NMJ Pharmacology

Question 1

Tetrodotoxin

Answer 1

Puffer fish poison
Inhibition of voltage-gated Na+ channels and blocks axonal conduction
Weakness, dizziness, generalized paralysis

Question 2

Local anesthetics

Answer 2

Inibition of voltage-gated Na+ channels inhibit axonal conduction
Lidocaine, bupivacaine, etc
Pain control

Question 3

Botulinum toxin

Answer 3

Clostridium botulinum
Cleaves components of the core SNARE complex involved in exocytosis of ACh-prevents release
Acute onset of bilateral cranial neuropathies
No sensory deficits except blurred vision
Clinically used to improve lines/wrinkles of the face, prophylaxis of chronic migraine headaches

Question 4

Tetanus Toxin

Answer 4

NS disorder characterized by muscle spasms that is caused by Clostridium tetani
Block fusion of synaptic vesicles by targeting synaptobrevin
Becomes internalized in spinal cord
Blocks release of inhibitory NTs that normally serve to relax contracted muscle by inhibiting excitatory motor neurons
Spastic paralysis

Question 5

Neuromuscular blocking drugs

Answer 5

Both agonists and antagonists of the nAChR can prevent synaptic transmission
Agonist: activate the receptor to signal as a direct result of binding to it
Antagonist: bind to receptors but do not activate generation of a signal

Question 6

Curare alkaloids

Answer 6

Antagonist
D-tubocurarine
Competes with Ach for the nAChR on the motor end plate
Nondepolarizing competitive nAChR antagonist
Inhibition of ACh binding to the nAChR leads to flaccid paralysis of skeletal muscle
Paralysis reversed by increasing ACh int he NMJ (AChE inhibitor)
Used during anesthesia to relax skeletal muscle

Question 7

Succinylcholine

Answer 7

Agonist
Depolarizing neuromuscular blocker that binds to skeletal muscle nAChRs and initially causes depolarization
Continued depolarization leads to receptor blockade and paralysis
Induction agent for anesthesia
Paralysis reversed by termination of succinylcholine’s effects

Question 8

Depolarizing vs nondepolarizing

Answer 8

Nondepolarizing blocker: keeps the receptor in the closed state by blocking the ability for the receptor to open
Depolariing blocker: binds to receptor and opens the channel, allows ions to come in; however, channel stays open but is blocked at the pore which causes inability for cell to repolarize—>flaccid paralysis

Question 9

Cholinesterase inhibitors

Answer 9

Cholinesterase breaks down ACh
Bind to AChE and block its enzymatic activity
Increase the concentration of ACh at the NMJ
Helps with dementia
Reversal of neuromuscular blockade during anesthesia

Question 10

Dantrolene

Answer 10

Inhibits ryanodine receptors in the SR and blocks release of Ca2+
Malignant myperthermia, spasticity associated with upper motor neuron disorders