Isoflurane isomers

Lysco GS, Robinson JL, Caste R, et al. The stereospecific effects of isoflurane isomers in vivo. Eur J Pharmacol 1994 263 25-29. 

An isomer of enflurane named isoflurane (l-chloro-2,2,2-tnfluoroethyl difluoromethyl ether) does not produce uncontrolled movements, is nonflammable, and IS metabolized to an even lesser extent than enflurane [7] As of this wntmg, isoflurane is the fastest growing anesthebc m more economically developed coun tries, but because of cost, it has not overtaken halothane in the rest of the world... 

Metabotropic G-protein linked receptors are also modulated by general anesthetics. In particular, the current produced through activation of muscarinic receptors (Ml) for acetylcholine and the serotonergic receptor 5HT2 is inhibited by halothane, isoflurane and enflurane (Lin et al., 1993 Minami et al., 1994 Durieux, 1995). Ketamine inhibits muscarinic receptors although there is no stereospecificity of inhibition (Durieux Nietgen, 1997). The S-isomer of ketamine is more potent as an anesthetic than the R-isomer (Benthuysen et al., 1989). It is thus unlikely that the Ml muscarinic receptor plays a role in... 

Isoflurane, an isomer of enflurane, together with sevoflurane are the most commonly used inhalation anesthetics in humans. Isoflurane does not sensitize the myocardium to catecholamines, has muscle relaxing action so less neuromuscular blocker is required and causes less hepatotoxicity and renal toxicity than halothane. 

Isoflurane (Forane) is a structural isomer of enflurane and produces similar pharmacological properties some analgesia, some neuromuscular blockade, and depressed respiration. In contrast, however, isoflurane is considered a particularly safe anesthetic in patients with ischemic heart disease, since cardiac output is maintained, the coronary arteries are dilated, and the myocardium does not appear to be sensitized to the effects of catecholamines. Also, blood pressure falls as a result of vasodilation, which preserves tissue blood flow. Isoflurane causes transient and mUd tachycardia by direct sympathetic stimulation this is particularly important in the management of patients with myocardial ischemia. 

Isoflurane was discovered by Terrell in 1965. It is a halogenated methyl ethyl ether and is a structural isomer of enflurane (Figure 3.2). It became commercially available in the UK in 1982. Physical characteristics (Table 3.2)... 

Enflurane is a structural isomer of isoflurane. It is more soluble than isoflurane. It causes more respiratory depression than the other volatile anaesthetics and hypercapnia is almost inevitable in patients breathing spontaneously. It causes more cardiovascular depression than isoflurane and is occasionally associated with cardiac arrythmias. Two percent of enflurane is metabolised and prolonged administration or use in enzyme-induced patients generates sufficient free inorganic fluoride from the drug molecule to cause polyuric renal failure. There have been a few cases of jaimdice and heptatoxicity associated with enflurane but the incidence of about one in 1-2 million anaesthetics is lower than with halothane. 

Isoflurane is a potent inhalation anesthetic. An isomer of enflurane, it has many of the same adverse effects. It is hardly metabolized (about 0.2%), which has encouraged its prolonged use as a sedative agent or bronchodilator in patients with acute severe asthma. However, it may not be as inert in all patients. 

Isoflurane (CHFjOCHjClCFj) is an isomer of enflurane and has been in clinical use for about twenty years. It has a very low degree of defluorination [51]. Approximately 0.2-0.4 % of a given dose is metabolized. Fluoride levels in humans after isoflurane anesthesia peak at 4-6 pM, which represents only a modest rise over basal fluoride levels. Although enzyme induction increases defluorination somewhat, it is not associated with plasma fluoride concentrations of clinical significance [52, 53]. 

Graf BM, Boban M, Stowe DF, et al. Lack of stereospecific effects of isoflurane and desflurane isomers in isolated guinea pig hearts. Anesthesiology 1994 81 129-136. 

Moody, E.J. Harris, B. Hoehner, P. Skolnick, P. Inhibition of [3H]isradi-pine binding to L-type calcium channels by the optical isomers of isoflurane. Lack of stereospedfidty. Anesthesiology 1994, 81, 124-128. 

It has also been suggested that for mivacurium, higher plasma levels, especially of the potent trans-trans isomer, occur in the presence of isoflurane, and these could contribute to the enhanced neuromuscular blockade observed. ... 

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