Halothane inhaled anesthetic

Clinically important, potentially hazardous interactions with aminoglycosides, betamethasone, cyclosporine, gentamicin, halothane, inhalational anesthetics, kanamycin, magnesium salts, neomycin, quinidine, streptomycin, succinylcholine, tazobactum, tobramycin... 

Summary 27-year-old male with acute appendicitis undergoing a halothane inhaled anesthetic with acute onset of hyperthermia, tachypnea, respiratory acidosis, hyperkalemia, and family history of similar events. The tentative diagnosis is MH. 

Inhalation Anesthetics. Examples of highly duorinated halocarbons and ethers are halothane [151-67-7], duroxene [406-90-6], endurane... 

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. 

In veterinary medicine, the Hst of inhalation anesthetics generally includes only two agents, halothane [151 -67-7] and methoxyflurane [76-38-0]. Although ether (ethyl ether) is used extensively in experimental work with laboratory animals, the risks associated with its use and the advantages of halothane and methoxyflurane have removed ether from general use by the practitioner. 

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. 

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... 

Selection of a specific anesthetic or combination of anesthetics is made depending on the type of medical intervention. For a long time, ether, chloroform, tricholoroethylene, ethyl chloride or chloretane, and also cyclopropane were widely used as inhalation anesthetics. Today, the following anesthetics are used most regularly in medicine halothane, enflurane, isoflurane, metoxyflurane, and nitrous oxide. Researchers are also actively exploring the use of xenon as an anesthetic. 

Halothane is a modem and widely used inhalation anesthetic. It begins to act very quickly, which is pleasing to patients, and it is very safe. The only drawback to using it is its hepa-totoxicity. It is used in both short and long-lasting surgical operations. The most common synonym of halothane is fluothane. 

Gas should be differentiated from volatile liquids which are used as inhalation anesthetics. A gas such as nitrous oxide exists in the gaseous form at room temperature and sea-level barometric pressure while vapors are the gaseous states of agents, like halothane, which at room temperature and pressure are liquids. 

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. 

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. 

Inhalation anesthetics, such as isoflurane, enflurane, halothane, and nitrous oxide, potentiate the action of nondepolarizing blockers, either through modification of end plate responsiveness or by alteration of local blood flow. The extent of potentiation depends on the anesthetic and the depth of anesthesia. The dose of muscle relaxant should be reduced when used with these 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). 

The concentration of an inhaled anesthetic in the inspired gas mixture has direct effects on both the maximum tension that can be achieved in the alveoli and the rate of increase in its tension in arterial blood. Increases in the inspired anesthetic concentration increase the rate of induction of anesthesia by increasing the rate of transfer into the blood according to Fick s law (see Chapter 1). Advantage is taken of this effect in anesthetic practice with inhaled anesthetics that possess moderate blood solubility (eg, enflurane, isoflurane, and halothane). For example, a 1.5% concentration of isoflurane may be administered initially to increase the rate of rise in the brain concentration the inspired concentration is subsequently reduced to 0.75-1% when an adequate depth of anesthesia is achieved. In addition, these moderately soluble anesthetics are often administered in combination with a less soluble agent (eg, nitrous oxide) to reduce the time required for loss of consciousness and achievement of a surgical depth of anesthesia. 

Inhaled anesthetics that are relatively insoluble in blood (ie, possess low blood gas partition coefficients) and brain are eliminated at faster rates than the more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, leading to a more rapid recovery from their anesthetic effects compared with halothane and isoflurane. Halothane is approximately twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide and desflurane its elimination therefore takes place more slowly, and recovery from halothane- and isoflurane-based anesthesia is predictably less rapid. 

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. 

After its introduction in 1956, halothane was the standard of comparison for inhaled anesthetics. However, the... 

Inhaled anesthetics change heart rate either directly by altering the rate of sinus node depolarization or indirectly by shifting the balance of autonomic nervous system activity. Bradycardia can be seen with halothane, probably because of direct vagal stimulation. In contrast, enflurane, and sevoflurane have little effect, and both desflurane and isoflurane increase heart rate. In the case of desflurane, transient sympathetic activation with elevations in catecholamine levels can lead to marked increases in heart rate and blood pressure when high inspired gas concentrations are administered. 

Inhaled (volatile) anesthetics potentiate the neuromuscular blockade produced by nondepolarizing muscle relaxants in a dose-dependent fashion. Of the general anesthetics that have been studied, inhaled anesthetics augment the effects of muscle relaxants in the following order isoflurane (most) sevoflurane, desflurane, enflurane, and halothane and nitrous oxide (least) (Figure 27-9). The most important factors involved in this interaction are the following (1) nervous system depression at sites proximal to the neuromuscular junction (ie, central nervous system) (2) increased muscle blood flow (ie, due to peripheral vasodilation produced by volatile anesthetics), which allows a larger fraction of the injected muscle relaxant to reach the neuromuscular junction and (3) decreased sensitivity of the postjunctional membrane to depolarization. 

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. 

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. 

The chemical structures of the currently available inhaled anesthetics are shown in Figure 25-1. Nitrous oxide, a gas at ambient temperature and pressure, continues to be an important component of many anesthesia regimens. Halothane, enflurane, isoflurane, desflurane, sevoflurane, and methoxyflurane are volatile liquids. 

An increase in pulmonary blood flow (increased cardiac output) slows the rate of rise in arterial tension, particularly for those anesthetics with moderate to high blood solubility. This is because increased pulmonary blood flow exposes a larger volume of blood to the anesthetic thus, blood "capacity" increases and the anesthetic tension rises slowly. A decrease in pulmonary blood flow has the opposite effect and increases the rate of rise of arterial tension of inhaled anesthetics. In a patient with circulatory shock, the combined effects of decreased cardiac output (resulting in decreased pulmonary flow) and increased ventilation will accelerate the induction of anesthesia with halothane and isoflurane. This is not likely to occur with nitrous oxide, desflurane, or sevoflurane because of their low blood solubility. 

Inhaled anesthetics that are relatively insoluble in blood (low blood gas partition coefficient) and brain are eliminated at faster rates than more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, which leads to a more rapid recovery from their anesthetic effects compared to halothane and isoflurane. Halothane is approximately twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide and desflurane its elimination therefore takes place more slowly, and recovery from halothane anesthesia is predictably less rapid. The duration of exposure to the anesthetic can also have a marked effect on the time of recovery, especially in the case of more soluble anesthetics. Accumulation of anesthetics in tissues, including muscle, skin, and fat, increases with continuous inhalation (especially in obese patients), and blood tension may decline slowly during recovery as the anesthetic is gradually eliminated from these tissues. Thus, if exposure to the anesthetic is short, recovery may be rapid even with the more soluble agents. However, after prolonged anesthesia, recovery may be delayed even with anesthetics of moderate solubility such as isoflurane. 

Clearance of inhaled anesthetics by the lungs into the expired air is the major route of their elimination from the body. However, metabolism by enzymes of the liver and other tissues may also contribute to the elimination of volatile anesthetics. For example, the elimination of halothane during recovery is more rapid than that of enflurane, which would not be predicted from their... 

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