Pharm of the Neuromuscular Junction

Question 1

nAChRs (nicotinic)

Answer 1

activated by ACh and nicotine
ligand-gated ion channel (Na)
Pre and post junctional
NMJ: Na increase causes mm action potential

Question 2

mAChRs (muscarinic)

Answer 2

activated by ACh and muscarine
G-protein coupled receptor
Pre and post junctional
NOT located at skeletal NMJ

Question 3

nAChRs skeletal m

Answer 3

skeletal NMJ postjunctional 
excitatory, contraction
increased cation permeability (Na and K)
ACh, nicotine, succinyl choline 
atracurium, vecuronium, d-tubocuraine, Pancuronium

Question 4

nAChRs peripheral neuronal

Answer 4

autonomic ganglia, adrenal medulla
excitatory, depolarization
increased cation permeability (Na and K)
ACh, nicotine
mecamylamine

Question 5

nAChRs central neuronal

Answer 5

CNS
excitatory, pre-junctional control of ACh release
increased cation permeability (Na, K, and Ca)
cytisine, anatoxin A
mecamylamine

Question 6

Tetrodotoxin

Answer 6

puffer fish poison
MOA: inhibition of VG NA channels blocks axonal conduction
Symptoms: weakness, dizziness, paresthesias of the face and extremities, loss of reflexes, hypotension, generalized paralysis, and death due to respiratory failure and hypotension

Question 7

Local Anesthetics

Answer 7

MOA: inhibition of VG Na channels inhibition axonal conduction
utilized for pain control during a variety of clinical procedures
lidocaine, bupivacaine, procaine
Batrachotoxin
causes an increase in permeability of Na channels and induces a persistent depolarization
one of the most potent toxins

Question 8

Botulinum toxin

Answer 8

botulism is caused by Clostridium botulinum, a heterogenoeous group of gram positive rod shaped spore forming obligate anaerobic bacteria
vegetables, fruits, seafood, exist in soil and marine sediment worldwide
8 toxin type cause human disease: A B E and rearely F G H
MOA: cleaves components of the core SNARE complex involved in exocytosis preventing the release of Ach

Question 9

Tetanus toxin

Answer 9

tetanus is a nervous system disorder characterized by mm spasms that is caused by the toxin-producing anaerobe clostridium tetani which is found in the soil
MOA: block fusion of synaptic vesicles by tareting synaptobrevin
After binding to the presynaptic membrane of the NMJ tetanus toxin is internalized and transported retroxonally to the spinal cord
spastic paralysis is caused by the toxins actions on the spinal inhibitory interneurons, blacking release of inhibitory NT that normally serve to relax contracted m by inhibiting excitatory motor neurons

Question 10

Curare Alkaloids

Answer 10

d-tubocuraine is the prototype
MOA: competes with ACh for the nAChR on the motor end plate which decreasing the size of the EPP (nondepolarizing competitive nAChR antagonist)
inhibition of AcH binding to the nAChR leads to faccid paralysis of skeletal mm
used during anesthesia to relax skeletal mm
paralysis reversed by increasing ACh in NMJ (AChE inhibitor)

Question 11

Succinylcholine

Answer 11

MOA: depolarizing neuromuscular blocker that binds to skeletal m nAChRs and initially causes depolarization (Acts as and agonist) continued depolarization leads to receptor blockade and paralysis
used as an induction agent for anesthesia
paralysis reversed by termination of succinylcholine’s effects

Question 12

cholinesterase inhibitors

Answer 12

bind to AChE and block its enzymatic activity
increase the concentration of ACh at the NMJ
Clinical uses include dementia associated with Alzheimer or Parkinson disease, myasthenia gravis, nerve gas and organophosphate pesticide exposure, reversal of neuromuscular blockade during anestheisa

Question 13

Tetrodotoxin

Answer 13

blocks the outer mouth of Na channels and inhibits action potentials

Question 14

Dantrolene

Answer 14

inhibits ryanodine receptors in the sarcoplasmic reticulum and blacks release of Ca
clinical uses include malignant hyperthermia spasticity associated with upper motor neuron disorders