Lecture 15: Pharmacology of the Neuromuscular Junction (DSA+CIS) Flashcards Preview

04. MSK Exam 2 Final > Lecture 15: Pharmacology of the Neuromuscular Junction (DSA+CIS) > Flashcards

Flashcards in Lecture 15: Pharmacology of the Neuromuscular Junction (DSA+CIS) Deck (20)
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1

What do you call transmitters that utilize Acetylcholine?

Cholinergic 

2

What does the enzyme choline acetyltransferase do?

 

Synthesis of choline and acetyl CoA to make Acteylcholine

3

In Alzheimer's Disease, what enzyme deficiency do they have?

Choline acetyltransferase

Leads to decreased ACh production

4

What happens to newly syntheszied Acetylcholine?

ACh is shuttled into sorage vesicles via ACh vesicular transporters.

5

How does ACh leave the vesicles?

 

  • Calcium enters the cell and depolazies the membrane 
    • The vesicles with ACh move toward pre-synaptic membranes and fuse with them 
  • VAMPs and SNAPs assist the fusion and release of ACh
    • ACh is released into synaptic cleft via exocytosis 

6

What blocks the fusion of ACh vesicles to the pre-synaptic membrane?

Botulinum Toxin 

  • Heterogenous group of gram-positive, spore-forming anaerobic bacteria
  • Can be found on vegetables, fruits, seafood. this bacteria exists in soil and marine sediment.

7

How is ACh recycled back into the pre-synaptic cell?

  • Acetylcholinesterase cleaves ACh into choline and acetate 
  • ACh returns via choline transporter
  • Endocytosis can also reclaim ACh molecules 

8

What are some key differences between Nictonic and Muscarinic ACh receptors?

Nicotinic Acetylcholine Receptor (Ionotropic)

  • Found on Skeletal Muscles
  • Ligand Gated Ion Channel
    • Super fast (milliseconds)

Muscarinic Acetylcholine Receptor (Metabotropic)

  • Found on Smooth and Cardiac Muscles
  • G-protein Coupled Receptor
    • Second Messenger
    • Measured in seconds 

9

How do nicotinic ACh receptors select for positively charged ions to let through?

The inside of the receptor's channel is coated with negative charges 

Example: Aspartic Acid and Glutamic Acid

10

Tetrodotoxin

What is its mechanism?

How can you come into contact with this toxin?

  • Mechanism: Inhibition of voltage gated sodium channels
    • Can lead to paralysis, weakness, and even death (high dose) 
  • From puffer fish poison (more seen in Japan) 

11

Local Anesthetics

What is its mechanism?

Where do you see it being used?

  • Mechanism: Inhibition of voltage gated sodium channels
  • Can be used for many clincal procedures

 

Lidocaine, Bupivacaine, Procaine

12

Botulinum Toxin

What is its mechanism?

What are its symptoms?

How can it be used clincally?

  • Mechanism: Cleaves components of the SNARE complex, preventing ACh release
    • Can cause bilateral cranial neuropathies associated with symmetric descending weakness
    • Foodborne anaerobic bacteria: nausea, vomiting, abdominal pain, diarrhea
  • Clincial Use: Improve wrinkles and prophylaxis of chronic migraine headaches 

13

Tetanus Toxin

What is its mechanism?

What are its symptoms?

Where does it come from?

  • Mechanism: Blocks fusion of synpatic vesibles by targeting synaptobrevin and prevents release of inhibitory neurotransmitters
    • Causes spastic paralysis (e.g. lockjaw) 
  • Origin: Clostridium tetani produces this toxin and is found in the soil.

     

14

Curare Alkaloids (d-tubocurarine)

What is its mechanism?

What can it be used for?

  • Mechanism: Antagonist that competes with ACh and can decrease size of action potential
    • Relaxes skeletal muscles during anesthesia 

 

Competes with ACh and does not lead to an action potential

15

How would you reverse the effect of a Curare Alkaloid?

Increase the amount of ACh in the neuromuscular junction

 Ex: Utilize an acetylcholinesterase inhibitor

16

Succinylcholine

What is its mechanism?

What is it used for?

  • Mechanism: An agonist that depolarizes nicotinic nACh receptors and can cause continued depolarization
    • Receptor is blocked and can cause paralysis 
    • Can cause muscle fasciculations (twitch) 
  • Used as an induction for anesthesia
    • ​Takes much longer than ACh to break down 
      • ACh: broken down in milliseconds
      • Succinylcholine: broken down in minutes
  • Eventually reversed by time 

 

 

17

Cholinesterase Inhibitor

What is its mechanism?

What is it used for?

  • Mechanism: Binds to and inactivates acetylcholine esterase, increaseing ACh at NMJ
  • Clinical Use: 
    • Treatment of nerve gas and pesticide exposure

    • Myasthenia Gravis

    • Reversing neuromuscular blockade during anesthesia

18

Dantroline

What is its mechanism?

What is the clincal use?

  • Mechanism: Ryanodine (RyR) inhibitor that stops muscle contraction by blocking calcium release
    • Inhibits ACh release
  • Clincal Use:
    • Treatment of malignant hyperthermia, since the elevation of body temperature is related to muscle contractions
    • Treats muscle spasms

19

What is Myasthenia Gravis?

Immune Disorder: Antibodies against nicotinic ACh receptors

  • Weakness and fatigue 
  • Worsens with activity and better with rest
  • Symptoms
    • Ptosis, droopy eyelids
    • Jaw Fatigue 

20

Malignant hyperthermia?

What is this condition?

What can happen if left untreated?

How can you treat this?

  • Fast rise in body temperature and severe muscle contractions
    • Hyper metabolic repsonse 
  • Patients w/ this disease can see a mutation in Ryanodine Receptor (deals with Calcium storage) 
  • If left untreated, can lead to kidney failure
  • Treat with Dantrolene