Cholinergic Agonists (cholinesterase inhibitors)

Question 1

what are the two types of cholinesterases

Answer 1

acetylcholinesterase and plasma cholinesterase

Question 2

which cholinesterase is located in synapses

Answer 2

acetylcholinesterase

Question 3

AChE has the (highest/lowest) turnover rate of any known mammalian enzyme

Answer 3

highest

Question 4

what are the two main sites of acetylcholinesterase

Answer 4

anionic site and esteratic site

Question 5

what is the critical step in the hydrolysis of acetylcholine

Answer 5

reactivated enzyme, reactivated by water

Question 6

give an example of a reversible anticholinesterase agent

Answer 6

edrophonium

Question 7

give an example of an irreversible anticholinesterase agent

Answer 7

organophosphates

Question 8

name the 3 reversible carbamates (also anticholinesterase agents)

Answer 8

physostigmine, neostigmine, pyridostigmine

Question 9

name 3 organophosphates

Answer 9

echothiophate, sarin, malathion

Question 10

Edrophonium, neostigmine, and pyridostigmine all share what action

Answer 10

inhibition of acetylcholinesterase

Question 11

edrophonium (covalently/noncovalently) binds to acetylcholinesterase

Answer 11

noncovalently

Question 12

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

Answer 12

a. edrophonium

Question 13

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

Answer 13

b. pyridostigmine

Question 14

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

Answer 14

c. neostigmine

Question 15

“stigmines” as substrates that are more _______ _________ than ACh

Answer 15

slowly hydrolyzed

Question 16

clinical use of physostigmine

Answer 16

antidote to antimuscarinic poisoning

Question 17

T/F most organophosphates are toxic

Answer 17

True

Question 18

action of echothiophate

Answer 18

inhibition of acetylcholinesterase: BUT its long-acting and irreversible

Question 19

what drug? Action: strong nucleophile, will hydrolyze organophosphate if treated before aging occurs- this will regenerate acetylcholinesterase. does not cross the BBB

Answer 19

pralidoxime (2-pam)

Question 20

clinical use of pralidoxime

Answer 20

treatment of organophosphate toxicity

Question 21

2 drugs used for antidotal therapy for acute organophosphate intoxication

Answer 21

pralidoxime and atropine

Question 22

Blocks access to muscarinic receptor (antagonist). Can’t block action at nicotinic receptors

Answer 22

Atropine

Question 23

Strong nucleophile. Can’t cross BBB

Answer 23

pralidoxime

Question 24

Target of pralidoxime

Answer 24

neuromuscular junction;
muscle weaknsess-> respiratory-> DEATH

Question 25

what disease causes widening of sulci and thinning of gyri in the brain

Answer 25

alzheimers

Question 26

loss of cholinergic neurons in brain

Answer 26

alzheimers

Question 27

4 drugs used to treat alzheimers

Answer 27

donepezil (aricept), rivastigmine (exelon), galantamine (razadyne), memantine (namenda)

Question 28

just try to hit all the points on the donepezil slide

Answer 28

binds to anionic site and blocks ACh binding, reversible, noncovalent, enhances cognitive ability, does not slow progression of disease

Question 29

hit the points on the rivastigmine slide

Answer 29

reversible carbamate AChE inhibitor, enhances cognitive ability by increasing cholinergic function, loses effectiveness as disease progresses

Question 30

side effects of rivastigmine

Answer 30

nausea, vomiting, anorexia, and weight loss

Question 31

talk about the galantamine (razadyne) slide

Answer 31

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

Question 32

talk about memantine (namenda) slide

Answer 32

NMDA receptor antagonist. Glutamate regulators to improve cognitive function. Approved for moderate-to-severe disease, favorable adverse effect profile

Question 33

two alzheimers drugs approved for moderate-to-severe alzheimers

Answer 33

donepezil and memantine

Question 34

type of inhibition: Edrophonium

Answer 34

reversible

Question 35

type of inhibition: neostigmine

Answer 35

reversible

Question 36

type of inhibition: Physostigmine

Answer 36

reversible

Question 37

type of inhibition: Donepezil

Answer 37

reversible

Question 38

type of inhibition: Echothiophate

Answer 38

Irreversible

Question 39

Route of administration: Edrophonium

Answer 39

IM or IV

Question 40

Route of administration: Neostigmine

Answer 40

IM, IV, or oral

Question 41

Route of administration: Physostigmine

Answer 41

IM, IV, or local

Question 42

Route of administration: Donepezil

Answer 42

oral

Question 43

Route of administration: Echothiophate

Answer 43

local

Question 44

clinical use: Edrophonium

Answer 44

Diagnostic for MG

Question 45

clinical use: Neostigmine

Answer 45

MG, post-op ileus and bladder distention

Question 46

clinical use: physostigmine

Answer 46

glaucoma, alzheimers, antidote to anticholinergic overdose

Question 47

clinical use: donepezil

Answer 47

alzheimers

Question 48

clinical use: Echothiophate

Answer 48

glaucoma

Question 49

cholinergic agonists side effects

Answer 49

DUMBBELS: diarrhea, urination, miosis, bradycardia, brochoconstriction, emesis, lacrimation, salivation, +sweating (SNS effect)

Question 50

When to be cautious with cholinergic agonists

Answer 50

patients with asthma, coronary insufficiency, or peptic ulcer