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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Androstanols, Animals, Cholinesterase Inhibitors, Cholinesterase Reactivators, Diaphragm, Dose-Response Relationship, Drug, Drug Interactions, Male, Neuromuscular Nondepolarizing Agents, Paraoxon, Phrenic Nerve, Pralidoxime Compounds, Rats, Rats, Wistar, Rocuronium, Time Factors.
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Does pralidoxime inhibit paraoxon-induced depression of rocuronium-neuromuscular block in a time-dependent fashion? Context: The composite effects of organophosphorus (OP)-cholinesterase (ChE) inhibitors and oximes on the actions of nondepolarizing neuromuscular blockers in acute OP-ChE inhibitor intoxication have not been evaluated in detail. We investigated the effects of paraoxon (Pox) (an OP-ChE inhibitor) and pralidoxime (PAM) (an oxime) on the nondepolarizing neuromuscular blocking action of rocuronium. Isometric twitch tensions of rat left phrenic nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Analysis of variance with post hoc testing was used for statistical comparison, and P < .05 was accepted as significant. Rocuronium reduced the indirectly elicited twitch tensions in normal (50% inhibitory concentration [IC(50)], 9.84 [9.64-10.04] μM, mean [95% confidence interval]) and all pretreated diaphragms (P < .01, n = 6) in a concentration-dependent fashion. Paraoxon caused a rightward shift in the rocuronium concentration-twitch tension curve (IC(50), 15.48 [15.24-15.72] μM). The rightward shift was completely inhibited by previous copretreatment (IC(50), 9.98 [9.77-10.20] μM) and partially inhibited by simultaneous copretreatment (IC(50), 11.68 [11.45-11.91] μM) with PAM but was not inhibited by subsequent copretreatment (IC(50), 13.69 [13.39-13.99] μM) with PAM (P < .01, n = 6). Atropine did not influence the rightward shift (P < .01, n = 6).
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Paraoxon depressed rocuronium-induced neuromuscular block by inhibiting ChEs, and the action of Pox was inhibited by PAM. Pralidoxime acts more intensely when applied earlier. The time-dependent effect of PAM indicates that the preceding presence of PAM in proximity to ChEs before Pox is necessary for definite suppression of the Pox-induced ChE inhibition. Final Decision: yes