Synaptic Transmission Disruption Flashcards
What nerve agent disrupts transmission at NMJ?
Novichok
What is Novichok’s MoA?
Prevents breakdown of ACh -> enhnaced ACh at NMJ
What is the result of increased ACh at NMJ?
Involuntary contraction of skeletal muscles
Respiratory failure and cardiac arrest
What are 4 pathological disorders of the NMJ?
Myasthenia Gravis
Lambert Eaton Syndrome
Tetanus toxin
Botulinum toxin
What is Myasthenia gravis?
Autoimmune synpaptopathy
What are the symptoms of Myasthenia gravis?
Long-term skeletal muscle weakness eg. drooping of eyelids
How could Myasthenia gravis symptoms be reversed?
By using inhibitors of AChE
What is Myasthenia gravis’ MoA?
Production of antibodies against ACh at NMJ
Decreases availability of ACh receptors
Inhibits muscle contraction
Receptor loss by phagocytosis
What causes Myasthenia gravis?
Autoimmune disease
Bacterial or viral infection
Thymomas
What can treat Myasthenia gravis?
No known cure
Increasing rest periods
AChE inhibitors
Immunosuppressant treatment
What is Lambert-Eaton syndrome?
Pre-synaptic autoimmune disease targeting the NMJ
What are the symptoms of Lambert-Eaton syndrome?
Muscle weakness in limbs
Reduced reflexes
Weakness in respiratory muscles
What is Lambert-Eaton syndrome’s MoA?
Production of antibodies directed against VGCCs
Bind to domain III S5-S6 linker peptide
Reduce influx of Ca2+ to pre-synaptic terminl
What is the treatment for Lambert-Eaton syndrome?
No known cure
Chemo and radiotherapy
Surgery
Repeated stimulation of the synapse
Amifampridine can block efflux of K+ prolonging action potential
What is Tetanus caused by?
Infection from Clostridium tetani
What are the symptoms of tetanus?
Spasmogenic toxicity
Respiratory problems
Difficulty swallowing
Uncontrolled urination/defecation
What is Tetanus MoA?
Enters at NMJ
Enters CNS by retrograde axonal transport
Transcytosis from axon into inhibitory interneurons of spinal cord
Cleaves synaptobrevin (VAMP)
Inhibits vesicle fusion
Interferes with glycine release
How is Tetanus treated?
Tetanus vaccine for prevention
antibodies to reduce toxin production
muscle relaxants
What is Botulism caused by?
Neurotoxin produced by Clostridium botulinium
What are symptoms of Botulism?
Muscle weakness
Blurred vision
Fatigue
Paralysis
Respiratory failure
What is Botulism MoA?
heavy chain binds to glycoprotein structures found in cholinergic nerve terminals
light chain binds with high affinity to SNARE complex
Prevents ACh vesicle docking
Blocks vescile fusion
How is Botulism treated?
Food borne: Induced vomiting
Wound infection: surgery,
Botulinum antitoxin: removes toxin from bloodstream
What are other uses of Botulism?
Biological warfare
Botox
Treats overactive muscle movement, excess sweating and salivation and migraines
