ABSTRACT
The mechanism of hepatotoxicity caused by paracetamol (acetaminophen) overdose and the treatment of patients is reviewed. Paracetamol is widely used over-the-counter drug with analgesic and antipyretic properties. Although it is considered to be safe at therapeutic doses, the incidence of hepatotoxicity caused by overdose or inadvertent application has been increasing lately. N-acetyl-p-benzoquinonimine, one of the metabolites formed from paracetamol is responsible for the hepatotoxicity. Until now there is no complete therapeutic strategy for the effective treatment of hepatotoxicity caused by paracetamol. Gut decontamination, N-acetylcysteine antidote administration and enhancement of elimination is used for the management of paracetamol overdose. Those with severe hepatotoxicity and neurological symptoms can benefit from removal of necrotic liver and undergo transplantation.
Subject(s)
Acetaminophen/adverse effects , Analgesics, Non-Narcotic/adverse effects , Liver Failure, Acute/chemically induced , Liver Failure, Acute/therapy , Liver/drug effects , Acetaminophen/administration & dosage , Acetaminophen/pharmacokinetics , Acetylcysteine/therapeutic use , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/pharmacokinetics , Antidotes/therapeutic use , Cimetidine/therapeutic use , Drug Overdose , Humans , Liver Failure, Acute/drug therapy , Liver Failure, Acute/metabolism , Liver Failure, Acute/prevention & controlABSTRACT
In this review we focus on human hydrolytic enzymes that participate in the metabolism of xenobiotics. Although hydrolysis in most of the cases result in detoxication, in some cases hydrolysis may lead to activated molecules that may attack macromolecules (proteins, RNAs, DNAs), resulting in toxicity. We have summarised the data available on these enzymes concerning their catalytic profile and specificity, inhibition, induction properties, their possible role in the generation of toxic compounds, their importance in clinical practice and drug development.
