NMJ Flashcards
How does acetylcholinesterase breakdown acetylcholine?
Two steps:
1) A serine in the active site hydrolyzes the bond between the choline and acetyl groups by forming a covalent bond to the acetyl group
2) water hydrolyzes the bond between the acetyl group and the enzyme
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What are the classes of acetylcholinesterases?
1) competitive inhibitors that don’t form covalent bonds with acetylcholinesterase
* donepazil, edrophonium, galantamine
2) competitive inhibitors that form covalent bonds with acetylcholinesterase
- carbamates
- carbamyl-enzyme bond
- organophosphates
- phosphate-enzyme bond
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What are the carbamate drugs? What diseases are they used to treat?
Neostigmine - myasthenia gravis
pyridostigmine - myasthenia gravis (first line)
physostigmine - atropine poisoning/overdose
rivastigmine - dementia
What are the acetylcholinesterases used to treat/diagnose myasthenia gravis?
What are the acetylcholinesterases used to treat dementia?
treat MG - pyridostigmine, neostigmine
diagnose MG - edrophonium (Tensilon test)
Dementia - donepezil, galantamine, rivastigmine
What is the only clincially approved drug in the organophosphate category of acetylcholinesterases?
Echothiophate - not used clinically except for glaucoma
What are the two mechanisms to block the NMJ?
1) non-depolarizing blockade: competitive inhibitors of the nicotinic AChRs block ACh
2) depolarizing blockade: nicotinic agonists produce sustained membrane depolarization so that voltage gated Na+ channels inactivate
What drugs are non-depolarizing neuromuscular blockers? What drugs are depolarizing neuromuscular blockers?
non-depolarizing (“-curium”) - cisatracurium, mivacurium, tubocurarine, pancuronium, rocuronium
Depolarizing - succinylcholine
What classes of drugs have important interactions with neuromuscular blockers? What are those interactions?
General anesthetics - makes neuromuscular blockers more potent and can lead to malignant hyperthermia
Antibiotics - makes non-depolarizing neuromuscular blockers more potent by decreasing stimulation-induced acetylcholine release
What are the adverse effects of neuromuscular blockers?
post-operative pain
histamine release -> increased vascular permeability -> hypotension
effects on ANS ganglia, especially cardiovascular effects