Komisky MS Flashcards
2 line MS
Alemtuzumab, natalizumab, mitoxantrone
IV injection, can be life threatening side effects
Corticosteroids
Symptomatic management- for moderate to severe exacerbations
IV methylprednisone 500 mg/day for five days
Delay neuro events and hasten recovery
DOES NOT ALTER COURSE
Interferon beta MOA
MOA: reduce production of the TNFa and T cells
Reduce inflammation by switching cytokines from type 1 to type 2 (anti inflammatory)
Decrease antigen presentation
Affects adhesion molecules, chemokines, proteases -reduces ability of immune cells to cross BBB
Interferon
Relapsing forms of MS
Reduces rate of clinical relapse, development of new lesions, and volume of lesions
SE: flu like symptoms, chills, fever, muscle aches, asthenia, injection site rxns
Uncommon: severe depression, suicide, seizures, cardiac effects, anemia, elevated liver enzymes, hepatic injury
Glatiramer acetate
Reduces frequency of relapse in pts with RRMS, moderately reduces development of new lesions
Synthetic chain of four amino acids, resembles myelin protein
Blocks immune system from attacking myelin
Switches immune response to anti inflammatory
SE: injection site rxns, chest pain (transient just scary)
Uncommon: N/ V dizziness
First line MS drugs
Interferon beta 1b, peginterferon b-1a, glatiramer acetate –self injection
Oral: fingolimod, teriflunomide, dimethyl fumarate
Fingolimod MOA
Sphingosine-1-phosphate receptor modulator - internalization of receptor- needs this to circulate (still have circulating T cells)
Sequesters circulating lymphocytes into secondary lymphoid organs
May inhibit production of IL 17
SIP receptors located within CNS
May have neuro protective properties
Fingolimod efficacy and side effects
Remains in blood for up to 2 months, immunosuppressants should be avoided
Treatment: up to 73% relapse free at 36 months
Ketoconazole- increases fingolimod
SE: reduction in heart rate, elevated bp, elevated liver enzymes, macular edema, infections, malignancies, blood lymphocyte count reductions
Drug interaction: antineoplastic/immunosuppressive, vaccines, drugs affecting hr, ketoconazole
Dimethyl fumarate
MOA: is unclear, suppresses macrophage and inflammatory activation of astrocytes and glioma cells, inhibits expression of adhesion molecules
Increases nrf2 DNA binding protein
Oral medication- reduced relapse rate, MRI outcomes, disability
SE: flushing and diarrhea, nasipharyngitis and headaches
Better than glatiramer
Teriflunomide
Once daily, oral medication: Reversibly inhibits dihydro-orotate dehydrogenase important role in pyrimidine synthesis - lymphocyte cannot proliferate
30% reduction in relapse frequency
SE: diarrhea, nausea, hair loss, abnormal hepatic biochemistry
Alemtuzumab
Given two times, one year apart IV4hrs, 5 days
Binds to CD52 on B cells and then it will get destroyed
SE: rash, headache, fever, N/V, fatigue, insomnia, nasal congestion
Immune thrombocytopenia, anti-glomerular basement membrane disease, bone marrow suppression, serious infections, infusion rxns, risk of cancer (thyroid, melanoma..)
Natalizumab
Monthly IV infusion
Selective adhesion inhibitor, monoclonal against alpha 4 integrin
(T cells can’t bind to enter into blood stream)
Risk of PML ( if taking it with additional immunosuppressive drug)
Mitoxantrone
Reduction of relapse rate in SPMS, PRMS, RRMS
Short IV very three months
Inhibits or prevents uncontrolled growth, suppresses B and T cell
SE: bone marrow suppression (neutropenia and thrombocytopenia, AML), cardiac toxicity(CHF, LVEF), increased liver enzymes, nausea, alopecia
Contraindications:,cardiac problems, myelosuppresion, neutropenia, pregnant or breast feeding
Dalfampridine
Improves walking speed in pts with MS- not disease modifying
K channel blockade
SE: seizures
Cost : 15,000 per year. Significantly cheaper than others
