Local Anesthetics and Antidysrhythmics

Local anesthetics have actions on the presynaptic, postsynaptic, and muscle membranes. In large intravenous doses, most local anesthetics block neuromuscular transmission; in smaller doses, they enhance the neuromuscular block from both nondepolarizing and depolarizing neuromuscular blockers.^{[518] [519]} The ability of neostigmine to antagonize a combined local anesthetic-neuromuscular blockade has not been studied. Procaine also inhibits butyrylcholinesterase and may augment the effects of succinylcholine and mivacurium by decreasing their hydrolysis by the enzyme.

In small intravenous doses, local anesthetics depress post-tetanic potentiation, and this depression is thought to be a neural, prejunctional effect. ^[520] At higher doses, local anesthetics block acetylcholine-induced muscular contractions, which suggests that local anesthetics have a stabilizing effect on the postjunctional membrane.^[521] Procaine has been shown to displace calcium from the sarcolemma and thus inhibit caffeine-induced contracture of skeletal muscle.^[522] Most of these mechanisms of action probably apply to all the local anesthetics.

Several drugs used for the treatment of dysrhythmias augment the block from neuromuscular blockers, particularly that of dTc.^[523] Quinidine potentiates the neuromuscular block from both nondepolarizing and depolarizing neuromuscular blockers.^[524] Edrophonium is ineffective in antagonizing a nondepolarizing blockade after quinidine. In clinical doses, quinidine appears to act at the prejunctional membrane as judged by its lack of effect on acetylcholine-evoked twitch.

In a rat phrenic-hemidiaphragm preparation, Salvador and coworkers ^[525] showed substantial potentiation of succinylcholine by diltiazem or verapamil and potentiation of pancuronium by nicardipine. These interactions were not found in humans.^{[526] [527]} Clinical reports have suggested potentiation of neuromuscular blockade with verapamil ^[528] and impaired reversal of vecuronium in a patient receiving disopyramide.^[529] The clinical significance of these interactions is probably minor.