Anesthetics, inhaled

One of the chief uses of chloromethane is as a starting material from which sili cone polymers are made Dichloromethane is widely used as a paint stripper Trichloromethane was once used as an inhalation anesthetic but its toxicity caused it to be replaced by safer materials many years ago Tetrachloromethane is the starting mate rial for the preparation of several chlorofluorocarbons (CFCs) at one time widely used as refrigerant gases Most of the world s industrialized nations have agreed to phase out all uses of CFCs because these compounds have been implicated m atmospheric processes that degrade the Earth s ozone layer... 

Infringement search Infusion botanical extract Infusion mashing Infusors Ingrain Blue 2 1 Ingrain dyes Inhalation anesthetics Inherent viscosity Inhibin... 

Inhalation Anesthetics. Examples of highly duorinated halocarbons and ethers are halothane [151-67-7], duroxene [406-90-6], endurane... 

Difluoroethanol is prepared by the mercuric oxide cataly2ed hydrolysis of 2-bromo-l,l-difluoroethane with carboxyHc acid esters and alkaH metal hydroxides ia water (27). Its chemical reactions are similar to those of most alcohols. It can be oxidi2ed to difluoroacetic acid [381-73-7] (28) it forms alkoxides with alkaH and alkaline-earth metals (29) with alkoxides of other alcohols it forms mixed ethers such as 2,2-difluoroethyl methyl ether [461-57-4], bp 47°C, or 2,2-difluoroethyl ethyl ether [82907-09-3], bp 66°C (29). 2,2-Difluoroethyl difluoromethyl ether [32778-16-8], made from the alcohol and chlorodifluoromethane ia aqueous base, has been iavestigated as an inhalation anesthetic (30,31) as have several ethers made by addition of the alcohol to various fluoroalkenes (32,33). Methacrylate esters of the alcohol are useful as a sheathing material for polymers ia optical appHcations (34). The alcohol has also been reported to be useful as a working fluid ia heat pumps (35). The alcohol is available ia research quantities for ca 6/g (1992). 

The primary site of action is postulated to be the Hpid matrix of cell membranes. The Hpid properties which are said to be altered vary from theory to theory and include enhancing membrane fluidity volume expansion melting of gel phases increasing membrane thickness, surface tension, and lateral surface pressure and encouraging the formation of polar dislocations (10,11). Most theories postulate that changes in the Hpids influence the activities of cmcial membrane proteins such as ion channels. The Hpid theories suffer from an important drawback at clinically used concentrations, the effects of inhalational anesthetics on Hpid bilayers are very small and essentially undetectable (6,12,13). 

An ideal inhalation anesthetic would exhibit physical, chemical, and pharmacological properties allowing safe usage in a variety of surgical interventions. 

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. 

Table 1. Properties and Partition Coefficients of Inhalation Anesthetics...

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. 

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. 

These have generally been replaced in veterinary medicine by inhalation anesthetics. Phenobarbital /T(9-(9G, phenytan [57-41-0], and primidone [125-33-7] are used as anticonvulsants. 

In veterinary medicine, the Hst of inhalation anesthetics generally includes only two agents, halothane [151 -67-7] and methoxyflurane [76-38-0]. Although ether (ethyl ether) is used extensively in experimental work with laboratory animals, the risks associated with its use and the advantages of halothane and methoxyflurane have removed ether from general use by the practitioner. 

Vinyl Ether. Vinyl ether is manufactured by the pyrolytic dehydrochlorination of 1,1 -dichloroethyl ether. Vinyl ether is used as a general inhalation anesthetic for procedures of short duration. Approximately 4% ethanol is added to the vinyl ether used as an anesthetic to reduce ice formation in the masks used for adrninistration (see also Vinyl polymers). 

There are relarively few important drugs which are alicyclic. Other than inhalation anesthetics, which are a special case, the compounds in the acyclic aliphatic class owe their activity to the functionality present and its specific spacing on the aliphatic framework. Thus, in most instances, the framework itself is not of comparable importance to the functionality attached to it. 

Therapeutic Function Inhalation anesthetic Chemical Name (2,2,2-trlfluoroethoxy)ethene Common Name 2,2,2-trifluoroethyl vinyl ether Structural Formula CF3CH20CH=CH2 Chemical Abstracts Registry No. 406-90-6... 

Therapeutic Function Inhalation anesthetic Chemical Name 2-bromo-2-chloro-1,1,1-trifluoroethane Common Name —... 

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. 

Various consumer products have been found to contain trichloroethylene. These include wood stains, varnishes, and finishes lubricants adhesives typewriter correction fluids paint removers and cleaners (Frankenberry et al. 1987). Trichloroethylene use as an inhalation anesthetic, fumigant, and extractant for decaffeinating coffee has been discontinued in the United States (EPA 1985c). 

Land PC, Owen EL, Linde HW. 1981. Morphologic changes in mouse spermatozoa after exposure to inhalation anesthetics during early spermatogenesis. Anesthesiology 54 53-56. 

Other important alternate electrochemical methods under study for pCO rely on measuring current associated with the direct reduction of CO. The electrochemistry of COj in both aqueous and non-aqueous media has been documented for some time 27-29) interferences from more easily reduced species such as O2 as well as many commonly used inhalation anesthetics have made the direct amperometric approach difficult to implement. One recently described attempt to circumvent some of these interference problems employs a two cathode configuration in which one electrode is used to scrub the sample of O by exhaustive reduction prior to COj amperometry at the second electrode. The response time and sensitivity of the approach may prove to be adequate for blood ps applications, but the issue of interfering anesthetics must be addressed more thorou ly in order to make the technique a truly viable alternative to the presently used indirect potentiometric electrode. 

The ability of differential pulse polarography to resolve multicomponent systems and evaluate concentrations with excellent sensitivity has made this technique an attractive candidate for simultaneous measurement of CO, O, and some inhalation anesthetics Though very preliminary, the results appear promising and will likely lead to more intensive investigation of the approach. 

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