Noninhalation Anesthetics

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In order to place a patient under narcosis in modern anesthesiology, multiple drugs are used both prior to using inhalation anesthetics and during the procedure. The compounds used (with a few special exceptions) are formally classified as noninhalation anesthetics and are representative of other pharmacological classes of compounds (analgesics, tranquilizers, neuroleptics, and others). It is worth mentioning that during noninhalation anesthesia, control and regulation during the procedure is significantly harder to accomplish that with inhalation anesthesia. However, the simplicity of intravenous anesthesia equipment and the various combinations (neuroleptanalgesia, ataragesia, tranquilizeresia) make the general anesthetic options extremely beneficial in clinical use.

For general anesthesia, ketamine and ethomidate are used as short-lasting, special drugs for noninhalation narcosis, as are a number of drugs that belong to completely different chemical classes, including: short-lasting barbiturates (thiopental, methohexital), opioid analgesics (morphine, fentanyl), and also a number of benzodiazepine tranquilizers (diazepam, lorazepam, and midazolam), which are drugs that refer in the given section, noninhalation anesthetics, despite the fact that formally they are not referred to them because they do not display all of the four characteristics that are unique to anesthetics by definition.

Ketamine: Ketamine, 2-(o-chlorophenyl)-2-(2-methylamino)cyclohexanone (1.2.4), is synthesized from 2-chlorobenzonitrile, which reacts with cyclopentylmagnesium bromide to give 1-(2-chlorobenzoyl)cyclopentane (1.2.1). The next step is bromination using bromine to the corresponding bromoketone (1.2.2), which upon interaction with an aqueous solution of methylamine forms the methylamino derivative (1.2.3). During this reaction a simultaneous hydrolysis of the tertiary bromine atom occurs. On further heating the reaction product in decaline, a ring expansion rearrangement occurs, causing formation of ketamine. Other possible mechanism of the transformation of the methylamino derivative (1.2.3) into the final product has also been suggested. One of them, in particular, suggested the formation of an epoxide intermediate; however, none of these proposed mechanisms can be regarded as completely proven [12,13].


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