Halothane Phenobarbital

Acute hepatocellular necrosis. This reaction varies from a transient disturbance of liver function tests to acute hepatitis. It can be induced by several drugs including general anaesthetics (halothane), antiepileptics (carbamazepine, phenytoin, sodium valproate, phenobarbital), antidepressants (MAO inhibitors), antiinflammatory drugs (indomethacin, ibuprofen), antimicrobials (isoniazid, sulphonamides, nitrofurantoin) and cardiovascular drugs (methyldopa, hydralazine). 

Reynolds, E. S., Moslen, M. T. Liver injury following halothane anesthesia in phenobarbital-pretreated rats. Biochem. Pharmacol. 23, 189 (1974). 

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... 

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. 

K7 Kaufmann, R., Helmer, K. H., Kouros, M. and Kuns, W. Influence of halothane and phenobarbital on the incorporation of orotic acid into pyrimidinenucleotides, poly (A)-RNA and ribosomal RNA of liver. Arch. Pharm., 293 (Suppl.), 123 (1976)... 

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