Inhalant properties anesthetics

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...

In other applications of CT, orally administered barium sulfate or a water-soluble iodinated CM is used to opacify the GI tract. Xenon, atomic number 54, exhibits similar x-ray absorption properties to those of iodine. It rapidly diffuses across the blood brain barrier after inhalation to saturate different tissues of brain as a function of its lipid solubility. In preliminary investigations (99), xenon gas inhalation prior to brain CT has provided useful information for evaluations of local cerebral blood flow and cerebral tissue abnormalities. Xenon exhibits an anesthetic effect at high concentrations but otherwise is free of physiological effects because of its nonreactive nature. 

Absorption of trichloroethylene in humans is very rapid upon inhalation exposure. Trichloroethylene has a blood/gas partition coefficient that is comparable to some other anesthetic gases (i.e., chloroform, diethylether, and methoxyfluorene), but it is much more lipophilic than these gases. As a consequence of these properties, the initial rate of uptake of inhaled trichloroethylene in humans is quite high, with the rate leveling off after a few hours of exposure (Fernandez et al. 1977). The absorbed dose is proportional to the inhaled trichloroethylene concentration, duration of exposure, and alveolar ventilation rate at a given inhaled air concentration (Astrand and Ovrum 1976). Several studies indicate that 37-64% of inhaled trichloroethylene is taken up from the lungs (Astrand and Ovrum 1976 Bartonicek 1962 Monster et al. 1976). 

In the past, trichloroethylene was used as a human anesthetic. Trichloroethylene has also been used by individuals who intentionally inhale it for its narcotic properties. Therefore, most of the information regarding the effects of trichloroethylene in humans comes from case studies and experiments describing effects of trichloroethylene after inhalation exposure. These studies indicate that the primary effect of exposure to trichloroethylene is on the central nervous system. Effects include headache, vertigo, fatigue, short-term memory loss, decreased word associations, central nervous system depression, and anesthesia. 

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 ... 

Anesthesiologists must have an intimate knowledge of the chemical and physical properties of gases. Many anesthetics are inhaled and are delivered to the bloodstream by diffusion. The speed at which diffusion occurs between the lungs, the blood, and other tissues of the body depends on a constant called the partition coefficient This constant is a ratio that describes the equilibrium concentrations of a solute that is dissolved in two separate phases. The solute becomes separated (partitioned) between the two solvents in such a way that its concentration in one is directly proportional to its concentration in the other. 

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. ... 

Like many volatile halocarbons and other hydrocarbons, inhalation exposure to carbon tetrachloride leads to rapid depression of the central nervous system. Because of its narcotic properties, carbon tetrachloride was used briefly as an anesthetic in humans, but its use was discontinued because it was less efficacious and more toxic than other anesthetics available (Hardin 1954 Stevens and Forster 1953). Depending on exposure levels, common signs of central nervous system effects include headache, giddiness, weakness, lethargy, and stupor (Cohen 1957 Stevens and Forster 1953 Stewart and Witts 1944). Effects on vision (restricted peripheral vision, amblyopia) have been observed in some cases (e.g., Johnstone 1948 Smyth et al. 1936 Wrtschafter 1933), but not in others (e.g., Stewart and Wtts 1944). In several fatal cases, microscopic examination of brain tissue taken at autopsy revealed focal areas of fatty degeneration and necrosis, usually associated with congestion of cerebral blood vessels (Ashe and Sailer 1942 Cohen 1957 Stevens and Forster 1953). 

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. 

Ensuring an adequate depth of anesthesia depends on achieving a therapeutic concentration of the anesthetic in the CNS. The rate at which an effective brain concentration is achieved (ie, time to induction of general anesthesia) depends on multiple pharmacokinetic factors that influence the brain uptake and tissue distribution of the anesthetic agent. The pharmacokinetic properties of the intravenous anesthetics (Table 25-1) and the physicochemical properties of the inhaled agents (Table 25-2) directly influence the pharmacodynamic effects of these drugs. These factors also influence the rate of recovery when the administration of anesthetic is discontinued. 

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... 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

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. 

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