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, cerebral vasoconstriction 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.
  4. Mahmoud, Ahmed Abdelaal Ahmed, Amr Zaki Mansour, Hany Mahmoud Yassin, Hazem Abdelwahab Hussein, Ahmed Moustafa Kamal, Mohamed Elayashy, Mohamed Farid Elemady, et al. ‘Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache: A Randomized Controlled Trial’ 127, no. 6 (2018): 6.
Last updated 2019-07-02

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