Pharmacology for Anaesthesia and Intensive Care

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9780521704632c11 CUFX213A/Peck 9780521618168 December 28, 2007 12:5

11 Muscle relaxants and anticholinesterases

Non-depolarizing muscle relaxants fall into one of two chemical groupings:


Aminosteroidal compounds – vecuronium, rocuronium, pancuronium


Benzylisoquinolinium compounds – atracurium, mivacurium, tubocurarine

Across the two chemical groups the drugs can be divided according to their duration

of action:


Short – mivacurium


Intermediate – atracurium


Long – pancuronium

Owing to their relatively polar nature, non-depolarizing drugs are unable to cross

lipid membranes resulting in a small volume of distribution. Some are hydrolyzed

in the plasma (atracurium, mivacurium) while others undergo a degree of hepatic

metabolism (pancuronium, vecuronium). The unmetabolized fraction is excreted in

the urine or bile.

Muscle relaxants are never given in isolation and so their potential for drug inter-

action should be considered (Table11.3).

Vecuronium

Vecuronium is a ‘clean’ drug, so called because it does not affect the cardiovascular

system or precipitate the release of histamine. Its chemical structure differs from

pancuronium by a single methyl group making it the monoquaternary analogue.

Presentation and uses

Vecuronium is potentially unstable in solution and so is presented as 10 mg freeze-

dried powder containing mannitol and sodium hydroxide and is dissolved in 5 ml

water before administration. At 0.1 mg.kg−^1 satisfactory intubating conditions are

reached in about 90–120 seconds. It has a medium duration of action.

Other effects


Cardiovascular – vecuronium has no cardiac effects but, unlike pancuronium or

tubocurarine, it may leave unchecked the bradycardias associated with fentanyl

and propofol.


Critical illness myopathy – this is seen most frequently in critically ill patients

in association with corticosteroids and/or muscle relaxants and may involve a

prolonged recovery.

Kinetics

Like pancuronium, vecuronium is metabolized in the liver by de-acetylation to 3-

and 17-hydroxy and 3,17-dihydroxy-vecuronium. Again the 3-hydroxy metabolite

carries significant muscle-relaxant properties, but unlike 3-hydroxypancuronium

it has a very short half-life and is of little clinical significance with normal renal