The biochemical basis of anesthetic toxicity.
The inhalational anesthetics reversibly inhibit mitochondrial electron transport from NADH-linded substrates at the level of the enzyme NADH-dehydrogenase. The effect of this inhibition on ATP production is probably not the basis of the anesthetic state, as the level of high-energy phosphate in the brain does not decrease during anesthesia. Anesthetics, therefore, interfere with brain energy untilization, in addition to brain energy production. Inhibition by anesthetics of mitochondrial calcium uptake, which results from the inhibition of electron transport, may be an important anesthetic effect if it raises the intracellular calcium level. Other areas of investigation which have not been discussed here include the effects of anesthetics on glycolytic and other enzyme systems, ion fluxes, neurotransmitter synthesis and release, and on the structure of natural and artificial membranes. It is now appreciated that most of the inhalational anesthetics are metabolized by the endoplasmic reticulum of hepatocytes. The biotransformation of several anesthetics can be increased by drugs which induce hepatic microsomal enzymes. The organ toxicities of chloroform, trichloroethylene, fluroxene, methoxyflurane, and possibly of halothane and enflurane are related to their intermediary or final metabolites. It is of anesthetic drugs for an individual patient.
D000769:Anesthesia, Inhalation; D000777:Anesthetics / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D001711:Biotransformation; D050260:Carbohydrate Metabolism; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D003864:Depression, Chemical; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008660:Metabolism / Q000187:drug effects*; D008862:Microsomes, Liver / Q000201:enzymology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010088:Oxidoreductases / Q000502:physiology; D051381:Rats
D000777:Anesthetics; D001463:Barbiturates; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases