Local anesthesia results when sensory transmission from a local area of the body to the CNS is blocked. The local anesthetics constitute a group of chemically similar agents (esters and amides) that block the sodium channels of excitable membranes. Because these drugs can be administered by injection in the target area, or by topical application in some cases, the anesthetic effect can be restricted to a localized area (eg, the cornea or an arm). When given intravenously, local anesthetics have effects on other tissues, for example, heart.
Most local anesthetic drugs are esters or amides of simple benzene derivatives. Subgroups within the local anesthetics are based on this chemical characteristic and on duration of action. The commonly used local anesthetics are weak bases with at least one ionizable amine function that can become charged through the gain of a proton (H+). As discussed in Chapter 1, the degree of ionization is a function of the pKa of the drug and the pH of the medium. Because the pKa of most local anesthetics is between 8.0 and 9.0 (benzocaine is an exception), variations in pH associated with infection (infected tissues can be as low as 6.4) can have significant effects on the proportion of ionized to nonionized drug. The question of the active form of the drug (ionized versus nonionized) is discussed later.
Many shorter-acting local anesthetics are readily absorbed into the blood from the injection site after administration. The duration of local action is therefore limited unless blood flow to the area is reduced. This can be accomplished by administration of a vasoconstrictor (usually an α-agonist sympathomimetic) with the local anesthetic agent. Cocaine is an important exception because it has intrinsic sympathomimetic action due to its inhibition of norepinephrine reuptake into nerve terminals. The longer-acting agents (eg, bupivacaine, ropivacaine, tetracaine) are also less dependent on the coadministration of vasoconstrictors. Surface activity (ability to reach superficial nerves when applied to the surface of mucous membranes) is a property of certain local anesthetics, especially cocaine and benzocaine (both only available as topical forms), lidocaine, and tetracaine.
Metabolism of ester local anesthetics is carried out by plasma cholinesterases (pseudocholinesterases) and is very rapid for procaine (half-life, 1–2 min), slower for cocaine, and very slow for tetracaine. The amides are metabolized in the liver, in part by cytochrome P450 isozymes. The half-lives of lidocaine and prilocaine are approximately 1.5 h. Bupivacaine and ropivacaine are the longest-acting amide local anesthetics with half-lives of 3.5 and 4.2 h, respectively. Liver dysfunction may increase the elimination half-life of amide local anesthetics (and increase the risk of toxicity).
Acidification of the urine promotes ionization of local anesthetics; the charged forms of such drugs are more rapidly excreted than nonionized forms.