Mivacurium chloride

Mivacurium chloride (Mivacron) is a newer agent that is chemically related to atracurium. The primary mechanism of inactivation is hydrolysis by plasma cholinesterase. Although it is useful for patients with renal or hepatic disease, some caution is warranted, since these individuals may have reduced plasma cholinesterase as a result of the disease. Mivacurium has an onset of action (1.8 minutes) and duration of effect (20 minutes) only twice that of succinylcholine, and in this respect, it is the most similar to succinylcholine of all of the nondepolarizing agents. 

The muscle relaxant mivacurium chloride is a mixture of stereoisomers. Calculate how many isomers are theoretically possible with the constitution shown below. 

Mivacurium chloride is a non-depolarizing muscle relaxant, a benzylisoquinolinium diester compound with a duration of approximately twice that of suxamethonium. In vitro (1), it is metabolized to a significant extent by plasma cholinesterase, and minimally by acetylcholinesterase. The rate of metabolism in vitro is directly related to plasma cholinesterase activity. In pooled human plasma the rate of hydrolysis of mivacurium was 70% that of suxamethonium. Its half-life is 5-10 minutes compared with 2-5 minutes for suxamethonium. The in vitro hydrolysis of mivacurium by purified human plasma cholinesterase occurs at 88% of the rate for suxamethonium (2). There was a poor correlation between the duration of action of bolus doses of mivacurium and the plasma cholinesterase activity in individual patients (2), a finding that has also been reported by others (3). However, the average infusion rate to maintain around 95 % blockade in individual patients correlated significantly with the patients plasma cholinesterase activities (4). While metabolites have been detected in both urine and bile, mivacurium seems to depend principally on ester hydrolysis for its plasma clearance, so that reduced activity of plasma cholinesterase is likely to result in a prolonged duration of action. 

Cook DR, Stiller RL, Weakly JN, Chakravorti S, Brandom BW, Welch RM. In vitro metabolism of mivacurium chloride (BW B1090U) and succinylcholine. Anesth Analg 1989 68(4) 452-6. 

Choi WW, Mehta MP, Murray DJ, Sokoll MD, Forbes RB, Gergis SD, Abou-Donia M, Kirchner J. Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia. Can J Anaesth 1989 36(6) 641-50. 

Ah HH, Savarese JJ, Embree PB, Basta SJ, Stout RG, Bottros LH, Weakly JN. Clinical pharmacology of mivacurium chloride (BW B1090U) infusion comparison with vecuronium and atracurium. Br J Anaesth 1988 61(5) 541-6. 

Savarese JJ, Ah HH, Basta SJ, Scott RP, Embree PB, Wastila WB, Abou-Donia MM, Gelb C. The cardiovascular effects of mivacurium chloride (BW B1090U) in patients receiving nitrous oxide-opiate-barbiturate anesthesia. Anesthesiology 1989 70(3) 386-94. 

Stoops CM, Curtis CA, Kovach DA, McCammon RL, Stoelting RK, Warren TM, MUler D, Bopp SK, Jugovic DJ, Abou-Donia MM Hemodynamic effects of mivacurium chloride administered to patients during oxygen-sufentanil anesthesia for coronary artery bypass grafting or valve replacement. Anesth Analg 1989 68(3) 333-9. 

Caldwell JE, Kitts JB, Heier T, Fahey MR, Lynam DP, Miller RD. The dose-response relationship of mivacurium chloride in humans during nitrous oxide-fentanyl or nitrous oxide-enflurane anesthesia. Anesthesiology 1989 70(l) 31-5. 

From RP, Pearson KS, Choi WW, Abou-Donia M, Sokoll MD. Neuromuscular and cardiovascular effects of mivacurium chloride (BW B1090U) during nitrous oxide-fentanyl-thiopentone and nitrous oxide-halothane anaesthesia. Br J Anaesth 1990 64(2) 193-8. 

Short-acting ester-containing neuromuscular drugs, such as succinylcholine (Anec-tine, 2) (Fig. 15.3) and mivacurium chloride (Mivacron) (61) designed to undergo hydrolysis by human plasma cholinesterase, also exploit similar principles, to ensure fast and spontaneous recovery upon cessation of administration. Hence, their durations of action are only 6-8 and 12-18 min, respectively,and the corresponding elimination routes remain functional even in renal failure. 

Mivacurium chloride is a mixture of three stereoisomers, with the trans-trans (92-96%) and the cis-trans diesters being equipotent. The cis-cis diester produces only minimal (<5%) neuromuscular blockade. It is hydrophilic, has a small volume of distribution, and is distributed primarily to extracellular fluids. Mivacurium is short acting (Table 12.4), with mean elimination half-lives for the trans-trans and cis-trans stereoisomers of 2.0 and 1.8 minutes, respectively, in adults receiving opioid/nitrous oxide/oxygen anesthesia. It is rapidly hydrolyzed and does not undergo... 

I. Mivacurium chloride (Mivacron) 0.5 mg/mL and 2 mg/mL in 5- and 10-mL single-use vials. The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is four 10-mL vials or equivalent. 

Naguib M. Neuromuscular effects of rocuronium bromide and mivacurium chloride administered alone and in combination. Anes iesiology (1994) 81,388-95. 

In a comparative study, two optimized approaches to mivacurium chloride (and other skeletal muscle relaxants) were reported. (i )-5 -Methoxylaudanosine was prepared by ATH of a dihydroisoquinoline, and the process was compared to a resolution strategy [56]. 

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