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Drug hepatotoxicity
Body_ID: HC028035
Drugs that exert their toxic effects on the liver may do so through the hepatic production of a toxic metabolite. Drug toxicity may occur in all individuals exposed to a sufficient concentration of a particular drug. A drug may even be toxic in some individuals at concentrations normally tolerated by most patients prescribed the drug. This phenomenon is known as idiosyncratic drug toxicity, and may be due to a genetic or immunologic cause.
Body_ID: P028042
Commonly prescribed drug, acetaminophenView drug information (paracetamol) is hepatotoxic toxic in excess
Body_ID: HC028037
Acetaminophen is widely used as a painkiller. Taken in the usual therapeutic doses, it is conjugated with glucuronic acid or sulfate, which is then excreted by the kidneys. In overdose, the capacity of these conjugation pathways is overwhelmed, and acetaminophenView drug information is then oxidized by a liver P450 cytochrome to N-acetyl benzoquinoneimine (NABQI), which can cause a free-radical-mediated peroxidation of membrane lipids, and thereby hepatocellular damage. NABQI may be detoxified by conjugation with glutathione, but in acetaminophenView drug information overdose these glutathione stores also become exhausted, and hepatotoxicity ensues (Fig. 28.7). Therapeutically, the sulfhydryl compound, N-acetyl cysteine (NAC), which promotes detoxification of NABQI by the glutathione pathway and also scavenges free radicals, is routinely used as an antidote to acetaminophenView drug information poisoning. The risk of hepatotoxicity can be reliably predicted from measurement of the plasma concentration of acetaminophenView drug information, and then NAC can be given to those patients at risk of liver damage.
Body_ID: P028043
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