In Medicine Lecture Series Anesthesiology researcher studies drug metabolism in the liver UW researchers led by Dr. Evan D. Kharasch, professor of anesthesiology, have concluded studies that may eliminate a fatal problem associated with what is historically one of the most widely used anesthetic agents in the world. For four decades, this problem has been recognized in anesthesia, yet the mechanism by which it occurs has been incompletely understood. Drug metabolism is the process by which our bodies transform and eliminate foreign compounds.
Halothane is transformed in the liver into a molecule that binds to liver proteins.
In most people, this process has no significance, but in a few people these liver proteins stimulate the formation of antibodies that seriously damage the liver. The reason why some patients are susceptible remains a mystery. In a study published in the Lancet in 1996, Kharasch identified P450 2E1 as the enzyme responsible for the metabolism of halothane, which can trigger the formation of antibodies. More recently, Kharasch and colleagues have shown that they can chemically inhibit P450 2E1 from carrying out this unwanted mission by giving patients a drug called disulfiram before anesthesia. We manipulate the activity of the enzyme with disulfiram, known by the trade name Antabuse.