Inhaled anesthetics toxicity

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... 

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. 

Ingot casting, 23 266 Ingot production, titanium, 24 857 Inhalation. See also Dust inhalation hydrogen fluoride, 14 17-18 influence on toxicity, 25 211 of PVC dust, 25 676-677 of sodium tetrasulfide, 22 875 studies of, 25 227t of sulfuric acid, 23 794 of toluene, 25 179t of VDC, 25 692-694 Inhalation anesthetics, 11 867-868 Inhalation exposure... 

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. 

Isoflurane, an isomer of enflurane, together with sevoflurane are the most commonly used inhalation anesthetics in humans. Isoflurane does not sensitize the myocardium to catecholamines, has muscle relaxing action so less neuromuscular blocker is required and causes less hepatotoxicity and renal toxicity than halothane. 

The metabolism of enflurane and sevoflurane results in the formation of fluoride ion. However, in contrast to the rarely used volatile anesthetic methoxyflurane, renal fluoride levels do not reach toxic levels under normal circumstances. In addition, sevoflurane is degraded by contact with the carbon dioxide absorbent in anesthesia machines, yielding a vinyl ether called "compound A," which can cause renal damage if high concentrations are absorbed. (See Do We Really Need Another Inhaled Anesthetic ) Seventy percent of the absorbed methoxyflurane is metabolized by the liver, and the released fluoride ions can produce nephrotoxicity. In terms of the extent of hepatic metabolism, the rank order for the inhaled anesthetics is methoxyflurane > halothane > enflurane > sevoflurane > isoflurane > desflurane > nitrous oxide (Table 25-2). Nitrous oxide is not metabolized by human tissues. However, bacteria in the gastrointestinal tract may be able to break down the nitrous oxide molecule. 

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. 

Inhaled anesthetics currently in use include halo-genated volatile liquids such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane (Table 11-1). These volatile liquids are all chemically similar, but newer agents such as desflurane and sevoflurane are often used preferentially because they permit a more rapid onset, a faster recovery, and better control during anesthesia compared to older agents such as halothane.915 These volatile liquids likewise represent the primary form of inhaled anesthetics. The only gaseous anesthetic currently in widespread use is nitrous oxide, which is usually reserved for relatively short-term procedures (e.g., tooth extractions). Earlier inhaled anesthetics, such as ether, chloroform, and cyclopropane, are not currently used because they are explosive in nature or produce toxic effects that do not occur with the more modern anesthetic agents. 

Methoxyflurane This agent is the most potent inhalation anesthetic because of its high solubility in lipid. Prolonged administration of methoxyflurane [meth ox ee FLURE ane] is associated with the metabolic release of fluoride, which is toxic to the kidneys. Therefore, methoxyflurane is rarely used outside of obstetric practice. It finds use in child-birth because it does not relax the uterus when briefly inhaled. 

Kenna JG, Jones RM. The organ toxicity of inhaled anesthetics. Anesth Analg 1995 81(Suppl 6) S51-66. 

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. 

Atropine and scopolamine are used for pre-medication before the administration of some inhalation anesthetics, to reduce excessive salivary and bronchial secretions. Atropine and related agents have been used in the treatment of renal colic and hyperhidrosis, and to control sweating that may aggravate certain dermatologic disorders. Atropine also may be used to counteract the toxicity of certain cholinergic drugs and anticholinesterase agents. 

For many years chloroform (CHCI3) was used as an inhalation anesthetic in spite of the fact that it is also a toxic substance that may cause severe liver, kidney, and heart damage. Calculate the percent composition by mass of this compound. 

Methoxyflurane is the most potent of the inhalational anesthetics. It is metabolized extensively to fluoride and other nephrotoxic products. Because methoxyflurane does not alter uterine contraction during labor, it is valuable for obstetric anesthesia. Its toxic effects on the respiration and... 

Sodium pentothal (also called thiopental sodium) is commonly used as an intravenous anesthetic. The onset of anesthesia and the loss of consciousness occur within seconds of its administration. Care must be taken when administering sodium pentothal because the dose for effective anesthesia is 75% of the lethal dose. Because of its toxicity, it cannot he used as the sole anesthetic. It is generally used to induce anesthesia before an inhalation anesthetic is administered. Propofol is an anesthetic that has all the properties of the perfect anesthetic It can he used as the sole anesthetic by intravenous drip, it has a rapid and pleasant induction period and a wide margin of safety, and recovery from the drug is rapid and pleasant. 

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