Fluorinated anesthetics

A number of inhalation anesthetics have been introduced to clinical practice, some of which are Hsted in Table 1. AH agents introduced after 1950, except ethyl vinyl ether, contain fluorine. Agents such as ether, chloroform, trichloroethylene (Tdlene), cyclopropane, and fluoroxene (Fluoromar), which were once used, have been displaced by the newer fluorinated anesthetics. 

Desflurane is less potent than the other fluorinated anesthetics having MAC values of 5.7 to 8.9% in animals (76,85), and 6% to 7.25% in surgical patients. The respiratory effects are similar to isoflurane. Heart rate is somewhat increased and blood pressure decreased with increasing concentrations. Cardiac output remains fairly stable. Desflurane does not sensitize the myocardium to epinephrine relative to isoflurane (86). EEG effects are similar to isoflurane and muscle relaxation is satisfactory (87). Desflurane is not metabolized to any significant extent (88,89) as levels of fluoride ion in the semm and urine are not increased even after prolonged exposure. Desflurane appears to offer advantages over sevoflurane and other inhaled anesthetics because of its limited solubiHty in blood and other tissues. It is the least metabolized of current agents. 

A hydrogen bond, involving an acidic hydrogen atom borne by a fluorine-substituted or halogen-substituted carbon, seems to contribute to the activity and selectivity of volatile fluorinated anesthetics (Table 3.2). These molecules, although nonfunctional, can bind stereoselectively with protein targets of the central nervous system. Different biological behaviors have been reported for both enantiomers of isoflurane (cf. Chapter 8). ... 

The main difficulty in the preparation of fluorinated anesthetics is to obtain the desired compound with the required degree of purity these fluorinated molecules are gaseous or very volatile and have a poor polarity. Some examples of the synthesis of these compounds are given in Figure 8.91. ... 

Eger et al. (1988) determined minimum alveolar concentration of fluorinated anesthetics in pigs. 

This patient had multiple risk factors for anesthesia-induced hepatitis, including obesity, middle age, female sex, a history of drug allergies, and multiple exposures to fluorinated anesthetic agents. Desflurane has a very low rate of hepatic oxidative metabolism (0.02 versus 20% for halothane), and is considered to be one of the safest volatile agents as far as hepatotoxicity is concerned. Nevertheless, this case shows that it can cause severe hepatotoxicity. 

Currently, the most used fluorinated anesthetics are halothane, enflurane, isoflurane, sevoflurane and desflurane isoflurane stands out as the most pwpnilar at present times. 

Table 7. Blood concentration in deaths related to fluorinated anesthetics (Baselt, 2004)...

Localized in vivo F NMR spectroscopy has been used to monitor the distribution of drugs. Unlike NMR spectroscopy, there is no need to suppress the large water resonance, and the relatively high sensitivity of fluorine NMR makes this an attractive approach. The advantage of spectroscopy is that it yields both spatial and chemical information at the same time. For example, the methods have been applied to the neuroleptic drug trifluoroperazine in the rat brain and extensive studies have concentrated on the uptake and elimination of fluorinated anesthetics because of the relatively high concentrations that can be achieved in vivo. Detailed pharmacokinetic studies have also been undertaken using F NMR in vivo, especially for 5-FU. 

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