What are the clinical differences between the ester and amide local anesthetics?
The important differences between ester and amide local anesthetics relate to the mechanisms by which they are metabolized and their potential to produce allergic reactions.
Ester local anesthetics undergo rapid hydrolysis by plasma pseudocholinesterases and to a lesser extent in the liver with resulting pharmacologically inactive metabolites. However, para-aminobenzoic acid is one of the metabolites that has been associated with allergic reactions in a small percentage of patients. Cerebrospinal fluid lacks the pseudocholinesterase enzyme, so ester local anesthetics administered intrathecally will persist until they have been absorbed by the bloodstream. Patients with atypical plasma pseudocholinesterase are at increased risk for toxic side-effects because of impaired metabolism. Plasma pseudocholinesterase activity may also be decreased in patients with liver disease or those taking certain chemother-apeutic drugs. Cocaine is the only ester local anesthetic not metabolized in the plasma; rather it undergoes significant liver metabolism.
Amide local anesthetics undergo enzymatic degradation in the liver, which in general is much slower than ester hydrolysis. Patients with decreased liver function (e.g., liver cirrhosis) or decreased liver blood flow (e.g., congestive heart failure) are predisposed to systemic toxicity from impaired metabolism. The amide local anesthetics are not metabolized to para-aminobenzoic acid, and allergic reactions are extremely rare. However, solutions of these drugs may contain preservatives (paraben family, whose structure is similar to para-aminobenzoic acid) or additives (sodium bisulfite) that are the frequent culprits of adverse reactions.