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