Document Detail


Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure.
MedLine Citation:
PMID:  7657281     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatic injury in alcoholics due to intake of acetaminophen (APAP or acetylparaaminophenol) with therapeutic intent has been reported, but the extent of the phenomenon is not clear, pertinent details of the association remain insufficiently clarified, and the importance of the phenomenon is not widely appreciated. The present report describes 67 patients who developed hepatic injury after ingestion of APAP with therapeutic intent. All were regular users of alcohol. Sixty-four percent of the patients were considered to be "alcoholic" or reported intakes greater than 80 g/d, 35% took 60 g/d or less, and the remainder were vague in their reporting. Doses of APAP were in the "nontoxic" range ( < 6 g/d) in 60% of the group, within the recommended range ( < 4 g/d) in 40%, and at 4.1 to 6 g/d in 20%. Characteristic feature was the towering level reached by aspartate transaminase (AST) with figures ranging from 3,000 to 48,000 IU in more than 90% of cases. Almost 20% of the patients died. The data on these patients were similar to 94 cases of injury from APAP taken with therapeutic intent reported in the literature. This study provides further evidence of hepatic injury in regular uses of alcohol, especially chronic alcoholics, who take APAP with therapeutic intent. Susceptibility is presumably caused by induction of cytochrome P-4502EI by ethanol and by depletion of glutathione (GSH) because of the effects of alcohol, the malnutrition often associated with alcoholism, and the depletion associated with chronic use of APAP and impaired glucuronidation caused by fasting perhaps as well. The syndrome of liver injury is distinctive, marked by uniquely elevated levels of AST, and poses a significant threat.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
H J Zimmerman; W C Maddrey
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  22     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  1995 Sep 
Date Detail:
Created Date:  1995-10-04     Completed Date:  1995-10-04     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  767-73     Citation Subset:  IM    
Affiliation:
George Washington University, Washington, DC 20306-6000, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetaminophen / blood,  therapeutic use,  toxicity*
Adult
Alcoholism / physiopathology*
Aspartate Aminotransferases / blood
Dose-Response Relationship, Drug
Drug Interactions
Female
Humans
Liver / drug effects*
Male
Middle Aged
Chemical
Reg. No./Substance:
103-90-2/Acetaminophen; EC 2.6.1.1/Aspartate Aminotransferases
Comments/Corrections
Erratum In:
Hepatology 1995 Dec;22(6):1898

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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