1. CHOLINESTERASES ANTICHOLINESTERASES PROPERTIES AND USES
PHA 303

2. CHOLINESTERASES (ENZYMES)
TYPES
Acetylcholinesterase (True cholinesterase -AChE)
Butyrylcholinesterase (Pseudocholinesterase - BuChE)

3. ACETYLCHOLINESTERASE
Distribution:
Present in Cerebrospinal fluid, cholinergic synapses, gray matter
Function:
To hydrolyse acetylcholine and thereby terminate its action rapidly at the cholinergic receptors.
Other substrates:
Methacholine

4. BUTYRYLCHOLINESTERASE
Distribution:
Present in plasma, liver, skin, brain, GIT smooth muscle
Function:
To hydrolyse butyrylcholine, cetylcholine and drugs below thereby terminating their action in circulation
Other substrates:
Procaine
Suxamethonium

5. ANTICHOLINESTERASES (DRUGS)
Action:
These agents interact with AChE in place of ACh thereby preventing the hydrolysis of ACh.
Classification:
Reversible: (hydrolysis takes a short time)
Edrophonium – short acting
Physostigmine (Eserine) occurs naturally in Calabar bean
Neostigmine
Pyridostigmine

6. ANTICHOLINESTERASES (DRUGS)
Irreversible: (hydrolysis takes long or never occurs)
Also referred to as organophosphates.
Dyflos
Parathion
Malathion
Echothiophate (reversed after a few days)
Propoxur

7. PROPERTIES Form irreversible bonds with AChE
Also block other enzymes like trypsin and thrombin
Organophosphates are highly lipid soluble
Autonomic effects- increased secretions i.e salivation, lacrimation, GIT glands, bronchial, increased peristalsis, bronchoconstriction, bradycardia, hypotension, miosis, reduced intra ocular pressure.
NB:Anticholinesterase poisoning

8. PROPERTIES
Neuromuscular effects- increased muscle twitching and muscle tension
Peripheral neurotoxicity leading to nerve degeneration
CNS effects- can penetrate the CNS rapidly to cause convulsion followed by depression. Also unconsciousness and respiratory failure.
NB: Antidote is atropine

9. USES As pesticides and insecticides e.g. propoxur
Weapon of warfare (Nerve gases)e.g. Tabun, Sarin, Soman
Treatment of glaucoma
Treatment of Myasthenia gravis

10. USES
To reverse the action of non-depolarizing neuromuscular blocking drugs at the end of an operation (atropine also used to reduce CNS effects)
Edrophonium is used to diagnose myasthenia gravis
Treatment of Alzheimer’s disease – donezepil, rivastigmine
As an antidote for atropine poisoning

11. CHOLINESTERASE REACTIVATORS
These are used to restore enzyme activity after organophosphate anticholinesterase poisoning
Pralidoxime
Limitation of ‘aging’

12. MYASTHENIA GRAVIS
Its an autoimmune disease where antibodies are directed at the neuromuscular nicotinic ACh receptors.
Reduced nACh receptors for ACh interaction before hydrolysis
Muscular weakness
Diagnosed by edrophonium
Treated with neostigmine, corticosteroids, removal of antibodies by plasmaphoresis

13. GLAUCOMA