Summary
In summary, anaesthetics and drugs used perioperatively are all xenobiotics and can be metabolized mainly by microsomal enzyme systems, which have a high activity in the liver. These enzyme systems are induced by repeated pre-administration of drugs, such as barbiturates and others which are used during the preoperative period. However, according to some reports, aerobic and anaerobic metabolism is inhibited by the simultaneous administration of drugs, such as isoflurane and halothane, halothane and enflurane, and cimetidine and halothane.
Hypoxia is also an important factor in hepatic disorders and it is well known that anaerobic metabolism of halothane is increased by hypoxia and its intermediate production produces a free radical. Theoretically, this free radical is involved in hepatic disorders.
In practice, in order to prevent hepatic dysfunction before, during and after anaesthesia, hypoxia and repeated pre-administration of enzyme-inducing drugs should be avoided. However, the choice and combination of drugs which inhibit drug metabolism and prevent hepato and/or nephro toxicity should be examined by further investigation.
Résumé
Les agents anesthésiques et autres médicaments utilisés dans la période péri-opératoire sont tous xénobiotiques et peuvent être métabolisés surtout par les systèmes enzymatiques du microsome, qui ont une activité élevée dans le foie. Ces systèmes enzymatiques sont induits par une pré-administration répétée de certaines substances, telles les barbituriques et autres qui sont utilisés pendant la période pré-opératoire. Cependant, selon certains travaux, le métabolisme aérobique et anaérobique est inhibé par l’administration simultanée de substances, telles l’isoflurane et l’halothane, l’halothane et l’enflurane, et la cimetidine et l’halothane.
L’hypoxie est aussi un facteur important dans 1’apparition des problèmes hépatiques et il est bien connu que le métabolisme anaérobique de l’halothane est augmenté par l’hypoxie, et à un stage intermédiaire produit des radicaux libres. Sur une base théorique ces radicaux libres sont impliqués dans les dysfonctions hépatiques.
En pratique, dans le but de prévenir la dysfonction hépatique avant, pendant et après l’anesthésie, il faut éviter l’hypoxie et l’administration répétée d’inducteurs enzymatiques avant l’anesthésie. Cependant, le choix et la combinaison de substances qui inhibent le métabolisme des médicaments et préviendront l’hépato ou la néphrotoxicité devrait faire 1’objet de travaux dans le futur.
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Morio, M., Yuge, O. & Fujii, K. Biotransformation and toxicity of inhalational anaesthetics. Can J Anaesth 37 (Suppl 1), Scxvi–Scxxiii (1990). https://doi.org/10.1007/BF03006280
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DOI: https://doi.org/10.1007/BF03006280