Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: Analysis of instances of therapeutic misadventure

  title={Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: Analysis of instances of therapeutic misadventure},
  author={Hyman J. Zimmerman and Willis C. Maddrey},
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… 

Mild hepatitis at recommended doses of acetaminophen in patients with evidence of constitutionally enhanced cytochrome P450 system activity

Two patients who experienced subclinical hepatotoxic reactions after taking acetaminophen at therapeutic doses are described and the results of an antipyrine metabolism test suggest the presence of constitutional hyperactivity of the cytochrome P450‐dependent mixed function oxidative system in both patients.


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Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases.

Findings are limited by low patient numbers, publication bias and the accuracy of the histories in reported cases, but suggest a low risk of subsequent liver damage.

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Increase the public’s awareness of the problem through an enhanced public education, improving labeling, eliminating combination products, decreasing the amount of acetaminophen per dosage unit, and lowering the maximum recommen ded doses.

Management of Paracetamol Overdose

Paracetamol overdose during pregnancy should be treated with either oral or intravenous NAC according to the regular protocols in order to prevent maternal, and potentially fetal, toxicity, and the lower line should be used when risk factors are present.

Update: the clinical importance of acetaminophen hepatotoxicity in non‐alcoholic and alcoholic subjects

The authors review mainly the management of acetaminophen toxicity in both users and nonusers of alcohol, and considers physiological and clinical changes, as well as the diagnosis and treatment ofacetaminophen poisoning.

Acute Liver Failure in Two Patients with Regular Alcohol Consumption Ingesting Paracetamol at Therapeutic Dosage

In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested and it is proposed that the paracetamol dose should not exceed 2 g/day in such patients and that their liver function should be monitored closely while being treated with par acetamol.

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Overall, in a large, well-educated cohort of patients, knowledge about the adverse effects of acetaminophen, the additional risks with alcohol and composition of various retailed products was suboptimal, suggesting that consumer ignorance is a significant reason whyacetaminophen is a leading cause of acute liver failure.



The spectrum of paracetamol (acetaminophen) overdose: clinical and epidemiological studies.

The insidious and delayed onset of toxicity in overdose and ineffectiveness of late treatment argues for controlling availability of paracetamol to the general public.

Acetaminophen hepatotoxicity in alcoholics. A therapeutic misadventure.

Despite the low frequency of ethanol-potentiatedacetaminophen hepatotoxicity, alcoholics should be cautioned about the use of acetaminophen while they persist in heavy consumption of alcohol.

The Effect of Chronic Alcohol Intake on Prognosis and Outcome in Paracetamol Overdose

Chronic alcohol intake above suggested limits is an adverse prognostic feature in cases of severe paracetamol overdose and is partly related to increased nephrotoxicity.

Paracetamol medication and alcohol abuse: a dangerous combination for the liver and the kidney.

It seems reasonable to recommend that paracetamol should be prescribed with great caution to alcoholics, and absolutely not for continuous use.

Increased metabolism of acetaminophen in chronically alcoholic patients.

It is confirmed that the metabolism of acetaminophen increases in chronic alcoholism and consequently the production of its hepatotoxic metabolite is enhanced, and its potential liver toxicity might be enhanced.

Acetaminophen hepatotoxicity associated with alcoholic pancreatitis.

Patients with alcoholic pancreatitis may be more prone to acetaminophen hepatotoxicity because of their taking supratherapeutic amounts of acetamine for pain and using alcohol for long periods, which induces the hepatic—mixed function oxidases that induce hepatotoxic activity.

Hepatotoxicity due to repeated intake of low doses of paracetamol

In both patients starvation, due to abdominal pain, nausea and vomiting or diarrhoea, was probably contributing to the toxic effect of the drug.

Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics.

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Potentiation of acetaminophen hepatotoxicity by alcohol.

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[Hepatic and renal toxicity of paracetamol in chronic alcoholic patient].

The potentiation of acetaminophen renal and hepatic toxicity by alcohol toxicity is discussed, and the principal mechanism of enhancement is the activation of the cytochrome P 450 system associated with depletion of intracellular glutathione.