Ketamine administration, brain

Honey RA, Honey GD, O Loughlin C, Sharar SR, Kumaran D, et al. 2004. Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task An FMRI study. Neuropsychopharmacology 29 ... 

Ketamine has been traditionally contraindicated in patients with increased ICP or reduced cerebral compliance because it increases CMR02, CBF and ICP. These deleterious effects can be antagonised by the concomitant administration of propofol, or thiopentone, and benzodiazepines. Furthermore, ketamine is an antagonist at the NMDA receptor. Nevertheless, ketamine can adversely affect neurological outcome in the presence of brain ischaemia. 

There is ample evidence that ketamine is an effective analgesic that acts at the level of both the spinal cord and the brain. In horses, epidural administration of ketamine provided perineal analgesia for up to 75 min (Gomez de Segura et al 1998). Epidural ketamine reduced the MAC of halothane for hind- but not forelimb procedures, indicating a localized effect in the spinal cord after epidural administration (Doherty et al 1997c). Constant rate i.v. infusions of ketamine caused a reduction in the MAC value for halothane in the horse when plasma ketamine concentrations exceeded 1 (ig/ml (Muir Sams 1992). 

Ketamine is a low-molecular-weight, highly lipid- and water-soluble molecule. As such, it can quickly cross the blood-brain barrier, producing a maximal effect in the CNS within 1 min of i.v. administration. Ketamine exists as a racemic mixture of the two optical isomers S(+)-ketamine and R(-)-ketamine. The majority of the hypnosis and analgesia produced by ketamine is contributed by the S(+)-isomer (Joo et al 2000, Muir Hubbell 1988, Redig et al 1984). A purified S(+)-ketamine pharmaceutical product is not yet available commercially for veterinary use and the possible advantages of such a product in the horse have not been established. Ketamine is 45-60% bound to equine plasma proteins (Kaka et al 1979) meaning that the maximal effect of ketamine is unlikely to be altered substantially by hypoproteinemic states. 

Ketamine has a short duration of effect after i.v. bolus administration. Ketamine induction after xylazme sedation generally provides 12-20 min duration of anesthesia (Muir et al 1977). The termination of the effects of ketamine in the CNS primarily results from redistribution of the drug from the brain to other tissues (Waterman et al... 

Bioavailability of ketamine is 90-93% after intramuscular injection, 16% after oral administration, and 77% after epidural injection. Protein binding of ketamine is 47%, and it is initially distributed to highly perfused tissues such as brain, heart, and the lungs. There the concentration can reach up to five times the plasma concentration. Redistribution is similar to thiopental. The distribution half-life after intravenous administration is 7 tol7 minutes, and the volume of distribution is 2 to 3 L/kg. 

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