Halothane Rifampicin

It seems possible that the general adverse hepatotoxic effects of halothane can slow the normal rate of phenytoin metabolism. One suggested explanation for the increased adverse effects on the liver is that, just as in animals, pre-treatment with phenobarbital and phenytoin increases the rate of drug metabolism and therefore the hepatotoxicity of halogenated hydrocarbons, including carbon tetrachloride and halothane. As well as increased metabolism, the halothane-rifampicin interaction might also involve additive hepatotoxicity. 

Halothane also reduces liver blood flow during anesthesia, and this could increase the release of potentially hepatotoxic halothane metabolites. The role of reduced halothane metabolites and inorganic fluoride, which may covalently link to liver macromolecules, has been stressed in keeping with this hypothesis is the observation of halothane hepatitis in patients who simultaneously take enzyme-inducing agents, for example barbiturates (41) or rifampicin (42). 

Phenytoin toxicity occurred in a child following halothane anaesthesia. A near fatai hepatic reaction occurred in a woman given rifampicin (rifampin) after haiothane anaesthesia, and hepatitis occurred in a patient taking phenobarbitai who was given halothane anaesthesia. See aiso Anaesthetics, generai H- Isoniazid , p.lOO and Anaesthetics, general Methoxyflurane H- Antibacterials or Barbiturates , p.l07. 

A woman taJdng promeliiazine and phenobarbital 60 mg three times daily died from halothane associated hepatitis within 6 days of being given halothane for the firsttime. A nearly fatal shock-producing hepatic reaction occurred in a woman 4 days after having halothane anaesthesia immediately followed by a course of rifampicin 600 mg daily and isoniazid 300 mg daily... 

Liver Halothane hepatitis has again been described [2 ]. Susceptibility factors are increasing age, female sex, obesity, autoimmune disease, and previous exposure to hepatotoxic drugs such as isoniazid or rifampicin. 

This child developed halothane hepatitis after her first vapor anesthetic but she had susceptibility factors of obesity, female sex, and previous exposure to isoiuazid and rifampicin, albeit 4 years before. Isoiuazid induces CYP2E1 and therefore increases the metabolism of halothane, perhaps placing her at increased risk. Although there is no defined diagnostic test for halothane hepatitis, most experts feel that the presence of hepatitis, eosinophUia, CYP2E1 or ERp58 autoantibodies, or trifluoroacetyl chloride specific IgG antibodies after the exclusion of infection increases the probabUity. 

---