BASIC PHARMACOLOGY OF LOCAL ANESTHETICS

Molecular structure:  Most local anesthetic agents consist of a lipophilic group (eg, an aromatic ring) connected by an intermediate chain via an ester or amide to an ionizable group (eg, a tertiary amine). In addition to the general physical properties of the molecules, specific stereochemical configurations are associated with differences in the potency of stereoisomers (eg, levobupivacaine, ropivacaine). Because ester links are more prone to hydrolysis than amide links, esters usually have a shorter duration of action. L ocal anesthetics are weak bases and are usually made available clinically as salts to increase solubility and stability. In the body, they exist either as the uncharged base or as a cation. The relative proportions of these two forms are governed by their pKa and the pH of the body fluids according to the Henderson-Hasselbalch equation, which can be expressed as:  pKa = pH – log [base]/[conjugate acid]  If the concentration of base and conjugate acid are equal, the second portion of the right side of the equation drops out, as log 1 = 0, leaving:  pKa = pH (where base = conjugate acid)