Anticholinesterase Flashcards
Acetylcholinesterase
Present at NM junction Anchored to ECM Does not hydrolyze butylcholine Extremely fast Uses serine reside to function
Plasmacholinesterase
Made in liver secreted into blood
Hydrolyzes both cholines
Only matters if Ach like drugs administered in blood
What is the mechanism of Acetylcholinesterase
ACh binds to active site
Serine attacks causing acyl intermediate
Water hydrolyzes the intermediate leaving acyl group and enzyme that is ready to go again
What are the effects of increased Ach
Decreased heart rate
Arteriolar vasodilation
Increased parastalsis, Increased ureter tone, bronchoconstriction
Increased secretions
Decreased iris diameter
Muscle contraction becomes inhibition at high conc
What Ach inhibitors are clinically relevant?
Quaternary alcohols
Carbamates (Neostigmine etc)
Donezapil, Galantamine
Organophosphates
What are medical uses of AchE inhibitors
Myasthenia gravis (neostigmine) Reversal of anesthesia Donezapil for alzheimers Physostigmine or DFP for glaucoma Physostigmine as antidote for antihistamine/anticholinergic overdose Neostigmine for bladder control Physostigmine gel for dry mouth
Edrophonium
Short lived
Acts at NM
Used for diagnosis of MG or reversal of anesthesia
Neostigmine
1-2hrs
Acts at NM
For treatment of MG or reversal of anesthesia
Adverse visceral effects
Physostigmine
12-40hrs
Postganglionic parasympathetic action
Treat glaucoma
Pyridostigmine
2-4hrs
Acts at NM
Treat MG
Donezapil
70hrs
Brain action
Treat alzheimers
Many side effects
DPF
10 days
Glaucoma
What are symptoms of organophosphate poisoning?
Miosis Profuse secretion defecation/urination/nausea and vomiting bradycardia Hypotension muscle twitches convulsions respiratory failure
How do you treat organophosphate poisoning?
Remove source
Give atropine to stop secretions
Give pralidoxime immediately to regenerate enzyme
Use benzos to stop convulsions
Give other supportive measures like a respirator
What can be used for Nerve Gas prophylaxis?
Pyridostigmine to inhibit some enzymes with a spontaneously reversible drug so that they are available for breakdown of Ach
