Isoflurane

Trifluoroethanol is also the starting material for the anesthetic Isoflurane (l-chloro-2,2,2-trifluoroethyl difluoromethyl ether [26675-46-7]) (55,56) and Desflurane (2-difluoromethoxy-l,l,l,2-tetrafluoroethane [57041-67-5]) (57). 

Although most anesthetics are achiral or are adininistered as racemic mixture, the anesthetic actions are stereoselective. This property can define a specific, rather than a nonspecific, site of action. Stereoselectivity is observed for such barbiturates as thiopental, pentobarbital, and secobarbital. The (3)-enantiomer is modestly more potent (56,57). Additionally, the volatile anesthetic isoflurane also shows stereoselectivity. The (3)-enantiomer is the more active (58). Further evidence that proteins might serve as appropriate targets for general anesthetics come from observations that anesthetics inhibit the activity of the enzyme luciferase. The potencies parallel the anesthetic activities closely (59,60). 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

Isoflurane is the most widely used inhalational anesthetic and more closely approaches the ideal than other marketed dmgs. It has found appHcation in the anesthetic management of all types of surgical procedures. 

Sevoflurane. Sevoflurane, l,l,l,3,3,3-hexafluoro-2-propyl fluromethyl ether [28523-86-6] is nonpungent, suggesting use in induction of anesthesia. The blood/gas partition coefficient is less than other marketed products (Table 1) yet similar to nitrous oxide, suggesting fast onset and recovery. In animal studies, recovery was faster for sevoflurane than for isoflurane, enflurane, or halothane (76). Sevoflurane is stable to light, oxygen, and metals (28). However, the agent does degrade in soda lime (77). 

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. 

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... 

In the onginal route to isoflurane, the methyl ether of tnfluoroethanol is made with dimethyl sulfate [.S] followed by careful chlorination of the methyl group to make the dichloromethyl ether. This ether is fluorinated with hydrogen fluoride and an antimony catalyst and the final step is monochlorination of the a carbon of the ethyl group [S] (equation 2)... 

In a later version of the synthesis [9], the trifluoroethyl difluoromethyl ether IS made directly from tnlluoroethanol and chlorodifluoromethane (equation 2) and then chlorinated to give the final product. Again, the major problem is overchlorination, because all the hydrogens are readily replaced by chlorine. Separation of the overchlonnated by-products poses a special problem because of close boiling points. This problem can be solved by adding acetone to create a more easily separable azeotrope of acetone and isoflurane [10]. 

Chloro-2 -trifluoroethyl dichloro-methyl ether Isoflurane... 

Fontego - Bumetanide Fonzylane - Buflomedil Forane Isoflurane Fordex - Tolbutamide Fordiuran Bumetanide Foreart Inosine Forenol -Niflumic acid Forhistal Dimethindene maleata Foristal - Dimethindene maleate Formaftil - Formocortal acetate Formulex Dicyclomine HCI Fortabol -Methenolona acetate Fortabolin - Nandrolone decanoate Fortapen - Ampicillin Fortasec - Loperamide HCI Fortecortin Dexamethasone acetate Fortesul Sulfameter... 

Two methods of anaesthesia are currently in use, the application of inhaled gaseous or volatile anaesthetics such as halothane, sevoflurane and isoflurane to maintain a level of anaesthesia. Older compounds in this category include nitrous oxide and chloroform. 

General anaesthetics are administered for many surgical procedures where the patient is likely to undergo a severely painful procedure, and complete unconsciousness and immobility is required for the surgety to be performed. The most commonly used volatile anaesthetics are halothane, isoflurane and sevoflurane. Nitrous oxide is also commonly used, particularly during... 

Isoflurane (Forane) is a volatile liquid given by inhalation. It is used for induction and maintenance of anesthesia. 

CjjH(,F2N20S 97963-62-7) see Pantoprazole sodium 4-(difluoromethoxy)-2-nitrobenzenamine (C7H(,F2N203, 97963-76-3) see Pantoprazole sodium A -[4-(difluoromethoxy)phenyl]acetamide (0)HyF2N02 22236-11-9) see Pantoprazole sodium 2-(difluoromethoxy)-l,l,l-trifiuoroethane (C3H3F5O 1885-48-9) see Isoflurane (5)-9,10-difluoro-3-methyI-7-oxo-2,3-dihydro-7/f-pyrb do[l,23-d ]-Iy4 benzoxazine-6-carboxylic acid (C,3Hyp2N04 100986-89-H) see Levofloxacin... 

On the other hand, clinical and laboratory studies in humans have demonstrated the development of tolerance to the amnestic and analgesic effects of nitrous oxide and isoflurane (see Arnold et al. 1993 Avramov et al. 1990 Rupreht et al. 1985 Whitwam et al. 1976) and, in the case of ether or chloroform, to its reinforcing effects (Krenz et al. 2003). No studies have shown the development of tolerance to the reinforcing effects of nitrous oxide. 

Severe withdrawal symptoms, including insomnia, irritability, agitation, withdrawal seizures, and delirium, have been described in both mice and humans chronically exposed to the anesthetics nitrous oxide, ether, and isoflurane (Arnold et al. 1993 Delteil et al. 1974 Deniker et al. 1972 Harper et al. 1980 Smith et al. 1979 Tobias 2000). These symptoms were controlled with the administration of y-aminobutyric acid (GABA)-ergic agents such as pentobarbital, midazolam, and diazepam (Arnold et al. 1993 Hughes et al. 1993). 

Arnold JH, Truog RD, Rice SA Prolonged administration of isoflurane to pediatric patients during mechanical ventilation. Anesth Analg 76 520—526, 1993... 

Hughes J, Leach HJ, Choonara I Hallucinations on withdrawal of isoflurane used as sedation. Acta Paediatr 82 885—886, 1993... 

Yamakura T, Harris RA Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels comparison with isoflurane and ethanol. Anesthesiology 93 1093-1101,2000... 

Hypnotics. Common hypnotics are thiopental, propofol, midazolam, etomidate, ketamine and inhaled anesthetics. The incidence of hypersensitivity reactions with thiopental is rare. Recently, thiopental was involved in less than 1% of allergic reactions in France [9]. Ever since Cremophor EL, used as a solvent for some non-barbiturate hypnotics, has been avoided, many previously reported hypersensitivity reactions have disappeared. In the last French surveys, reactions to propofol accounted for less than 2.5% of allergic reactions, and reactions to midazolam, etomidate or ketamine appear to be really rare [9]. Finally, no immune-mediated immediate hypersensitivity reaction involving isoflurane, desflurane or sevoflurane has been reported despite their wide use. 

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