Potentiation of neuromuscular blockade in man produced by combinations of pancuronium and metocurine or pancuronium and d-tubocurarine.
Simultaneous administration of combinations of pancuronium, metocurine, and d-tubocurarine (dTc) were given to A.S.A. class I-II surgical patients during N2O-narcotic-thiopental anesthesia to determine the degree of neuromuscular blockade produced. The pancuronium-metocurine and the pancuronium-dTc combinations were each significantly more potent (p < 0.05) than the additive effects of each of the individual drugs given alone. This greater than additive neuromuscular blocking effect was not seen with the metocurine-dTc combination. Despite the potentiation of neuromuscular blocking intensity by the pancuronium-metocurine and the pancuronium-dTc combination, the duration of blockade was not prolonged. Possibly, such potentiation of neuromuscular blockade might be attributed to simultaneous pre- and postjunctional receptor inhibition. Additional mechanisms might involve augmented conformational attachment to pre- and postjunctional cholinergic receptors or altered protein binding such that a greater than expected proportion of unbound drug reaches its neuromuscular site of activity. Regardless of mechanism, combining pancuronium with dTc or with metocurine can provide surgical relaxation or ideal conditions for endotracheal intubation with smaller amounts of each drug than would be anticipated if their effects were simply additive.
D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage* / Q000494:pharmacology; D010197:Pancuronium / Q000008:administration & dosage* / Q000494:pharmacology; D014403:Tubocurarine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology
D009466:Neuromuscular Blocking Agents; D010197:Pancuronium; C032943:metocurine; D014403:Tubocurarine