Fluorination anesthetic agents

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. 

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. 

Table 8.2 Fluorinated general anesthetic agents data ...

Protein Theories. The direct interaction of inhalation anesthetics and proteins has been proposed as the cause of anesthesia. An inhalation agent, whether a noble gas or a fluorinated ether, could dissolve asymmetrically in a protein, Resultant conformational changes in the protein, if these changes occur, could then cause changes in biological activity. 

Modem inhalation anesthetics are fluorinated to reduce the flammabihty. They were initially considered to be biochemically inert substances. However, with time came the recognition that not only are inhaled anesthetics metabolized in vivo [27] but also that their metabolites are responsible for both acute and chronic toxicities [28, 29]. Information gained from research over the past 30 years has led to changes in anesthesia practice, discontinuing the use of some anesthetics, for example methoxyflurane, due to its nephrotoxicity and more selective use of others, i.e. halothane, due to its rare liver toxicity. It has also provided the impetus for the development of new agents, isoflurane and desflurane, with properties that lower their toxic potential. The result has been improved safety but room remains for further improvement as our insight into toxicological mechanisms expands. 

Several of the agents used as general anesthetics are chiral and used as the racemate. This group includes parentally administered agents such as thiopental and ketamine, and a number of fluorinated agents administered by inhalation, including halothane, enflurane, isoflurane, and desflurane. 

Uses Solvent for PAN, PS, fluorinated hydrocarbons, cellulose triacetate, shellac used In paint removers, petrol, processing, hectograph process, specialty Inks reaction and diluent solvent for pesticides Intermediate for aliphatic and cyclic compds., prod, of Vitamins B1 and E, alkaloids, analgesics, anesthetics used in dyeing of acetate wetting agent for cellulose acetate films, fibers, solvent welding of plastic films in adhesive applies. 

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