Effects of changes in acid-base balance on neuromuscular blockade produced by ORG-NC 45.
The effects of acute acid-base changes on the neuromuscular blocking action of ORG NC 45 (a monoquaternary homologue of pancuronium) were measured in 10 cats, utilizing a constant infusion technique. Partial NC 45 blockade was antagonized slightly in the tibialis, soleus, and diaphragm during respiratory alkalosis (pH 7.53; PaCO2 1.9 kPa), whereas metabolic alkalosis (pH 7.64; Paco2 3.5 kPa) produced significant antagonism of NC 45 block in those muscles. Respiratory acidosis (pH 6.98; Paco2 10.3 kPa) and metabolic acidosis (p H 7.13; PaCO2 4.9 kPa) significantly potentiated partial NC 45 blocks in the tibialis, soleus, and diaphragm (except in the diaphragm during metabolic acidosis). Cumulative dose responses studied in six cats showed that the NC 45 dosage required to produce 85--95% tibialis block was slightly greater than controls during respiratory and metabolic alkalosis. Conversely, significantly less NC 45 was needed to produce the same degree of block during respiratory and metabolic acidosis. In vitro studies in rat hemidiaphragms likewise showed minimal NC 45 block antagonism when pH was raised to 7.68, and significant potentiation under acidotic conditions (pH 7.05). These actions are attributed in part to an increased rate of NC 45 metabolism by alkaline hydrolysis in alkalotic states and greater molecular stability during acidosis. Possible clinical implications are discussed.
D000138:Acidosis / Q000503:physiopathology; D000142:Acidosis, Respiratory / Q000503:physiopathology; D000471:Alkalosis / Q000503:physiopathology; D000472:Alkalosis, Respiratory / Q000503:physiopathology; D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage; D010197:Pancuronium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D014673:Vecuronium Bromide
D009466:Neuromuscular Blocking Agents; D014673:Vecuronium Bromide; D010197:Pancuronium