Anaesthetics halogenated

Gases of interest are nitrous oxide and the inhalation vapours (or volatile halogenated anaesthetics) such as halothane (CF3CHBrCl), isoflurane (CHF2OCHCICF3) and enflurane (CHCIFCF2OCHF2). In this section electrochemical studies on nitrous oxide, halothane and isoflurane will be discussed. 

The only documented reaction which could be due to allergy is the liver damage (hepatitis-like picture) which may be attributed to halogenated anaesthetics. 

Other halogenated anaesthetics also rarely cause jaundice due to massive liver cell necrosis, but more frequently they cause subclinical hepatocellular damage as... 

Isoflurane is more resistant to biotransformation in man than are other volatile halogenated anaesthetics [201,241,245] although there can be metabolic variations in different animal species [245], An average recovery of95 percent has been obtained in exhaled air, while post-operative urinary excretion of ionic and bound organic fluoride accounted for less than 0.2 per cent of the total fluorine dose [201]. In a separate study of 9 surgical patients, serum inorganic fluoride levels were 4.4 0.4 umol dm 6 h after anaesthesia [241 ]. 

Routine Direct Injection Gas-Liquid Chromatographic Procedure for the Analysis of Volatile Halogenated Anaesthetics in Whole Blood Using a New External Injection Port J. Chromatogr. 146(2) 297-310 (1978) CA 89 190684j... 

Since measurable concentrations of BTEX are present in the blank matrix, detection limits were determined using the corresponding deuterated compounds. Iso-topically labeled compounds are also useful to improve specificity and to ensure precision in peak assignment. Limits of detection were 5 ng/L for benzene and toluene, and 10 ng/L for ethylbenzene and xylenes. Detection limits of 10 to 20 ng/L were also obtained for halogenated anaesthetics. The sensitivity of SPME depends on Kfs values and is not enhanced by larger sample volumes, especially for compounds with Kf < 500 [12]. 

Lee, K.H., McIntosh, A.R., and Boucher, F., The interaction between halogenated anaesthetics and bacteriorhodopsin in purple membranes as examined by intrinsic ultraviolet fluorescence, Biochem. Cell Biol, 69, 2-3, 178-184,1991. 

Haloalkanes can be regarded as substituted alkanes in which one or more of the hydrogen atoms is replaced by a halogen atom. They are named in a similar fashion to branched-chain alkanes with the halogen atoms treated like branches. For example, the anaesthetic halothane has the structure shown in the diagram and is called 2-bromo-2-chloro-l,l, 1-trifluoroethane. 

Halogen-substituted T,2, 3, 4 -tetrahydro-l-naphthyl-1,4,5,6-tetrahydropyri-midines, such as (XCVll), and their non-toxic water-soluble salts, are useful as hypotensive agents [681] 2-(p-Aminophenyl)-l,4,5,6-tetrahydropyrimidines (XCVlll), prepared from p-aminobenzoic acid ester and a,co-diaminoalkanes, are active as local anaesthetics over a wide pH range [682]. 

Hydrogen bond involving an acidic hydrogen atom borne by a fluorine-substituted or halogen-substituted carbon seems to contribute to the activity and the selectivity of volatile fluorinated anaesthetics (Table 2). These molecules, although non-functional, can bind stereoselectively with protein targets of the central nervous system [33,34]. 

Halothane and Adrenaline (S) Anaesthetic sensitises other halogenated (epinephrine) and myocardium to adrenaline,... 

The correlation between anaesthetic potency and lipid solubility shown in Fig. 2.10 is valid for most inhaled anaesthetics and the product MAC X oil/gas partition coefficient (which should of course be a constant) varies by only a factor of 2 or 3 for potencies ranging over 100 000-fold. This constancy implies that inhaled anaesthetics act in the same manner at a specific hydrophobic site (the so-called unitary theory of anaesthesia). This has been challenged by more recent work that has identified compounds, including alkanes and poly-halogenated and perfluorinated compounds, which do not obey the Meyer- Overton hypothesis. It has been suggested that a contributory cause of deviation from this hypothesis may be the choice of lipid to represent the anaesthetic site of action of these compounds, implying that there may be multiple sites of action for inhaled anaesthetics. 

Halogen atoms may be removed from xenobiotics in an oxidative reaction catalysed by cytochromes P-450. For example, the anaesthetic halothane is metabolized to trifluoroacetic acid via several steps, which involves the insertion of an oxygen atom and the loss of chlorine and bromine (figure 4,28). This is the major metabolic pathway in man and is believed to be involved in the hepatotoxicity of the drug. Trifluoroacetyl chloride is thought to be the reactive intermediate (see Chapter 7). 

Isoflurane is a halogenated ether and potent anaesthetic. It is stable chemically (and therefore less toxic than halothane), photochemically and electrochemically. This obviously presents problems when trying to develop methods of measuring its concentration using chemical or electrochemical means. 

Aliphatic halogenated hydrocarbons Anaesthetizing irritant to mucous membranes liver damage kidney damage impaired vision loss of consciousness sometimes convulsions, oedema, death some compounds are carcinogenic Effects depend on the nature of the halogen atoms excretion almost exclusively after metabolism Chemical industry solvents refrigeration plant... 

The anaesthetic agents that have gained cognizanee today are invariably hydrocarbons and ethers with halogen (F, Br, Cl) substitution. 

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