Fontana RJ, Schiødt FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137(12):947-54. DOI:10.7326/0003-4819-137-12-200212170-00007
13. Green C, Krafft H, Guyatt G, Martin D. Symptomatic fever management in children: A systematic review of national and international guidelines. PLoS One. 2021;16(6):e0245815. DOI:10.1371/journal.pone.0245815
14. Björnsson ES. Drug-induced liver injury: an overview over the most critical compounds. Arch Toxicol. 2015;89(3):327-34. DOI:10.1007/s00204-015-1456-2
15. Romanov BK, Olefir YuV, Alyautdin RN, et al. Drug Safety for Children — International Monitoring Data for 50 Years. Safety and Risk of Pharmacotherapy. 2019;7(2):57-64 (in Russian). DOI:10.30895/2312-7821-2019-7-2-57-64
16. Lukina MV, Andrushchishina TB, Dronov IA, et al. Safety of paracetamol during pregnancy: literature review. Problems of Gynecology, Obstetrics and Perinatology. 2020;19(6):96-101 (in Russian). DOI:10.20953/1726-1678-2020-6-96-101
17. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; Clinical Practice Guideline Panel: Chair; Panel members; EASL Governing Board representative. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019;70(6):1222-61. DOI:10.1016/j.jhep.2019.02.014
18. Rowden AK, Norvell J, Eldridge DL, Kirk MA. Updates on acetaminophen toxicity. Med Clin North Am. 2005;89(6):1145-59. DOI:10.1016/j.mcna.2005.06.009
19. Prescott LF. Gastrointestinal absorption of drugs. Med Clin North Am. 1974;58(5):907-16. DOI:10.1016/s0025-7125(16)32088-0
20. Lee WM. Acetaminophen (APAP) hepatotoxicity-Isn’t it time for APAP to go away? J Hepatol. 2017;67(6):1324-31. DOI:10.1016/j.jhep.2017.07.005
21. Ishitsuk Y, Kondo Y, Kadowaki D. Toxicological properties of acetaminophen: dark side of a safe antipyretic/analgesic drug? Biol Pharm Bull. 2020;43:195-206.
DOI:10.1248/bpb.b19-00722
22. McGill MR, Jaeschke H. Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res. 2013;30(9):2174-87. DOI:10.1007/s11095-013-1007-6
23. Yoon E, Babar A, Choudhary M, et al. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update. J Clin Transl Hepatol. 2016;4(2):131-42. DOI:10.14218/JCTH.2015.00052
24. Jaeschke H, Williams CD, Ramachandran A, Bajt ML. Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int. 2012;32(1):8-20. DOI:10.1111/j.1478-3231.2011.02501.x
25. Hossen MS, Akter A, Azmal M, et al. Unveiling the molecular basis of paracetamol-induced hepatotoxicity: Interaction of N-acetyl-p-benzoquinone imine with mitochondrial succinate dehydrogenase. Biochem Biophys Rep. 2024;38:101727. DOI:10.1016/j.bbrep.2024.101727
26. Lee H, Yang X, Jin PR, et al. The Discovery of Gut Microbial Metabolites as Modulators of Host Susceptibility to Acetaminophen-Induced Hepatotoxicity. Drug Metab Dispos. 2024;52(8):754-64. DOI:10.1124/dmd.123.001541
27. Van der Marel CD, Anderson BJ, van Lingen RA, et al. Pharmacokinetics of paracetamol and metabolites in infants. Eur J Clin Pharmacol. 2003;59;243-51.
DOI:10.1007/s00228-003-0608-0
28. Guo W, Liu J, Sun J, et al. Butyrate alleviates oxidative stress and regulates NRF2 nuclear accumulation and H3K9/14 acetylation via GPR109A in bovine mammary and breast epithelial cells. Free Radical Biol Med. 2020;152:728-42.
29. Gamal W, Treskes P, Samuel K, et al. Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver. Sci Rep. 2017;7:37541. DOI:10.1038/srep37541
30. Wong A, Graudins A. Risk prediction of hepatotoxicity in paracetamol poisoning. Clin Toxicol (Phila). 2017;55(8):879-92. DOI:10.1080/15563650.2017.1317349
31. Melnikova LI, Ilchenko LYu, Dunaeva EA, et al. Diagnosis of gilbert’s syndrome via pyrosequencing in clinical practice. The Russian Archives of Internal Medicine. 2019;9(6):475-82 (in Russian). DOI:10.20514/2226-6704-2019-9-6-475-482
32. Luzhnikov EA, Sukhodolova GN. Pediatricheskaia klinicheskaia toksikologiia. Rostov-na-Donu: Feniks, 2013 (in Russian).
33. Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950-66. DOI:10.1038/ajg.2014.131
34. Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014;60(4):1399-408. DOI:10.1002/hep.27317
35. Kesar V, Channen L, Masood U, et al. Liver Transplantation for Acute Liver Injury in Asians Is More Likely Due to Herbal and Dietary Supplements. Liver Transpl. 2022;28(2):188-99. DOI:10.1002/lt.26260
36. Zakharova IN, Berezhnaya IV, Sugyan NG, et al. Treatment of fever in acute upper respiratory tract infections in children. Medical Council. 2022;16(1):88-95 (in Russian). DOI:10.21518/2079-701X-2022-16-1-88-95

Авторы

И.Н. Захарова¹, И.В. Бережная*¹, Н.Г. Сугян^1,2

¹ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
²ГБУЗ МО «Химкинская больница», Химки, Россия
*berezhnaya-irina26@yandex.ru

________________________________________________

Irina N. Zakharova¹, Irina V. Berezhnaya*¹, Narine G. Sugian^1,2

¹Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
²Khimki Hospital, Khimki, Russia
*berezhnaya-irina26@yandex.ru

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