Lidocaine

Lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide; CAS 137-58-6; molecular formula C14H22N2O; molecular weight 234.34) is the prototype amide-class local anesthetic, synthesized by Nils Lofgren and Bengt Lundqvist at AB Astra in 1943 and introduced clinically in 1948 (Xylocaine). The compound replaced procaine and the ester-class anesthetics as the first-line choice owing to faster onset, longer duration, and substantially lower allergic potential (the amide linkage is metabolized hepatically rather than producing the para-aminobenzoic acid metabolite of ester anesthetics, the dominant allergen in that class). Mechanism is voltage-gated sodium channel blockade, predominantly at the inactivated state, with state-dependent kinetics that produce greater block in rapidly firing tissues (the basis for both local anesthetic action on small unmyelinated C fibers and antiarrhythmic action on ventricular tissue). The pKa is 7.9; at physiologic pH approximately 25 percent of the molecule is uncharged and able to cross neural and cardiac membranes, with reprotonation in the cytoplasm to engage the sodium channel pore from the intracellular side. Onset is fast (1 to 5 minutes for infiltration); duration is 1 to 2 hours unless coadministered with epinephrine, which extends duration through vasoconstriction and reduced systemic absorption. Systemic toxicity (LAST, local anesthetic systemic toxicity) presents at elevated plasma concentrations with progression from perioral numbness, tinnitus, and metallic taste through generalized seizures to cardiovascular collapse; intravenous lipid emulsion (Intralipid 20 percent) is the rescue therapy. Antiarrhythmic indications are ventricular arrhythmias particularly in the postinfarction period; lidocaine is largely displaced by amiodarone in advanced cardiac life support but retains a role in specific contexts.