氯氨酮和依托咪酯详解.pptVIP

氯氨酮和依托咪酯 钟静 KETAMINE－ Mechanisms of Action multiple effects on the central nervous system blocking polysynaptic reflexes in the spinal cord inhibiting excitatory neurotransmitter effects in selected areas of the brain KETAMINE-Mechanisms of Action functionally dissociates the thalamus from the limbic cortex the thalamus: which relays sensory impulses from the reticular activating system to the cerebral cortex the limbic cortex: which is involved with the awareness of sensation this state of dissociative anesthesia causes the patient to appear conscious (eg, eye opening, swallowing, muscle contracture) but unable to process or respond to sensory input KETAMINE-Mechanisms of Action an N-methyl-D-aspartate receptor antagonist The existence of specific ketamine receptors and interactions with opioid receptors has been postulated KETAMINE-Structure–Activity Relationships a structural analogue of phencyclidine It is one-tenth as potent, yet retains many of phencyclidines psychotomimetic effects Even subtherapeutic doses of ketamine can cause hallucinogenic effects The increased anesthetic potency and decreased psychotomimetic side effects of one isomer (S[+] versus R[–]) imply the existence of stereospecific receptors KETAMINE-Pharmacokinetics Absorption: administered intravenously or intramuscularly Peak plasma levels are usually achieved within 10–15 min after intramuscular injection Distribution: more lipid soluble and less protein bound than thiopental equally ionized at physiological pH lead to rapid brain uptake and subsequent redistribution (the distribution half-life is 10–15 min) awakening is due to redistribution to peripheral compartments KETAMINE-Pharmacokinetics Biotransformation in the liver some of which (eg, norketamine) retain anesthetic activity Induction of hepatic enzymes may lead to the tolerance in patients who receive multiple doses of ketamine EXCRETION By kidney KETAMINE -Effects on Organ Systems Cardiovascular indirect ca