[Paracetamol: therapeutic action, pathogenesis and treatment of acute poisonings complicated by severe liver damage].
The biosynthesis of prostaglandins proceeds in the presence of fatty acid cycloxygenases (COX-1, COX-2). COX-1 is responsible for the synthesis of prostaglandins indispensable for normal homeostasis, while COX-2 regulates local expression of pro-inflammatory prostaglandins. Paracetamol is a selective inhibitor of COX-2 thus having an analgesic and antipyretic potential. The drug is metabolised primarily in the liver. About 5% of the dose transforms into N-acetylo-p-benzoquinoneimine (NAPQI), a highly active compound. Ingestion of a single paracetamol dose higher than 8 g leads to a depletion of hepatic glutathione reserves and a loss of the detoxifying property of the liver. As a result, hepatic necrosis develops. The specific antidote is N-acetylcysteine (NAC). If applied within 10-15 h since the poisoning it enables complete survival. The efficacy of specific treatment decreases after 24 h but blood paracetamol is an indication for NAC therapy. The surviving patients with advanced paracetamol poisoning require long-lasting conservative treatment with ornithine and phospholipids as well as a light diet.
Klinika Ostrych Zatruć Instytutu Medycyny Pracy im. prof. J. Nofera w Łodzi, ul. Sw. Teresy 8, 90-950 Łódź, skr. poczt. 199.
Zbigniew
Z
Kołaciński
Piotr
P
Rusiński
D000082:Acetaminophen / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016227:Benzoquinones / Q000378:metabolism; D051545:Cyclooxygenase 1; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D007097:Imines / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D017114:Liver Failure, Acute / Q000139:chemically induced*; D008565:Membrane Proteins / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D007097:Imines; D007527:Isoenzymes; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D000082:Acetaminophen; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C093750:COX3 protein, S cerevisiae; D003576:Electron Transport Complex IV; C028473:N-acetyl-4-benzoquinoneimine