Esters undergo rapid hydrolysis in blood, catalyzed by
pseudocholinesterase.3,4,7 Procaine and benzocaine are
metabolized to para-aminobenzoic acid (PABA), the species underlying anaphylaxis
to these agents.4 The amides undergo metabolism in the
liver. Lidocaine undergoes oxidative N-dealkylation (by the cytochromes CYP
1A2 and CYP 3A4 to monoethyl glycine xylidide and glycine
xylidide).3,4,7 Bupivacaine, ropivacaine, mepivacaine, and
etidocaine also undergo N-dealkylation and
hydroxylation.3,4,7 Prilocaine is hydroxylized to
o-toluidine, which causes methemoglobinemia.4,24 Prilocaine
doses >8 mg/kg may be expected to produce sufficient
methemoglobin concentrations to cause clinical cyanosis. Amide LA
clearance is highly dependent on hepatic blood flow, hepatic extraction, and
enzyme function, and is reduced by factors that decrease hepatic blood flow,
such as β-adrenergic receptor or H2-receptor
blockers, and by heart or liver failure.3,4,7