Articles: anesthetics.
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Anaesthesiol Reanim · Jan 1991
ReviewPain control with intrathecally and peridurally administered opioids and other drugs.
Sharp pain is conducted rapidly by myelinated delta A fibers and diffused pain slowly by nonmyelinated C fibers to pseudobipolar neurons in the posterior ganglion and from there to neurons located in the posterolateral horn of the spinal cord. From here on nociferous impulses are transmitted by excitatory peptides (e.g. substance P) or amino acids (e.g. glutamate, aspartate) through interconnecting neurons of the pain pathways, primarily on the contralateral side, to the brain stem and from there to the sensory cortex, where they are appreciated and acted upon. There are specific inhibitory receptors located on axon terminals, near to the release sites of the excitatory amino acids and peptides. ⋯ Several different approaches are being investigated for the production of selective spinal analgesia without side effects. They include: a. the use of more lipophilic, long-lasting opioids (e.g. lofentanil) which would be almost completely absorbed by the spinal cord and therefore would not reach the medullary centers; b. the development of opioids with specific affinity to kappa- and for delta- and little or no affinity to mu-receptors, primarily responsible for side effects; and c. combining lower doses of opioid agonists with alpha 2-adrenergic agonists (e.g. clonidine) or with somatostatin. It is conceivable that in the not-too-distant future, it will be possible to achieve through these measures, selective spinal analgesia without side effects.
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Ann. N. Y. Acad. Sci. · Jan 1991
ReviewSaturable binding of anesthetics to nicotinic acetylcholine receptors. A possible mechanism of anesthetic action.
Recent controversies in the existence of saturable binding of general anesthetics in brain tissues prompted a careful examination of specific binding of anesthetics to neural receptors. We examined the binding of both local and general anesthetics using electron spin resonance and radioligand criteria. ⋯ Association of anesthetic at this crevice is in turn dependent on the anesthetic concentration in the lipid phase of the membrane. The hypothesis provides a mechanism for the saturable interaction of anesthetics with their protein target site in the membrane without violating the correlations expressed by the Meyer-Overton rule of anesthetic action.
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Despite its severity, the disposition of women towards pain during childbirth is influenced by many complex personal and cultural factors. Such influences may inspire a degree of stoicism towards labour pain which would be extraordinary in other painful circumstances. Nevertheless, the majority of women who deliver in a modern obstetric unit request some form of pharmacological pain relief. ⋯ Recent advances have demonstrated that many of the adverse effects traditionally associated with epidural analgesia can be substantially reduced by administering local anaesthetics in smaller doses. It is becoming apparent that additional patient benefits are possible when epidural opioids are also used in combination with local anaesthetics. Techniques which allow the mother to exercise personal control over her epidural analgesia requirements are received more favourably and may help reduce the need for obstetric intervention.
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Ann. N. Y. Acad. Sci. · Jan 1991
ReviewRole of signal transduction in anesthetic action. Alpha 2 adrenergic agonists.
The molecular mechanism for general anesthetic action is not known. The alpha 2 adrenergic agonists represent a novel class of "anesthetic-like" agent because of their selectivity for receptor binding sites and because the transmembrane signaling systems mediating their biologic responses in non-CNS systems are known. We have begun to characterize the signal transduction pathway involved in the anesthetic-like action of the alpha 2 adrenergic agonists. ⋯ Subsequently, data using molecular biologic techniques suggested that the alpha 2 C4 isoreceptor was the probable receptor that mediated the anesthetic response. We further explored the postreceptor effector mechanism for the signal transduction pathway for alpha 2 anesthetic action and identified the participation of two other molecular components, namely, a pertussis-toxin-sensitive G protein and a 4-aminopyridine-sensitive ion channel. Whether the signal transduction pathway for alpha 2 anesthetic action mediates the further response to other non-alpha 2 anesthetic agents needs to be defined.