Sounding Board

You have full text access to this OnlineOpen article

Acetaminophen misconceptions

  1. Barry H. Rumack M.D.†,*

Article first published online: 30 JUN 2004

DOI: 10.1002/hep.20300

Issue

Hepatology

Hepatology

Volume 40, Issue 1, pages 10–15, July 2004

Additional Information

How to Cite

Rumack, B. H. (2004), Acetaminophen misconceptions. Hepatology, 40: 10–15. doi: 10.1002/hep.20300

Author Information

  1. University of Colorado School of Medicine, Greenwood Village, CO

  1. †

    fax: (720) 294-1281

*Rocky Mountain Poison and Drug Center, Clinical Professor of Pediatrics, University of Colorado School of Medicine, 33 Silver Fox Circle, Greenwood Village, CO 80121

Publication History

  1. Issue published online: 30 JUN 2004
  2. Article first published online: 30 JUN 2004
  3. Manuscript Accepted: 10 APR 2004
  4. Manuscript Received: 8 MAR 2004

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (128K)

References

  • 1
    Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol 2002; 40: 3–20.
  • 2
    Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics 1975; 55: 871–876.
  • 3
    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) [see comments]. N Engl J Med 1988; 319: 1557–1562.
  • 4
    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: 363–368.
  • 5
    Rumack BH, Peterson RC, Koch GG, Amara IA. Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med 1981; 141(3 Spec No): 380–385.
  • 6
    Yoshiba M, Dehara K, Inoue K, Okamoto H, Mayumi M. Contribution of hepatitis C virus to non-A, non-B fulminant hepatitis in Japan. HEPATOLOGY 1994; 19: 829–835.
    Direct Link:
  • 7
    Feranchak AP, Tyson RW, Narkewicz MR, Karrer FM, Sokol RJ. Fulminant Epstein-Barr viral hepatitis: orthotopic liver transplantation and review of the literature. Liver Transpl Surg 1998; 4: 469–476.
    Direct Link:
  • 8
    Furuta S, Ozawa Y, Maejima K, Tashiro H, Kitahora T, Hasegawa K, et al. Anorexia nervosa with severe liver dysfunction and subsequent critical complications. Intern Med 1999; 38: 575–579.
  • 9
    Giercksky T, Boberg KM, Farstad IN, Halvorsen S, Schrumpf E. Severe liver failure in exertional heat stroke. Scand J Gastroenterol 1999; 34: 824–827.
  • 10
    Mathurin P, Durand F, Ganne N, Mollo JL, Lebrec D, Degott C, et al. Ischemic hepatitis due to obstructive sleep apnea. Gastroenterology 1995; 109: 1682–1684.
  • 11
    Dart RC, Kuffner EK, Rumack BH. Treatment of pain or fever with paracetamol (acetaminophen) in the alcoholic patient: a systematic review. Am J Ther 2000; 7: 123–134.
  • 12
    Kuffner EK, Dart RC, Bogdan GM, Hill RE, Casper E, Darton L. Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients. Arch Intern Med 2001; 161: 2247–2252.
  • 13
    Smilkstein MJ, Rumack BH. Chronic ethanol use and acute acetaminophen overdose toxicity [abstract]. Clin Toxicol 1998; 36: 476.
  • 14
    Thummel KE, Slattery JT, Ro H, Chien JY, Nelson SD, Lown KE, et al. Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults. Clin Pharmacol Ther 2000; 67: 591–599.
  • 15
    Badger TM, Huang J, Ronis M, Lumpkin CK. Induction of cytochrome P450 2E1 during chronic ethanol exposure occurs via transcription of the CYP 2E1 gene when blood alcohol concentrations are high. Biochem Biophys Res Commun 1993; 190: 780–785.
  • 16
    Ronis MJ, Huang J, Crouch J, Mercado C, Irby D, Valentine CR, et al. Cytochrome P450 CYP 2E1 induction during chronic alcohol exposure occurs by a two-step mechanism associated with blood alcohol concentrations in rats. J Pharmacol Exp Ther 1993; 264: 944–950.
  • 17
    Takahashi T, Lasker JM, Rosman AS, Lieber CS. Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA. HEPATOLOGY 1993; 17: 236–245.
  • 18
    Tsutsumi M, Lasker JM, Shimizu M, Rosman AS, Lieber CS. The intralobular distribution of ethanol-inducible P450IIE1 in rat and human liver. HEPATOLOGY 1989; 10: 437–446.
    Direct Link:
  • 19
    Chien JY, Thummel KE, Slattery JT. Pharmacokinetic consequences of induction of CYP2E1 by ligand stabilization. Drug Metab Dispos 1997; 25: 1165–1175.
  • 20
    Girre C, Lucas D, Hispard E, Menez C, Dally S, Menez JF. Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics. Biochem Pharmacol 1994; 47: 1503–1508.
  • 21
    Manyike PT, Kharasch ED, Kalhorn TF, Slattery JT. Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin Pharmacol Ther 2000; 67: 275–282.
  • 22
    Lee TD, Sadda MR, Mendler MH, Bottiglieri T, Kanel G, Mato JM, et al. Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis. Alcohol Clin Exp Res 2004; 28: 173–181.
    Direct Link:
  • 23
    Gabrielle L, Leterrier F, Molinie C, Essioux H, Cristau P, Laverdant C. Determination of human liver cytochrome P-450 by a micromethod using the electron paramagnetic resonance. Study of 141 liver biopsies (author's transl) [in French]. Gastroenterol Clin Biol 1977; 1: 775–782.
  • 24
    Poulsen HE, Ranek L, Andreasen PB. The hepatic glutathione content in liver diseases. Scand J Clin Lab Invest 1981; 41: 573–576.
  • 25
    Schoene B, Fleischmann RA, Remmer H, von Oldershausen HF. Determination of drug metabolizing enzymes in needle biopsies of human liver. Eur J Clin Pharmacol 1972; 4: 65–73.
  • 26
    Siegers CP, Bossen KH, Younes M, Mahlke R, Oltmanns D. Glutathione and glutathione-S-transferases in the normal and diseased human liver. Pharmacol Res Commun 1982; 14: 61–72.
  • 27
    George J, Liddle C, Murray M, Byth K, Farrell GC. Pre-translational regulation of cytochrome P450 genes is responsible for disease-specific changes of individual P450 enzymes among patients with cirrhosis. Biochem Pharmacol 1995; 49: 873–881.
  • 28
    Zhao P, Kalhorn TF, Slattery JT. Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver. HEPATOLOGY 2002; 36: 326–335.
    Direct Link:
  • 29
    Zhao P, Slattery JT. Effects of ethanol dose and ethanol withdrawal on rat liver mitochondrial glutathione: implication of potentiated acetaminophen toxicity in alcoholics. Drug Metab Dispos 2002; 30: 1413–1417.
  • 30
    Hong JY, Pan JM, Gonzalez FJ, Gelboin HV, Yang CS. The induction of a specific form of cytochrome P-450 (P-450j) by fasting. Biochem Biophys Res Commun 1987; 142: 1077–1083.
  • 31
    Raucy JL, Lasker JM, Kraner JC, Salazar DE, Lieber CS, Corcoran GB. Induction of cytochrome P450IIE1 in the obese overfed rat. Mol Pharmacol 1991; 39: 275–280.
  • 32
    Dilger K, Metzler J, Bode JC, Klotz U. CYP2E1 activity in patients with alcoholic liver disease. J Hepatol 1997; 27: 1009–1014.
  • 33
    George J, Murray M, Byth K, Farrell GC. Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. HEPATOLOGY 1995; 21: 120–128.
  • 34
    George J, Byth K, Farrell GC. Influence of clinicopathological variables on CYP protein expression in human liver. J Gastroenterol Hepatol 1996; 11: 33–39.
    Direct Link:
  • 35
    Cederbaum AI, Wu D, Mari M, Bai J. CYP2E1-dependent toxicity and oxidative stress in HepG2 cells. Free Radic Biol Med 2001; 31: 1539–1543.
  • 36
    Lauterburg BH, Velez ME. Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut 1988; 29: 1153–1157.
  • 37
    Lauterburg BH. Analgesics and glutathione. Am J Ther 2002; 9: 225–233.
  • 38
    Zenger F, Russmann S, Junker E, Wuthrich C, Bui MH, Lauterburg BH. Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury? Eur J Clin Nutr 2004; 58: 238–243.
  • 39
    Jung D. Disposition of acetaminophen in protein-calorie malnutrition. J Pharmacol Exp Ther 1985; 232: 178–182.
  • 40
    Mehta S, Nain CK, Yadav D, Sharma B, Mathur VS. Disposition of acetaminophen in children with protein calorie malnutrition. Int J Clin Pharmacol Ther Toxicol 1985; 23: 311–315.
  • 41
    Newman TJ, Bargman GJ. Acetaminophen hepatotoxicity and malnutrition. Am J Gastroenterol 1979; 72: 647–650.
  • 42
    Rumack BH, Holtzman J, Chase HP. Hepatic drug metabolism and protein malnutrition. J Pharmacol Exp Ther 1973; 186: 441–446.
  • 43
    Whitcomb DC, Block GD. Association of acetaminophen hepatotoxicity with fasting and ethanol use [see comments]. JAMA 1994; 272: 1845–1850.
  • 44
    Schenker S, Speeg KV Jr, Perez A, Finch J. The effects of food restriction in man on hepatic metabolism of acetaminophen. Clin Nutr 2001; 20: 145–150.
  • 45
    Price VF, Schulte JM, Spaethe SM, Jollow DJ. Mechanism of fasting-induced suppression of acetaminophen glucuronidation in the rat. Adv Exp Med Biol 1986; 197: 697–706.
  • 46
    Price VF, Miller MG, Jollow DJ. Mechanisms of fasting-induced potentiation of acetaminophen hepatotoxicity in the rat. Biochem Pharmacol 1987; 36: 427–433.
  • 47
    Price VF, Jollow DJ. Mechanism of decreased acetaminophen glucuronidation in the fasted rat. Biochem Pharmacol 1988; 37: 1067–1075.
  • 48
    Price VF, Jollow DJ. Effects of sulfur-amino acid-deficient diets on acetaminophen metabolism and hepatotoxicity in rats. Toxicol Appl Pharmacol 1989; 101: 356–369.
  • 49
    Price VF, Jollow DJ. Effect of glucose and gluconeogenic substrates on fasting-induced suppression of acetaminophen glucuronidation in the rat. Biochem Pharmacol 1989; 38: 289–297.
  • 50
    Prescott LF. Kinetics and metabolism of paracetamol and phenacetin. Br J Clin Pharmacol 1980; 10(Suppl 2): 291S–298S.
  • 51
    Prescott LF. Drug conjugation in clinical toxicology. Biochem Soc Trans 1984; 12: 96–99.
  • 52
    Blackledge HM, O'Farrell J, Minton NA, McLean AE. The effect of therapeutic doses of paracetamol on sulphur metabolism in man. Hum Exp Toxicol 1991; 10: 159–165.
  • 53
    Gelotte C, Auiler J, Lynch J, Temple A, Bowen D. Tolerability and repeat-dose pharmacokinetics (PK) of acetaminophen (APAP) at 4, 6 and 8g/d in healthy adults. Toxicol Sci 2003; 72(Suppl 1): 145.
  • 54
    Schiodt FV, Rochling FA, Casey DL, Lee WM. Acetaminophen toxicity in an urban county hospital. N Engl J Med 1997; 337: 1112–1117.
  • 55
    Dart RC, Rumack, BH. Acetaminophen (paracetamol). In: DartRC, ed. Medical Toxicology, 3rd edition. Philadelphia, PA; Lippincott, Williams & Wilkins; 2004: 723–738.
View Full Article (HTML) Get PDF (128K)