Multiple Sclerosis Flashcards
A patient with a long history of relapsing-remitting MS comes in with an acute exacerbation. What do you prescribe? What are alternate therapies if she is allergic or unresponsive to the first-line treatment?
- start with methylprednisone
- other options are ACTH or plasmaphoresis
What is the theory behind the MOA of anti-inflammatory agents in an acute attack?
- suppress both T and B cells
- transiently reduces cytokine release
- whatever they do, the goal is to shorten the attack and expedite the recovery
What are the two IFN-beta-1a drugs?
- Avonex and Rebif (rebif is same molecule in higher dose)
- like natural IFN
- Rebif shown to be more efficacious in trial
What are the potential mechanisms of action of IFN-beta drugs when treating MS?
- inhibit T cell activation
- cytokine shift from Th1 to Th2
- inhibits lymphocyte migration to CNS
- antiproliferative effect
- apoptosis of autoreactive T cells
- IFN-gamma antagonism
- antiviral
What are the two IFN-beta-1b drugs?
- Betaseron and Extavia
- different than natural IFN
What are potential side effects of Rebif, Betaseron, and Extavia (the IFN-beta drugs given in high doses)?
- flu-like symptoms,
- leukopenia/anemia
- menstrual irregularities
- depression
- increased LFTs
- hypothyroidism
What are the potential side effects of Avonex (lower dose IFN-beta)?
- flu-like symptoms
- mild anemia
- increased LFTs
- hypothyroidism
After prolonged use of IFN-beta drugs, a certain reaction is almost guaranteed to take place, which when persistent renders these drugs useless. What is this reaction?
- neutralizing antibodies are formed
- can be transient, but when persists will cross react to all IFN’s
You’re treating a patient with RRMS and you decide to prescribe a drug that is a myelin basic protein analog. What drug is this and what is the MOA?
- glatiramer acetate
- causes T cell apoptosis
- shifts Th1 to Th2
- induces Tregs by inducing anergy
- neuroprotection
- stays in CNS and decreases brain atrophy
What are the general summaries of the studies done on 1st line therapies for MS?
- early therapy is better
- higher, more frequent dosing is better
- glatiramer acetate is as efficacious as high dose interferons
- rebif is probably the interferon of choice (less Nabs, more efficacious)
What is the MOA of natalizumab and what is an important side effect?
- MAB that binds VLA-4 (which is expressed on the surface of all leukocytes) and inhibits leukocyte migration across BBB
- important side effect: can cause PML (especially if patient has + JC virus Ab)
You want to use a drug to treat MS that works by sequestering circulating lymphocytes in lymph nodes. What drug do you use, what antibodies must you check for before you prescribe, and what tests do you have to run while they are on it?
- fingolimod, a prodrug
- must have VZV antibodies prior to starting
- run EKG for first 6 hours (can cause heartblock)
- give ophthalmology exam before and after 3 months (can cause macular edema)
How does teriflunomide work?
- blocks de novo pyrimidine synthesis, which reduces T and B cell proliferation
- preserves replication of cells replicating from the salvage pathway (hematopoietic, memory T cells)
What are the two black box warnings of terflunomide?
- hepatotoxicity and teratogenicity
A recently diagnosed MS patient comes in with a history of psoriasis that is ready to start treatment of her RRMS. What drug can you prescribe that will help both medical conditions and how does this drug work?
- dimethyl fumarate
- for MS: activates Nrf2 pathway, induces antioxidant enzyme production (reduces oxidative stress)
- may also cause a Th1 to Th2 shift
