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
