Omeprazole potentiates atracurium and succinylcholine paralysis in vivo in rats.
We examined the effect of proton pump inhibitor omeprazole on neuromuscular paralysis induced with either nondepolarizing or depolarizing neuromuscular blocking drugs in anesthetized and mechanically ventilated rats. Neuromuscular paralysis, as judged by tibialis anterior muscle twitch tension in response to sciatic nerve stimulation, was maintained at about 50% with intravenous (i.v.) bolus and infusion regimens of either atracurium or succinylcholine. Omeprazole, 0.5, 1, and 10 mg/kg i.v., was then administered at 10-min intervals while the infusion of the neuromuscular blocker was continued. Omeprazole at all three doses increased the steady-state neuromuscular paralysis produced with either atracurium (pre-omeprazole versus final post-omeprazole paralysis; mean +/- SE, n = 6, 53.0% +/- 2.3% vs 80.0% +/- 5.3%) or succinylcholine (50.8% +/- 1.5% vs 86.4% +/- 5.1%). Omeprazole, 0.5, 1.0, and 10 mg/kg i.v., given directly and without any neuromuscular blocker, produced approximately 5% depression of the muscle twitch response. Omeprazole, i.v. at human therapeutic doses, alters neuromuscular function and enhances the action of both atracurium and succinylcholine in vivo in rats.
Fu
C
C
Department of Pharmacy, University of Sydney, New South Wales, Australia.
Mishra
Y
Y
Ramzan
I
I
D000818:Animals; D001279:Atracurium / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D009853:Omeprazole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013390:Succinylcholine / Q000494:pharmacology*
D001279:Atracurium; D013390:Succinylcholine; D009853:Omeprazole