Anesthesia/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. 

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. 

Feldman HS, Dvoskin S, Halldin MH et al. (1997) Comparative anesthetic efficacy and pharmacokinetics of epidurally administered ropivacaine and bupivacaine in the sheep. Regional Anesthesia 22 451 160... 

Fentanyl (0.001 mg/kg i.v.) can be used with xylazine (0.44 mg/kg i.v.) for anesthetic premedication. Fentanyl is sometimes used as an anesthetic adjunct during inhalation anesthesia to improve analgesia. The pharmacokinetics of fentanyl make it ideal for administration by constant rate infusion and it can be administered intra-operatively at a rate of 0.001-0.004 mg/kg/h after a 0.001 mg/kg loading dose. To prevent excitement or locomotory stimulation in recovery, the infusion should be discontinued 30 min prior to recovery or the horse should be sedated with xylazine (0.1 mg/kg i.v.) prior to recovery. 

Anesthetics. The use of anesthetics or sedatives for restraint in sampling or cannulation procedures can, as in mammals, cause difficulties when used in conjunction with pharmacokinetic and metabolic studies. Anesthesia with MS-222, one of the most common fish anesthetics, has been shown under certain... 

In considering the pharmacokinetics of anesthetics, one important parameter is the speed of anesthetic induction. Anesthesia is produced when anesthetic partial pressure in brain is >MAC. Because the brain is well perfused, anesthetic partial pressure in brain becomes equal to the partial pressure in alveolar gas (and in blood) over the course of several minutes. Therefore, anesthesia is achieved shortly after alveolar partial pressure reaches MAC. WhUe the rate of rise of alveolar partial pressure will be slower for anesthetics that are highly soluble in blood and other tissues, this limitation on speed of induction can be overcome largely by delivering higher inspired partial pressures of the anesthetic. 

A. Classification and Pharmacokinetics The agents currently used in inhalation anesthesia are nitrous oxide (a gas) and several easily vaporized liquid halogenated hydrocarbons, including halothane, desflurane. enflurane, isoflurane, sevoflurane, and methoxyflurane. They are administered as gases their partial pressure, or tension, in the inhaled air or in blood or other tissue is a measure of them concentration. Since the standard pressure of the total inhaled mixture is atmospheric pressure (760 mm Hg at sea level), the partial pressure may also be expressed as a percentage. Thus 50% nitrous oxide in the inhaled air would have a partial pressure of 380 mm Hg. The speed of induetion of anesthetic effects depends on several factors ... 

---