Msk 12 Flashcards
Binding of released ACh to ______ receptors depolarizes the motor end-plate.
Nicotinic
Binding of _____ to LRP4, and_______ complex, clusters AChR at the NMJ.
Agrin
Muscle Specific Tyrosine Kinase (MuSK)
Myasthenia gravis results from autoantibodies to _____, ______, or ________.
AChR
MuSK
LRP4
What are the two reversible AChE inhibitors?
Edrophonium & Ambenonium
What are the 3 slowly reversible inhibitors of AChE?
Neostigmine (Prostigmin®)
Pyridostigmine (Mestinon®)
Physostigmine
What is the general type of inhibitor used for cholinesterase inhibition?
Carbamate inhibitors
What are the trade names for Edrophoinium, a drug used as a diagnostic agent in myasthenia gravis?
Why is it used as a diagnostic agent?
Tensilon
Enlon
Short duration of action (5-15 min)
What are the 3 drugs used to treat Myasthenia Gravis?
Pyridostigmine
Neostigmine
Ambenonium
Increased ACh levels in autonomic synapses activates ________ receptors.
What can be done to block this?
Muscarinic
Causes:
Bradycardia
Increased GI motility
Salivation
Miosis
Administer atropine with the carbamate inhibitor
What is the most often used inhibitor for Myasthenia Gravis?
Pyridostigmine (3-6 hours)
What are the two aminopyridines that block voltage-dependent K+ channels at the neuromuscular jxn?
Dalfampridine
- 4-aminopyridine - Ampyra®
3,4-diaminopyridine
How do aminopyridines work?
Blocking K+ channels enhances Ach release at the synapse
Keeps the endplate depolarized longer
What are aminopyridines used to treat?
Lambert-Eaton Myasthenic Syndrome
How do we treat the autoimmune component of myasthenic diseases?
Glucocorticoids - Prednisone (Deltasone®)
Azathioprine (Imuran®)
In the treatment of myasthenic diseases, how do glucocorticoids work?
Steroid receptor activation –> reduced phagocytic cell migration to sites such as NMJ
Decreases antigen-presenting fxn of phagocytic cells
High doses can reduce antibody production
For a patient complaining of muscle weakness but already receiving drug therapy to manage her Myasthenia Gravis, how can we determine if she is taking an inadequate dosage or if she is overdosing?
Administer Tensilon test
Inadequate dosage = immediate improvement in muscle strength
Overdose = no effect or symptoms worsen
Name some adverse effects related to glucocorticoid treatment.
Moon facies
weight gain
muscle wasting
hyperglycemia
osteoporosis
hypokalemia
hypertension
infections
How does Azathioprine (Imuran®) work?
Azathioprine converted to 6-mercaptopurine
6-mercaptopurine blocks de novo purine synthesis in lymphocytes to prevent T cell proliferation during antigen challenge
What are some adverse effects of Azathioprine?
Affects rapidly growing cells (e.g. bone marrow, GI tract)
Leukopenia, thrombocytopenia
NVD
Increased risk of infections, neoplasias
Additive with other myelosuppressive agents
