Nonspecific Stimulation of Drug-Metabolizing Enzymes by Inhalation Anesthetic Agents

Hw, Linde; Ml, Berman

doi:10.1097/00132586-197208000-00010

Cited by 10 publications

(6 citation statements)

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“…Halothane anaesthesia induces drug metabolism in humans (as measured with antipyrine clearance) 4 days postoperatively . This is also compatible with a number of reports from animal studies (Linde & Berman 1971;Rietbrock 1974). The mechanism may be induction of NADPHcytochrome P-450 reductase (Dale et al 1983;Rietbrock 1974).…”

Section: Pharmacokinetic Drug Interactionssupporting

confidence: 92%

Clinical Pharmacokinetics of the Inhalational Anaesthetics

Dale

Brown

1987

Clinical Pharmacokinetics

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At present, the most widely used inhalational anaesthetics are the halogenated, inflammable vapours halothane, enflurane, isoflurane and the gas nitrous oxide. The anaesthetic effect of these agents is related to their tension or partial pressure in the brain, represented at equilibrium by the alveolar concentration. The minimum alveolar concentration for a specific agent is remarkably constant between individuals. The uptake and distribution of inhalational anaesthetics depends on inhaled concentration, pulmonary ventilation, solubility in blood, cardiac output and tissue uptake. Inhalational anaesthetics are mainly eliminated by pulmonary exhalation, but significant amounts of halothane are removed by hepatic metabolism. Inhalational agents currently in use have acceptable pharmacokinetic characteristics, and clinical acceptance depends on their potential for adverse effects. Induction of anaesthesia with halothane is rapid and relatively pleasant and it is the agent of choice for paediatric anaesthesia. Between 20 and 50% is metabolised, and the parent drug is a potent inhibitor of drug metabolism. Post-operatively enzyme induction may follow. The major disadvantages of halothane are myocardial depression, propensity to evoke cardiac arrhythmias and the rare but serious halothane hepatitis. Induction and recovery from enflurane anaesthesia is rapid. Metabolism accounts for 5 to 9% of the elimination. The metabolic product inorganic fluoride may in rare cases cause renal toxicity. Enflurane is a weak inhibitor of drug metabolism at anaesthetic concentrations. Enflurane depresses circulation more than halothane by reducing both myocardial contractility and systemic vascular resistance, but cardiac rhythm is stable. Enflurane anaesthesia may, unlike the other agents, induce epileptic activity. Enflurane is widely used as replacement for halothane in adults. Despite its low blood-gas solubility, the airway irritability of isoflurane precludes a faster induction of anaesthesia than with halothane. Isoflurane is almost resistant to biodegradation. Myocardial contractility is maintained during isoflurane anaesthesia and cardiac rhythm is stable except for the occurrence of tachycardia in some patients. Isoflurane is the inhalational agent of choice for neurosurgical operations. Sevoflurane is an experimental ether vapour: induction and recovery is fast and pleasant. It is metabolised to the same extent as enflurane and subnephrotoxic concentrations of inorganic fluoride may result. Sevoflurane has fewer respiratory and cardiovascular depressant effects than halothane and may be a future alternative for paediatric anaesthesia.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Pharmacokinetic Drug Interactionssupporting

confidence: 92%

Clinical Pharmacokinetics of the Inhalational Anaesthetics

Dale

Brown

1987

Clinical Pharmacokinetics

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“…:;0 with diethyl ether. A similar increase in cytochrome P 4;;" has not been demonstrated for halothane or for nitrous oxide to our knowledge, although metabolic enhancement of hexobarbitone metabolism has been claimed for halothane (Linde and Berman 1971).…”

Section: Table Isupporting

confidence: 62%

“…Diethyl ether has been shown to cause enzyme induction in the rat (Brown and Sagalyn 1974). Similarly, hexobarbitone sleeping time was shortened in rats exposed to sub-anaesthetic concentrations of ether, halothane and enflurane, but not nitrous oxide (Linde and Berman 1971). In man, the evidence for enzyme induction caused by anaesthetic agents IS more circumspect.…”

Section: Introductionmentioning

confidence: 99%

Altered Drug Metabolism in Anaesthetists Exposed to Volatile Anaesthetic Agents

Frewin

et al. 1978

Anaesth Intensive Care

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Antipyrine kinetics were measured on saliva in eight anaesthetists during a period when they were giving general anaesthetics and a period when they were working exclusively in intensive care. During the anaesthesia period there was a reduction in antipyrine half-life and the clearance of antipyrine increased. A nalysis of the data in groups failed to detect these changes because of the wide variation in metabolism between subjects. Exposure to anaesthetic agents under non-scavenging operating theatre conditions appears to enhance hepatic metabolism.

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“…The increase in the enzyme quantity may affect the biotransformation both of the inducer itself (autoinduction) and of other substances (cross-induction). Among the enzymatic inducers we have the inhalation anaesthetics, such as diethyl ether, fluroxene, halothane, methoxyflurane and isoflurane (Berman and Bochantin, 1970;Linde and Berman, 1971;Brown and Sagalyn, 1974).…”

mentioning

confidence: 99%

“…In this work, we have tried to determine the possible cross-induction capacity of enflurane, which itself is thought to be relatively resistant to biotransformation (Halsey et al, 1971;Cousins et al, 1976;Dooley et al, 1979). Previous reports on this subject are limited (Linde and Berman, 1971;Berman et al, 1976).…”

mentioning

confidence: 99%

Effects of the Inhalation of Enflurane on Hepatic Microsomal Enzymatic Activities in the Rat

Rocha-Reis¹,

Hipólito-Reis²

1982

British Journal of Anaesthesia

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We have investigated the possible hepatic microsomal enzyme induction effect of enflurane, administered by inhalation in anaesthetic doses for periods of 1 h a day. In 15 experimental groups, differing from one another in anaesthetics concentration (1, 2 and 3% enflurane) and in the number of days of treatment (3, 7, 10, 14, 21 and 24) we found (1) no alteration either in the ratio of liver to body weight or in the microsomal protein content; (2) no modifications in aniline hydroxylase activity; (3) a decrease in the aminopyrine demethylase activity after a number of exposures, varying with the dose.

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Nonspecific Stimulation of Drug-Metabolizing Enzymes by Inhalation Anesthetic Agents

Cited by 10 publications

References 0 publications

Clinical Pharmacokinetics of the Inhalational Anaesthetics

Clinical Pharmacokinetics of the Inhalational Anaesthetics

Altered Drug Metabolism in Anaesthetists Exposed to Volatile Anaesthetic Agents

Effects of the Inhalation of Enflurane on Hepatic Microsomal Enzymatic Activities in the Rat

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