Halogenated anesthetics

Polyhalogenated Hydrocarbons Used as Anesthetics Halogenation A Medical Perspective ... 

Flurothyl [333-36-8] (bis-(2,2,2-trifluoroeth5i)ether) (9), an analeptic having strong convulsant properties, has been used for chemical shock therapy (13). The compound is unique in that it is a volatile fluorinated ether and its stmcture resembles those of many halogenated general anesthetics. Chemical shock therapy is rarely used. 

Compounds that Cause Kidney Damage Several drugs and some anesthetic compounds such as methoxyflurane cause kidney damage when present at high doses. Kidney-toxic compounds found in occupational environments include mycotoxins, halogenated hydrocarbons, several metals, and solvents (see Table 5.16). 

Uses. n-Pentane has found use as an anesthetic an expl suppressant when mixed with a halogen-ated hydrocarbon and included in aircraft fuel (Ref 13) a jet engine fuel (Ref 16a) as a base for synthetic rubbers and plastics a parent compd for the formation of nitropentanes and azido nitro pentanes used as expls and propints (Refs 15a, 15b 21a) also, as a parent compd for fluorine-contg resin binders which impart both thermal stability and, in conjunction with metal hydrides, high impulse to solid propints (Ref 15b)... 

Hoffmaim P, Heinroth K, Richards D, et al. 1994. Depression of calcium dynamics in cardiac myoc54es - a common mechanism of halogenated hydrocarbon anesthetics and solvents. J Mol Cell Cardiol 26 579-589. 

Anesthetics General anesthetics Alkanols Halothane Enflurane Isoflurane Halogenated cyclobutanes Xenon... 

FIG. 1 Molecular structures of the drugs examined in the delivery study the general anesthetics, alkanols (I), halothane (II), enflurane (III), isoflurane (IV), halogenated cyclobutane (V) the local anesthetics, dibucaine hydrochloride (VI), procaine hydrochloride (VII), tetracaine hydrochloride (VIII), lidocaine hydrochloride (IX), benzyl alcohol (X) the endocrine disruptor, bisphenol A (XI), and alkylbenzenes, benzene (XII), toluene (XIII), ethylbenzene (XIV), and propylbenzene (XV). 

The halogenated hydrocarbons are generally of low acute toxicity, but several are associated with anesthetic effects and cardiac sensitization. Cardiac sensitization to halogenated alkanes appears related to the number of chlorine or fluorine substitutions. Halogenated alkanes in which >75% of the... 

McCarty LP, Malek RS, Larsen ER. 1979. The effects of deuteration on the metabolism of halogenated anesthetics in the rat. Anesthesiology 51 106-110. 

The mechanism of action of inhalational anesthetics is unknown. The diversity of chemical structures (inert gas xenon hydrocarbons halogenated hydrocarbons) possessing anesthetic activity appears to rule out involvement of specific receptors. According to one hypothesis, uptake into the hydrophobic interior of the plasmalemma of neurons results in inhibition of electrical excitability and impulse propagation in the brain. This concept would explain the correlation between anesthetic potency and lipophilicity of anesthetic drugs (A). However, an interaction with lipophilic domains of membrane proteins is also conceivable. Anesthetic potency can be expressed in terms of the minimal alveolar concentration (MAC) at which 50% of patients remain immobile following a defined painful stimulus (skin incision). Whereas the poorly lipophilic N2O must be inhaled in high concentrations (>70% of inspired air has to be replaced), much smaller concentrations (<5%) are required in the case of the more lipophilic halothane. 

Volatile anesthetic agents - Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated inhalational anesthetics. 

Inhalation anesthetics still in use include nitrous oxide and the halogenated hydrocarbon inhalation anesthetics such as halothane, isoflurane, methoxyflurane and sevoflurane. 

Halogenated hydrocarbon inhalation anesthetics may increase intracranial and CSF pressure. Cardiovascular effects include decreased myocardial contractility and stroke volume leading to lower arterial blood pressure. Malignant hyperthermia may occur with all inhalation anesthetics except nitrous oxide but has most commonly been seen with halothane. Especially halothane but probably also the other halogenated hydrocarbons have the potential for acute or chronic hepatic toxicity. Halothane has been almost completely replaced in modern anesthesia practice by newer agents. 

Desflurane, like other halogenated hydrocarbon anesthetics, causes a decrease in blood pressure. The reduced pressure occurs primarily as a consequence of decreased vascular resistance, and since cardiac output is well maintained, tissue perfusion is preserved. 

Sevoflurane undergoes hepatic biotransformation (about 3% of the inhaled dose), and it is somewhat degraded by conventional CO2 absorbents. The degradation product from the absorbent has been reported to be nephrotoxic, although the report is controversial and not substantiated by more recent studies. Sevoflurane s actions on skeletal muscle and on vascular regulation within the CNS are similar to those described for the other halogenated hydrocarbon anesthetics. 

A) All halogenated hydrocarbon inhalational anesthetics sensitize the myocardium to catecholamine-induced cardiac arrhythmias. 

A hydrogen bond, involving an acidic hydrogen atom borne by a fluorine-substituted or halogen-substituted carbon, seems to contribute to the activity and selectivity of volatile fluorinated anesthetics (Table 3.2). These molecules, although nonfunctional, can bind stereoselectively with protein targets of the central nervous system. Different biological behaviors have been reported for both enantiomers of isoflurane (cf. Chapter 8). ... 

Of the inhaled anesthetics, nitrous oxide is the least likely to increase cerebral blood flow. At low concentrations, all of the halogenated agents have similar effects on cerebral blood flow. However, at higher concentrations, the increase in cerebral blood flow is less with the less soluble agents such as desflurane and sevoflurane. If the patient is hyperventilated before the volatile agent is started, the increase in intracranial pressure can be minimized. 

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