3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.1. Pharmacology principles
                      3.1.3.1.3. Pharmacogenetics
 3.1.3.1.3.2. Atypical plasma cholinesterase 

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 = E1u
  • Atypical plasma cholinesterase gene = E1a
    * Most common
  • Fluoride gene = E1f
  • Silent gene = E1s

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 (E1a E1a)
    --> Dibucaine causes 20% inhibition of plasma cholinesterase
    --> Dibucaine number of 20
  • Heterozygous atypical cholinesterase enzyme (E1u E1a)
    --> 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 (E1a E1a) = 1 in 3,200
  • Heterozygous (E1u E1a) = 1 in 480
  • Other types
    * (E1u E1f) = Dibucaine number of 75 = 1 in 200
    * (E1f E1a) = 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