20 - Local Anesthetics

Abstract

Local anesthetics are a group of structurally related compounds which share as principal mechanism of action the blockade of voltage-gated sodium channels, resulting in reversible interruption of nerve signal transduction. Currently used local anesthetics are divided into amino amides, or amino esters. Each substance has distinct physicochemical properties, and local anesthetics can be administered continuously or together with adjuvants, allowing clinicians to tailor their anesthetic to procedure and patient. Next to sodium channel blockade, local anesthetics interact with other targets, for example calcium and potassium channels, and G-protein coupled receptors. The latter mode of action explains the anti-inflammatory properties of local anesthetics. Clinical application of existing local anesthetics, and development of novel local anesthetics, is hampered by systemic and local toxicity. Among the additives to local anesthetics, epinephrine is helpful in prolonging duration of action of medium-acting local anesthetics, and to reduce systemic absorption of any local anesthetic. Buprenorphine is an effective additive and has local anesthetic properties but causes excessive nausea and vomiting. Dexmedetomidine and clonidine are popular additives as well but can cause dose-dependent systemic side effects such as sedation, bradycardia and hypotension. Dexamethasone has the least systemic side effects, and the longest prolongation of nerve block duration. Emerging developments in the field of local anesthetics include the development of subtype-specific sodium channel blockers, cell type-specific or heat-assisted delivery, and various modes of encapsulation.