References

rmt

Общая реаниматология

General Reanimatology

1813-97792411-7110

FSBI "SRIGR" RAMS

10.15360/1813-9779-2007-1-57-65

rmt-1088

Research Article

ОБЗОРЫ И КРАТКИЕ СООБЩЕНИЯ

REVIEWS & SHORT COMMUNICATIONS

Парацетамол: терапевтическое применение и проблема острых отравлений

Paracetamol: Therapeutic Use and the Problem of Acute Intoxications

Шифман

Е. М.

Shifman

Ye. M.

Ершов

А. В.

Yershov

A. L.

Республиканский перинатальный центр, Петрозаводск, Республика КарелияRepublican Perinatal Center, Petrozavodsk, Republic of Karelia

Всероссийский центр экстренной и радиационной медицины МЧС России, СанктПетербургAll-Russian Center of Emergency and Radiation Medicine, Ministry of Emergencies of Russia, Saint Petersburg

2007

20022007

Том III № 1 2007 г.

5765

2007

Шифман Е.М., Ершов А.В.

Shifman Y.M., Yershov A.L.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.reanimatology.com/rmt/article/view/1088

В форме обзора литературы обсуждаются вопросы механизмов действия и терапевтического применения одного из самых известных и широко применяемых лекарственных средств — парацетамол. В 1995 г. эксперты ВОЗ провели сравнительную оценку препаратов разных групп с сочетанным анальгетическим и антипиретическим действием. По критерию «эффективность/безопасность» первое место получил парацетамол. Интерес к механизму действия и обсуждение безопасности применения возобновились с новой силой в связи с появившейся возможностью применения внутривенной формы парацетамола для обезболивания в послеоперационном периоде. На основании обзора литературы, авторы делают вывод о том, что парацетамол может с успехом использоваться в практической работе ОРИТ. Этот препарат обладает собственным достаточно выраженным обезболивающим и антипиретическим эффектом, а его совместное использование с наркотическими анальгетиками приводит к синергизму действия и снижению расхода опиоидов. При применении в терапевтических дозах парацетамол практически безопасен, но требует взвешенного подхода при назначении пациентам из групп риска.

As a review of literature, the authors discuss the mechanisms of action and the therapeutic use of paracetamol, one of the most known and widely used drugs. In 1995, the WHO experts comparatively evaluated drugs from different groups, which have a combined analgesic and antipyretic activity. Paracetamol holds the lead in its efficacy/safety. An interest in the mechanism of action of the drug, as well as discussion of its safe use have again quickened due to the given ability to administer intravenous paracetamol for postoperative analgesia. Based on the review of literature, the authors draw a conclusion that paracetamol may be successfully used in practice of an intensive care unit. This drug has rather marked intrinsic analgesic and antipyretic effects and its coadministration with narcotic analgesics leads to synergism and reduces needs for opioids. When used in therapeutic doses, paracetamol is practically safe, but requires that a weighed approach be applied to its use in risk-group patients.

paracetamolanalgesiaantipyretic effectnarcotic analgesicsreductionopioidsrisk groups

References1

Prescott L. F. Paracetamol: past, present and future. Am. J. Ther. 2000; 7: 143—147.

Davies N. M., Good R. L., Roupe K. A., Yáñez J. A. Cyclooxygenase-3: axiom, dogma, anomaly, enigma or splice error? — not as easy as 1, 2, 3. J. Pharm. Pharmaceut. Sci. 2004; 7 (2): 217—226.

Bannwarth B., Netter P., Lapicque F. et al. Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol. Br. J. Clin. Pharmacol. 1992; 34: 79—81.

Piletta P., Porchet H. C., Dayer P. Central analgesic effect of acetaminophen but not of aspirin. Clin. Pharmacol. Ther. 1991; 49: 350—354.

Romsing J., Moiniche S., Dahl B. Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia. Br. J. Anaesth. 2002; 88: 215—226.

Piquet V., Desmeules J., Dayer P. Lack of acetominophenceiling effect on R-III nociceptive flexion reflux. Eur. J. Clin. Pharmacol. 1998; 53: 321—324.

Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin like drugs. Nat. New Bio 1971; 231 (25): 232—235.

Fu J. Y., Masferrer J. L., Seibert K. et al. The induction and suppression of prostaglandin H-2 synthase (cylooxygenase) in human monocytes. J. Biol. Chem. 1990; 265 (28): 1727—1740.

Simon L. S. COX-2 inhibitors. Are they nonsteroidal anti-inflammatory drugs with a better safety profile? Gastroenterol. Clin. North Am. 2001; 30: 1011—1025.

Chandrasekharan N. V., Dai H., Roos K. L. et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic /antipyretic drugs: cloning, structure, and expression. Proc. Nation. Acad. Sci. USA 2002; 99 (21): 13926—13931.

Simmons D. L., Botting R. M., Robertson M. et al. Induction of an aceta-minophensensitive cyclooxygenase with reduced sensitivity to nonsteroid antiinflammatory drugs. Proc. Nation. Acad. Sci. USA. 1999; 96 (6): 3275—3280.

Zhu X., Conklin D., Eisenach J. C. Cyclooxygenase-1 in the spinal cord plays an important role in postoperative pain. Pain 2003; 104 (1—2): 15—23.

Graham G. G., Scott K. F. Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology 2003; 11: 401—413.

Serhan C. N. Lipoxins and aspirin-triggered 15-epilipoxin biosynthesis: an update and role in antiinflammation and pro-resolution. Prostaglandins Other Lipid Mediat. 2002; 68—69: 433—455.

Serhan C. N., Hong S., Gronert K. et al. Resolvins: a family of bioactive products of omega 3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 2002; 196 (8): 1025—1037.

Roberts D. W., Bucci T. J., Benson R. W. et al. Immunohistochemical localization and quantification of the 3-(cysteine-S-yl)-acetaminophen protein adduct in acetaminophen hepatotoxicity. Am. J. Pathol. 1991; 138: 359—371.

Wallace C. I., Dargan P. I., Jones A. L. Paracetamol overdose: an evidence based flowchart to guide management. Emerg. Med. J. 2002; 19 (3): 202—205.

Kehlet H., Dahl J. B. The value of 'multimodal' or 'balanced analgesia' in postoperative pain treatment. Anesth. Analg. 1993; 77: 1048—1056.

Kehlet H., Dahl J. B. Are perioperative nonsteroidal anti-inflammatory drugs ulcerogenic in the short term? Drugs 1992; 44: 38—41.

Marret E., Kurdi O., Zufferey P., Bonnet F. Effects of non-steroidal anti-inflammatory drugs on patient-controlled analgesia morphine side effects: meta analysis of randomized controlled trials. Anesthesiology 2005; 102 (6): 1249—1260.

Cobby T. F., Crighton I. M., Kyriakides K., Hobbs G. J. Rectal paracetamol has a significant morphine sparing effect after hysterectomy. Br. J. Anaesth. 1999; 83: 253—256.

Delbos A., Boccard E. The morphine-sparing effect of propacetamol in orthopedic postoperative pain. J. Pain Symptom Manage 1995; 10: 279—286.

Peduto V. A., Ballabio M., Stefanini S. Efficacy of propacetamol in the treatment of postoperative pain. Morphine-sparing effect in orthopedic surgery. Italian Collaborative Group on Propacetamol. Acta Anaesthesiol. Scand. 1998; 42: 293—298.

Remy C., Marret E., Bonnet F. Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials. Br. J. Anaesthesia 2005; 94 (4): 505—513.

Benhamou D., Bouaziz H., Zerrouk N., Preaux N. Audit of ketoprofen prescribing after orthopedic and general surgery. Can. J. Anaesth. 1999; 46: 109—113.

Marret E., Flahault A., Samama C. M., Bonnet F. Effects of postoperative, nonsteroidal, antiinflammatory drugs on bleeding risk after tonsillectomy: meta-analysis of randomized, controlled trials. Anesthesiology 2003; 98: 1497—1502.

Viel E., Langlade A., Osman M. et al. Propacetamol: from basic action to clinical utilization. Ann. Fr. Anesth. Reanim. 1999; 18: 332—340.

Aubrun F., Kalfon F., Mottet P. et al. Adjunctive analgesia with intravenous propacetamol does not reduce morphine related adverse effects. Br. J. Anaesth. 2003; 90: 314—319.

Fletcher D., Negre I., Barbin С. et al. Postoperative analgesia with i. v. propacetamol and ketoprofen combination after disc surgery. Can. J. Anaesth. 1997; 44: 479—485.

Hernandez-Palazon J., Tortosa J. A., Martinez-Lage J. F. et al. Intravenous administration of propacetamol reduces morphine consumption after spinal fusion surgery. Anesth. Analg. 2001; 92: 1473—1476.

Mimoz O., Incagnoli P., Josse C. et al. Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection. Anaesthesia. 2001; 56: 520—525.

Schug S. A., Sidebotham D. A., McGuinnety M. et al. Acetaminophen as an adjunct to morphine by patientcontrolled analgesia in the management of acute postoperative pain. Anesth. Analg. 1998; 87: 368—372.

Siddik S. M., Aouad M. T., Jalbout M. I. et al. Diclofenac and/or propacetamol for postoperative pain management after cesarean delivery in patients receiving patient controlled analgesia morphine. Reg. Anesth. Pain Med. 2001; 26: 310—315.

Pettersson P. H., Jakobsson J., Owall A. Intravenous acetaminophen reduced the use of opioids compared with oral administration after coronary artery bypass grafting. J. Cardiothorac. Vasc. Anesth. 2005; 19 (3): 306—309.

Sinatra R. S., Jahr J. S., Reynolds L. W. et al. Efficacite. antalgique et tole. rance du Perfalgan 1 g dans la douleur postope. ratoire en chirurgie orthopedique. Ann. Fr. Anesth. Reanim. 2001; 20 (Suppl. 1): 170.

Prescott L. F., Illingworth R. N., Critchley J. A., Proudfoot A. T. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. B. M. J. 1979; 2: 1097—1100.

Litovitz T. L., Klein=Schwartz W., Rodgers G. C. et al. 2001 annual report of the American association of poison control centers toxic exposure surveillance system. Am. J. Emerg. Med. 2002; 20: 391—452.

Litovitz T. L., Klein-Schwartz W., White S. et al. 2000 Annual report of the American association of poison control centers toxic exposure surveillance system. Am. J. Emerg. Med. 2001; 19: 337—395.

Gyamlani G. G., Parikh C. R. Acetaminophen toxicity: suicidal vs accidental. Crit. Care 2002; 6: 155—159.

Dargan P. I., Ladhani S. L., Jones A. L. Measuring paracetamol concentrations in all patients with drug overdose or altered consciousness: does it change outcome? Emerg. Med. J. 2001; 18: 178—182.

Dargan P. I., Jones A. L. Accidental staggered paracetamol overdoses in the UK: epidemiology and outcome. Emerg. Med. J. 2002; 19 (3): 202—205. No abstract available. Erratum in: Emerg. Med. J. 2002; 19 (4): 376.

Jones A. L., Dargan P. I. Over the counter analgesics: a toxicological perspective. Trends Pharmacol. Sci. 2003; 24 (4): 154—157.

Bessems J. G., Vermeulen N. P. Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Crit. Rev. Toxicol. 2001; 31: 55—138.

James L. P., McCullough S. S., Knight T. R. et al. Acetaminophen toxicity in mice lacking NADPH oxidase activity: role of peroxynitrite formation and mitochondrial oxidant stress. Free Radic. Res. 2003; 37 (12): 1289—1297.

James L. P., McCullough S. S., Lamps L. W. et al. Effect of N-acetylcysteine on acetaminophen toxicity in mice: relationship to reactive nitrogen and cytokine formation. Toxicol. Sci. 2003; 75: 458—467.

Nelson S. G., Wan Z., Stan M. A. S(N)2 ring opening of beta-lactones: an alternative to catalytic asymmetric conjugate additions. J. Org. Chem. 2002; 67: 4680—4683.

Gujral J. S., Knight T. R., Farhood A. et al. Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? Toxicol. Sci. 2002; 67: 322—328.

Lawson J. A., Fisher M. A., Simmons C. A. et al. Inhibition of Fas receptor (CD95)-induced caspase activation and apoptosis by acetaminophen in mice. Toxicol. Appl. Pharmacol. 1999; 156: 179—186.

Mitchell J. R., Jollow D. G., Potter W. Z. et al. Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Ther. 1973; 187: 211—217.

Chen W., Koenigs L. L., Thompson S. J. et al. Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. Chem. Res. Toxicol. 1998; 11: 295—301.

Patten C. J., Thomas P. E., Guy R. L. et al. Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics. Chem. Res. Toxicol. 1993; 6: 511—518.

Thummel K. E., Lee C. A., Kunze K. L. et al. Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone imine by human CYP3A4. Biochem. Pharmacol. 1993; 45: 1563—1569.

Pumford N. R., Hinson J. A., Potter D. W. et al. Immunochemical quantitation of 3-(cysteine-S-yl)acetaminophen adducts in serum and liver proteins of acetaminophen-treated mice. J. Pharmacol. Exp. Ther. 1989; 248: 190—196.

Pumford N. R., Roberts D. W., Benson R. W., Hinson J. A. Immunochemical quantitation of 3-(cysteine-S-yl)acetaminophen protein adducts in subcellular liver fractions following a hepatotoxic dose of acetaminophen. Biochem. Pharmacol. 1990; 40: 573—579.

Muldrew K. L., James L. P., Coop L. et al. 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. Drug Metab. Dispos. 2002; 30: 446—451.

Nelson S. D. Molecular mechanisms of the hepatotoxicity caused by acetaminophen. Semin. Liver. Dis. 1990; 10: 267—278.

Tsokos-Kuhn J. O., Hughes H., Smith C. V., Mitchell J. R. Alkylation of the liver plasma membrane and inhibition of the Ca2-ATPase by acetaminophen. Biochem. Pharmacol. 1988; 37: 2125—2131.

Qiu Y., Benet L. Z., Burlingame A. L. Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry. J. Biol. Chem. 1998; 273: 17940—17953.

Coles B., Wilson I., Wardman P. et al. The spontaneous and enzymatic reaction of N-acetyl-p-benzoquinonimine with glutathione: a stopped-flow kinetic study. Arch. Biochem. Biophys. 1988; 264: 253—260.

Dai Y., Cederbaum A. I. Cytotoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells. J. Pharmacol. Exp. Ther. 1995; 273: 1497—1505.

Nakae D., Yoshiji H., Yamamoto K. et al. Influence of timing of administration of liposome-encapsulated superoxide dismutase on its prevention of acetaminophen-induced liver cell necrosis in rats. Acta Pathol. Jpn. 1990; 40: 568—573.

Sakaida I., Kayano K., Wasaki S. et al. Protection against acetaminophen-induced liver injury in vivo by an iron chelator, deferoxamine. Scand. J. Gastroenterol. 1995; 30: 61—67.

Schnellmann J. G., Pumford N. R., Kusewitt D. F. et al. Deferoxamine delays the development of the hepatotoxicity of acetaminophen in mice. Toxicol. Lett. 1999; 106: 79—88.

James L. P., Farrar H. C., Sullivan J. E. et al. Measurement of acetaminophen-protein adducts in children and adolescents with acetaminophen overdoses. J. Clin. Pharmacol. 2001; 41: 846—851.

Laskin D. L., Gardner C. R., Price V. F., Jollow D. J. Modulation of macrophage functioning abrogates the acute hepatotoxicity of acetaminophen. Hepatology 1995; 21: 1045—1050.

Blazka M. E., Wilmer J. L., Holladay S. D. et al. Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol. Appl. Pharmacol. 1995; 133: 43—52.

Bourdi M., Masubuchi Y., Reilly T. P. et al. Protection against acetaminophen-induced liver injury and lethality by interleukin 10: role of inducible nitric oxide synthase. Hepatology 2002; 35: 289—298.

Bourdi M., Reilly T. P., Elkahloun A. G. et al. Macrophage migration inhibitory factor in drug-induced liver injury: a role in susceptibility and stress responsiveness. Biochem. Biophys. Res. Commun. 2002; 294: 225—230.

Hogaboam C. M., Bone-Larson C. L., Steinhauser M. L. et al. Exaggerated hepatic injury due to acetaminophen challenge in mice lacking C-C chemokine receptor 2. Am. J. Pathol. 2000; 156: 1245—1252.

Goldin R. D., Ratnayaka I. D., Breach C. S. et al. Role of macrophages in acetaminophen (paracetamol)-induced hepatotoxicity. J. Pathol. 1996; 179: 432—435.

Ju C., Reilly T. P., Bourdi M. Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice. Chem. Res. Toxicol. 2002; 15 (12): 1504—1513.

Hinson J. A., Pike S. L., Pumford N. R., Mayeux P. R. Nitrotyrosine-protein adducts in hepatic centrilobular areas following toxic doses of acetaminophen in mice. Chem. Res. Toxicol. 1998; 11: 604—607.

Pryor W. A., Squadrito G. L. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am. J. Physiol. 1995; 268 (1): 699—722.

Beckman J. S., Koppenol W. H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad and ugly. Am. J. Physiol. 1996; 271 (1): С1424—C1437.

Davis K. L., Martin E., Turko I. V., Murad F. Novel effects of nitric oxide. Annu. Rev. Pharmacol. Toxicol. 2001; 41: 203—236.

Thomas D. D., Espey M. G., Vitek M. P. et al. Protein nitration is mediated by heme and free metals through Fenton-type chemistry: an alternative to the NO/O2 reaction. Proc. Nation. Acad. Sci. USA 2002; 99: 12691—12696.

Blazka M. E., Elwell M. R., Holladay S. D. et al. Histopathology of acetaminophen-induced liver changes: role of interleukin 1 alpha and tumor necrosis factor alpha. Toxicol. Pathol. 1996; 24: 181—189.

Simpson K. J., Lukacs N. W., McGregor A. H. et al. Inhibition of tumor necrosis factor alpha does not prevent experimental paracetamol induced hepatic necrosis. J. Pathol. 2000; 190; 489—494.

Baugh J. A., Bucala R. Macrophage migration inhibitory factor. Crit. Care Med. 2002; 30 (Suppl): S27—S35.

Lawson J. A., Farhood A., Hopper R. D. et al. The hepatic inflammatory response after acetaminophen overdose: role of neutrophils. Toxicol. Sci. 2000; 54: 509—516.

Hogaboam C. M., Simpson K. J., Chensue S. W. et al. Macrophage inflammatory protein-2 gene therapy attenuates adenovirus- and acetaminophen-mediated hepatic injury. Gene Ther. 1999; 6: 573—584.

Puntarulo S., Cederbaum A. I. Role of cytochrome P-450 in the stimulation of microsomal production of reactive oxygen species by ferritin. Biochim. Biophys. Acta 1996; 1289: 238—246.

Jones A. L. Recent advances in the management of late paracetamol poisoning. Emerg. Med. (Aust. ) 2000; 12: 14—21.

Harrison P. M., O'Grady J. G., Keays R. T. et al. Serial prothrombin time as a prognostic indicator in paracetamol induced fulminant hepatic failure. B. M. J. 1990; 301: 964—966.

Ellis A., Wendon J. Circulatory, respiratory, cerebral and renal derangements in acute liver failure: pathophysiology and management. Semin. Liv. Dis. 1996; 16: 379—388.

Bernal W., Donaldson N., Wyncoll D., Wendon J. Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study. Lancet 2002; 359: 558—563.

O'Grady J. G., Alexander G. J., Hayllar K. M., Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989; 97: 439—445.

Mitchell I., Bihari D., Chang R. et al. Earlier identification of patients at risk from acetaminophen-induced acute liver failure. Crit. Care Med. 1998; 26: 279—284.

The authors declare that there are no conflicts of interest present.