Anesthesia and analgesia
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Anesthesia and analgesia · Mar 2006
Comparative StudyDeterminants of volatile general anesthetic potency: a preliminary three-dimensional pharmacophore for halogenated anesthetics.
We investigated the molecular basis for the immobilizing activity of halogenated volatile anesthetics using comparative molecular field analysis. In vivo potency data (expressed as minimum alveolar concentrations) for 69 structurally diverse anesthetics were obtained from the literature. The drugs were randomly divided into a training set (n = 52) used to derive the activity model and a test set (n = 17) used to independently assess the model's predictive power. ⋯ The final model explained 94.2% of the variance in the observed activities of the training set compounds. The model showed good predictive capability for both the training set (cross-validated r2 = 0.705) and randomly excluded test set anesthetics (r2 = 0.837). Three-dimensional pharmacophoric maps were derived to identify the spatial distribution of key areas where steric and electrostatic interactions are important in determining immobilizing activity of the halogenated drugs and were compared with our previously published maps obtained for nonhalogenated volatile anesthetics.
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Anesthesia and analgesia · Mar 2006
Comparative StudyIntravenous anesthetics are more effective than volatile anesthetics on inhibitory pathways in rat hippocampal CA1.
In this study, we have examined the effects of both volatile and IV general anesthetics on excitatory synaptic transmission, with and without recurrent inhibition, to clarify whether excitatory or inhibitory synapses are the major targets of action. Field population spike amplitudes (fPSs) of CA1 pyramidal neurons were recorded in rat hippocampal slices. Schaffer-collateral-commissural fibers (Sch) were stimulated orthodromically, and the evoked fPSs (PS[Sch]) in CA1 area were measured. ⋯ The effects of the IV anesthetics with recurrent inhibition were antagonized in the presence of the gamma-aminobutyric acid-A-receptor antagonist bicuculline methiodide. In addition, all anesthetics prolonged recurrent inhibition from 100 ms (sevoflurane and isoflurane) to 400 ms (propofol). The results suggest that sevoflurane and isoflurane inhibit mainly on glutamate-mediated orthodromic pathways, whereas thiopental and propofol enhance gamma-aminobutyric acid-A-mediated recurrent inhibitory pathways in CA1 neurons, thus providing further evidence that the mechanisms of general anesthetics are drug- and pathway-specific.
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Anesthesia and analgesia · Mar 2006
Comparative StudyPharmacokinetics and pharmacodynamics of a 0.1 mg/kg dose of cisatracurium besylate in children during N2O/O2/propofol anesthesia.
We studied the pharmacokinetics and pharmacodynamics of cisatracurium in 9 children (mean weight, 17.1 kg) aged 1-6 yr (mean, 3.75 yr) during propofol-nitrous oxide anesthesia. Neuromuscular monitoring was performed. Venous samples were taken before injection of a 0.1 mg/kg dose of cisatracurium and then at 2, 5, 10, 30, 60, 90, and 120 min. ⋯ Steady-state volume of distribution (0.207 +/- 0.031 L/kg) and total body clearance (6.8 +/- 0.7 mL/min/kg) were significantly larger than those published for adults. Pharmacodynamic results were comparable to those obtained in pediatric studies during halothane or opioid anesthesia with the exception of a longer recovery to 25% baseline. Although the plasma-effect compartment equilibration rate constant was twofold faster (0.115 +/- 0.025 min(-1)) than that published for cisatracurium in adults, the effect compartment concentration corresponding to 50% block was similar (129 +/- 27 ng/mL).