ISSN:
1438-8359
Keywords:
Halothane
;
Enzyme inhibition
;
Analgesics
;
Hypnotics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Enzyme inhibition on anaerobic dehalogenation of halothane by various analgesic or hypnotic agents was investigated in vitro using rat liver microsomal fraction. The production rate of chloro-difluoro-ethylene (CDE) and chloro-trifluoro-ethane (CTE), anaerobic metabolites of halothane, was measured when various concentrations of analgesic or hypnotic agents (fentanyl, morphine, pentazocine, buprenorphine, ketamine, diazepam, chlorpromazine and hydroxyzine) were supplemented. Inhibitor constant (Ki) of each agent was calculated and compared with each other. The activity of NADPH-cytochrome c reductase (fp2) and NADH-ferricyanide reductase (fp1) was measured when each agent was added. The values of inhibitor constants (Ki) for CDE and CTE formation were in the following order from large to small values; morphine (656 µM and 2570 µM), chlorpromazine (49.7 µM and 68.1 µM), ketamine (24.9 µM and 64.4 µM), fentanyl (23.9 µM and 34.6 µM), hydroxyzine (19.2 µM and 50.8 µM), diazepam (17.0 µM and 13.9 µM), buprenorphine (11.2 µM and 22.4 µM), and pentazocine (1.96 µM and 6.67 µM) respectively. Pentazocine inhibited the formation of CDE 300 fold greater than morphine. The activity of fp2 and fp1 did not change by the addition of these analgesic or hypnotic agents. These results indicate that various analgesic or hypnotic agents, which are commonly used with halothane in clinical anesthesia, suppress the anaerobic dehalogenation of halothane in vitro. They also imply that the suppression of production of halothane metabolites is the result of direct enzyme inhibition on cytochrome P-450, since these agents did not affect the activity of fp2 and fp1 which are flavoproteins existing in the microsomal electron transport system. (Yamanoue T, Kikuchi H, Fujii K, et al.: Enzyme Inhibition by Analgesic and Hypnotic Agents on Anaerobic Dehalogenation of Halothane. J Anesth 5: 331–337, 1991)
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s0054010050331
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