Should a lower treatment line be used when treating paracetamol poisoning in patients with chronic alcoholism?: a case against.
The widespread practice of using a lower plasma paracetamol (acetaminophen) concentration threshold for the treatment of paracetamol poisoning in patients with chronic alcoholism has been introduced on the basis of anecdotal case reports. In animals, acute alcohol loading inhibits toxic metabolic activation of paracetamol whilst chronic alcohol administration results in cytochrome P450 (CYP) 2E1 induction with increased toxic metabolic activation of paracetamol by CYP2E1 and increased hepatotoxicity. However, due to species differences in CYP expression, activity and induction, it is not possible extrapolate the results of these animal studies to clinical situations in humans. Isoenzymes are also responsible for the metabolic activation of paracetamol in humans and human studies to date have not convincingly demonstrated increased toxic metabolic activation of paracetamol in patients with chronic alcoholism. Acute alcohol ingestion at the time of a paracetamol overdose is probably protective and the timing and chronicity of alcohol intake is therefore crucial in the interpretation of the effects of alcohol on paracetamol overdose. One of the problems in the interpretation of the literature to date is that insufficient information is available on the timing of alcohol intake in relation to the ingestion of paracetamol. Whilst it is possible that chronic exposure to excessive amounts of alcohol does predispose patients with paracetamol overdose to hepatotoxicity, a critical review of the literature reveals that the evidence to date does not support this. A prospective, controlled study is required. On the basis of the scientific evidence to date, use of the 100 line for patients with chronic alcoholism, in countries where the 200 line represents the standard treatment line, is unjustified.
Dargan
Paul I
PI
National Poisons Information Service, London, United Kingdom.
Jones
Alison L
AL
D000082:Acetaminophen / Q000097:blood / Q000506:poisoning*; D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000437:Alcoholism / Q000150:complications*; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008099:Liver / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D016166:Free Radical Scavengers; D000082:Acetaminophen; D000111:Acetylcysteine