Hi, nach ein bisschen googlen hab ich zwar nichts zum cumulative effect gefunden (Suchbegriff: cumulative liver damage through paracetamol), aber vielleicht googlest du ja nochmal selber.
Ansonsten hat Sharon hier toll die Bedeutung von cumulative erklärt.
Hier sind aber noch nen paar Sachen, die ich gefunden habe.
Fazit ist zumindest, dass es, selbst wenn Du keine Alkoholikerin bist, keine gute Idee ist, Deinen Kater mit paracetamol auszukurieren.
Gruss, Isabel
http://www.bsg.org.uk/pdf_word_docs/adult_liver.pdf
‘Indications for referral and assessment in adult liver transplantation: a clinical guideline‘
(…) Paracetamol hepatoxicity is the commonest cause of acute liver failure in the UK. Deliberate self-poisoning with this drug is commonest in young people, usually in the absence of any serious psychiatric morbidity. It is estimated tht 30000-70000 cases of paracetamol overdose reach medical attention and with an estimated case fatality of 0.4% represents approximately 130-270 deaths annually. Community availability of paracetamol is paralleled by ist use in accidental overdoses and attempted suicide. In countries where access is restricted and overdoses involve fewer tablets, a considerably lower rate of fatality has been seen (0.4% risk of death in the UK versus 0.1% in France). An alarming increase in the usage of paracetamol in overdoses has been observed in this country which has prompted a recent review and constraint of marketing and packaging practice. (…)
http://www.blackwell-synergy.com/links/doi/10.1046/j…
http://www.google.com/search?q=cache:svuZot0g0ssJ:we…
Dept of Hepatology, University of Capetown, ZA, 2002 (on ACUTE liver failure)
The alcohol paracetamol interaction.
Paracetamol is metabolised to a toxic intermediate by the same cytochrome P450 isoforms as alcohol.
This enzyme is induced in people who drink regularly. If they then take paracetamol, it is more rapidly metabolised to the toxic product which causes severe hepatic necrosis. This is aggravated by the glutathione deficiency often present in alcoholics. As little as 4g (8 tablets) of paracetamol taken over a period of a few hours may cause acute liver failure in alcoholic subjects. This is often the case when paracetamol is taken not suicidally but to deal with a hangover. The clue is the markedly raised transaminases; these may be 1000 or more which is too high for alcoholic hepatitis. Therapy is with N-acetyl cysteine.
…
Toxic drug reactions
The most common example of this is paracetamol. It is also occasionally seen with carbon tetrachloride or amanita (mushroom) poisoning. This reaction is predictable and anybody who takes sufficient of the agent will show hepatocyte necrosis, hepatitis and perhaps liver failure.
Paracetamol is metabolised by cytochrome P450 to the toxic intermediate NAPQI. Protection against this is afforded by two mechanisms; conjugation of paracetamol with glucuronide and sulphate to prevent ist metabolism, and complexing of the NAPQI with glutathione to detoxify it. When large amounts of paracetamol are ingested, these safety mechanisms are overwhelmed and severe hepatocyte necrosis occurs.
Typically, hepatitis is noted 48-72 hours after the ingestion of paracetamol. Patients then become jaundiced and very high enzyme levels are noted. The condition may progress to acute liver failure. The best prognostic indicator is the INR; if this continues to increase on day 3, the prognosis is grave.
Whenever significant amounts of paracetamol have been ingested, specific therapy should be provided. Gastric lavage should be performed and charcoal placed in the stomach. Therapy with N-acetyl cysteine should be instituted in all cases where the dose ingested has been significant.
Beware of the drawbacks associated with the use of the action lines for paracetamol. Allow a wide margin of safety; better to treat unneccessarily than too late. Therapy should be instituted no matter how long after the ingestion the patient is seen. Even treatment as long as five days after the ingestion may have some beneficial effect.
Liver transplantation may be lifesaving for severe paracetamol overdose.
