Atypical plasma cholinesterase

[SH4:p219; CEACCP 2004 Vol 4(1) "Pharmacology of neuromuscular blocking drugs"]

@ Need to add: Fluoride number

Overview

• Often only recognised after an otherwise healthy individual experienced prolonged neuromuscular blockade (1-3 hours) after a normal dose of suxamethonium
• Several genetically determined variant
• Dibucaine-related is the most important

Genetics

Plasma cholinesterase is determined by a single gene on chromosome 3 (3q26)

• Normal plasma cholinesterase gene = E1^u
• Atypical plasma cholinesterase gene = E1^a
  * Most common
• Fluoride gene = E1^f
• Silent gene = E1^s

NB:

• The silent gene produces plasma cholinesterease which has virtually no capacity to hydrolyse suxamethonium
  --> Paralysis from suxamethonium from the homozygous type may last for several hours
  --> Non-specific plasma cholinestereases gradually clear the drug

Dibucaine

• Dibucaine = an amide local anaesthetic
• Inhibits the activity of normal plasma cholinesterase by about 80%
• But only inhibits the activity of atypical plasma cholinesterase by 20%

Dibucaine number

• Normal plasma cholinesterase enzyme
  --> Dibucaine causes 80% inhibition of plasma cholinesterase
  --> Dibucaine number of 80
• Homozygous atypical cholinesterase enzyme (E1^a E1^a)
  --> Dibucaine causes 20% inhibition of plasma cholinesterase
  --> Dibucaine number of 20
• Heterozygous atypical cholinesterase enzyme (E1^u E1^a)
  --> Dibucaine number of 40-60

NB:

• Dibucaine number reflects the quality, not the quantity, of cholinesterase enzyme
• Decreases in plasma cholinesterase activity due to liver disease or anticholinergic drugs
  --> Normal dibucaine number (i.e. 80)

Incidence

• Normal = 96%
• Homozygous (E1^a E1^a) = 1 in 3,200
• Heterozygous (E1^u E1^a) = 1 in 480
• Other types
  * (E1^u E1^f) = Dibucaine number of 75 = 1 in 200
  * (E1^f E1^a) = Dibucaine number of 45 = 1 in 20,000

Effects

• Normal plasma cholinesterase
  --> Suxamethonium duration = 3-5 minutes
• Homozygous atypical plasma cholinesterase
  --> Suxamethonium duration = 3 hours or even longer
• Heterozygous atypical plasma cholinesterase
  --> Suxamethonium duration = up to 30 minutes