Should a Lower Treatment Line Be Used When Treating Paracetamol Poisoning in Patients with Chronic Alcoholism?

  title={Should a Lower Treatment Line Be Used When Treating Paracetamol Poisoning in Patients with Chronic Alcoholism?},
  author={Nicholas A Buckley and Jayasri Srinivasan},
  journal={Drug Safety},
A lower threshold for treatment of paracetamol (acetaminophen) poisoning has been advocated in chronic heavy users of alcohol, based originally on animal studies indicating that chronic alcohol ingestion increased hepatotoxicity. This was attributed to increased production of the toxic metabolite, N-acetyl-p-benzoquinoneimine, by cytochrome P450 (CYP)2E1 induction. The clinical evidence for increased risk is limited to four retrospective studies with potential for referral and reporting bias… 

Tolerability of Paracetamol

Preliminary studies indicate that therapeutic doses of paracetamol are an unlikely cause of hepatotoxicity in patients who ingest moderate to large amounts of alcohol and appears to be well tolerated during pregnancy although prospective studies are required.

Comment on "Acute ethanol coingestion confers a lower risk of hepatotoxicity after deliberate acetaminophen overdose".

Investigation into the effect of acute ethanol coingestion on risk of hepatotoxicity among patients admitted to hospital for N-acetylcysteine (NAC) therapy after deliberate acetaminophen overdose finds an apparent protective effect, but further work is required to establish mechanisms by which ethanol might confer protection against hepatot toxicity.

Paracetamol toxicity: what would be the implications of a change in UK treatment guidelines?

A retrospective analysis of a series of acute single-time-point paracetamol poisonings presenting to an inner city emergency department found that a single 150 mg/L treatment line would simplify treatment algorithms and lead to a similar number of patients being treated with NAC overall.

Acute ethanol coingestion confers a lower risk of hepatotoxicity after deliberate acetaminophen overdose.

Acute ethanol intake is associated with a lower risk of hepatotoxicity after acetaminophen overdose, and this apparent protective effect cannot be explained solely by lower exposure toacetaminophen in this group, nor differences in the interval between ingestion and initiation of treatment.

Are recommended doses of acetaminophen hepatotoxic for recently abstinent alcoholics? A randomized trial

In conclusion, therapeutic doses of sustained-release acetaminophen cause a measurable decrease in serum α-GST during the first days of abstinence from chronic alcohol use, providing some reassurance that short courses ofacetaminophen are unlikely to cause subclinical hepatocellular injury in recently abstinent alcoholics.

Criteria for acetylcysteine treatment and clinical outcomes after paracetamol poisoning

  • W. Waring
  • Medicine
    Expert review of clinical pharmacology
  • 2012
The different indications for acetylcysteine used by the UK and USA would result in similar numbers of patients treated, although the criteria would define patients with different characteristics and patterns of overdose.

Acute acetaminophen overdose is associated with dose-dependent hypokalaemia: a prospective study of 331 patients.

Acetaminophen appears to cause concentration-dependent hypokalaemia after overdose, and the pharmacological basis requires further consideration.

Acetaminophen Intoxication and Length of Treatment: How Long Is Long Enough?

The evidence that supports reducing the course of N‐acetylcysteine therapy from 72 hours to 24 or 36 hours is critically evaluated and offers important benefits for both the patient and the patient's family, such as increased drug tolerability and reduced hospital stay.



Paracetamol, alcohol and the liver.

  • L. Prescott
  • Medicine
    British journal of clinical pharmacology
  • 2000
Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insufficient evidence to support the alleged major toxic interaction.

Recent Developments in the Management of Paracetamol (Acetaminophen) Poisoning

As survival following liver transplantation is now increasing, it is important to identify early prognostic indicators in fulminant hepatic failure, so that those patients with a high chance of fatal outcome can be considered for transplantation.

Paracetamol hepatotoxicity and alcohol consumption in deliberate and accidental overdose.

It was unable to demonstrate that heavy drinkers develop more severe hepatotoxicity following paracetamol overdose than non-drinkers, and from the material reported in this study, accidental overdose is a better defining term than therapeutic misadventure.

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.

Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)

It is concluded that N-acetylcysteine treatment should be started within eight hours of an acetaminophen overdose, but that treatment is still indicated at least as late as 24 hours after ingestion, and it may be superior when treatment is delayed.

Potentiation of acetaminophen hepatotoxicity by alcohol.

It is suggested that alcohol enhances acetaminophen hepatotoxicity in mice and provides supportive evidence that these three alcoholic patients probably had a similar pathophysiological basis for their liver disease.

Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial.

Repeated administration of the maximum recommended daily doses of acetaminophen to long-term alcoholic patients was not associated with evidence of liver injury.

Recent advances in the management of late paracetamol poisoning

The best prognostic marker for paracetamol poisoning in ‘established hepatotoxicity’ is the prothrombin time and the putative mechanisms of action of N-acetylcysteine and its practical use are discussed.

Paracetamol Toxicity: is Enzyme Induction Important?

A female patient receiving carbamazepine developed severe liver damage after an overdose of paracetamol. Antidotal therapy was not administered because her plasma paracetamol concentration was below