How do drugs other than antibiotics affect neuro-muscular blockade?
Local anesthetics and class IA anti–arrhythmic drugs block sodium channels and may decrease neuromuscular transmission throughout the neuromuscular chain of events, affecting axonal conduction and acetylcholine release. In larger concentrations, they may decrease end-plate and muscle membrane ion conductance. Both suc-cinylcholine and nondepolarizing muscle relaxants are affected. Calcium-channel blockers interfere with calcium conductance in the neuromuscular system and may poten-tiate depolarizing and nondepolarizing neuromuscular blockade. The effects of lithium are controversial, but it may potentiate both depolarizing and nondepolarizing neuromuscular blockade. High serum levels of magne-sium, such as occur in pre-eclamptic and eclamptic patients, profoundly potentiate both depolarizing and nondepolar-izing neuromuscular blockade by blocking calcium con-ductance in the nerve terminal and by stabilizing the postjunctional muscle fiber membrane. Calcium readily reverses the former effect, whereas it is less predictable for the latter effect. However, attempts to reverse the effects of magnesium and magnesium-like effects with calcium should be made. Dantrolene causes weakness by blocking excitation–contraction coupling, augmenting the effects of muscle relaxants. Echothiophate is a cholinesterase inhibitor used occasionally in the treatment of glaucoma. It signifi-cantly interferes with plasma cholinesterase, prolonging the duration of action of succinylcholine. The chemotherapeutic agent cyclophosphamide significantly decreases plasma cholinesterase concentrations, decreasing the metabolic rate of succinylcholine degradation. The immunosuppressant cyclosporine potentiates the effects of atracurium and vecuronium.
Thus far, the interactions discussed have focused on those that potentiate neuromuscular blockade. Several drugs induce resistance to neuromuscular muscle relaxants, such as corticosteroids, methylxanthines, and antiepileptic drugs. Corticosteroids may induce resistance to nondepo-larizing muscle relaxants by increasing presynaptic acetyl-choline levels. The clinical relevance of this effect remains controversial. Methylxanthines may induce resistance through a phosphodiesterase-dependent mechanism.