Anesthetics halothane

STEROID (alphaxalone, allopregnanolone) VOLATILE ANESTHETIC (halothane)... 

Levetiracetam, topiramate, and the general anesthetics, halothane, isoflu-rane, and ketamine are being evaluated for refractory GCSE, but their efficacy, safety, or overall suitability have not been established to date. 

Jaloszynski P, Kujawski M, Wasowicz M, et al Genotoxicity of inhalation anesthetics halothane and isoflurane in human lymphocytes studied in vitro using the comet assay. Mutat Res-. 439(2) 199-206, 1999... 

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). 

Oxidative dehalogenation. Halogen atoms may be removed from xenobiotics in an oxidative reaction catalyzed by cytochromes P-450. For example, the anesthetic halothane is metabolized to trifluoroacetic acid via several steps, which involves the insertion of an oxygen atom and the loss of chlorine and bromine (Fig. 4.28). This is the major metabolic pathway in man and is believed to be involved in the hepatotoxicity of the drug. Trifluoroacetyl chloride is thought to be the reactive intermediate (see chap. 7). 

Literally hundreds of substances in addition to ether and chloroform have subsequently been shown to act as inhaled anesthetics. Halothane, enflurane, isoflurane, and methoxyflurane are at present the most commonly used agents in hospital operating rooms. All four are potent at relatively low doses, are nontoxic, and are nonflammable, an important safety feature. 

The studied molecules include such diverse compounds as volatile anesthetics (halothane), local anesthetics of the cocaine type, calcium channel-blocking agents such as verapamil, antidepressants (chlorpromazine), and anti cancer drugs such as adriamycin. It is argued that the factor of interest to the physiological effect may not... 

The above reaction is of particular interest because the product Y is the well-known inhalation anesthetic Halothane that replaced ether and other flammable and therefore dangerous anesthetics in the late 1950s. Nowadays, Halothane is, at least in the United States, replaced by even better fluorinated inhalation anesthetics. 

In the study described here, VSFS spectra of a series of phospholipid monolayers at the CCU/water interface were acquired and the effect of a common inhaled anesthetic, halothane (CFsCHClBr), on their conformation was examined [62]. Phospholipid mono-layers at an organic/aqueous interface are a useful model system for the study of cell membranes because they provide a realistic model of the hydrophilic and hydrophobic environments commonly found in vivo. In addition, the understanding and thermodynamics of these monolayer systems has been extensively described and rigorous theoretical analyses have been reported [63]. In these studies, the CCI4/D2O interface was used for experimental convenience, and although this interface is non-biological, it does mimic the hydrophobic/aqueous interface found in many biological systems [64]. 

As discussed in Chapter 16, dehalogenation by liver enzymes of a number of inhalation anesthetics (halothane, methoxyflurane) and halogenated solvents yields chemically reactive free radicals that play an important role in the hepatotoxicity of these compounds. Dehalogenation produces a free radical... 

Amouzadeh HR, Bourdi M, Martin JL, Martin BM, Pohl LR. LJDP-glucose glycoprotein glucosyltransfer-ease associates with endoplasmic reticulum chaperones and its activity is decreased in vivo by the inhalation anesthetic halothane. Chern Res Toxicol 1997 10 59-63. 

EXAMPLE R —CO, — R—CHQ2 (a i" tbe transfonnalion of carbon tetrachloride or the anesthetic halothane)... 

Figure 15 Enantiomer separation of inhalation anesthetics halothane and isoflurane on a 25-m fused silica capillary with per-pe-a-CD at 35°C.

Inhalants include many different compounds related more by their method of administration than by their pharmacology. Some categories of inhalants, such as the medical anesthetics (halothane and nitrous oxide), arc true depressant drugs, but inhalants also include a variety of products with widely varying pharmacologies, including glue, paint, butane gas, correction fluid, and many others (see Table 14.4 for a more... 

The major inhalation anesthetics (halothane, ether, and methoxyflurane) trigger a reaction in susceptible people, which results in the uncoupling of o,xidative phosphorylation from electron transport. ATP production decreasesTlieat is generated andtheTemperature rises markedly, the TCA cycle is stimulated, and excessive CD2 production leads to a respiratory acidosis. 

The inhalational anesthetics halothane, isoflurane, and enflu-rane all have been reported to have a positive effect in children and adults with severe asthma that is unresponsive to standard medical therapy. The proposed mechanisms for inhalational anesthetics include direct action on bronchial smooth muscle, inhibition of airway reflexes, attenuation of histamine-induced bronchospasm, and interaction with /32-adrenergic receptors. Well-controlled trials with these agents have not been completed. Potential adverse effects include myocardial depression, vasodilation, arrhythmias, and depression of mucociliary function. In addition, the practical problem of delivery and scavenging these agents in the intensive care environment as opposed to the operating room is a concern. The use of volatile anesthetics cannot be recommended based on insufficient evidence of efficacy. 

Figure 18-1. Direct and indirect effects of Ca + release in aberrant response to anesthetics halothane and succinylcholine.

Hepatotoxic substances interfere with phagocytosis causing transient changes, such as inhomogeneous or irregular distribution of radiocolloids in the liver/spleen, or a shift of uptake from liver to spleen and/or bone marrow. Anesthetics (halothane) affect both phagocytic and catabolic RES function, resulting in an increased uptake in the spleen (Hladik et al. 1987). 

The mechanism of cytochrome P-450 destruction by CCl or the related anesthetic halothane must take into account the reductive formation of a reversible complex with an absorbance maximum at 454 or 469 nm, respectively.It is believed, but has yet to be clearly demonstrated, that these complexes involve coordination of the prosthetic heme iron with halocarbon-derived carbenes or anions,... 

Hinkley RE, Wright BD. 1986. Effects of the volatile anesthetic halothane on fertilization and early development in the sea urchin Lytechinus variegatus. evidence that abnormal development is due to polyspermy. Teratology 34 291-301. 

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