Cholinergic nervous system functions

Question 1

T/F: Cholinergic synapses in the parasympathetic nervous system are always preganglionic

Answer 1

False: Cholinergic synapses in the parasympathetic nervous system can be both pre- and post- ganglionic

Question 2

What are the 3 sites that are targets of drug action involving the cholinergic synapses

Answer 2

Biosynthesis of acetylcholine, uptakes of choline and acetylcholine, release of acetylcholine

Question 3

What is the enzyme, substrate, and coenzyme needed to create Acetylcholine

Answer 3

Choline, acetyl-CoA, choline acetyltransferase

Question 4

What compound is a choline acetelytransferase inhibitor, how

Answer 4

NVP, imitates Acetyl-CoA and blocks binding

Question 5

What are the major components for NVP to be an effective choline acetyltransferase inhibitor

Answer 5

napathalene ring and pyridine ring

Question 6

What is the rate limiting step in acetylcholine production

Answer 6

uptake of choline

Question 7

What protein is responsible for reuptaking choline into presynaptic nerve terminals

Answer 7

Carrier protein A

Question 8

What is the competitive uptake inhibitor that reduces the amount of choline in presynaptic cells, how

Answer 8

Hemicholinium-3, it has choline like moieties that bind to the carrier protein

Question 9

How many carrier proteins are inhibited by hemicholinium-3

Answer 9

2

Question 10

T/F: Hemichlonium-3 is not acetlylated in presynaptic cell because it only blocks the carrier but never enters the cell

Answer 10

True

Question 11

What is the false neurotransmitter the competes with choline for uptake by protein carrier A

Answer 11

Triethycholine (TEC)

Question 12

T/F: Triethylcholine does not enter the cell

Answer 12

False: TEC does enter the cell and goes through the same process that choline goes through therefore competing with choline. The differece is that it is too bulky to bind to cholinergic receptors

Question 13

What experimental drug prevents uptake of acetylcholine into vesicles

Answer 13

L-vesamicol

Question 14

T/F: L-vesamicol does not bind competitively but instead allosterically to prevent acetylcholine binding

Answer 14

True

Question 15

What antibiotic has a secondary effect that leads to less release of acetylcholine at a synapse, how

Answer 15

Tetracycline, complexes with calcium causing less calcium to induce release of vesicles holding acetylcholine

Question 16

How does Botox (botulinum toxin) reduce the release of Acetylcholine

Answer 16

cleaves SNAP-25: SNAP 25 is essential for successful docking and release of acetylcholine from vesicles

Question 17

What is the MOA of beta-Bungarotoxin

Answer 17

Causes excess release of acettylcholine that will lead to exhaustion of acetlycholine stores in the nerve terminal preventing further release of acetylcholine

Question 18

What are the two types of receptors that bind acetylcholine

Answer 18

Muscarinic and Nicotinic

Question 19

T/F: There are muscarinic and nicotinic receptors in the CNS, Autonomic, and neuromuscular regions of the nervous system

Answer 19

False: There are only nicotinic receptors in the neuromuscular region of the nervous system. CNS and autonomic have both

Question 20

What toxin is a direct nicotinic receptor antagonist, what is the MOA

Answer 20

alpha-bungarotoxin, when replacing the calcium that keeps the sulfide bridges closed it also binds the free sulfide that would cause a conformational change that would open the channel

Question 21

Which muscarinic receptors are excitatory, what enzymes create which 2nd messengers

Answer 21

M1/M3/M5, Phospholipase C, calcium

Question 22

Which muscarinic receptors are inhibitory, what enzyme creates which 2nd messengers

Answer 22

M2/M4, Adenylate cyclase, cAMP

Question 23

T/F: Ach allows for infinite rotation around the alpha carbon but the best conformation to binding to receptors is when the quaternary amine and acetyl group are at a 90 degree angle

Answer 23

True

Question 24

What molecule could replace the nitrogen in Ach

Answer 24

Sulfur

Question 25

What are the two key needs to bind to Ach receptor

Answer 25

A positively charged group, a minimum of two methyl groups on the charged functional group

Question 26

What occurs if a methyl group is added to the alpha carbon of the ethylene bridge, what occurs when added to the beta carbon

Answer 26

selective nicotinic agonist activity, selective muscarinic agonist activity

Question 27

T/F: If a methyl group is added to the alpha and beta carbons of the ethylene bride of Ach it becomes more potent to binding to Ach receptors

Answer 27

False: There is no activity if a methyl group is added to the beta and alpha carbon of the ethylene bridge because there is to much steric hindrance that does not allow for binding

Question 28

What happens if the acetyl group is replaced by a carbamoly group in Ach, why

Answer 28

The agent then becomes orally active, carbomyls are more stable to hydrolysis

Question 29

What are anticholinergics

Answer 29

Traditionally muscarinic antagonists

Question 30

What is the most common muscarine antagonists

Answer 30

Atropine

Question 31

What are chemical features that are essential for muscarinic antagonist function

Answer 31

A quatenary or tertiary amine bonded to at least two methyl groups (quatenary would be charged and cannot enter the BBB), an aromatic ring in the opposite directions at least 5 carbons apart

Question 32

What are chemical features that are beneficial for muscarinic antagonist function

Answer 32

Hydrophobic ring, hydrogen bonding group

Question 33

Why are anticholinergics used for people with Parkinson's disease

Answer 33

Decrease the levels of Ach to achieve a close balance with dopamine levels since Parkinson's Disease patients have less dopamine leading to tremor and rigid muscles and the anticholinergic drugs decrease levels of Ach

Question 34

Where do nicotinic antagonists usually act

Answer 34

preganglionic synapses and neuromuscular junctions

Question 35

T/F: Nicotinic antagonists in ganglia usually act as competitive or non-competitive receptor blockers

Answer 35

True

Question 36

What is the MOA of depolorizing neuromuscular blockers type of nicotinic antagonists

Answer 36

Bind tightly to the Ach binding site of the nictonic Ach receptors and over stimulate the receptors causing more depolarizaition exhausting the receptor

Question 37

What are two common depolarizing neuromuscular blockers

Answer 37

succniylcholine and decamethonium

Question 38

What are key features of competitive neuromuscular junction blockers type of nicotinic antagonists

Answer 38

Large, charged

Question 39

What do all reversible AchE inhibitors have in common

Answer 39

All have carbamate groups attached to aromatic rings (aryl carbamates)

Question 40

What do all irreversible AchE inhibitors have in common

Answer 40

They are organophosphates

Question 41

T/F: If the irreversible AchE inhibitor is a thiophosphate it is a prodrug that is nontoxic to mammals

Answer 41

True

Question 42

T/F: Acetylcholine is converted back to choline before it is reuptook by pre-synaptic cells, then is converted to acetylcholine again

Answer 42

True

Question 43

What is the aging process with regards to irreversible organophosphate poisoning, how can this be combated

Answer 43

Water adds to the organophosphate making the bond between the organophosphate and the drug unhydrolizable, 2-PAM interacts with the drug and site to cause hydrolysis before the aging process