Hepatotoxicity

Hepatotoxicity (from hepatic toxicity) is chemical-driven liverdamage. Chemicals that cause liver damage are called hepatoxins. It is a possible side-effectof certain medications, but can also be caused by chemicals used in laboratories and industry, and natural chemicals, like microcystins.

Types

Hepatotoxicity can be considered to occur in two forms, symptomatic or idiosyncratic.

Drugsor toxins that have a symptomatic hepatotoxicity are those that have predictable dose-response curves (higher concentrations cause more liver damage) and well characterized mechanisms of toxicity.

In contrast, idiosyncratic hepatotoxins are agents that cause liver damage in only a small fraction of the population that is exposed to the agent, does not have a clear dose-response or temporal relationship, and most often do not have predictive models. Idiosyncratic hepatotoxicity has led to the withdrawal of several drugs from market even after rigorous clinical testing as part of the FDA approval process - Rezulin®(troglitazone), Ranitidine(Zantac®), and trovafloxacin(Trovan®) are three prime examples of idiosyncratic hepatotoxins.

The main cause: acetaminophen

One of the main causes of drug-induced hepatotoxicity in western countries is acetaminophen(paracetamol) poisoning, which is a symptomatic hepatotoxin. Hepatic damage can sometimes be detected at advanced stages by the typical yellow skin (jaundice) that arises from defective bilirubinliver metabolism. For earlier stages, there are a number of convenient liver function tests. Acetylcysteinecan limit the severity of the liver damage by capturing the toxic acetaminophen metabolite.

Hepatic metabolism

Many common drugs are metabolisedby the liver in significant amounts. This, together with its role as first filter of bloodloaded with substances absorbed from the gut, makes hepatotoxicity one of the main concerns of pharmaceutical companies in their research for new drugs. All lead optimisationcascades must deal in some way with the issue of hepatic toxicity. An especially thorny issue in drug discoveryis enterohepatic circulation.

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It uses material from the http://en.wikipedia.org/wiki/Hepatotoxicity Wikipedia article Hepatotoxicity.