CHOLINESTERASES ANTICHOLINESTERASES PROPERTIES AND USES PHA 303 22.02.2017

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

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

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

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

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

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

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

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

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

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

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

GLAUCOMA