Anticholinesterases and Pesticides Flashcards
How do cholinesterases function?
Serine hydrolases
Catalytic subunit splits substrate choline esters by introducing water bond
Targeted to site by structural subunit
Is butyrylcholinesterase vital?
No
Will be fine without it, won’t know if you have mutation until given succinylcholine
Which cholinesterases can be recovered by pralidoxime?
Acetylcholine
Cholinesterase gets inhibited by organophosphate agents, oximes can reverse it
What are the categories of acetylcholinesterases and are they reversible or irreversible?
Quaternary amines - reversible in secs
Carbamates - reversible in mins
Organophosphates - irreversible (takes hours or longer)
What drugs are in the category of quaternary amines?
Edrophonium
What drugs are in the category of carbamates?
Neostigmine
Physostigmine
Pyridostigmine
What drugs are in the category of organophosphates?
Pesticides (malathion, diazanon, carbaryl) Chemical warfare (soman, sarin, VX)
What is the mechanism by which anticholinesterases inhibit AChE?
Form covalent bond with active site serine
Acylate AChE
Recovery of enzyme activity depends upon deacylation (hence reversible and irreversible)
In general, what results from the use of anticholinesterases?
Inactivation of AChE = excess ACh = parasympathetic stimulation (DUMBBELSS)
What anticholinesterases are used to treat paralytic ileus and atony of the bladder?
Neostigmine
often in conjunction with muscarinic agonist like bethanechol
What anticholinesterases are used to treat glaucoma?
Physostigmine
often in conjunction with muscarinic agonist like pilocarpine
What anticholinesterases are used to treat myasthenia gravis?
Neostigmine, pyridostigmine
in conjunction with muscarinic antagonist to counteract parasympathetic effects of ACh
What anticholinesterases are used to help with recovery of neuromuscular block following surgery?
Neostigmine
with muscarinic antagonist to counteract parasympathetic effects of ACh
What anticholinesterases are used to treat anticholinergic toxicity (e.g. atropine)?
Physostigmine
Which organophosphate pesticide is toxic to humans?
Parathion
