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Anesth Analg 1986; 65:481-488
© 1986 International Anesthesia Research Society
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The Effect of Cimetidine on Anesthetic Metabolism and Toxicity

Margaret Wood, MBChB, FFARCS, Jack Uetrecht, MD, PhD, James M. Phythyon, MD, Sheila Shay, BS, Brian J. Sweetman, PhD, Omar Shaheen, MD, PhD, and Alastair J. J. Wood, MBChB MRCP

Received from the Departments of Anesthesiology and Clinical Pharmacology, Vanderbilt University Medical School, Nashville, Tennessee.

Abstract

Because the H2-receptor antagonist cimetidine has been shown to inhibit drug metabolism, the effects of cimetidine on anesthetic metabolism and toxicity were investigated in a rat model. Cimetidine decreased inorganic plasma fluoride production after methoxyflurane administration both in 21% oxygen (P < 0.001) and in 100% oxygen (P < 0.001). Phenobarbital produces an increased fluoride formation after methoxyflurane anesthesia, and this flouride formation is also reduced by cimetidine (P < 0.005). There was no significant difference between the plasma fluoride levels in rats anesthetized with halothane or enflurane. Although cimetidine inhibited the in vivo defluorination of methoxyflurane, fluoride levels were still within the nephrotoxic range, and cimetidine is not likely to play a role as part of a preanesthetic regimen that would permit the increased clinical use of methoxyflurane. Cimetidine also inhibited the oxidative metabolism of halothane; cimetidine decreased (P < 0.05) trifluoroacetic acid concentrations after halothane anesthesia in 21% oxygen and in 100% oxygen and decreased (P < 0.05) bromide concentrations after halothane anesthesia in 100% oxygen. Trifluoroacetic acid levels were less (P < 0.02) after halothane anesthesia in 14% oxygen as compared with 100% oxygen, indicating a reduction in oxidative metabolism under hypoxic conditions. However, bromide concentrations were maximal after halothane anesthesia in 21% oxygen, and significantly (P < 0.001) less after halothane anesthesia in 14% and 100% oxygen. Bromide production, therefore, seems to be inhibited by both hypoxia and hyperoxia. Cimetidine decreased (P < 0.001) the severity of liver damage as assessed by histologic grading in the hypoxia-enzyme induced rat model of halothane hepatotoxicity but had no effect in the triiodothyronine-model of halothane hepatotoxicity. Thus cimetidine appears to afford partial protection against halothane-induced hepatic necrosis in the phenobarbital-hypoxia rat model.

Key Words: ANESTHETICS, INHALATION—halothane, enflurane, methoxyflurane • BIOTRANSFORMATION—metabolites, cimetidine • LIVER—hepatotoxicity, metabolism • PHARMACOLOGY—cimetidine






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 1986 by the International Anesthesia Research Society.