Advertisement

N-Acetylcysteine

Reference work entry
  • 267 Downloads

Abstract

-Acetylcysteine (NAC) was originally marketed in 1963 as Mucomyst® [1] for inhalation use as a mucolytic due to its ability to break disulfide bonds in mucoprotein complexes in chronic bronchopulmonary disease [2]. It was then studied as an antidote for acetaminophen (paracetamol; APAP) poisoning in the 1970s and since then has been the standard of care for treatment of APAP toxicity. NAC has also been investigated as an antidote for many other toxicants [3–13].

Keywords

N-Acetylcysteine Acetaminophen Paracetamol Glutahione 

Notes

Acknowledgment

Anthony S Manoguerra, PharmD, contributed to this chapter in the first edition.

References

  1. 1.
    U.S. Food and Drug Administration. FDA approved drug products. Acetylcysteine – Mucomyst 1963 [cited 2015 August 24th]. Available from: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails.
  2. 2.
    Santus P, Corsico A, Solidoro P, Braido F, Di Marco F, Scichilone N. Oxidative stress and respiratory system: pharmacological and clinical reappraisal of N-acetylcysteine. COPD. 2014;11(6):705–17.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lund ME, Clarkson TW, Berlin M. Treatment of acute methylmercury ingestion by hemodialysis with N-acetylcysteine (Mucomyst) infusion and 2,3-dimercaptopropane sulfonate. J Toxicol Clin Toxicol. 1984;22(1):31–49.CrossRefPubMedGoogle Scholar
  4. 4.
    Livardjani F, Ledig M, Kopp P, Dahlet M, Leroy M, Jaeger A. Lung and blood superoxide dismutase activity in mercury vapor exposed rats: effect of N-acetylcysteine treatment. Toxicology. 1991;66(3):289–95.CrossRefPubMedGoogle Scholar
  5. 5.
    Ruprah M, Mant TG, Flanagan RJ. Acute carbon tetrachloride poisoning in 19 patients: implications for diagnosis and treatment. Lancet. 1985;1(8436):1027–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Valles EG, de Castro CR, Castro JA. N-acetyl cysteine is an early but also a late preventive agent against carbon tetrachloride-induced liver necrosis. Toxicol Lett. 1994;71(1):87–95.CrossRefPubMedGoogle Scholar
  7. 7.
    Godfrey NF, Peter A, Simon TM, Lorber A. IV N-acetylcysteine treatment of hematologic reactions to chrysotherapy. J Rheumatol. 1982;9(4):519–26.PubMedGoogle Scholar
  8. 8.
    Flora SJ. Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol. 1999;26(11):865–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Pettila V, Takkunen O, Tukiainen P. Zinc chloride smoke inhalation: a rare cause of severe acute respiratory distress syndrome. Intensive Care Med. 2000;26:215–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Montanini S, Sinardi D, Praticò C, Sinardi AU, Trimarchi G. Use of acetylcysteine as the life-saving antidote in Amanita phalloides (death cap) poisoning. Case report on 11 patients. Arzneimittelforschung. 1999;49(12):1044–7.PubMedGoogle Scholar
  11. 11.
    Tong TC, Hernandez M, Richardson WH, Betten DP, Favata M, Riffenburgh RH, et al. Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model. Ann Emerg Med. 2007;50(3):282–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Jiminez JJ, Huang HS, Yunis AA. Treatment with ImuVert/N-acetylcysteine protects rats from cyclophosphamide/cytarabine induced alopecia. Cancer Invest. 1992;10:271–6.CrossRefGoogle Scholar
  13. 13.
    Schwartsmann G, Sander EB, Vinholes J, Sanvitto G, Marques AR, Wissmann G, et al. N-acetylcysteine protects skin lesion induced by local extravasation of doxorubicin in a rat model. Am J Pediatr Hematol Oncol. 1992;14(3):280–1.CrossRefPubMedGoogle Scholar
  14. 14.
    Mitchell JR, Jollow DJ, Potter WZ, Davis DC, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J Pharmacol Exp Ther. 1973;187(1):185–94.PubMedGoogle Scholar
  15. 15.
    Dahlin DC, Miwa GT, Lu AY, Nelson SD. N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. Proc Natl Acad Sci U S A. 1984;81(5):1327–31.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther. 1973;187(1):211–7.PubMedGoogle Scholar
  17. 17.
    Hinson JA, Roberts DW, James LP. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol. 2010;196:369.CrossRefGoogle Scholar
  18. 18.
    Jaeschke H, Bajt ML. Mechanisms of acetaminophen hepatotoxicity. In: McQueen CA, editor. Comprehensive toxicology. 9. 2nd ed. Elsevier Ltd, Kidlington. 2010. p. 457–73.Google Scholar
  19. 19.
    Prescott LF, Newton RW, Swainson CP, Wright N, Forrest AR, Matthew H. Successful treatment of severe paracetamol overdosage with cysteamine. Lancet (London, England). 1974;1(7858):588–92.CrossRefGoogle Scholar
  20. 20.
    Crome P, Vale JA, Volans GN, Widdop B, Goulding R. Oral methionine in the treatment of severe paracetamol (Acetaminophen) overdose. Lancet. 1976;2(7990):829–30.CrossRefPubMedGoogle Scholar
  21. 21.
    Douglas AP, Hamlyn AN, James O. Controlled trial of cysteamine in treatment of acute paracetamol (acetaminophen) poisoning. Lancet. 1976;1(7951):111–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Piperno E, Berssenbruegge DA. Reversal of experimental paracetamol toxicosis with N-acetylcysteine. Lancet. 1976;2(7988):738–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Rumack BH, Peterson RG. Acetaminophen overdose: incidence, diagnosis, and management in 416 patients. Pediatrics. 1978;62(5 Pt 2 Suppl):898–903.PubMedGoogle Scholar
  24. 24.
    Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977;2(8035):432–4.CrossRefPubMedGoogle Scholar
  25. 25.
    Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988;319(24):1557–62.CrossRefPubMedGoogle Scholar
  26. 26.
    U.S. Food and Drug Administration. Drug approval package: acetadote (acetylcysteine) injection 2004 [cited 2015 August 24th]. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-539_Acetadote.cfm.
  27. 27.
    Bakker J, Zhang H, Depierreux M, van Asbeck S, Vincent JL. Effects of N-acetylcysteine in endotoxic shock. J Crit Care. 1994;9(4):236–43.CrossRefPubMedGoogle Scholar
  28. 28.
    Sochman J, Peregrin JH. Total recovery of left ventricular function after acute myocardial infarction: comprehensive therapy with streptokinase, N-acetylcysteine and percutaneous transluminal coronary angioplasty. Int J Cardiol. 1992;35(1):116–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Harrison PM, Wendon JA, Gimson AE, Alexander GJ, Williams R. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med. 1991;324(26):1852–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Stravitz RT, Kramer AH, Davern T, Shaikh AOS, Caldwell SH, Mehta RL, et al. Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group. Crit Care Med. 2007;35(11):2498–508.CrossRefPubMedGoogle Scholar
  31. 31.
    Squires RH, Dhawan A, Alonso E, Narkewicz MR, Shneider BL, Rodriguez-Baez N, et al. Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial. Hepatology. 2013;57(4):1542–9.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Suter PM, Domenighetti G, Schaller MD, Laverrière MC, Ritz R, Perret C. N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study. Chest. 1994;105(1):190–4.CrossRefPubMedGoogle Scholar
  33. 33.
    Mahmoud KM, Ammar AS. Effect of N-acetylcysteine on cardiac injury and oxidative stress after abdominal aortic aneurysm repair: a randomized controlled trial. Acta Anaesthesiol Scand. 2011;55(8):1015–21.CrossRefPubMedGoogle Scholar
  34. 34.
    Tayman C, Tonbul A, Kosus A, Hirfanoglu IM, Uysal S, Haltas H, et al. N-acetylcysteine may prevent severe intestinal damage in necrotizing enterocolitis. J Pediatr Surg. 2012;47(3):540–50.CrossRefPubMedGoogle Scholar
  35. 35.
    Nur E, Brandjes DP, Teerlink T, Otten H-M, Oude Elferink RPJ, Muskiet F, et al. N-acetylcysteine reduces oxidative stress in sickle cell patients. Ann Hematol. 2012;91(7):1097–105.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kshirsagar AV, Poole C, Mottl A, Shoham D, Franceschini N, Tudor G, et al. N-acetylcysteine for the prevention of radiocontrast induced nephropathy: a meta-analysis of prospective controlled trials. J Am Soc Nephrol: JASN. 2004;15(3):761–9.CrossRefPubMedGoogle Scholar
  37. 37.
    Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med. 2006;354(26):2773–82.CrossRefPubMedGoogle Scholar
  38. 38.
    Gonzales DA, Norsworthy KJ, Kern SJ, Banks S, Sieving PC, Star RA, et al. A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity. BMC Med. 2007;5:32.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O, Baris N, et al. Sodium bicarbonate, N-acetylcysteine, and saline for prevention of radiocontrast-induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures. A single-center prospective controlled trial. Am Heart J. 2007;154(3):539–44.CrossRefPubMedGoogle Scholar
  40. 40.
    Traub SJ, Mitchell AM, Jones AE, Tang A, O’Connor J, Nelson T, et al. N-acetylcysteine plus intravenous fluids versus intravenous fluids alone to prevent contrast-induced nephropathy in emergency computed tomography. Ann Emerg Med. 2013;62(5):511–20.e25.CrossRefPubMedGoogle Scholar
  41. 41.
    Briguori C, Airoldi F, D’Andrea D, Bonizzoni E, Morici N, Focaccio A, et al. Renal insufficiency following contrast media administration trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation. 2007;115(10):1211–7.PubMedGoogle Scholar
  42. 42.
    Brueck M, Cengiz H, Boening A. N-acetylcysteine or ascorbic acid versus placebo to prevent contrast-induced nephropathy in patients with renal insufficiency undergoing elective cardiac catheterization: a single center, prospective, double-blind, placebo-controlled, randomized trial. J Am Coll Cardiol. 2011;57(14s1):E595.CrossRefGoogle Scholar
  43. 43.
    PWA Health Group. NAC Info Sheet 1997 [cited 2015 August 24th]. Available from: http://www.thebody.com/content/art4754.html.
  44. 44.
    Slattery KM, Dascombe B, Wallace LK, Bentley DJ, Coutts AJ. Effect of N-acetylcysteine on cycling performance after intensified training. Med Sci Sports Exerc. 2014;46(6):1114–23.CrossRefPubMedGoogle Scholar
  45. 45.
    Larson AM. Acetaminophen hepatotoxicity. Clin Liver Dis. 2007;11(3):525–48.CrossRefPubMedGoogle Scholar
  46. 46.
    Ruffmann R, Wendel A. GSH rescue by N-acetylcysteine. Klin Wochenschr. 1991;69(18):857–62.CrossRefPubMedGoogle Scholar
  47. 47.
    Buckpitt AR, Rollins DE, Mitchell JR. Varying effects of sulfhydryl nucleophiles on acetaminophen oxidation and sulfhydryl adduct formation. Biochem Pharmacol. 1979;28(19):2941–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Lauterburg BH, Corcoran GB, Mitchell JR. Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J Clin Invest. 1983;71(4):980–91.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Galinsky RE, Levy G. Dose- and time-dependent elimination of acetaminophen in rats: pharmacokinetic implications of cosubstrate depletion. J Pharmacol Exp Ther. 1981;219(1):14–20.PubMedGoogle Scholar
  50. 50.
    Saito C, Zwingmann C, Jaeschke H. Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetylcysteine. Hepatology. 2010;51(1):246–54.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Smilkstein MJ, Bronstein AC, Linden C, Augenstein WL, Kulig KW, Rumack BH. Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. Ann Emerg Med. 1991;20(10):1058–63.CrossRefPubMedGoogle Scholar
  52. 52.
    Keays R, Harrison PM, Wendon JA, Forbes A, Gove C, Alexander GJ, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ (Clinical Res Ed). 1991;303(6809):1026–9.CrossRefGoogle Scholar
  53. 53.
    Harrison PM, Keays R, Bray GP, Alexander GJ, Williams R. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet. 1990;335(8705):1572–3.CrossRefPubMedGoogle Scholar
  54. 54.
    Jones AL. Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. J Toxicol Clin Toxicol. 1998;36(4):277–85.CrossRefPubMedGoogle Scholar
  55. 55.
    North DS, Peterson RG, Krenzelok EP. Effect of activated charcoal administration on acetylcysteine serum levels in humans. Am J Hosp Pharm. 1981;38(7):1022–4.PubMedGoogle Scholar
  56. 56.
    Borgstrom L, Kagedal B, Paulsen O. Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol. 1986;31:217–22.CrossRefPubMedGoogle Scholar
  57. 57.
    Olsson B, Johansson M, Gabrielsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol. 1988;34(1):77–82.CrossRefPubMedGoogle Scholar
  58. 58.
    Prescott LF, Donovan JW, Jarvie DR, Proudfoot AT. The disposition and kinetics of intravenous N-acetylcysteine in patients with paracetamol overdosage. Eur J Clin Pharmacol. 1989;37(5):501–6.CrossRefPubMedGoogle Scholar
  59. 59.
    Ekins BR, Ford DC, Thompson MI, Bridges RR, Rollins DE, Jenkins RD. The effect of activated charcoal on N-acetylcysteine absorption in normal subjects. Am J Emerg Med. 1987;5(6):483–7.CrossRefPubMedGoogle Scholar
  60. 60.
    Renzi FP, Donovan JW, Martin TG, Morgan L, Harrison EF. Concomitant use of activated charcoal and N-acetylcysteine. Ann Emerg Med. 1985;14(6):568–72.CrossRefPubMedGoogle Scholar
  61. 61.
    Jones AL, Jarvie DR, Simpson D, Hayes PC, Prescott LF. Pharmacokinetics of N-acetylcysteine are altered in patients with chronic liver disease. Aliment Pharmacol Ther. 1997;11(4):787–91.CrossRefPubMedGoogle Scholar
  62. 62.
    Riggs BS, Bronstein AC, Kulig K, Archer PG, Rumack BH. Acute acetaminophen overdose during pregnancy. Obstet Gynecol. 1989;74(2):247–53.PubMedGoogle Scholar
  63. 63.
    Wang PH, Yang MJ, Lee WL, Chao HT, Yang ML, Hung JH. Acetaminophen poisoning in late pregnancy. A case report. J Reprod Med. 1997;42(6):367–71.PubMedGoogle Scholar
  64. 64.
    Horowitz RS, Dart RC, Jarvie DR, Bearer CF, Gupta U. Placental transfer of N-acetylcysteine following human maternal acetaminophen toxicity. J Toxicol Clin Toxicol. 1997;35(5):447–51.CrossRefPubMedGoogle Scholar
  65. 65.
    McElhatton PR, Sullivan FM, Volans GN. Paracetamol overdose in pregnancy analysis of the outcomes of 300 cases referred to the teratology information service. Reprod Toxicol. 1997;11(1):85–94.CrossRefPubMedGoogle Scholar
  66. 66.
    Miller LF, Rumack BH. Clinical safety of high oral doses of acetylcysteine. Semin Oncol. 1983;10(1 Suppl 1):76–85.PubMedGoogle Scholar
  67. 67.
    Scharman EJ. Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions. J Toxicol Clin Toxicol. 1998;36(1–2):19–25.CrossRefPubMedGoogle Scholar
  68. 68.
    Mroz LS, Benitez JG, Krenzelok EP. Angioedema with oral N-acetylcysteine (Letter). Ann Emerg Med. 1997;30(2):240–1.PubMedGoogle Scholar
  69. 69.
    Mohammed S, Jamal AZ, Robison LR. Serum sickness-like illness associated with N-acetylcysteine therapy. Ann Pharmacother. 1994;28(2):285.CrossRefPubMedGoogle Scholar
  70. 70.
    Bonfiglio MF, Traeger SM, Hulisz DT, Martin BR. Anaphylactoid reaction to intravenous acetylcysteine associated with electrocardiographic abnormalities. Ann Pharmacother. 1992;26(1):22–5.CrossRefPubMedGoogle Scholar
  71. 71.
    Bateman DN, Woodhouse KW, Rawlins MD. Adverse reactions to N-acetylcysteine. Hum Toxicol. 1984;3(5):393–8.CrossRefPubMedGoogle Scholar
  72. 72.
    Dawson AH, Henry DA, McEwen J. Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning. Med J Aust. 1989;150(6):329–31.PubMedGoogle Scholar
  73. 73.
    Mant TG, Tempowski JH, Volans GN, Talbot JC. Adverse reactions to acetylcysteine and effects of overdose. Br Med J (Clin Res Ed). 1984;289(6439):217–9.CrossRefGoogle Scholar
  74. 74.
    Anonymous. Death after N-acetylcysteine (notes and news). Lancet. 1984;1:1421.Google Scholar
  75. 75.
    Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol. 2009;47(2):81–8.CrossRefGoogle Scholar
  76. 76.
    Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med. 1998;31(6):710–5.CrossRefPubMedGoogle Scholar
  77. 77.
    Kerr F, Dawson A, Whyte IM, Buckley N, Murray L, Graudins A, et al. The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine. Ann Emerg Med. 2005;45(4):402–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Waring WS, Stephen AF, Robinson OD, Dow MA, Pettie JM. Lower incidence of anaphylactoid reactions to N-acetylcysteine in patients with high acetaminophen concentrations after overdose. Clin Toxicol. 2008;46(6):496–500.CrossRefGoogle Scholar
  79. 79.
    Zyoud SH, Awang R, Syed Sulaiman SA, Sweileh WM, Al-Jabi SW. Incidence of adverse drug reactions induced by N-acetylcysteine in patients with acetaminophen overdose. Hum Exp Toxicol. 2010;29(3):153–60.CrossRefPubMedGoogle Scholar
  80. 80.
    Lucena MI, López-Torres E, Verge C, Andrade RJ, Puche MJ, Seoane J, et al. The administration of N-acetylcysteine causes a decrease in prothrombin time in patients with paracetamol overdose but without evidence of liver impairment. Eur J Gastroenterol Hepatol. 2005;17(1):59–63.CrossRefPubMedGoogle Scholar
  81. 81.
    Whyte IM, Buckley NA, Reith DM, Goodhew I, Seldon M, Dawson AH. Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII. Ther Drug Monit. 2000;22(6):742–8.CrossRefPubMedGoogle Scholar
  82. 82.
    Pizon AF, Jang DH, Wang HE. The in vitro effect of N-acetylcysteine on prothrombin time in plasma samples from healthy subjects. Acad Emerg Med. 2011;18(4):351–4.CrossRefPubMedGoogle Scholar
  83. 83.
    Jang DH, Weaver MD, Pizon AF. In vitro study of N-acetylcysteine on coagulation factors in plasma samples from healthy subjects. J Med Toxicol. 2012;9(1):49–53.CrossRefPubMedCentralGoogle Scholar
  84. 84.
    Mullins ME, Vitkovitsky IV. Hemolysis and hemolytic uremic syndrome following five-fold N-acetylcysteine overdose. Clin Toxicol. 2011;49(8):755–9.CrossRefGoogle Scholar
  85. 85.
    Heard K, Schaeffer TH. Massive acetylcysteine overdose associated with cerebral edema and seizures. Clin Toxicol. 2011;49(5):423–5.CrossRefGoogle Scholar
  86. 86.
    Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol. 2012;50(2):91–8.CrossRefGoogle Scholar
  87. 87.
    Yarema MC, Johnson DW, Berlin RJ, Sivilotti MLA, Nettel-Aguirre A, Brant RF, et al. Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning. Ann Emerg Med. 2009;54:606–14.CrossRefPubMedGoogle Scholar
  88. 88.
    Woo OF, Mueller PD, Olson KR, Anderson IB, Kim SY. Shorter duration of oral N-acetylcysteine therapy for acute acetaminophen overdose. Ann Emerg Med. 2000;35(4):363–8.CrossRefGoogle Scholar
  89. 89.
    Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J. 1979;2(6198):1097–100.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Varney SM, Buchanan JA, Kokko J, Heard K. Acetylcysteine for acetaminophen overdose in patients who weigh >100 Kg. Am J Ther. 2014;21(3):159–63.CrossRefPubMedGoogle Scholar
  91. 91.
    Al Juma S, Villeneuve E, Elliot A, Palmer RB, Gosselin S. XXXV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 26–29 May 2015, St Julian’s, Malta. 43.Doubling the third dose of intravenous N-acetylcysteine survey: an international practice perspective. Clin Toxicol. 2015;53(4):253–4.Google Scholar
  92. 92.
    Gosselin S, Juurlink DN, Kielstein JT, Ghannoum M, Lavergne V, Nolin TD, et al. Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup. Clin Toxicol. 2014;52(8):856–67.CrossRefGoogle Scholar
  93. 93.
    Hayes BD, Klein-Schwartz W, Doyon S. Frequency of medication errors with intravenous acetylcysteine for acetaminophen overdose. Ann Pharmacother. 2008;42(6):766–70.CrossRefPubMedGoogle Scholar
  94. 94.
    Sung L, Simons JA, Dayneka NL. Dilution of intravenous N-acetylcysteine as a cause of hyponatremia. Pediatrics. 1997;100:389–91.CrossRefPubMedGoogle Scholar
  95. 95.
    Dart RC, Rumack BH. Patient-tailored acetylcysteine administration. Ann Emerg Med. 2007;50(3):280–1.CrossRefPubMedGoogle Scholar
  96. 96.
    Bond GR. Acetaminophen protein adducts: a review. Clin Toxicol. 2009;47(1):2–7.CrossRefGoogle Scholar
  97. 97.
    LeBlanc A, Shiao TC, Roy R, Sleno L. Absolute quantitation of NAPQI-modified rat serum albumin by LC–MS/MS: monitoring acetaminophen covalent binding in vivo. Chem Res Toxicol. 2014;27(9):1632–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of PharmacyMcGill University Health CentreMontrealCanada
  2. 2.Department of Medicine and Emergency MedicineMcGill University Health CentreMontrealCanada

Personalised recommendations