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[Update on the pharmacology and effects of local anesthetics].

Local anesthetics (LA) are broadly used in all disciplines and it could be considered that relatively little is reflected on the mechanisms of action of this old substance group. However, several molecular mechanisms of LAs mediating wanted and unwanted effects remain to be explored. Furthermore, the number of indications for application of LAs seems to be expanding. The local anesthetic effect of LAs is primarily mediated by a potent inhibition of voltage-gated sodium channels. However, this effect is due to much more than the interaction of LAs with one single molecule. Most recent studies indicated that the development of selective local anesthetics might be possible and LAs also interact with several other membrane molecules. Although the relevance of these effects is still unclear, they might play a role in systemic analgesia, tissue protection and anti-inflammatory effects of LA. The therapeutic index of systemically applied LA is very narrow. Systemic application is formally not permitted because the impending systemic toxicity is still a life-threatening complication. Although the cardiac and central nervous toxicity at least partly result from an unselective block of neuronal and cardiac sodium channels, preclinical studies suggest the involvement of several mechanisms. A local LA toxicity is less clinically impressive; however, all LAs induce a significant tissue toxicity for which the underlying mechanisms have been partly identified. This review reports on recent findings on mechanisms and on the clinical relevance of some LA-induced effects which are of relevance for anesthesiological activities.

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