Halothane idiosyncratic drug reactions

Halothane. Anaesthetic drug which causes hepatic damage. Mild hepatic dysfunction is common. Occasionally serious hepatic necrosis occurs which is an idiosyncratic reaction (factors multiple exposures sex—female> male obesity history of allergy). A reactive metabolite is produced which binds to hepatocyte protein (microsomal) and stimulates an immunological reaction involving T-lymphocytes and antibodies (Antibody-Dependent Cell Cytotoxicity). Hepatocytes are destroyed by lymphocyte-mediated cytolysis. 

Halothane is a very widely used anesthetic drug, which may cause hepatic damage in some patients. It seems that there are two types of hepatic damage, however. One is a very rare reaction, idiosyncratic, resulting in serious liver damage with an incidence of about 1 in 35,000. The other form of hepatotoxicity is a mild liver dysfunction, which is more common and occurs in as many as 20% of patients receiving the drug. The two different types probably involve different mechanisms. 

Centrolobular necrosis is often a dose-related, predictable reaction secondary to drugs such as acetaminophen however, it also can be associated with idiosyncratic reactions, such as those caused by halothane. Also called direct or metabolite-related hepatotoxic-ity, centrolobular necrosis is usually the result of the production of a toxic metabolite (see Fig. 38-1). The damage spreads outward from the middle of a lobe of the liver. 

A number of experimental and clinical reports have suggested that a variety of factors unrelated to drug metabolism and direct hepatotoxicity may also influence susceptibility to DILL In addition, the nature of idiosyncratic liver injuries suggests that a majority of these reactions involve an immune mechanism. Hepatic cellular dysfunction and death have the ability to initiate immunological reactions, including both adaptive and innate immune responses. This inflammatory process has been implicated in the development of liver injury induced by such drugs as APAP, dihydralazine, and halothane (Laskin and Gardner 2003 Liu and Kaplowitz 2002 Luster et al. 2001). 

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