Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

The cis-cis isomer has about 10% of the potency of the other two isomers and

is not metabolized enzymatically. Its half-life is ten times that of the other two

isomers.

The main advantage of mivacurium is its short duration of action. Routine rever-

sal of mivacurium with neostigmine may not be required due to its rapid enzymatic

metabolism. In addition, neostigmine inhibits plasma cholinesterase and may pre-

vent its metabolism. Edrophonium may be a more suitable agent for the reversal of

neuromuscular block secondary to mivacurium.

Presentation and uses

Mivacurium is presented as an acidic (pH 3.5–5.0) aqueous solution containing

2 mg.ml−^1 in 5 and 10 ml ampoules. It has a shelf-life of 18 months when stored

below 25◦C.

Effects


Cardiorespiratory – high doses may release histamine, resulting in a fall in blood

pressure and bronchospasm.

Kinetics

Plasma cholinesterase is responsible for the metabolism of the cis-trans and trans-

trans isomers, so those patients with genetically low plasma cholinesterase levels

(cf. suxamethonium apnoea) are subject to prolonged neuromuscular blockade. Its

duration of action is significantly prolonged in patients with end-stage liver disease,

mainly due to reduced plasma cholinesterase activity.

Gallamine

Gallamine was introduced into anaesthesia in 1947 as the first synthetic muscle

relaxant. It currently has a limited role in anaesthesia, being used to reduce muscle

fasciculations induced by suxamethonium.

Itselectively blocks cardiac muscarinic receptors causing a tachycardia and may

also activate the sympathetic nervous system. As it is excreted unchanged by the

kidneys, renal failure significantly prolongs its half-life. Unlike other muscle relaxants

an alkalosis prolongs its duration of action while an acidosis shortens it.

Anticholinesterases

The enzyme AChE hydrolyzes ACh, terminating its effects. Anticholinesterases antag-

onize AChE so that more ACh is available at the NMJ. However, the actions of anti-

cholinesterases are not specific to the NMJ and autonomic cholinergic effects (brady-

cardia, salivation) are also seen. For this reason they are often given with an anti-

cholinergic (atropine or glycopyrrolate).