氯氨酮和依托咪酯

1、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 c

2、ortex 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 contrac

3、ture) 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-StructureActivity Relationships a structural analogue of

4、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 st

5、ereospecific receptors KETAMINE-Pharmacokinetics Absorption: administered intravenously or intramuscularly Peak plasma levels are usually achieved within 1015 min after intramuscular injection Distribution: more lipid soluble and less protein bound than thiopental equally ionized at physiological pH

6、 lead to rapid brain uptake and subsequent redistribution (the distribution half-life is 1015 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 en

7、zymes may lead to the tolerance in patients who receive multiple doses of ketamine EXCRETION By kidneyKETAMINE -Effects on Organ Systems Cardiovascular indirect cardiovascular effects: increase arterial blood pressure, heart rate, and cardiac output due to central stimulation of the sympathetic nerv

8、ous system and inhibition of the reuptake of norepinephrine increase in pulmonary artery pressure and myocardial work avoided in patients with coronary artery disease, uncontrolled hypertension, congestive heart failure, and arterial aneurysms are often beneficial to patients with acute hypovolemic

9、shock KETAMINE -Effects on Organ Systems direct cardiovascular effects myocardial depressant effects of large doses of ketamine due to inhibition of calcium transients are unmasked by sympathetic blockade (eg, spinal cord transection) or exhaustion of catecholamine stores (eg, severe end-stage shock

10、)KETAMINE -Effects on Organ Systems Respiratory Ventilatory drive is minimally affected by the customary induction doses of ketamine rapid intravenous bolus administration or pretreatment with opioids occasionally produces apnea a potent bronchodilator, making it a good induction agent for asthmatic

11、 patients Although upper airway reflexes remain largely intact, patients at increased risk for aspiration pneumonia should be intubated The increased salivation associated with ketamine can be attenuated by premedication with an anticholinergic agent KETAMINE -Effects on Organ Systems Cerebral incre

12、ase cerebral oxygen consumption, cerebral blood flow, and intracranial pressure preclude in patients with space-occupying intracranial lesions psychotomimetic side effects (eg, illusions, disturbing dreams, and delirium) during emergence and recovery are less common in children and in patients preme

13、dicated with benzodiazepines KETAMINE Of the nonvolatile agents, ketamine may be the closest to being a complete anesthetic as it induces analgesia, amnesia, and unconsciousness KETAMINE-Drug Interactions Nondepolarizing neuromuscular blocking agents are potentiated by ketamine The combination of th

14、eophylline and ketamine may predispose patients to seizures Diazepam attenuates ketamines cardiostimulatory effects and prolongs its elimination half-life KETAMINE-Drug Interactions Propranolol, phenoxybenzamine, and other sympathetic antagonists unmask the direct myocardial depressant effects of ke

15、tamine Ketamine produces myocardial depression when given to patients anesthetized with halothane or, to a lesser extent, other volatile anesthetics Lithium may prolong the duration of action of ketamineETOMIDATEETOMIDATE-Mechanisms of Action depress the reticular activating system and mimics the in

16、hibitory effects of GABA etomidate (particularly the R+ isomer) appears to bind to a subunit of the GABA type A receptor, increasing its affinity for GABA Unlike barbiturates, it may have disinhibitory effects on the parts of the nervous system that control extrapyramidal motor activity This disinhi

17、bition is responsible for a 3060% incidence of myoclonus ETOMIDATE-StructureActivity Relationships contain a carboxylated imidazole, is structurally unrelated to other anesthetic agents The imidazole ring provides water solubility in acidic solutions and lipid solubility at physiological pH dissolve

18、d in propylene glycol-This solution often causes pain on injection that can be lessened by a prior injection of lidocaine ETOMIDATE-Pharmacokinetics Absorption available only for intravenous administration and is used primarily for induction of general anesthesia Distribution Although it is highly p

19、rotein bound, etomidate is characterized by a very rapid onset of action due to its high lipid solubility and large nonionized fraction at physiological pH Redistribution is responsible for decreasing the plasma concentration to awakening levels ETOMIDATE-Pharmacokinetics Biotransformation Hepatic m

20、icrosomal enzymes and plasma esterases rapidly hydrolyze etomidate to an inactive metabolite The rate of biotransformation is five times greater for etomidate than for thiopental Excretion By kidneyETOMIDATE-Effects on Organ Systems Cardiovascular Etomidate has minimal effects on the cardiovascular

21、system A mild reduction in peripheral vascular resistance is responsible for a slight decline in arterial blood pressure Myocardial contractility and cardiac output are usually unchanged Etomidate does not release histamine ETOMIDATE-Effects on Organ Systems Respiratory Ventilation is affected less

22、with etomidate than with barbiturates or benzodiazepines Even induction doses usually do not result in apnea unless opioids have also been administered ETOMIDATE-Effects on Organ Systems Cerebral decrease the cerebral metabolic rate, cerebral blood flow, and intracranial pressure to the same extent as thiopental