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

Year 1: 04. MSK Exam 2 > 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
Q

What do you call transmitters that utilize Acetylcholine?

A

Cholinergic

2
Q

What does the enzyme choline acetyltransferase do?

A

Synthesis of choline and acetyl CoA to make Acteylcholine

3
Q

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

A

Choline acetyltransferase

Leads to decreased ACh production

4
Q

What happens to newly syntheszied Acetylcholine?

A

ACh is shuttled into sorage vesicles via ACh vesicular transporters.

5
Q

How does ACh leave the vesicles?

A
  • 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
Q

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

A

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
Q

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

A
  • Acetylcholinesterase cleaves ACh into choline and acetate
  • ACh returns via choline transporter
  • Endocytosis can also reclaim ACh molecules
8
Q

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

A

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
Q

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

A

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

Example: Aspartic Acid and Glutamic Acid

10
Q

Tetrodotoxin

What is its mechanism?

How can you come into contact with this toxin?

A
  • 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
Q

Local Anesthetics

What is its mechanism?

Where do you see it being used?

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

Lidocaine, Bupivacaine, Procaine

12
Q

Botulinum Toxin

What is its mechanism?

What are its symptoms?

How can it be used clincally?

A
  • 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
Q

Tetanus Toxin

What is its mechanism?

What are its symptoms?

Where does it come from?

A
  • 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
Q

Curare Alkaloids (d-tubocurarine)

What is its mechanism?

What can it be used for?

A
  • 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
Q

How would you reverse the effect of a Curare Alkaloid?

A

Increase the amount of ACh in the neuromuscular junction

Ex: Utilize an acetylcholinesterase inhibitor

16
Q

Succinylcholine

What is its mechanism?

What is it used for?

A
  • 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
Q

Cholinesterase Inhibitor

What is its mechanism?

What is it used for?

A
  • 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
Q

Dantroline

What is its mechanism?

What is the clincal use?

A
  • 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
Q

What is Myasthenia Gravis?

A

Immune Disorder: Antibodies against nicotinic ACh receptors

  • Weakness and fatigue
  • Worsens with activity and better with rest
  • Symptoms
    • Ptosis, droopy eyelids
    • Jaw Fatigue
20
Q

Malignant hyperthermia?

What is this condition?

What can happen if left untreated?

How can you treat this?

A
  • 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