Ketamine

Published on 07/02/2015 by admin

Filed under Anesthesiology

Last modified 07/02/2015

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Ketamine

Gilbert A. Blaise, MD

The ketamine molecule (2-(o-chlorophenyl)-2-methylamino-cyclohexamine) is chemically related to phencyclidine and contains a chiral center (C2 carbon of the cyclohexanone ring) with two optical isomers. The S-isomer is four times more potent, is associated with a faster recovery, and has a low incidence of psychomimetic effects, compared with the R-isomer. However, in North America, ketamine is sold primarily as a racemic mixture (Figure 74-1). It also contains benzethonium chloride as a preservative compound.

Figure 74-1 The molecular formula of ketamine hydrochloride, C₁₃H₁₆ClNO•HCl.

Designed to become the ideal anesthetic at a time when other anesthetic agents were particularly toxic and not easy to use, ketamine was introduced as a complete anesthetic agent in 1960. Its popularity was established in the mid-1970s during the Vietnam War, where it was deemed to be an “exceptional battlefield anesthetic.”

Administered intravenously or intramuscularly, it can evoke profound analgesia, loss of consciousness, amnesia, and immobility. The anesthesia produced by ketamine is termed dissociative because patients appear to be dissociated from their environment rather than simply nonreactive. Under ketamine anesthesia, the thalamus is no longer synchronized with the limbic system. Ketamine has a very high therapeutic index compared with other anesthetic medications. Ketamine is also a recreational drug of abuse (best known under the names vitamin K and special K).

Mechanisms of action

Ketamine is not a particularly selective drug, with multiple sites of action, including those in the central and peripheral nervous systems. The properties of ketamine are primarily mediated by noncompetitive antagonism at N-methyl-D-aspartate (NMDA) receptors, but the drug also has local anesthetic properties. The NMDA receptors consist of five subunits surrounding a central ion channel that is permeable to Ca²⁺, Na⁺, and K⁺ (Figure 74-2). Binding sites for Mg²⁺ and ketamine have been found inside this channel.

Figure 74-2 The properties of ketamine are primarily mediated by noncompetitive antagonism at NMDA receptors, which consist of five subunits surrounding a central ion channel that is permeable to Ca²⁺, Na⁺, and K⁺. GLY, Glycine; NMDA, N-methyl-D-aspartic acid; PCP, phencyclidine.

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