Cholinergic Agonists (cholinesterase inhibitors) Flashcards
what are the two types of cholinesterases
acetylcholinesterase and plasma cholinesterase
which cholinesterase is located in synapses
acetylcholinesterase
AChE has the (highest/lowest) turnover rate of any known mammalian enzyme
highest
what are the two main sites of acetylcholinesterase
anionic site and esteratic site
what is the critical step in the hydrolysis of acetylcholine
reactivated enzyme, reactivated by water
give an example of a reversible anticholinesterase agent
edrophonium
give an example of an irreversible anticholinesterase agent
organophosphates
name the 3 reversible carbamates (also anticholinesterase agents)
physostigmine, neostigmine, pyridostigmine
name 3 organophosphates
echothiophate, sarin, malathion
Edrophonium, neostigmine, and pyridostigmine all share what action
inhibition of acetylcholinesterase
edrophonium (covalently/noncovalently) binds to acetylcholinesterase
noncovalently
Match the clinical use with the following drugs: very short-acting (minutes); diagnosis of Myasthenia Gravis (MG)
(skeletal muscle weakness due to loss of skeletal muscle nicotinic receptors because of
autoimmune disease)
a. edrophonium
b. pyridostigmine
c. neostigmine
a. edrophonium
match the clinical use with the following drugs:
Used in treatment of MG, reversal of nondepolarizing neuromuscular blockade,
pretreatment for potential nerve gas exposure (occupy AChE so that nerve gas has
nowhere to go
a. edrophonium
b. pyridostigmine
c. neostigmine
b. pyridostigmine
match the clinical use with the following drugs:
Used for MG, reversal of nondepolarizing neuromuscular blockade, post-op urinary retention
a. edrophonium
b. pyridostigmine
c. neostigmine
c. neostigmine
“stigmines” as substrates that are more _______ _________ than ACh
slowly hydrolyzed
clinical use of physostigmine
antidote to antimuscarinic poisoning
T/F most organophosphates are toxic
True
action of echothiophate
inhibition of acetylcholinesterase: BUT its long-acting and irreversible
what drug? Action: strong nucleophile, will hydrolyze organophosphate if treated before aging occurs- this will regenerate acetylcholinesterase. does not cross the BBB
pralidoxime (2-pam)
clinical use of pralidoxime
treatment of organophosphate toxicity
2 drugs used for antidotal therapy for acute organophosphate intoxication
pralidoxime and atropine
Blocks access to muscarinic receptor (antagonist). Can’t block action at nicotinic receptors
Atropine
Strong nucleophile. Can’t cross BBB
pralidoxime
Target of pralidoxime
neuromuscular junction;
muscle weaknsess-> respiratory-> DEATH
what disease causes widening of sulci and thinning of gyri in the brain
alzheimers
loss of cholinergic neurons in brain
alzheimers
4 drugs used to treat alzheimers
donepezil (aricept), rivastigmine (exelon), galantamine (razadyne), memantine (namenda)
just try to hit all the points on the donepezil slide
binds to anionic site and blocks ACh binding, reversible, noncovalent, enhances cognitive ability, does not slow progression of disease
hit the points on the rivastigmine slide
reversible carbamate AChE inhibitor, enhances cognitive ability by increasing cholinergic function, loses effectiveness as disease progresses
side effects of rivastigmine
nausea, vomiting, anorexia, and weight loss
talk about the galantamine (razadyne) slide
reversible competitive AChE inhibitor, loses effectiveness as disease progresses, may be a nicotinic receptor agonist, inhibitors of P450 enzymes (3A4, 2D6) will increase galantamine bioavailability
talk about memantine (namenda) slide
NMDA receptor antagonist. Glutamate regulators to improve cognitive function. Approved for moderate-to-severe disease, favorable adverse effect profile
two alzheimers drugs approved for moderate-to-severe alzheimers
donepezil and memantine
type of inhibition: Edrophonium
reversible
type of inhibition: neostigmine
reversible
type of inhibition: Physostigmine
reversible
type of inhibition: Donepezil
reversible
type of inhibition: Echothiophate
Irreversible
Route of administration: Edrophonium
IM or IV
Route of administration: Neostigmine
IM, IV, or oral
Route of administration: Physostigmine
IM, IV, or local
Route of administration: Donepezil
oral
Route of administration: Echothiophate
local
clinical use: Edrophonium
Diagnostic for MG
clinical use: Neostigmine
MG, post-op ileus and bladder distention
clinical use: physostigmine
glaucoma, alzheimers, antidote to anticholinergic overdose
clinical use: donepezil
alzheimers
clinical use: Echothiophate
glaucoma
cholinergic agonists side effects
DUMBBELS: diarrhea, urination, miosis, bradycardia, brochoconstriction, emesis, lacrimation, salivation, +sweating (SNS effect)
When to be cautious with cholinergic agonists
patients with asthma, coronary insufficiency, or peptic ulcer
