Anesthesia and analgesia
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Anesthesia and analgesia · Aug 1997
Structure-affinity relationships and stereospecificity of several homologous series of local anesthetics for the beta2-adrenergic receptor.
Local anesthetics inhibit binding of ligands to beta2-adrenergic receptors (beta2ARs), and, as a consequence, inhibit intracellular cAMP production. We hypothesized that among homologous local anesthetics, their avidity at inhibiting binding of tritiated dihydroalprenolol (3H-DHA) to beta2ARs would increase with increasing length of alkyl substituents and would demonstrate stereospecificity. Specific binding of 3H-DHA to human beta2ARs was assayed in the presence of six different members of the 1-alkyl-2,6-pipecoloxylidide class of local anesthetics (including mepivacaine, ropivacaine, and bupivacaine), the R(+) and S(-) bupivacaine enantiomers, lidocaine, prilocaine, etidocaine, procaine, and tetracaine. Avidity of binding to beta2ARs increased with increasing length of the alkyl chain (pKi values = 2.4, 3.6, 4.3, 4.1, 4.1, 5.9 for the methyl [mepivacaine], ethyl, S(-)propyl [ropivacaine], butyl [bupivacaine], pentyl, and octyl derivatives, respectively). We found no evidence for bupivacaine stereospecificity (pKi values = 4.3 and 4.9 for the S(-) and R(+) isomers, respectively). Other amide and ester local anesthetics also showed increasing potency with increasing length of alkyl substituents (pKi values = 3.6, 3.8, and 4.3 for lidocaine, prilocaine, and etidocaine; 4.2 and 5.6 for procaine and tetracaine, respectively). The correlation between increased inhibition of beta2AR binding and alkyl chain length resembles the correlation between local anesthetic potency at nerve block and increased alkyl chain length. The lack of clear stereospecificity is consistent with the relatively low potency these agents demonstrate at inhibition of beta2AR binding. Finally, the relatively potent inhibition of beta2ARs by etidocaine, tetracaine, and bupivacaine suggests that their propensity for cardiovascular depression after accidental intravenous overdose could result from beta2AR or beta1AR blockade and inhibition of cAMP production. ⋯ Local anesthetics demonstrate a rank order of avidity for displacing ligands from beta2-adrenergic receptors such that larger molecules displace ligands at lower concentrations than smaller local anesthetic molecules. This relationship between molecular size and receptor avidity could explain the greater propensity for cardiovascular toxicity of relatively large local anesthetics such as bupivacaine.
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Anesthesia and analgesia · Aug 1997
Safe epidural analgesia in thirty parturients with platelet counts between 69,000 and 98,000 mm(-3).
Regional anesthesia is a popular form of pain relief for the management of labor and delivery. Thrombocytopenia is considered a relative contraindication to the administration of regional anesthesia. Some authorities have recommended that an epidural anesthetic be withheld if the platelet count is <100,000 mm(-3). ⋯ Of these 80, 30 had an epidural anesthetic placed when the platelet count was <100,000 mm(-3) (range 69,000-98,000 mm(-3)), 22 had an epidural anesthetic placed with a platelet count >100,000 mm(-3) that subsequently decreased below 100,000 mm(-3), and 28 did not receive a regional anesthetic. We found no documentation of any neurologic complications in the medical records. We conclude that regional anesthesia should not necessarily be withheld when the platelet count is <100,000 mm(-3).
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Anesthesia and analgesia · Aug 1997
The effects of sevoflurane on population spikes in CA1 and dentate gyrus of the rat hippocampus in vitro.
We studied the effects of sevoflurane on population spikes (PSs) in two synaptic pathways in rat hippocampal slices. Stimulating electrodes were placed on Schaffer collateral fibers or perforant path to activate inputs to CA1 pyramidal neurons or dentate gyrus (DG) neurons, respectively. Extracellular glass microelectrodes were used to record PSs. The paired-pulse stimulus was used to induce the paired-pulse facilitation (PPF). Sevoflurane (0.4-5.0 vol%) significantly decreased the amplitudes of PSs of CA1 and DG in a dose-dependent and reversible manner (25% effective dose values were 4.1 and 0.9 vol%, respectively). The stimulus-response relationships for PS amplitudes revealed that sevoflurane increased the threshold for PS generation in CA1 and DG. Sevoflurane (2.0 vol%) significantly enhanced PPF from 127% and 263% to 153% and 494% in CA1 and DG, respectively. The results imply that the effects of sevoflurane on PSs are greater in DG than in CA1 neurons, that sevoflurane enhances the PPF in both CA1 and DG, and that the actions of sevoflurane are not similar to those of other volatile or intravenous anesthetics previously reported in hippocampal preparations. ⋯ The volatile anesthetic sevoflurane alters neural excitability of individual pathways in the hippocampus in a manner different from other general anesthetics. The results are consistent with a site-specific mechanism of action for general anesthesia.