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Clinical use of local anesthetics in anesthesia

John F Butterworth, IV, MD
Laura Lahaye, MD
Section Editor
Robert Maniker, MD
Deputy Editor
Marianna Crowley, MD


Local anesthetics (LAs) are used to block transmission of impulses in nerve fibers, to reduce or eliminate sensation. LAs may be used for neuraxial analgesia and anesthesia, peripheral nerve blocks, subcutaneous and tissue infiltration, and topical anesthesia. This topic will discuss the mechanism of action of LAs, the properties that distinguish LAs and determine their effects, and the ways in which LAs are used in anesthesia.

The doses and effects of LAs used for specific regional anesthesia techniques are discussed separately. (See "Spinal anesthesia: Technique", section on 'Local anesthetics' and "Epidural and combined spinal-epidural anesthesia: Techniques", section on 'Local anesthetics' and "Overview of peripheral nerve blocks", section on 'Local anesthetics'.)

Mechanism of action of local anesthetics — Local anesthetics reversibly inhibit nerve transmission by binding voltage-gated sodium channels (Nav) in the nerve plasma membrane. Nav channels are integral membrane proteins, anchored in the plasma membrane. When local anesthetics bind the sodium channel, they render it impermeable to Na, which prevents action potential initiation and propagation [1]. (See "Subcutaneous infiltration of local anesthetics", section on 'Anatomy and physiology'.)

Basic structure/classes — As noted above, the commonly used local anesthetics have similar structural characteristics and (with the sole exception of articaine) consist of a lipophilic aromatic ring and a hydrophilic tertiary amine. These two moieties are linked by either a carboxylic ester (-CO-) or amide (-NHC-) bond. This linkage determines whether a LA is designated an amino ester or amino amide. Commonly used ester LAs include chloroprocaine, procaine, and tetracaine. The commonly used amide LAs include lidocaine, bupivacaine, ropivacaine, mepivacaine, and outside the United States, levobupivacaine. Articaine is an amide LA used primarily in dentistry.

Local anesthetics are weak bases that exist in solution in both charged and uncharged forms. All clinically-used local anesthetics share certain structural features. The aromatic (benzene) ring leads to greater lipid solubility. Lipid solubility declines (and aqueous solubility increases) when the amine nitrogen (at the end of the molecule opposite to the aromatic ring) is protonated (quaternary). When this amine nitrogen is in a tertiary form, it is uncharged and more lipid soluble. The uncharged, more liphophilic form more readily permeates nerve membranes, whereas the charged, more water soluble form binds with greater affinity for the sodium channel. Local anesthetics (save for benzocaine) are supplied by the manufacturer in quaternary form as hydrochloride salts. The proportion of charged and uncharged forms (and, as a consequence, the speed with which they permeate the plasma membrane and produce their clinical effects) is determined by the pKa of the drug, and in vivo, by tissue pH.

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Literature review current through: Oct 2017. | This topic last updated: Jul 25, 2017.
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