Chemistry

Chemistry. Local anesthetics are weak bases whose structure consists of an aromatic moiety connected to a substituted amine through an ester or amide linkage. The pK_a values of local anesthetics are near physiologic pH; thus, in vivo, both charged (protonated) and uncharged (unprotonated) forms are present. The degree of ionization is important because the uncharged form is more lipophilic and is able to gain access to the axon. The clinical differences between the ester and amide local anesthetics involve their potential for producing adverse effects and the mechanisms by which they are metabolized.

1. Esters. Procaine, cocaine, chloroprocaine, and tetracaine. The ester linkage is cleaved by plasma cholinesterase. The half-life of esters in the circulation is very short (about 1 minute). The degradation product of ester metabolism is p-aminobenzoic acid.
2. Amides. Lidocaine, mepivacaine, bupivacaine, etidocaine, and ropivacaine. The amide linkage is cleaved through initial N-dealkylation followed by hydrolysis, which occurs primarily in the liver. Patients with severe hepatic disease may be more susceptible to adverse reactions from amide local anesthetics. The elimination half-life for most amide local anesthetics is 2 to 3 hours.