alexa [The clinical pharmacology of new benzylisoquinoline-diester compounds, with special consideration of cisatracurium and mivacurium].
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Savarese JJ, Lien CA, Belmont MR, Wastila WB

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Abstract The benzylisochinoline muscle relaxants have a highly selective affinity to the motor endplate which is associated with an absence of autonomic side effects such as ganglionic and vagus block. The requirement of only low clinical doses also reduces histamine liberation. Muscle relaxants with high neuromuscular blocking potency have a slow onset. Both atracurium and cisatracurium undergo Hofmann-Elimination in the plasma whereas mivacurium is hydrolyzed by pseudocholinesterase. The difference in kinetics between these pathways render atracurium and cisatracurium muscle relaxants of intermediate duration of action while mivacurium is short acting. Cisatracurium, one of the ten stereoisomeres of atracurium, is 3 to 4 times as potent as atracurium, does not release histamine, has no cardiovascular side effects and, due to the small clinical doses resulting from its high neuromuscular blocking potency, produces only negligible quantities of laudanosine. Its ED95 is 0.05 mg/kg. Good intubation conditions can be expected within 1.5 to 2 min following 3- to 4-times the ED95. Thereafter is takes about 65 min for T1 to recover to 25\% of control. Maintenance doses of 0.02 to 0.04 mg/kg have a duration of action of 15 to 20 min. An infusion of cisatracurium of 1.0 to 2.0 mcg/kg/min, is adequate to maintain a 90 to 95\% neuromuscular block. The time of recovery is largely independent on the total dose of cisatracurium administered by either repeated injection or infusion. Mivacurium is a racemate of 3 stereoisomeres of which the trans-trans- and the cis-trans-compound account for 95\% of the neuromuscular blocking effect. In adults the ED95 is 0.08 mg/kg. The ensuing recovery of T1 to 25\% of control is about 15 min. Rapid injection of 3xED95 may transiently lower the arterial blood pressure and may produce skin flushing in an incidence of 30 to 40\%. Larger doses should be injected slowly with 30 to 60 s. The onset of mivacurium neuromuscular block following 3xED95 is relatively slow (2 min). Maintenance doses of 0.05 to 0.1 mg/kg have a duration of action of 5 to 10 min. A 95\% neuromuscular block may be maintained by an infusion of 3 to 12 micrograms/kg/min. The time of recovery does not depend on the total cumulative dose given by either repeated injection or by infusion. The duration of mivacurium neuromuscular block may be drastically prolonged in the presence of low or atypical plasmacholinesterase. Both neostigmine and edrophonium are suitable reversal agents. None of the presently available benzylisochinoline muscle relaxants has the potential to completely replace succinylcholine. This article was published in Anaesthesist and referenced in Journal of Bioequivalence & Bioavailability

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