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42 Cards in this Set
- Front
- Back
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Ocular manifestations of MS (2)
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blurred vision and diplopia
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Cerebellar manifestations of MS (3)
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ataxic walk, vertigo and nystagmus
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Autonomic manifestations of MS (2)
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urinary continence and sexual disorders
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Motor manifestations of MS (3)
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reduced strength/activity, muscle spasms, and muscle weakness
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Sensory manifestations of MS (3)
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sensory changes, hypesthesia, and progressive sensory loss
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Diagnostic tests of MS (4)
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-evoked potential (abnormal neural transmission
-reflexes and sensativity -analysis of CSF -neuroimaging |
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How much does axonal density decrease by(%) in the corpus callosum of MS patients?
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35%
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Neurodegeneration
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process of neuronal, myelin, or tissue breakdown, the degradative products of which evoke a reaction of phagocytosis and cellular astrogliosis
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What are the three immune-mediated factors of MS?
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-many inflammatory cell types located at lesion site
-inflammatory cells are dysregulated -levels of several inflammatory cytokines are increased in serum, CSF, and CNS |
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What happens when a mouse is injected with myelin basic protein and complete Freund's adjuvant?
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demyelinating disease (EAE)
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What mediates EAE?
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myelin basic protein-specific Th1 cells
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What do they transfer between animals to transmit EAE?
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T cells
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What risk is increased after inflammatory-mediated tissue damage?
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Increased risk of ischemic stroke
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What is the result of myelin damage and reduced axonal activity?
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chronic hypoperfusion (decreased blood flow through organ)
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What are two characteristics of a novel agent necessary to treat MS?
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protection/repair of CNS and targeting inflammation
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Immunoregulator
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drug or compound able to regulate the activity of the immune system, both in a positive and negative direction.
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Immunosuppressor
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type of immunoregulator that decreases the activity and efficacy of the immune system
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What risk increase is associated with immunosuppressors?
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risk of developing neoplasms
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Anti-mitotic agents
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drugs that inhibit proliferation of cells with high mitotic activity such as immune cells
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Anti-mitotic agents can be used as what?
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immunosuppressors
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Humanized monoclonal antibodies
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antibodies directed against an epitope(part of antigen recognized by immune system)
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What is the result of presenting GA peptide as an antigen?
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it generates GA-specific T cells of Th2 bias
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What is the function of interferon-beta?
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acts through its receptor and inhibits antigen presentation and T cell activity decreasing pro-inflammatory Th1 cytokines
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What are five emerging MS therapies/strategies?
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-age specific therapies
-combination therapies -oral IMs -cytotoxic agents -monoclonal Ab |
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What are two examples of combination therapy?
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IFNbeta + MP and INFbeta and GA
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What are three examples of oral IMs?
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-BG-12
-laquinimod -teriflunomide |
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What is an example of a monoclonal Ab?
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alemtuzumab
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Mechanism of signal mediated through S1P (3)
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-lymphocytes circulate between blood and secondary lymphoid organs looking for antigens
-during immune response induced by encounter with antigen, lymphocytes internalize S1P allowing clonal expansion -increase in S1P allows activated lymphocyte to exit into blood stream |
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What is the function of tysabri?
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it inhibits CNS trafficking by attaching to the leukocyte antigen in circulation so the vcam-1 antibody cannot recognize it in tissue
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What does the efficacy-adverse events ratio of natalizumab indicate?
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the risks outweigh the benefits due to risks of hypersensitivity, infections, and progressive multifocal leukoencephaly
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What is the consequences of prior immunosuppressant use before natalizumab treatment?
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it increases the risk of getting PML from 2.8/1000 to 8.1/1000 after natalizumab treatments of two years
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Teriflunomide(oral) effects (3)
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-reduced relapse rates
-disability progression -improved MRI outcomes in longterm |
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BG-12(oral) effects (2)
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-significantly reduced relapse rates
-improved MRI with BID and TID dosing |
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Laquinimod(oral) effects (2)
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-significant disability progression reduction
-significant brain atrophy reduction |
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Alemtuzumab(injectable) effects (2)
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-ARR reduced by half compared to INFbeta-1a
-new lesion formation significantly reduced compared with INFbeta-1a |
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Daclizumab(injectable) effects (1)
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-quickly reduced ARR by about half
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Where is fingolimod derived from and what structure is it similar too?
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miriocine isolated from the fungus is aria sinclairii with a similar structure to sphingosine
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Sphingosine
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natural sphingolipid that acts as an intracellular messenger on the surface of the cell through receptor S1P after phosphorilation
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What is the treatment objective for early stage MS
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use immunomodulators for neuroprotection and to enhance repair
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What is the treatment objective for late stage MS?
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neuroprotection and to enhance repair
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What are two future drug strategies for the treatment of MS, and what system(s) does each act on?
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-GrB inhibitors (IS and CNS)
-neurosteroids(CNS) |
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What is the relationship between orals or injectables and their safety/efficacy?
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-injectables have either high efficacy with poor safety or low efficacy with high safety
-orals have a balance between efficacy and safety |
