Anticholinesterases

Anticholinesterases antagonise AChE, decreasing the breakdown of ACh and therefore increasing its availability at the:

  • Nicotinic receptor
    Increases muscle strength.
    • Reversal of non-depolarising neuromuscular blockade
  • Muscarinic receptor
    Increases parasympathetic tone.

Acetylcholinesterases can be:

  • Reversible
  • Form a carbamylated enzyme complex
  • Irreversible
Property Neostigmine Organophosphates
Class Quaternary amine, forms carbamylated enzyme complex Irreversible anticholinesterase
Uses Reversal of non-depolarising NMB, myasthenia gravis, analgesia Insecticides, pesticides, chemical weapons
Presentation Clear, colourless, light stable solution at 2.5mg.ml-1
Route of Administration PO, IV, intrathecal Topical
Dosing 0.05mg.kg-1 for reversal, 15-30mg PO for MG
Absorption Low PO bioavailability Rapid topical absorption due to high lipid solubility
Distribution Does not cross BBB, VD 0.7L.kg-1 Crosses BBB
Metabolism Majority by plasma esterases to quaternary alcohol, with some hepatic metabolism Not metabolised
Elimination 55% unchanged in urine t1/2α of weeks
Duration 50 minutes Until new AChE is synthesised
Resp Bronchospasm, ↑ secretion Bronchospasm, ↑ secretion
CVS ↓ HR (may be profound), ↓ CO ↓ HR, ↓ CO
CNS N/V and analgesic when administered intrathecally Central cholinergic syndrome
MSK Reversal of NMB, ↑ fasciculations, ↑ sweating, may cause paralysis Paralysis
GIT ↑ Peristalsis, ↑ LoS tone, N/V ↑ Peristalsis, ↑ LoS tone, N/V
Other Muscarinic receptors affected at low dose, nicotinic receptors at high dose May be reversed in initial stages (before organophosphate-AChE complex has 'aged') with pralidoxime

References

  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. ANZCA 2007 Feb/April
  3. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
Last updated 2017-09-23

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