Liver damage with non-narcotic analgesics.
Non-narcotic analgesics can produce a variety of hepatic lesions but clinically significant liver damage is uncommon with normal therapeutic use. The pattern of hepatotoxicity caused by the salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen) and the pyrazolones differs but many of these drugs can cause generalised reactions which involve the liver. Depending on the drugs in question, the risks of liver injury may be conditioned by factors such as age, sex, dose and duration of treatment. Hepatotoxicity associated with the use of salicylates and most NSAIDs has been reported most often in females with collagen diseases but this may simply reflect the greater use of these drugs in such patients. Paracetamol-induced liver damage occurs almost exclusively as a result of overdosage. Except for the microvesicular fatty changes in hepatocytes in patients with Reye's syndrome attributed to salicylate, the acute centrilobular necrosis caused by paracetamol in overdosage and the marked cholestasis produced by benoxaprofen, the pathological changes in hepatic reactions to non-narcotic analgesics are rather variable and nonspecific. About 50% of patients given salicylate in full anti-inflammatory dosage develop minor abnormalities of liver function. There is usually a mild to moderate increase in plasma aminotransferase activity with patchy necrosis and degeneration of hepatocytes. These changes are related to plasma salicylate concentration and are usually rapidly reversible. In a small minority of patients, particularly the young, liver damage is more severe and may be associated with liver failure, acidosis, hypoglycaemia and encephalopathy. This picture closely resembles Reye's syndrome. In overdosage, paracetamol can cause acute hepatic necrosis. Without specific treatment, some 8% of adults suffer severe liver damage with plasma aminotransferase activity greater than 1000 U/L and about 1% die with hepatic failure and encephalopathy. The administration of sulfhydryl compounds such as N-acetylcysteine within 8 to 10 hours effectively prevents liver damage and death. Liver damage has been attributed to the therapeutic use of paracetamol. However, in most reports the dose was excessive and many patients were chronic alcoholics (who seem to be at increased risk). In these cases the features were typical of acute overdosage. A consistent and characteristic pattern of hepatotoxicity is evident with relatively few non-steroidal anti-inflammatory and pyrazolone analgesics. A rank order of relative risk cannot be established and the incidence in relation to use is not known.(ABSTRACT TRUNCATED AT 400 WORDS)
D000082:Acetaminophen / Q000009:adverse effects; D000700:Analgesics / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D010653:Phenylbutazone / Q000009:adverse effects; D012202:Reye Syndrome / Q000139:chemically induced; D012459:Salicylates / Q000009:adverse effects
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012459:Salicylates; D000082:Acetaminophen; D010653:Phenylbutazone