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

Rocha-Reis, M.G.F. Da; Hipólito-Reis, C.

doi:10.1093/bja/54.1.97

Cited by 6 publications

(2 citation statements)

References 17 publications

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“…Three male Sprague Dawley rats (3 months old) were anesthetized with enflurane, and the liver, kidneys, lungs, and brain were excised and immediately frozen in liquid nitrogen. The single use of enflurane is unlikely to have a relevant influence on microsomal enzyme activities ( , ). After homogenization of the pooled organs in 3 vol of 0.1 M phosphate buffer, pH 7.4, microsomes were isolated by centrifugation at 10 000 g and 100 000 g , resuspended in 0.1 M phosphate buffer, pH 7.4, and again centrifuged at 100 000 g ; the pellets formed were stored at −80 °C until use.…”

Section: Methodsmentioning

confidence: 99%

Studies on Metabolic Pathways of Cocaine and Its Metabolites Using Microsome Preparations from Rat Organs

Toennes

Thiel

Walther

et al. 2003

Chem. Res. Toxicol.

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Cocaine metabolism has been studied previously with respect to the formation of predominant hydrolytic or hepatotoxic metabolites via oxidative pathways. In the present study, cocaine and eight of its metabolites (norcocaine, ecgonine methyl ester, benzoylecgonine, benzoylnorecgonine, 3-hydroxy-benzoylecgonine, cocaethylene, norcocaethylene, and ecgonine ethyl ester) were incubated with microsomes from rat liver, kidney, lung, and brain. Qualitative analysis of the metabolites produced was performed using solid phase extraction (SPE), trimethylsilylation, and GC/MS. It was found that the metabolites with a free carboxylic group (e.g., benzoylecgonine) were not further oxidized by microsomal enzymes and their presence in urine or blood may therefore be due to hydrolysis of the respective alkylated entities. Although microsomes from all organs exhibited oxidative metabolism, significant differences were noted. Kidney microsomes produced essentially the same results as liver, but aryl hydroxylated metabolites were not found in incubations with lung and brain microsomes. N-Hydroxy-norcocaine was found only in traces with brain microsomes. It appears that cocaine is converted to N-hydroxy-norcocaine (which is the precursor of toxic metabolites) not only in the liver but also in other organs of rat. This might be relevant in the development of lung toxicity observed in smokers of cocaine ("crack").

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Section: Methodsmentioning

confidence: 99%

Studies on Metabolic Pathways of Cocaine and Its Metabolites Using Microsome Preparations from Rat Organs

Toennes

Thiel

Walther

et al. 2003

Chem. Res. Toxicol.

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“…The potency of enflurane in this respect is probably lower than for halothane, as indicated by in vivo experiments with antipyrine and verapamil in rats and dogs, respectively Wood & Wood 1984). Enflurane is a weaker inducer of drug metabolising enzymes after exposure in animals than halothane (Dale et al 1983;Rietbrock 1974;Rocha-Reis & Hipolito-Reis 1982) and enflurane does not induce drug metabolism postoperatively in humans (Duvaldestin et al 1981 c). On the other hand, enflurane displaces diazepam significantly more than halothane from serum proteins in clinically relevant conditions in vitro (Dale & Nilsen 1984.…”

Section: Pharmacokinetic Drug Interactionsmentioning

confidence: 99%

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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2‐Chlor‐1,1,2‐trifluorethyldifluormethylether (Enfluran) [MAK Value Documentation in German language, 1994]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 20. Lieferung, Ausgabe 1994 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Toxikokinetik Aufnahme Verteilung Metabolismus Ausscheidung Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Sonstige Wirkungen Tierexperimentelle Befunde und in‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Sonstige Wirkungen Bewertung

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

Cited by 6 publications

References 17 publications

Studies on Metabolic Pathways of Cocaine and Its Metabolites Using Microsome Preparations from Rat Organs

Studies on Metabolic Pathways of Cocaine and Its Metabolites Using Microsome Preparations from Rat Organs

Clinical Pharmacokinetics of the Inhalational Anaesthetics

2‐Chlor‐1,1,2‐trifluorethyldifluormethylether (Enfluran) [MAK Value Documentation in German language, 1994]

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