Rochet and Dr.Ott MS drug classes Flashcards
What drugs are used for treatment of acute attacks in MS
Methylprednisolone
Prednisone
Adrenocorticotropic hormone
Explain the benefits of disease modifying therapies in MS
- These can reduce relapse rates and may lead to slower progression oof disability
- Generally used to treat relapsing rather than progressive forms of MS
what are first line drugs used for disease modifying in MS
Interferon B1a (Avonex, Rebif)
Interferon B1b (Betaseron, Extavia)
Glatiramer acetate ( Copaxone)
Fingolimod (gilenya)
what are second line drugs used for disease modifying in MS
Natalizumab (Tysabri)
Mitoxantrone (novantrone)
what are the new drugs used for disease modifying in MS
Teriflunomide (aubagio)
Dimethyl fumarate (Tecfidera)
Cladribine (Mylinax)
Which MS treatments act only in the Periphery
glateramer acetate ( copaxone)
Natalizumab (tysabri) - at BBB
Which MS treatments act only in the CNS
Which MS treatments act in both Periphery and CNS
Fingolimod (gilenya)
Interferons B1a (Avonex, Rebif) and Interferons B1b (betaseron, Extavia) MOA and clinical feature
Work at periphery by blocking the activation of T cells by dendritic cells
Work at BBB by reducing MMP thus inhibiting the penetration of B cells and T cells to the CNS
First line drugs. but their efficacy is reduced by neutralizing antibodies immune response
Can be given SubQ or IM every other day to every 2 weeks
Side effects: flu like symptoms (can avoid by taking NSAID before dose or IM dosing at bedtime) depression, suicidal thinking
Monitor
- LFTs and TSH as these medications can elevate liver function tests and thyroid dysfunction
Glatiramer acetate (copaxone) MOA and clinical features
Works in the periphery
mimics myelin presenting proteins and modulates antigen presenting cells like dendritic cells to decrease T cell activation
Side effects: injection site reaction, post injection reaction (flushing, sweating, chest pain, anxiety, itching)
May be an option for pregnancy if treatment is needed
Fingolimod (Gilenya) MOA and clinical feature - MEM STRUCTURE
Works in CNS to stimulate oligodendrocyte survival and thus promote remyelination
Works in lymph nodes to decrease the release of lymphocytes from the nodes (decrease release of T cells)
MONITOR:
- for 6 hours after first dose due to bradycardia (EKG at baseline)
- Monitor CBC as patient is at increased risk for infection, routine eye exam
Side affects: include progressive multifocal leukoencephalopathy (PML) - this is a potentially lethal brain infection
- discontinuation can result in significant worsening of MS symptoms
CONTRAINDICATED with past arrythmia diagnosis
Natalizumab (Tysabri) MOA and clinical features
- humanized monoclonal antibody that will bind to VLA-4 which is a product of alpha-4 and B 1 integrin binding.
By binding to VLA-4 it blocks binding for T and B cells to bind to alpha-4 and thus interfering with their movement thru BBB and into the CNS
Side effect - can cause PML (lethal brain infection) and can induce development of neutralizing antibodies and cause an allergic reaction
mitoxantrone (Novantrone) MOA
has cytotoxic activity
- works in the peripheral to reduce number of T and B cells by inducing DNA strand breaks and delaying DNA repair by inhibiting Topoisomerase II
Teriflunomide (aubagio)
Cytotoxic agent that inhibits the growth and proliferation of T and B cells
Dimethyl fumarate (tecfidera)
Diroximel fumarate (Vumerity)
Monomethyl fumarate (bafiertam)
MOA and clinical feature
Work in both CNS and Peripheral
- In CNS they stimulate Nrf-2 mediated cellular antioxidant responses and anti-inflammatory pathways
- in Periphery they suppress activated T cells (dendritic cells)
- Capsule should not be opened and sprinkled on food, do not crush or chew
AE: could include PML, Flushing (can take aspirin 30min prior to dose)
Siponimod (Mayzent)
Ozanimod (Zeposia)
Ponesimod (Ponvory)
MOA
S1P receptor modulators
Work in the CNS to stimulate oligodendrocyte survival to promote remyelination
and interfere with release of T cells from lymph nodes
MONITOR:
- for 6 hours after first dose due to bradycardia (EKG at baseline)
- Monitor CBC as patient is at increased risk for infection, routine eye exam
Side affects: include progressive multifocal leukoencephalopathy (PML) - this is a potentially lethal brain infection
- discontinuation can result in significant worsening of MS symptoms
CONTRAINDICATED with past arrythmia diagnosis
Cladribine (Mylinax) - MUST MEM STRUCTURE
MOA
Acts as a pro-drug
taken up in lymphocytes and nonocytes and turned into active form which damages DNA and interferes with DNA metabolism which results in cell death and lymphocyte depeltion
Alemtuzumab (Compath)
MOA
effective in treating the early phase of MS
targets CD52
Contraindicated in HIV infection - prolonged decrease in CD4 count
Rituximab (rituxan)
also known as ocrelizumab
Stops RRMS and effective for some PPMS
Works in periphery and targets CD20 which is present on surface of B cells
- does not bind to CD20 on stem cells or plasma cells
- decreases the disease progression in PPMS
- Decreased relapse rate in RRMS
CONTRAINDICATED in active hepatitis B
ONLY FDA APPROVED FOR PPMS
Treatment of acute attacks
Corticosteroids
Methylpredinisolone 500mg-1000mg IV daily for 3 to 7 days, with or without an oral taper over 1-3 weeks
IF OUTPATIENT: Oral prednisone 1250mg every other day x 5 doses without need for taper
Disease modifying drugs
ORAL medications
Dimethyl fumurate
Diroximel fumarate
Fingolimod
Ozanimod
Ponesimod
siponimod
Teriflunomide
Disease modifying drugs
Injectable medications
Interferon B1a
Peginterferon B1a
Interferon B1b
Glantiramer acetate
Disease modifying drugs
Infusion medications
Alemtuzumab
Natalizumab
Ocrelizumab
Must complete vaccinations at leas ___ weeks before starting treatment with monoclonal antibodies
6 weeks
what should we do if a patient on teriflunomide gets pregnant
COMPLETELY CONTRAINDICATED
we should D/C medication immediately and place patient on activated charcoal for 11 days
Mitoxantrone and preganacy
contraceptive required for treatment
must get pregnancy test before each infusion
Fingolimod and pregnancy
Contraception during treatment and for at least 2 months affter D/C
spironolactone and pregnancy
contraceptive during treatment and for at least 10 days after D/C
Ocrelizumab and preganacy
contraceptive during treatment and for at least 6 months after D/C
Cladribine and preganacy
contraceptive required and barrier method for at least 6 months after D/C
Contraindicated in breast feeding
What is Pseudobulbar affect and what is used to treat it
Pseudobulbar is frequent and inappropriate episodes of laughing or crying unrelated to actual mood
can be treated with Neudexta (dextromethorphan/quinidine)
Treatment for gait abnormalities
Dalfampridine (ampyra)
may improve walking speed
IR dose associated with seizures and contraindicated in patients with a history of seizures (ER is preferred)
