Pharmacodynamic and pharmacokinetic aspects of local anesthetics

The clinically useful local anesthetic agents can be divided chemically into the amino-esters, e.g., procaine, chloroprocaine and tetracaine, and the amino-amides, e.g., lidocaine, mepivacaine, prilocaine, bupivacaine and etidocaine. Pharmacologically, these agents can be categorized as agents of low potency and short duration of action, e.g., procaine and chloroprocaine; agents of intermediate potency and duration of action, e.g., lidocaine, mepivacaine and prilocaine; and agents of high potency and long duration, e.g., tetracaine, bupivacaine and etidocaine. The blood level of local anesthetics is determined by the rate of uptake, tissue redistribution, metabolism and excretion. The rate of vascular absorption is a function of the site of injection, dosage, inclusion of a vasoconstrictor in the local anesthetic solution and the specific drug employed. The amino esters are eliminated by means of enzymatic hydrolysis in blood while the amino amides are metabolized primarily in the liver. Among the ester agents chloroprocaine is cleared most rapidly due to its fast rate of hydrolysis. Within the amide series, prilocaine is cleared most rapidly due to its fast rate of tissue redistribution and its rapid hepatic metabolism. Bupivacaine is cleared most slowly due primarily to its decreased rate of hepatic degradation.