General anesthetics pharmacokinetics

Several general anesthetics (isoflurane, ketamine, thiopental, etomidate) have one or more chiral carbons and thus exist as pairs ot stereoisomers. In many cases one stereoisomer is more potent than the other at providing anesthesia despite little difference in pharmacokinetics (Christensen Lee, 1973 Benthuysen et ak, 1989 Harris et ak, 1992 Dickinson et ak, 1994). The stereoisomers have equal hydrophobic properties and partition equally into the membrane. 

Krasowski M D, Nishikawa K, Nikolaeva N et al 2001 Methionine 286 in transmembrane domain 3 of the GABAa receptor beta subunit controls a binding cavity for propofol and other alkylphenol general anesthetics. Neuropharmacology 41 952-964 Kristinsson J, Thordarson T H, Johannesson T 1996 Pharmacokinetics of lignocaine in Icelandic horses after infiltration anaesthesia. Veterinary Record 138 111-112... 

Ensuring an adequate depth of anesthesia depends on achieving a therapeutic concentration of the anesthetic in the CNS. The rate at which an effective brain concentration is achieved (ie, time to induction of general anesthesia) depends on multiple pharmacokinetic factors that influence the brain uptake and tissue distribution of the anesthetic agent. The pharmacokinetic properties of the intravenous anesthetics (Table 25-1) and the physicochemical properties of the inhaled agents (Table 25-2) directly influence the pharmacodynamic effects of these drugs. These factors also influence the rate of recovery when the administration of anesthetic is discontinued. 

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