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Section IICoredrugs in anaesthetic practiceTable 11.2.Some genetic variants of plasma cholinesterase.Genotype Incidence Duration of block Dibucaine number
Eu:Eu 96% normal 80
Eu:Ea 1:25 + 60
Eu:Es 1:90 + 80
Eu:Ef 1:200 + 75
Ea:Ea 1:2800 ++++ 20
Ea:Ef 1:20 000 ++ 50
Es:Ea 1:29 000 ++++ 20
Es:Es 1:100 000 ++++ −
Ef:Es 1:150 000 ++ 60
Ef:Ef 1:154 000 ++ 70Dibucaine (cinchocaine) is an amide local anaesthetic that inhibits normal plasma
cholinesterase. However, it inhibits the variant forms of plasma cholinesterase less
effectively. At a concentration of 10−^5 mol.l−^1 , using benzylcholine as a substrate,
dibucaine inhibits the Eu:Eu form by 80% but the Ea:Ea form by only 20%. Other
combinations are inhibited by 20–80% depending on the type involved. The per-
centage inhibition is known as the ‘Dibucaine number’ and indicates the genetic
makeup for an individual but makes no assessment of the quantity of enzyme in the
plasma (Table11.2).
Acquired factors associated with reduced plasma cholinesterase activity include:
Pregnancy
Liver disease
Renal failure
Cardiac failure
Thyrotoxicosis
Cancer
Drugs – either directly or by acting as substrate or inhibitor to AChE. Metoclo-
pramide, ketamine, the oral contraceptive pill, lithium, lidocaine, ester local anaes-
thetics, cytotoxic agents, edrophonium, neostigmine and trimetaphanNon-depolarizing muscle relaxants
Non-depolarizing muscle relaxants inhibit the actions of ACh at the NMJ by binding
competitively to theαsubunit of the nicotinic ACh receptor on the post-junctional
membrane.
There is a wide safety margin at the NMJ to ensure muscle contraction, so that more
than 70% of receptors need to be occupied by muscle relaxant before neuromuscular
blockade can be detected by a peripheral nerve stimulator. The non-depolarizing
block has essentially the same characteristics as the Phase II block (Table11.1).