Inhaled anesthetics properties

Anesthesia. Materials that have unquestionable anesthetic properties are chloral hydrate [302-17-0] paraldehyde, dimethoxymethane [109-87-5] and acetaldehyde diethyl acetal. In iadustrial exposures, however, any action as an anesthesia is overshadowed by effects as a primary irritant, which prevent voluntary inhalation of any significant quantities. The small quantities which can be tolerated by inhalation are usually metabolized so rapidly that no anesthetic symptoms occur. 

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. 

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

The distribution of anesthetic throughout the entire body may be viewed as an equilibration process (Fig. 7.1.13), with tissues characterized by high blood flows reaching equilibration faster than muscle and fatJ4 Nevertheless, an anesthetic that is excessively soluble in blood will not partition substantially into brain and other tissues. The anesthetic properties of nitrous oxide and diethyl ether have been known since the 1840s. Zeneca Pharmaceuticals introduced the first modem inhalation anesthetic fluothane in 1957. Methoxyfluorane followed in 1960, enflurane 1973, isoflurane 1981, desflurane by Anaquest (Liberty Comer, NJ) in 1992, and sevoflurane by Abbott Laboratories in 1995J6 ... 

Voluntary inhalation of butane has led to numerous deaths. Possible mechanisms for the cause of death included the central respiratory and circulatory sequelae of the anesthetic properties of butane, laryngeal edema, chemical pneumonia, and the combined effects of cardiac toxicity and increased sympathetic activity. ... 

The inhalational anesthetics can be divided into two classes based on their physical properties. N2O and cyclopropane are gases at room temperature and are supplied in gas tanks that are regulated by the anesthesia machine. The others are liquids that are volatile following the application of low heat, which is supplied by a vaporizer attached to the anesthesia machine. The halo-genated hydrocarbons are among the most potent volatile anesthetics. 

Chlorofluorocarbon (CFC) replacements have recently been used for their lower stability and because they have carbon-hydrogen bonds, which means that their atmospheric lifetime is expected to be much shorter than those of CFCs. The adsorption properties of l,l,2-trichloro-l,2,2-trifluoroethane (CFC 113) and its replacement compounds, l,l-dichloro-2,2,2-trifluoroethane (HCFC123), 1,1-dichloro-l-fluoroethane (HCFC141b), and l,l-dichloro-l,2,2,3,3-pentafluoropropane (HCFC225ca) on four kinds of activated carbons were investigated. The adsorption isotherms of inhalational anesthetics (halothane, chloroform, enflurane, isoflurane, and methoxyflurane) on the activated carbon were measured to evaluate the action mechanism of inhalational anesthesia. The anesthesia of CFC replacements can be estimated by the Freundlich constant N of the adsorption isotherms (Tanada et al., 1997). 

Toxicity of EtnO (Ref 17, pp 314—15 Spec MIL-E-52171). Liquid EtnO, concentrated or dilute, when exposed to the skin can cause -severe delayed bums. Short exposures produce mild first degree bums, but prolonged exposures produce second degree bums with the formation of large blisters. Exposure to the vapor results in systemic manifestations and irritation to the respiratory system. Inhalation of ethylene oxide vapors, if. prolonged, results in severe systemic poisoning with the symptoms of nausea, vomiting, headache, dysnea, and diarthea. The anesthetic properties are similar to chloroform, but with pronounced undesirable side and after effects. 

The concentration of an inhaled anesthetic in a mixture of gases is proportional to its partial pressure (or tension). These terms are often used interchangeably in discussing the various transfer processes involving anesthetic gases within the body. Achievement of a brain concentration of an inhaled anesthetic necessary to provide an adequate depth of anesthesia requires transfer of the anesthetic from the alveolar air to the blood and from the blood to the brain. The rate at which a therapeutic concentration of the anesthetic is achieved in the brain depends primarily on the solubility properties of the anesthetic, its concentration in the inspired air, the volume of pulmonary ventilation, the pulmonary blood flow, and the partial pressure gradient between arterial and mixed venous blood anesthetic concentrations. 

In the last two decades there has been increasing use of intravenous anesthetics in anesthesia, both as adjuncts to inhaled anesthetics and as part of techniques that do not include any inhaled anesthetics (eg, total intravenous anesthesia). The properties of some of the commonly used intravenous anesthetics are summarized in Table 25-1. Unlike inhaled anesthetics, intravenous agents do not require specialized vaporizer equipment for their delivery or facilities for... 

TABLE 1. PROPERTIES AND PARTITION COEFFICIENTS OF INHALATION ANESTHETICS... 

These substances have excellent solvent properties for nonpolar and slightly polar substances. Chloroform once was used widely as an inhalation anesthetic. However, it has a deleterious effect on the heart and is oxidized slowly by atmospheric oxygen to highly toxic carbonyl dichloride (phosgene, COCl2)-Commercial chloroform contains about 1% ethanol, which destroys any COCl2 formed by oxidation. 

CAUTION This step should be carried out in a fume hood to avoid inhalation of the vapors. Chloroform is a known carcinogen. It is toxic by inhalation and has anesthetic properties. Contact with skin should be avoided. Prolonged inhalation or ingestion can lead to liver and kidney damage and may be fatal. 

Peripheral neuropathy has been reported in two healthy men anesthetized with 1.25 MAC sevoflurane at 21/minute fresh gas flow for 8 hours. Their average concentrations of compound A were 45 and 28 ppm. Both had had previous minor injuries in the regions in which the neuropathies were reported. The authors suggested that compound A, or other factors associated with sevoflurane anesthesia, may predispose patients to peripheral neuropathy. Both men were volunteers for earlier published studies comparing the nephrotoxic properties of sevoflurane and desflurane, sponsored by Baxter PPD, New Jersey, the manufacturer of desflurane, a rival inhalational anesthetic agent these reports need to be regarded with caution. 

Modem inhalation anesthetics are fluoiinated to reduce flammabihty. Initially, these inhaled agents were believed to be biochemically inert. Over the past 30 years, however, research findings have demonstrated that not only are inhaled anesthetics metabolized in vivo [27], but their metabolites are also responsible for both acute and chronic toxicities [28,29]. Therefore, the use of some anesthetics has been discontinued, including methoxyflurane because of its nephrotoxicity and other anesthetics are more selectively used, e.g. halothane due to a rare incidence of liver toxicity. Studies have also provided the impetus to develop new agents - isoflurane and desflurane - with properties that lower their toxic potential. The result has been improved safety, but there is room for further improvement as our insight into toxicological mechanisms expands. 

Nitrous oxide (laughing gas) has been used as an inhalant anesthetic since 1844 and is still widely used in human anesthesia because of its potent analgesic actions. Although it has many desirable properties, including rapid onset and recovery, limited cardiopulmonary depression and minimal toxicity, it is a weak anesthetic. Its lack of potency, its relatively high cost and its possible contribution to hypoxia and accumulation in gas-filled spaces limits its use in the horse. 

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