General anesthetics metabolites

The answer is d. (Hardman, pp 308-313.) Halothane is a substituted alkane general anesthetic. It undergoes significant metabolism in humans with about 20% of the absorbed dose recovered as metabolites. Halothane can cause postoperative jaundice and hepatic necrosis with repeated administration in rare instances. 

Benzodiazepines—including diazepam, lorazepam, and midazolam—are used intravenously in anesthesia (see Chapter 25), often in combination with other agents. Not surprisingly, benzodiazepines given in large doses as adjuncts to general anesthetics may contribute to a persistent postanesthetic respiratory depression. This is probably related to their relatively long half-lives and the formation of active metabolites. However, such depressant actions of the benzodiazepines are usually reversible with flumazenil. 

The macromolecular complex containing GABA-regulated chloride channels also may be a site of action of general anesthetics, ethanol, inhaled drugs of abuse, and certain metabolites of endogenous steroids. 

Methoxyflurane (Fig. 18.6) is seldom used beoause of its propensity to cause renal toxicity. It is the most potent of the agents discussed here, and it has the highest solubility in blood. Induotion and recovery would be expected to be slow. Chemically, it is rather unstable, and as much as 50% of an administered dose can be metabolized. Toxic metabolites significantly limit its utility as a general anesthetic (Fig. 18.7). 

Parent substances and metabolites may be stored in tissues, such as fat, from which they continue to be released following cessation of exposure to the parent material. In this way, potentially toxic levels of a material or metabolite may be maintained in the body. However, the relationship between uptake and release, and the quantitative aspects of partitioning, may be complex and vary between different materials. For example, volatile lipophilic materials are generally more rapidly cleared than nonvolatile substances, and the half-lives may differ by orders of magnitude. This is exemplified by comparing halothane and DDT (see Anesthetics Insectconthol technology). 

Droperidol is used as an adjunct for induction and maintenance of general anesthesia and as an anesthetic in diagnostic procedures. Droperidol, which has antiemetic properties, causes marked sedation and potentiates the CNS depressant effects of alcohol, hypnotic-sedatives, and numerous psychoactive agents. Droperidol is absorbed well through an IM injection—sedation begins in 3 minutes, peaks at 30 minutes, and lasts for 2 to 4 hours. Droperidol is metabolized by the liver to p-fluoro-phenylacetic acid and p-hydroxypiperidine, and its metabolites are excreted in urine and feces. 

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