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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What do you call transmitters that utilize Acetylcholine?



What does the enzyme choline acetyltransferase do?


Synthesis of choline and acetyl CoA to make Acteylcholine


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

Choline acetyltransferase

Leads to decreased ACh production


What happens to newly syntheszied Acetylcholine?

ACh is shuttled into sorage vesicles via ACh vesicular transporters.


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 


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.


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 


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 


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



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) 


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


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 


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.



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


How would you reverse the effect of a Curare Alkaloid?

Increase the amount of ACh in the neuromuscular junction

 Ex: Utilize an acetylcholinesterase inhibitor



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 




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



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


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 


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