Hepatic drug metabolism and anesthesia.
Anesthetic agents, including most inhalation anesthetics, the barbiturates, narcotics, local anesthetic amides and curare-like compounds are metabolized inside the liver cell. Consequently, drug metabolism in the liver has become an increasingly important consideration in the practice of anesthesiology. Hepatic metabolism is, first and foremost, a mechanism that converts drugs and other compounds into products that are more easily excreted and that usually have a lower pharmacologic activity than the partent compound. Thus, duration and intensity of drug action are limited. However, there are exceptions. In certain instances a metabolite may have higher activity and/or greater toxicity than the original drug. Intrahepatic metabolism hinges upon the oxidative reactions that are catalyzed by a group of mixed oxidases, the P-450 cytochromes. Their concentration and activity can be enhanced by certain drugs or environmental chemicals that are ingested by the individual. This usually is beneficial, in that this mechanism of enzyme induction promotes the detoxification of pharmaca, which is the normal aspect of drug metabolism. If, however, the normal metabolite is more toxic than the parent compound, or there exists an alternate, abnormal metabolic pathway that produces a toxic metabolite, then enzyme induction may have serious consequences. Inorganic fluoride is a normal metabolite of methoxyflurane. It is responsible for the high-output renal failure that can be observed after anesthesia with this inhalation agent. A patient with induced enzyme activity is especially at risk to develop methoxyflurane-related renal failure. The picture of halothane toxicity is not as clear. There are indications that an abnormal metabolite, produced in sufficient quantities via an alternate pathway with induced enzyme activity, may be capable of causing liver damage.
D058186:Acute Kidney Injury / Q000139:chemically induced; D000777:Anesthetics / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005459:Fluorides / Q000009:adverse effects; D006221:Halothane / Q000009:adverse effects; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008733:Methoxyflurane / Q000378:metabolism; D008748:Methylcholanthrene / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology
D000777:Anesthetics; D001713:Biphenyl Compounds; D002273:Carcinogens; D008733:Methoxyflurane; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D005459:Fluorides; D006221:Halothane; D010634:Phenobarbital