Pharm MSK

Question 1

Synthesis of ACh

Answer 1

1) Choline transport via Choline transporter

2) Choline Acyltransferase: produces ACh via Choline and Acetyl-CoA

Question 2

Storage of ACh

Answer 2

1) ACh into the vesicle via ACh vesicular transporter

2) ATP-dependent

Question 3

ACh release

Answer 3

1) Action potential triggers Voltage Gated Ca2+ channels
2) Ca2+ enters cell –> promote fusion of vesicles via Synaptoagmin
3) VAMPs and SNAPs initiate vesicle fusion and release of ACh

Question 4

VAMPs

Answer 4

Synaptobrevin

Question 5

SNAPs

Answer 5

SNAP-25 and Syntaxin

Question 6

What prevents SNAP-25 and Syntaxin complex formation

Answer 6

N-Sec-1

Question 7

What associates with SNAP-25 and Syntaxin complex to form a Ternary

Answer 7

Synaptobrevin

Question 8

What allows for recycling of vesicle

Answer 8

NSF (ATPase) + SNAP bind and hydrolysisze ATP–> ADP

Question 9

ACh action termination

Answer 9

1) Acetylcholinesterase: ACh –> Acetate and Choline
2) Acetate diffuses out of cleft
3) Choline recycled via choline transporter

Question 10

Structure of nAChR

Answer 10

5 subunits surrounding a central pore w/ negative charge aa

Question 11

Agents that affect nerve action potential

Answer 11

1) Tetrodotoxin

2) Local Anesthetics: Lidocaine, Bupivacaine, Procaine

Question 12

Local anesthetics are useful for what?

Answer 12

Pain control

Question 13

Tetrodotoxin and Local anesthetics are agents that affects nerve action potential. What’s their MOA

Answer 13

Blocks voltage-gated Na+ channels

Question 14

What agents affect vesicular acetylcholine release

Answer 14

1) Botulinum Toxin

2) Tetanus Toxin

Question 15

Botulinum Toxin affects vesicular acetylcholine release. What is the MOA of Botulin Toxin

Answer 15

Cleaves SNAREs and prevents ACh

Question 16

Tetanus Toxin is an agent that affects vesicular acetylcholine release. What’s its MOA

Answer 16

1) Targets Synaptobrevin of inhibitory neurons of spinal cord

Question 17

Spastic Paralysis and Lock jaw are common synptoms of what>

Answer 17

Tetanus Toxin

Question 18

Why is Botulinum Toxin Clinically Relevant?

Answer 18

1) Temporary improvement in lines and wrinkles of face

2) Prophylaxis of Chronic Migraine Headache

Question 19

What’s the class name of agents that affect depolarization

Answer 19

1) Neuromuscular Blocking Drugs

Question 20

Neuromuscular blocking drugs are drugs that affect depolarization. List some common drugs that are affected with this?

Answer 20

1) Curare Alkaloids (d-tubocurarine)

2) Succinylcholine

Question 21

Neuromuscular drugs can either be agonist or antagonist. Describe both.

Answer 21

1) Agonist: Activate nAChR and generate signal
- succinylcholine

2) Antagonist: Bind but dont activate
- d-tubocurarine

Question 22

What neuromuscular drug causes transient muscle fasciculation due to agonist activity

Answer 22

Succinylcholine

Question 23

How is Succinylcholine paralysis reversed?

Answer 23

Time

Question 24

How in d-tubocurarine paralysis reversed

Answer 24

Increasing ACh via acetylcholine esterase inhibitor

Question 25

Agents that affect hydrolysis of ACh by AChE

Answer 25

AChE inhibitors

Question 26

Clinical use of AChE inhibitors

Answer 26

1) Dementia associated w/ Alzzheimer’s or Parkinsons disease, myasthenia gravis
2) Nerve gas and organophosphate pesticide exposure
3) Reversal of neuromuscular blockade during anestheia

Question 27

Agents that affect muscular contraction

Answer 27

Dantrolene

Question 28

Dantrolene MOA

Answer 28

Inhibits ryanodine receptors in the SR and blocks the release of Ca2+

Question 29

Clinical use of Dantrolene

Answer 29

Malignant Hyperthermia, Spasticity associated w/ upper motor neuron disorders