The safety of paracetamol usage in medical practice

Authors

  • O. O. Klekot Vinnytsia National Pirogov Memorial Medical University
  • O. O. Yakovleva Vinnytsia National Pirogov Memorial Medical University

Keywords:

paracetamol, biotransformation, cytochromes Р450, inductors of cytochromes, toxic metabolite NАРQI, acetylcysteine

Abstract

The article presents the pharmacological aspects of paracetamol usage in the context of current clinical guidelines. Attention is focused on pharmacokinetics studies, efficacy and safety of the drug in the treatment of pain and fever in adults and children. We analyzed possible ways and conditions of paracetamol biotransformation in the liver by microsomal oxidative system, which plays an important role in the development of adverse drug reactions. The review presents examples of drug pharmacological interactions with paracetamol, leading to hepatotoxic reactions. Some symptoms of intoxication with paracetamol, and the factors contributing to its development are given in the article. Detailed schemes of acetylcysteine antidote therapy for poisoning by paracetamol are also presented.

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References

Белоусов Ю. Б. Клиническая фармакокинетика. Практика дозирования лекарств / Ю. Б. Белоусов, К. Г. Гуревич. – Москва : Литтерра, 2005. – 288 с.

Вікторов О. П. Ефективне та безпечне медичне застосування анальгетиків-антипіретиків (погляд на проблему) / О. П. Вікторов, С. I. Деяк, О. Є. Базика та ін. // Укр. мед. часопис. – 2011. – № 6 (86). – С. 90–93 (http://www.umj.com.ua/article/12685).

Зобнин Ю. В. Отравление парацетамолом: клиника, диагностика, лечение / Ю. В. Зобнин. – Иркутск, 2002. – С. 37.

Кашуба О. В. Побічні реакції, спричинені застосуванням нестероїдних протизапальних препаратів — аналгетиків-антипіретиків / О. В. Кашуба // Український медичний часопис. – 2015. – № 3 (107). – С. 74–76.

Лужников Е. А. Детоксикационная терапия: Руководство для врачей / Е. А. Лужников, Ю. С. Гольдфарб, С. Г. Мусселиус. Серия “Мир медицины”. – СПб. : Лань, 2000. – 177 с.

Чекман І. С. Нестероїдні протизапальні препарати: їх ефективність і доступність, прийнятність для пацієнта / І. С. Чекман, О. П. Вікторов, Н. О. Горчакова, А. С. Свінціцький та ін. – Київ : Поліграф Плюс, 2011. – 118 с.

Яковлева О. А. Парацетамол и бронхиальная астма у детей. По материалам рекомендаций Европейского респираторного общества / О. А. Яковлева, И. А. Дорошкевич, А. О. Жамба // Рациональная фармакотерапия. – 2009. – № 2(11). – С. 58–89.

Adjei Araba A. Interindividual variability in acetaminophen sulfation by human fetal liver: implications for pharmacogenetic investigations of drug-induced birth defects / А. Adjei Araba, А. Gaedigk, S. D. Stephen et al. // Clinical and molecular teratology. – 2008. – № 82 (3). – Р. 156–165.

Bernal W. Blood lactates as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study / W. Bernal, N. Donaldson, D. Wyncoll, J. Wendon // Lancet. – 2002. – № 359. – P. 558–563.

Bessems J. G. Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches / J. G. Bessems, N. P. Vermeulen // Crit. Rev. Toxicol. – 2001. – № 31. – P. 55–138.

Bray G. P. Long-term anticolvunsant therapy worsens outcome in paracetamol-induced fulminant hepatic failure / G. P. Bray, P. M. Harrison, J. G. O’Grady et al. // Human and experimental toxicology. – 1992. – № 11 (4). – P. 265–270.

Chandrasekharan N. V. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic / N. V. Chandrasekharan, H. Dai, K. L. Roos et al. // Antipyretic drugs: cloning, structure and expression. Proc. Nation. Acad. Sci. USA, 2002. – № 99 (21). – P. 13926–13931.

Chen W. Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6 / W. Chen, L. L. Koenigs, S. J. Thompson et al. // Chem. Res. Toxicol. – 1998. – №11. – P. 295–301.

Court M. H. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferases isoforms / M. H. Court, S. X. Duan, L. L. von Moltke et al. // The J. Pharmacol. And Exp. Ther. – 2001. – № 299 (3). – P. 998–1006.

Crippin J. S. Acetaminophen hepatotoxicity: potentiation by isoniazid / J. S. Сrippin // The American J. of gastroenterology. – 1993. – № 88 (4). – P. 590–592.

Dai Y. Cytotoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells / Y. Dai, A. I. Cederbaum // The J. Pharmacol. аnd Exp. Ther. – 1995. – № 273. – P. 1497–1505.

Dargan P. I. Accidental staggered paracetamol overdoses in the UK: epidemiology and outcome / P. I. Dargan, A. L. Jones // Emerg. Med. J. – 2002. – № 19(3). – P. 202–205.

Davies N. M. Cyclooxygenase-3: axiom, dogma, anomaly, enigma or splice error? — not as easy as 1, 2, 3 / N. M. Davies, R. L. Good, K. A. Roupe, J. A. Yanez // J. Pharm. Pharmaceut. Sci. – 2004. – №7 (2). – P. 217–226.

Ellis A. Circulatory, respiratory, cerebral and renal derangements in acute liver failure: pathophysiology and management /A. Ellis, J. Wendon // J. Semin. Liv. Dis. – 1996. – № 16. – P. 379–388.

Freimuth R. R. Human cytosolic sulfotransferase database mining: identification of seven novel genes and pseudo genes / R. R. Freimuth, M. Wiepert, C. G. Chute et al. // The pharmacogenomics Journal. – 2004. – № 4 (1). – P. 54–65.

Fu J. Y. The induction and suppression of prostaglandin H2 synthase (cylooxygenase) in human monocytes / J. Y. Fu, J. L. Masferrer, K. Seibert et al. // J. Biol. Chem. – 1990. – № 265 (28). – P. 1727–1740.

Graham G. G. Mechanisms of action of paracetamol and related analgesics / G. G. Graham, K. F. Scott // Inflammopharmacology. – 2003. – № 11. – P. 401–413.

Gujral J. S. Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? / J. S. Gujral, T. R. Knight, A. Farhood et al. // Toxicol. Sci. – 2002. – № 67. – P. 322–328.

Gyamlani G. G. Acetaminophen toxicity: suicidal vs accidental. / G. G. Gyamlani, C. R. Parikh // Crit. Care. – 2002. – № 6. – P. 155– 159.

Harrison P. M. Serial prothrombin time as a prognostic indicator in paracetamol induced fulminant hepatic failure / P. M. Harrison, J. G. O’Grady, R. T. Keays et al. // B. M. J. – 1990. – № 301. – P. 964–966.

James L. P. Acetaminophen toxicity in mice lacking NADPH oxidase activity: role of peroxynitrite formation and mitochondrial oxidant stress / L. P. James, S. S. McCullough, T. R. Knight et al. // Free Radic. Res. – 2003. – № 37 (12). – P. 1289–1297.

James L. P. Effect of N-acetylcysteine on acetaminophen toxicity in mice: relationship to reactive nitrogen and cytokine formation / L. P. James, S. S. McCullough, L. W. Lamps et al. // Toxicol. Sci. – 2003. – № 75. – P. 458–467.

Jones A. L. Recent advances in the management of late paracetamol poisoning / A. L. Jones // Emerg. Med. (Aust.). – 2000. – № 12. – P. 14–21.

Jones A. L. Over the counter analgesics: a toxicological perspective / A. L. Jones, P. I. Dargan // Trends Pharmacol. Sci. – 2003. – № 24 (4). – P. 154–157.

Kostrubsky S. E. Phenobarbital and phenytoin increased acetaminophen toxicity due to inhibition of UDP- glucuronosyltransferases in culture human hepatocytes / S. E. Kostrubsky, J. F. Sinclair, S. C. Strom et al. // Official Journal of the Society of Toxicology. – 2005. – № 87 (1). – P. 146–155.

Lawson J. A. Inhibition of Fas receptor (CD95)-induced caspase activation and apoptosis by acetaminophen in mice / J. A. Lawson, M. A. Fisher, C. A. Simmons et al. // Toxicol. Appl. Pharmacol. – 1999. – № 156. – P. 179–186.

Litovitz T. L. 2000 Annual report of the American association of poison control centers toxic exposure surveillance system / T. L. Litovitz, W. Klein-Schwartz, G. C. Rodgers et al. // Am. J. Emerg. Med. – 2001. – № 19. – P. 337–395.

Litovitz T. L. 2001 Annual report of the American association of poison control centers toxic exposure surveillance system / T. L. Litovitz, W. Klein-Schwartz, G. C. Rodgers et al. // Am. J. Emerg. Med. – 2002. – № 20. – P. 391–452.

Mitchell I. Earlier identification of patients at risk from acetaminophen-induced acute liver failure / I. Mitchell, D. Bihari, R. Chang et al. // Crit. Care Med. – 1998. – № 26. – P. 279–284.

Mitchell J. R. Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione / J. R. Mitchell, D. G. Jollow, W. Z. Potter et al. // J. Pharmacol. Exp. Ther. – 1973. – № 187. – P. 211–217.

Muldrew K. L. Determination of acetaminophen-protein adducts in mouse liver and serum and human serum after hepatotoxic doses of acetaminophen using high-performance liquid chromatography with electrochemical detection / K. L. Muldrew, L. P. James, L. Coop et al. // Drug Metab. Dispos. – 2002. – № 30. – P. 446–451.

Mutlib A. E. Kinetics of acetaminophen glucuronidation by UDP-glucuronosyltransferases 1A1, 1A6, 1A9 and 2B15. Potential implications in acetaminophen-induced hepatotoxicity / A. E. Mutlib, T. C. Goosen, J. Bauman et al. // Chemical research in toxicology. – 2006. – №19 (5). – P. 705–709.

Nelson S. G. S (N) 2 ring opening of beta-lactones: an alternative to catalytic asymmetric conjugate additions / S. G. Nelson, Z. Wan, M. A. Stan // J. Org. Chem. – 2002. – № 67. – P. 4680–4683.

Patten C. J. Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics / C. J. Patten, P. E. Thomas, R. L. Guy et al. // Chem. Res. Toxicol. – 1993. – № 6. – P. 511–518.

Prescott L. F. Paracetamol: past, present and future / L. F. Prescott // Am. J. Ther. – 2000. – № 7. – P. 143–147.

Prescott L. F. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning / L. F. Prescott, R. N. Illingworth, J. A. Critchley, A. T. Proudfoot // B. M. J. – 1979. – № 2. – P. 1097–1100.

Pumford N. R. Immunochemical quantitation of 3-(cystein-S-yl) acetaminophen adducts in serum and liver proteins of acetaminophen-treated mice / N. R. Pumford, J. A. Hinson, D. W. Potter et al. // J. Pharmacol. Exp. Ther. – 1989. – № 248. – P. 190–196.

Pumford N. R. Immunochemical quantitation of 3-(cystein-S-yl) acetaminophen protein adducts in subcellular liver fractions following a hepatotoxic dose of acetaminophen / N. R. Pumford, D. W. Roberts, R. W. Benson, J. A. Hinson // Biochem. Pharmacol. – 1990. – № 40. – P. 573–579.

Qiu Y. Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry / Y. Qiu, L. Z. Benet, A. L. Burlingame // J. Biol. Chem. – 1998. – № 273. – P. 17940– 17953.

James L. P. Acetaminophen toxicity in mice lacking NADPH oxidase activity: role of peroxynitrite formation and mitochondrial oxidant stress / L. P. James, S. S. McCullough, T. R. Knight et al. // Free Radic. Res. – 2003. – № 37 (12). – P. 1289–1297.

James L. P. Effect of N-acetylcysteine on acetaminophen toxicity in mice: relationship to reactive nitrogen and cytokine formation / L. P. James, S. S. McCullough, L. W. Lamps et al. // Toxicol. Sci. – 2003. – № 75. – P. 458–467.

Roberts D. W. Immunohistochemical localization and quantification of the 3-(cystein-S-yl)-acetaminophen protein adduct in acetaminophen hepatotoxicity / D. W. Roberts, T. J. Bucci, R. W. Benson et al. // Am. J. Pathol. – 1991. – № 138. – P. 359–371.

Robin M. A. Plasma membrane cytochromes P450 as neoantigens and autoimmune targetts in drug-induced hepatitis / M. A. Robin, M. Le Roy, V. Descatoire et al. // J. of Hepatology. – 1997. – Vol. 26 (Suppl.1). – P. 21–30.

Serhan C. N. Lipoxins and aspirin-triggered 15-epilipoxin biosynthesis: an update and role in antiinflammation and pro-resolution / C. N. Serhan // Prostaglandins Other Lipid Mediat. – 2002. – № 8–69. – P. 433–455.

Simon L. S. COX-2 inhibitors. Are they nonsteroidal anti-inflammatory drugs with a better safety profile? / L. S. Simon // Gastroenterol. Clin. North Am. – 2001. – № 30. – P. 1011–1025.

Thummel K. E. Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone imine by human CYP3A4 / K. E. Thummel, C. A. Lee, K. L. Kunze et al. // Biochem. Pharmacol. – 1993. – № 45. – P. 1563–1569.

Tsokos-Kuhn J. O. Alkylation of the liver plasma membrane and inhibition of the Ca2-ATPase by acetaminophen / J. O. TsokosKuhn, H. Hughes, C. V. Smith, J. R. Mitchell // Biochem. Pharmacol. – 1988. – № 37. – P. 2125–2131.

Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs / J. R. Vane // Nat. New Biol. – 1971. – № 231 (25). – P. 232–235.

Wallace C. I. Paracetamol overdose: an evidence based flowchart to guide management / C. I. Wallace, P. I. Dargan, A. L. Jones//Emerg. Med. J. – 2002. – № 19 (3). – P. 202–205.

Zimmerman H. J. Drug-Induced Liver Injury / H. J. Zimmerman // Clinical and Pathological Correlations in Liver Disease: Approaching the Next Millennium (Annual Postgraduate Course of the American Association for the Study of Liver Diseases). – November 6–7, 1998. – P. 252–267.

Zimmerman H. J. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: Analysis of instances of therapeutic misadventure / H. J. Zimmerman, W. C. Maddrey // Hepatology. – 1995. – Vol. 22. – P. 767–773.

Hodgman MJ, Garrard AR. A review of acetaminophen poisoning. – Crit Care Clin. – 2012; 28(4) . – P. 499–516.

EK Kuffner, RC Dart, GM Bogdan. Acetaminophen toxicity in an urban county hospital. – N Engl J Med., 337. – 1997 . – P. 1112–1117.

Published

2016-09-01

How to Cite

1.
Klekot OO, Yakovleva OO. The safety of paracetamol usage in medical practice. PMJUA [Internet]. 2016 Sep. 1 [cited 2024 Mar. 29];1(3):41-8. Available from: https://painmedicine.org.ua/index.php/pnmdcn/article/view/22

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