Multiple Sclerosis Drugs Flashcards
What 2-corticosteroid combination is commonly used to treat an acute MS attack? Give their routes of administration.
Methylprednisone given IV for 3-5 days, followed by predisone taper given orally
What 2 treatments can be used to treat acute MS attacks in patients who are allergic or unresponsive to corticosteroids?
Plasmapharesis or ACTH
Name the 4 immunomodulators that are currently 1st-line treatments for relapsing-remitting MS, giving both the molecules and brand names
IFNβ-1a: Αvonex and Rebif
IFNβ-1b: Betaseron and Extavia
Which immunomodulator is currently first line treatment for relapsing-remitting MS? Does it work peripherally or centrally?
Rebif (IFNβ-1a), works peripherally (the INFs do not cross the BBB)
All the immunomodulators can decrease relapse rate and MRI lesions for RRMS. Which class of immunomodulators can also reduce disease progression?
IFNβ-1a (IFNβ-1b have no effect on disease progression)
Order the MS drugs from most efficacious to least efficacious, and from most to least neutralizing antibodies produced: Avonex, Rebif, Betaseron.
Efficacy: Rebif, Betaseron, Avonex (based on the fact that Rebif is 1st line for RRMS)
NAB: Betaseron, Rebif, Avonex
What kind of molecule is glatiramer acetate (Copaxone), what is its main mechanism of action, and does it work peripherally or centrally?
An analog of myelin basic protein (MBP), mainly causes T-cell apoptosis, works centrally
(secondary mechanisms are to induce Th1 –> Th2 shift, and to induce Treg cells)
Glatiramer acetate (Copaxone) can reduce relapse, MRI lesions, and brain atrophy in RRMS. Does it also reduce disease progression? What is its main side effect?
No effect on disease progression; side effect of panic attacks
Name the monoclonal antibody that is 2nd or 3rd line treatment for RRMS. Does it reduce disease progression?
Natalizumab; does not reduce disease progression (does greatly reduce relapse rate and MRI lesions)
Describe how natalizumab achieves its therapeutic effects.
Binds to VLA-4 subunit of leukocyte integrins, inhibiting leukocyte migration across the BBB
What is the most significant long term side effect that may result from using natalizumab? What factors make patients at greater risk for getting this problem?
Patients may get PML (progressive multifocal leukoencephalopathy); associated with JC virus reactivation so anti-JC seropositivity and previous immunosuppression are risk factors
How are the MS medications fingolimod, teriflunomide, and dimethyl fumarate (BG12) administered?
Orally (compared to the IFNβs, glatiramer acetate, and natalizumab, which are all injections)
What MS drug has structural similarity to sphingosine-1-phosphate? How does it work?
Fingolimod; induces endocytosis of the S1P receptor, which causes sequestration of circulating lymphocytes in the lymphoid organs
Give 3 significant side effects of fingolimod that require monitoring either before or during treatment (hint: not the reduced FEV1, increased LFTs, lymphopenia, leukopenia, asthenia, back pain, blurred vision, headache, dizziness, or infections…)
Bradycardia and heart block (requires EKG checks), macular edema (requires optho exams), and severe shingles (requires VZV immunity)
How does teriflunomide achieve its immunosuppressant action, and what disease does it treat?
Inhibits DHODH (dihydro-orotate dehydrogenase) –> reduced pyrimidine synthesis –> reduced T- and B-cell proliferation; treats RRMS
What are the 2 black box warnings for teriflunomide?
Hepatotoxicity and teratogenicity (so not recommended for pregnant women)
What anti-inflammatory, neuroprotective drug, related to a class of psoriasis-treating drugs, is used to slow the disease progression of MS?
Dimethyl fumarate (BG12)
Give the primary and secondary mechanisms of action of dimethyl fumarate (BG12).
Primary: enhance the Nrf2 pathway, which protects against oxidative stress
Secondary: induce a cytokine shift from Th1 to Th2
What anthracenedione drug is the only FDA approved treatment for secondary progressive MS? Does it slow disease progression?
Mitoxantrone; slows disease progression
How does mitoxantrone work, and what forms of MS is it used to treat?
Broadly immunosuppressive, modulates B-cells, T-cells, and macrophages; used to treat SPMS and RRMS (2nd line)
Is mitoxantrone given orally or via IV? What is its most limiting side effect?
IV; causes cardiac toxicity (deceased LVEF, irreversible CHF)
Mitoxantrone is associated with the induction of what kind of cancer?
Acute leukemia
What kind of drugs are methotrexate and cyclophosphamide? What kind of MS are they used to treat, and (review from unit 1) what are their significant side effects?
Immunosuppressants; treat SPMS; side effects are pulmonary fibrosis and hepatotoxicity for methotrexate, and hemorrhagic cystitis for cyclophosphamide
Azathioprine and mycophenolate mofetil are what kind of drugs, used to treat what kind of MS? Which one is given orally?
Immunosuppressants; for SPMS; mycophenolate mofetil is oral
Which group of MS-treating drugs must be monitored for systemic toxicity?
The immunosuppressants (methotrexate, cyclophosphamide, azathioprine, and mycophenolate mofetil)
What kinds of MS can pulse steroids be used to treat?
SPMS and PPMS (off label)
