Multiple Sclerosis Flashcards
Avonex
C: IFN-beta-1a
M: Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism
T: RRMS
SE: Mild anemia, increase LFT (monitor every 6 mo.), hypothyroid; least NAB formed** Flu-like, minor irritation at inject site, anemia
MISC: Doesn’t cross BBB; decreases relapse rate by 1/3 and reduces MRI lesions, with a trend toward decreasing disability and brain atrophy
Rebif
C: IFN-beta-1a
M: Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism
T: RRMS (high-dose); first-line treatment (more efficacious than Avonex in head-to-head trials)
SE: Anemia, leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.)** Flu-like, injection site reaction; neutropenia; thrombocytopenia
MISC: As with Avonex; significantly reduces new and enhancing MRI lesions, reduces disablity
Betaseron
C: IFN-beta-1b
M: Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism
T: RRMS (high-dose); more efficacious than Avonex in head-to-head trials
SE: Leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.); more NAB formed than avonex** Flu-like, inject site reaction, anemia
MISC: As with Avonex, but no effect on disease progression
Extavia
C: IFN-beta-1b
M: Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism
T: RRMS (high-dose)
SE: Leukopenia, menstrual irregularities, depression, increase LFT and hypothyroidism (monitor every 3 mo.)** Flu-like, inject site reaction, anemia
MISC: As with Avonex, but no effect on disease progression
Glatiramer acetate (Copaxone)
C: Myelin basic protein analog
M: Mixture of 4 AAs in myelin basic protein; causes T-cell apoptosis (looks like MBP), induces anti-inflammatory Th2 cells (cytokine shift from Th1), induces Treg with induction of anergy
T: RRMS
SE: Mild: injection site reaction, anxiety attack-like reaction
MISC: Active in CNS (not peripherally); try to use early; reduce relapse by 1/3, modest reduction in MRI lesion and reduction of atrophy, but no effect on disease progression
Natalizumab (Tysabri)
C: Monoclonal antibody
M: Binds VLA4 (integrin subunit), inhibiting leukocyte migration across BBB
T: RRMS (2nd line)
SE: PML (JC virus); acute urticaria, systemic hypersensitivity infusion reaction** Headache, dizziness, fatigue, arthralgia, rigors
MISC: Decrease relapse rate by 2/3, greatly reduce MRI lesions; once/month; antibodies to natalizumab cause it to stop working; side effects more common in patients positive for neutralizing antibodies
Fingolimod (Gilenya)
C: Sphingosine-1-phosphate analog
M: Prodrug; sequesters circulating lymphocytes in secondary lymphoid organs via induction of intracellular internalization of receptors on lymphocytes (no effect on lymphocyte induction, proliferation, or memory function)
T: RRMS
SE: Bradycardia and heartblock (EKG for first 6 hours); macular edema (need opthalmology exam before and after 3 months)** Reduced FEV1, increased LFTs, lymphopenia, leukopenia, asthenia, back pain, blurred vision, headache dizziness, infections
MISC: Patients must be VZV immune before prescription; oral daily
Teriflunomide (Aubagio)
C: Immunosuppressants
M: Selective dihydro-orotate dehydrogenase inhibitor; blocks de novo pyramidine synthesis, reducing T- and B-cell proliferation and function against autoantigens; preserves replication and function of cells living on salvage pathway (e.g., hematopoietic cells, memory cells)
T: RRMS
SE: Hepatotoxicity; teratogenicity (animal data)
MISC: Oral daily
Dimethyl fumarate (Tecfidera)
C: –
M: Enhances Nrf2 pathway; some Th1 -> Th2 sgift
T: –
SE: N & V; diarrhea; stomach pain; flushing** Itching, redness, rash
MISC: Oral BID
Mitoxantrone (Novantrone)
C: Anthracenedione
M: Broad immune suppression and modulation of B cells, T cells and macrophages; decreases frequency of clinical relapse, reduces disease progress, and reduces disability
T: SPMS; RRMS (2nd line)
SE: Dose-dependent cardiac toxicity (decreased LVEF, irreversible CHF); induction of acute leukemia** Nausea and vomiting, alopecia, menstrual irregularities, increased susceptibility to infection
MISC: IV; once/3 months
Azathioprine (Imuran)
C: Immunosuppressants
M: Immunosuppressive
T: SPMS (resistant, or as combination with other therapies)
SE: Systemic toxicity: monitor blood for changes
MISC: –
Methotrexate (Trexall)
C: Immunosuppressants
M: Immunosuppressive
T: SPMS (resistant, or as combination with other therapies)
SE: Systemic toxicity: monitor blood for changes
MISC: –
Cyclophosphamide (Cytoxan)
C: Immunosuppressants
M: Immunosuppressive
T: SPMS (resistant, or as combination with other therapies)
SE: Systemic toxicity: monitor blood for changes
MISC: –
Mycophenolate mofetil (CellCept)
C: Immunosuppressants
M: Immunosuppressive
T: SPMS (resistant, or as combination with other therapies)
SE: Systemic toxicity: monitor blood for changes
MISC: Oral
Methylprednisone (MTP)
C: Corticosteroid (immunosuppressant)
M: Unclear mechanism (suppress both B and T cells, may reduce cytokine release)
T: Acute MS attack, SPMS; shortens acute attack duration,speeds recovery
SE: Short-term: insomnia, mood changes, fluid retention, epigastric pain, hypertension; long-term: osteoporosis, cushingoid, secondary malignancies
MISC: Given IV with oral prednisone taper
