Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

Table 11.5.Kinetics some non-depolarizing muscle relaxants.

Protein bound Elimination (%)

(%)

Volume of

distribution

(l.kg−^1 )

Metabolized

(%) Bile Urine

Pancuronium 20–60 0.27 30 20 80

Vecuronium 10 0.23 20 70 30

Rocuronium 10 0.20 <5 60 40

Atracurium 15 0.15 90 0 10

Cis-atracurium 15 0.15 95 0 5

Mivacurium 10 *0.21–0.32 90 0 5

Tubocurarine 30–50 0.30 0 30 70

Gallamine 10 0.23 0 0 100

*Isomer specific

Presentation and uses

Cis-atracurium is presented as a colourless solution containing 2 or 5 mg.ml−^1 and

should be stored at 4◦C. It is about three to four times more potent than atracurium

and, therefore, has a slower onset time. However, the onset time can be improved by

increasing the dose as its potential for histamine release is extremely low.

Kinetics

Cis-atracurium has a similar kinetic profile to atracurium. However, it does not

undergo direct hydrolysis by plasma esterases and the predominant pathway for

its elimination is Hofmann elimination to laudanosine and a monoquaternary acry-

late. This is then hydrolyzed by non-specific plasma esterases to a monoquaternary

alcohol and acrylic acid. All of its metabolites are void of neuromuscular-blocking

properties.

It has been used safely in children from 2 years of age and in elderly patients with

minimal alteration of its kinetics. There is no change in its kinetic profile in patients

with end-stage renal or hepatic impairment (Table11.5).

Mivacurium

Mivacurium (a benzylisoquinolinium ester – similar to atracurium) is a chiral mixture

of three stereospecific isomers in the following proportions:


36% cis-trans


58% trans-trans


6% cis-cis