Current topics in medicinal chemistry
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Neural damage is a possible consequence of general anesthesia, central nervous system blockade, and regional anesthesia. Dainage may be caused by ischaemic and mechanical or chemical factors, which may occur either alone or in combination. ⋯ Neurological complications may also result from a direct neurotoxic effect of local anesthetic agents which is concentration and dose-dependent. A better understanding of these mechanisms will provide a reliable basis for the development of improved pharmaceutical therapy.
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Increasing insight into the mechanisms of perioperative physiologic responses and the resultant effects on patient outcome suggests that some responses may be detrimental to long-term recovery. Thus, initial belief in the adaptive "wisdom" of the body has been supplanted by the concept that a "stress-free" perioperative period may minimize detrimental physiologic responses and resultant morbidity. ⋯ Increasing evidence has emerged suggesting that such afferent nociceptive blockade may improve a variety of postoperative morbidity parameters and improve surgical outcome. We review the clinical evidence from studies examining the effects of regional anesthesia and analgesia on postoperative morbidity in specific physiologic systems.
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Central and regional block procedures have a well-defined role as safe and effective methods in modern anesthesia and analgesia with long-acting local anesthetics. Recent studies have shown that the incidence of intoxication by these drugs is a rare but catastrophic event. As classic neuronal sodium channel inhibitors, local anesthetics block peripheral fast voltage-gated sodium channels on neuronal axons, and these drugs have a particularly high level of activity in the CNS and the cardiovascular system. ⋯ Intracellular ATP-level may be involved in contractility and resuscitation of cardiomyocytes, as be proven by in-vitro and in-vivo data. Therefore the use of pure optical S-(-)-isomers of local anesthetics may help to reduce these rare but catastrophic events. Presently, ropivacaine appears to be the safest long-acting local anesthetic.
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Ropivacaine, the S-(-)-enantiomer of N-(2,6-dimethylphenyl)-1-propyl-2-piperidinecarboxamide is a new long-acting local anesthetic. This review demonstrates that it is effective in brachial plexus anesthesia. It is at least as efficient as bupivacaine in terms of quality, duration of analgesia, anesthesia, and motor block. ⋯ Further investigations are required to assess its efficacy during such block. Because of lower CNS and cardiac toxicity, ropivacaine is safer than bupivacaine. It would be thus the preferred local anesthetic for brachial plexus blockade when long-lasting anesthesia and analgesia is required.