791
Views
81
CrossRef citations to date
0
Altmetric
Review

Acetaminophen safety and hepatotoxicity – where do we go from here?

&
Pages 341-355 | Published online: 09 Aug 2007

Bibliography

  • BRODIE BB, AXELROD J: The fate of acetanilide in man. J. Pharmacol. Exp. Ther. (1948) 94(1):29-38.
  • PIGUET V, DESMEULES J, DAYER P: Lack of acetaminophen ceiling effect on R-III nociceptive flexion reflex. Eur. J. Clin. Pharmacol. (1998) 53(5):321-324.
  • GRAHAM GG, SCOTT KF: Mechanism of action of paracetamol. Am. J. Ther. (2005) 12(1):46-55.
  • BOUTAUD O, ARONOFF DM, RICHARDSON JH, MARNETT LJ, OATES JA: Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H(2) synthases. Proc. Natl. Acad. Sci. USA (2002) 99(10):7130-7135.
  • MUTH-SELBACH US, TEGEDER I, BRUNE K, GEISSLINGER G: Acetaminophen inhibits spinal prostaglandin E2 release after peripheral noxious stimulation. Anesthesiology (1999) 91(1):231-239.
  • FELDBERG W, GUPTA KP, MILTON AS, WENDLANDT S: Effect of pyrogen and antipyretics on prostaglandin acitvity in cisternal c.s.f. of unanaesthetized cats. J. Physiol. (1973) 234(2):279-303.
  • PILETTA P, PORCHET HC, DAYER P: Central analgesic effect of acetaminophen but not of aspirin. Clin. Pharmacol. Ther. (1991) 49(4):350-354.
  • ALLOUI A, CHASSAING C, SCHMIDT J et al.: Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an inflammatory pain model in rats. Eur. J. Pharmacol. (2002) 443(1-3):71-77.
  • BONNEFONT J, ALLOUI A, CHAPUY E, CLOTTES E, ESCHALIER A: Orally administered paracetamol does not act locally in the rat formalin test: evidence for a supraspinal, serotonin-dependent antinociceptive mechanism. Anesthesiology (2003) 99(4):976-981.
  • OTTANI A, LEONE S, SANDRINI M, FERRARI A, BERTOLINI A: The analgesicactivity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. Eur. J. Pharmacol. (2006) 531(1-3):280-281.
  • OUELLET M, PERCIVAL MD: Mechanism of acetaminophen inhibition of cyclooxygenase isoforms. Arch. Biochem. Biophys. (2001) 387(2):273-280.
  • STORK CM, REES S, HOWLAND MA, KAPLAN L, GOLDFRANK L, HOFFMAN RS: Pharmacokinetics of extended relief vs regular release Tylenol in simulated human overdose. J. Toxicol. (1996) 34(2):157-162.
  • WYNNE HA, COPE LH, HERD B, RAWLINS MD, JAMES OF, WOODHOUSE KW: The association of age and frailty with paracetamol conjugation in man. Age Ageing (1990) 19(6):419-424.
  • LEVY G, KHANNA NN, SODA DM, TSUZUKI O, STERN L: Pharmacokinetics of acetaminophen in the human neonate: formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and D-glucaric acid excretion. Pediatrics (1975) 55(6):818-825.
  • FORREST JA, ADRIAENSSENS P, FINLAYSON ND, PRESCOTT LF: Paracetamol metabolism in chronic liver disease. Eur. J. Clin. Pharmacol. (1979) 15(6):427-431.
  • BENSON GD: Acetaminophen in chronic liver disease. Clin. Pharmacol. Ther. (1983) 33(1):95-101.
  • 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):185-194.
  • MOORE M, THOR H, MOORE G, NELSON S, MOLDEUS P, ORRENIUS S: The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+. J. Biol. Chem. (1985) 260(24):13035-13040.
  • LEI XG, ZHU JH, MCCLUNG JP, AREGULLIN M, RONEKER CA: Mice deficient in Cu,Zn-superoxide dismutase are resistant to acetaminophen toxicity. Biochem. J. (2006) 399(3):455-461.
  • JAMES LP, MAYEUX PR, HINSON JA. Acetaminophen-induced hepatotoxicity. Drug Metab. Dispos. (2003) 31(12):1499-1506.
  • LARREY D, PAGEAUX GP: Genetic predisposition to drug-induced hepatotoxicity. J. Hepatol. (1997) 26(Suppl. 2):12-21.
  • SLATTERY JT, WILSON JM, KALHORN TF, NELSON SD: Dose-dependent pharmacokinetics of acetaminophen: evidence of glutathione depletion in humans. Clin. Pharmacol. Ther. (1987) 41(4):413-418.
  • RUMORE MM, BLAIKLOCK RG: Influence of age-dependent pharmacokinetics and metabolism on acetaminophen hepatotoxicity. J. Pharm. Sci. (1992) 81(3):203-207.
  • RUMACK BH, MATTHEW H: Acetaminophen poisoning and toxicity. Pediatrics (1975) 55(6):871-876.
  • 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):1557-1562.
  • KOBRINSKY NL, HARTFIELD D, HORNER H et al.: Treatment of advanced malignancies with high-dose acetaminophen and N-acetylcysteine rescue. Cancer Invest. (1996) 14(3):202-210.
  • DAVIDSON DG, EASTHAM WN: Acute liver necrosis following overdose of paracetamol. Br. Med. J. (1966) 2(5512):497-499.
  • THOMSON JS, PRESCOTT LF: Liver damage and impaired glucose tolerance after paracetamol overdosage. Br. Med. J. (1966) 2(5512):506-507.
  • PRESCOTT LF, ROSCOE P, WRIGHT N, BROWN SS: Plasma-paracetamol half-life and hepatic necrosis in patients with paracetamol overdosage. Lancet (1971) 1(7698):519-522.
  • DAVERN TJ II, JAMES LP, HINSON JA et al.: Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Gastroenterology (2006) 130(3):687-694.
  • PURKINS L, LOVE ER, EVE MD et al.: The influence of diet upon liver function tests and serum lipids in healthy male volunteers resident in a Phase I unit. Br. J. Clin. Pharmacol. (2004) 57(2):199-208.
  • ROSENZWEIG P, MIGET N, BROHIER S: Transaminase elevation on placebo during Phase I trials: prevalence and significance. Br. J. Clin. Pharmacol. (1999) 48(1):19-23.
  • WATKINS PB, KAPLOWITZ N, SLATTERY JT et al.: Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA (2006) 296(1):87-93.
  • PENNA A, BUCHANAN N: Paracetamol poisoning in children and hepatotoxicity. Br. J. Clin. Pharmacol. (1991) 32(2):143-149.
  • HENDRIX-Treacy S, WALLACE SM, HINDMARSH KW, WYANT GM, DANILKEWICH A: The effect of acetaminophen administration on its disposition and body stores of sulphate. Eur. J. Clin. Pharmacol. (1986) 30(3):273-278.
  • LESKO SM, MITCHELL AA: An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. JAMA (1995) 273(12):929-933.
  • PESSAYRE D, DOLDER A, ARTIGOU JY et al.: Effect of fasting on metabolite-mediated hepatotoxicity in the rat. Gastroenterology (1979) 77(2):264-271.
  • SATO C, MATSUDA Y, LIEBER CS: Increased hepatotoxicity of acetaminophen after chronic ethanol consumption in the rat. Gastroenterology (1981) 80(1):140-148.
  • SEEFF LB, CUCCHERINI BA, ZIMMERMAN HJ, ADLER E, BENJAMIN SB: Acetaminophen hepatotoxicity in alcoholics. A therapeutic misadventure. Ann. Int. Med. (1986) 104(3):399-404.
  • SATO C, NAKANO M, LIEBER CS: Prevention of acetaminophen-induced hepatotoxicity by acute ethanol administration in the rat: comparison with carbon tetrachloride-induced hepatoxicity. J. Pharmacol. Exp. Ther. (1981) 218(3):805-810.
  • ITO Y, ABRIL ER, BETHEA NW, MCCUSKEY RS: Ethanol binging enhances hepatic microvascular responses to acetaminophen in mice. Microcirculation (2004) 11(7):625-632.
  • LIEBER CS: Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968 – 1998) – a review. Alcohol. Clin. Exp. Res. (1999) 23(6):991-1007.
  • BRACKETT CC, BLOCH JD: Phenytoin as a possible cause of acetaminophen hepatotoxicity: case report and review of the literature. Pharmacotherapy (2000) 20(2):229-233.
  • TOMLINSON B, YOUNG RP, NG MC, ANDERSON PJ, KAY R, CRITCHLEY JA: Selective liver enzyme induction by carbamazepine and phenytoin in Chinese epileptics. Eur. J. Clin. Pharmacol. (1996) 50(5):411-415.
  • MURPHY R, SWARTZ R, WATKINS PB: Severe acetaminophen toxicity in a patient receiving isoniazid. Ann. Int. Med. (1990) 113(10):799-800.
  • NOLAN CM, SANDBLOM RE, THUMMEL KE, SLATTERY JT, NELSON SD: Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis. Chest (1994) 105(2):408-411.
  • SHRINER K, GOETZ MB: Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine. Am. J. Med. (1992) 93(1):94-96.
  • BURGER DM, MEENHORST PL, KOKS CH, BEIJNEN JH: Pharmacokinetics of zidovudine and acetaminophen in a patient on chronic acetaminophen therapy. Ann. Pharmacother. (1994) 28(3):327-330.
  • KAMALI F: The effect of probenecid on paracetamol metabolism and pharmacokinetics. Eur. J. Clin. Pharmacol. (1993) 45(6):551-553.
  • ABERNETHY DR, GREENBLATT DJ, AMEER B, SHADER RI: Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation. J. Pharmacol. Exp. Ther. (1985) 234(2):345-349.
  • SANAKA M, KUYAMA Y, MINESHITA S et al.: Pharmacokinetic interaction between acetaminophen and lansoprazole. J. Clin. Gastroenterol. (1999) 29(1):56-58.
  • ESTEBAN A, PEREZ-MATEO M: Gilbert's disease: a risk factor for paracetamol overdosage? J. Hepatol. (1993) 18(2):257-258.
  • SONG BJ, VEECH RL, SAENGER P: Cytochrome P450IIE1 is elevated in lymphocytes from poorly controlled insulin-dependent diabetics. J. Clin. Endocrinol. Metabol. (1990) 71(4):1036-1040.
  • O'Shea D, DAVIS SN, KIM RB, WILKINSON GR: Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe of CYP2E1 activity. Clin. Pharmacol. Ther. (1994) 56(4):359-367.
  • ERIKSSON LS, BROOME U, KALIN M, LINDHOLM M: Hepatotoxicity due to repeated intake of low doses of paracetamol. J. Int. Med. (1992) 231(5):567-570.
  • SCHENKER S, SPEEG KV Jr, PEREZ A, FINCH J: The effects of food restriction in man on hepatic metabolism of acetaminophen. Clinical Nutrition (Edinburgh, Scotland) (2001) 20(2):145-150.
  • ANDREASEN PB, HUTTERS L: Paracetamol (acetaminophen) clearance in patients with cirrhosis of the liver. Acta Med. Scand. Suppl. (1979) 624:99-105.
  • AL-Obaidy SS, MCKIERNAN PJ, LI WAN PO A, GLASGOW JF, COLLIER PS: Metabolism of paracetamol in children with chronic liver disease. Eur. J. Clin. Pharmacol. (1996) 50(1-2):69-76.
  • BATEMAN DN, GORMAN DR, BAIN M, INGLIS JH, HOUSE FR, MURPHY D: Legislation restricting paracetamol sales and patterns of self-harm and death from paracetamol-containing preparations in Scotland. Br. J. Clin. Pharmacol. (2006) 62(5):573-581.
  • INGLIS JH: Restricting sales of paracetamol tablets: effect on deaths and emergency admissions for poisoning in Scotland 1991 – 2002. Scott. Med. J. (2004) 49(4):142-143.
  • HAWTON K, TOWNSEND E, DEEKS J et al.: Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study. BMJ (2001) 322(7296):1203-1207.
  • BLOT WJ, MCLAUGHLIN JK: Over the counter non-steroidal anti-inflammatory drugs and risk of gastrointestinal bleeding. J. Epidemiol. Biostat. (2000) 5(2):137-142.
  • OFMAN JJ, MACLEAN CH, STRAUS WL et al.: A metaanalysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs. J. Rheumatol. (2002) 29(4):804-812.
  • SINGH G: Gastrointestinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, Rheumatism, and Aging Medical Information System. Am. J. Ther. (2000) 7(2):115-121.
  • LARSON AM, POLSON J, FONTANA RJ et al.: Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology (Baltimore, Md) (2005) 42(6):1364-1372.
  • 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):1058-1063.
  • SCHIODT FV, ATILLASOY E, SHAKIL AO et al.: Etiology and outcome for 295 patients with acute liver failure in the United States. Liver Transpl. Surg. (1999) 5(1):29-34.
  • OSTAPOWICZ G, FONTANA RJ, SCHIODT FV et al.: Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann. Int. Med. (2002) 137(12):947-954.
  • GOW PJ, SMALLWOOD RA, ANGUS PW: Paracetamol overdose in a liver transplantation centre: an 8-year experience. J. Gastroenterol. Hepatol. (1999) 14(8):817-821.
  • SCHIODT FV, ROCHLING FA, CASEY DL, LEE WM: Acetaminophen toxicity in an urban county hospital. N. Engl. J. Med. (1997) 337(16):1112-1117.
  • WILLIAMS HJ, WARD JR, EGGER MJ et al.: Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee. Arthritis Rheum. (1993) 36(9):1196-1206.
  • PINCUS T, KOCH GG, SOKKA T et al.: A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee. Arthritis Rheum. (2001) 44(7):1587-1598.
  • TEMPLE AR, BENSON GD, ZINSENHEIM JR, SCHWEINLE JE: Multicenter, randomized, double-blind, active-controlled, parallel-group trial of the long-term (6-12 months) safety of acetaminophen in adult patients with osteoarthritis. Clin. Ther. (2006) 28(2):222-235.
  • KUFFNER EK, TEMPLE AR, COOPER KM, BAGGISH JS, PARENTI DL: Retrospective analysis of transient elevations in alanine aminotransferase during long-term treatment with acetaminophen in osteoarthritis clinical trials. Curr. Med. Res. Opin. (2006) 22(11):2137-2148.
  • CARAVATI EM: Unintentional acetaminophen ingestion in children and the potential for hepatotoxicity. J. Toxicol. (2000) 38(3):291-296.
  • ALANDER SW, DOWD MD, BRATTON SL, KEARNS GL: Pediatric acetaminophen overdose: risk factors associated with hepatocellular injury. Arch. Pediatr. Adolesc. Med. (2000) 154(4):346-350.
  • HEUBI JE, BARBACCI MB, ZIMMERMAN HJ: Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children. J. Pediatr. (1998) 132(1):22-27.
  • RIVERA-Penera T, GUGIG R, DAVIS J et al.: Outcome of acetaminophen overdose in pediatric patients and factors contributing to hepatotoxicity. J. Pediatr. (1997) 130(2):300-304.
  • SCHMIDT LE, DALHOFF K, POULSEN HE: Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity. Hepatology (Baltimore, Md) (2002) 35(4):876-882.
  • 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: a randomized, double-blind, placebo-controlled trial. Arch. Int. Med. (2001) 161(18):2247-2252.
  • SCHIODT FV, LEE WM, BONDESEN S, OTT P, CHRISTENSEN E: Influence of acute and chronic alcohol intake on the clinical course and outcome in acetaminophen overdose. Aliment. Pharmacol. Ther. (2002) 16(4):707-715.
  • THUMMEL KE, SLATTERY JT, RO H et al.: Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults. Clin. Pharmacol. Ther. (2000) 67(6):591-599.
  • GIRRE C, HISPARD E, PALOMBO S, N’GUYEN C, DALLY S: Increased metabolism of acetaminophen in chronically alcoholic patients. Alcohol. Clin. Exp. Res. (1993) 17(1):170-173.
  • ZIMMERMAN HJ, MADDREY WC: Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. Hepatology (Baltimore, Md) (1995) 22(3):767-773.
  • WHITCOMB DC, BLOCK GD: Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA (1994) 272(23):1845-1850.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.