The new neuromuscular blocking agents: do they offer any advantages?

Abstract

The pharmacodynamics and pharmacokinetics of the two most recent aminosteroid neuromuscular blocking drugs to become available, rapacuronium bromide (Org 9487) and rocuronium bromide are reviewed. Two new classes of drug with neuromuscular blocking properties, the bis-tetrahydroisoquinolinium chlorofumarates and the tropinyl diester derivatives are introduced. Comparisons between these drugs and mivacurium and cisatracurium are made. Rapacuronium 1.5 mg kg(-1) (ED95 1 mg kg(-1)), produces maximal neuromuscular block in 54 s. Time to recovery of the train-of-four ratio to 0.7 is achieved within 20 min after neostigmiine 0.05 mg kg(-1) given at 2 min. The plasma clearance of rapacuronium is 7-8 ml kg(-1) min(-1). Rapacuronium undergoes hepatic metabolism: no prolongation of effect has been reported after a single bolus or a short infusion in patients with hepatic or renal failure. Org 9488 is the 3-desacetyl metabolite of rapacuronium, which has neuromuscular blocking properties. Its much lower clearance (1.28 ml kg(-1) min(-1)) and plasma equilibration constant (0.105 min(-1)) may limit the prolonged use of rapacuronium. Rocuronium given at 2xED95 produces maximal neuromuscular block in 1 min. Spontaneous recovery of the train-of-four ratio to 0.7 takes over 40 min. Rocuronium has a plasma clearance of 4 ml kg(-1) min(-1). Its pharmacodynamics are altered in hepatic and renal disease. A number of anaphylactoid reactions to rocuronium have been reported recently. The bis-tetrahydroisoquinolinium chlorofumarate GW280430A has an ED95 of 0.19 mg kg(-1). Given at three times this dose, onset of neuromuscular block occurs within 100 s; the duration of block is 8-9 min. Following a 2 h infusion, the recovery index does not seem to be increased. Early studies suggest that this drug has no adverse cardiovascular or respiratory side-effects. The tropinyl diester derivative G-1-64 will produce 80-90% neuromuscular block in less than 2 min using 3xED80. Ninety per cent recovery of the first twitch of the train-of-four occurs after 5-7 min using one ED80. A recovery index of less than 2 min has been reported in rats. All the tropinyl diesters appear to produce vagal block.

Infusions of rocuronium and cisatracurium exert different effects on rat diaphragm function

“…The use of prolonged infusions of rocuronium has been questioned recently because of the potential drug accumulation in patients with renal and/or hepatic failure [4]. Our data may provide another argument against this practice.…”

“…After diaphragm homogenization in KPO 4 buffer, equal amounts of protein were separated by SDS-polyacrylamide gel electrophoresis and transferred by semidry blotting. Blots were exposed to a monoclonal primary antibody to αII-spectrin (Biomol, PA).…”

“…In patients with acute respiratory distress syndrome the frequency (± 25%) and duration of NMBA use is even higher [3]. Both aminosteroidal and benzylisoquinoline NMBAs are being used for this purpose, and clinical preference for a specific non-depolarizing NMBA is often based on the pharmacokinetic properties [4]. NMBA use is a known trigger for myopathy development which can lead to prolonged MV and intensive care unit (ICU) stay [1,5].…”

Comparative Evaluation of Cisatracurium and Atracurium Action as Components of Endotracheal Anesthesia in Laparoscopic Surgeries

“…Показатели нервно-мышечной проводимости (Ме (25%-75%)) большинстве исследований, где изучалась без-опасность применения цисатракурия и атра-курия, было показано, что цисатракурий вы-зывает меньшее число побочных реакций и осложнений [9,10]. Однако в других работах достоверно значимых различий между дан-ными релаксантами выявлено не было [11].…”

Safety and Efficacy of Sugammadex for Neuromuscular Blockade Reversal

“…[8][9][10][11] Sugammadex quickly inactivated rocuronium by encapsulation, reversing its neuromuscular blocking effects. A number of animal studies followed, which confirmed the effectiveness of sugammadex at reversing aminosteroid muscle relaxants (with the greatest effect on rocuronium followed by vecuronium and pancuronium).…”