Exam 3 neuro therapeutics -MS Flashcards
What MS drugs act only in the periphery (including the blood-brain barrier)?
-interferon-B, glatirimer acetate, natalizumab, mitoxantrone, teriflunomide, cladribine, rituximab (ocrelizumab), ATL1102(antisense oligonucleotide)
What are MS drugs that act in the periphery and CNS?
-fingolimod, siponimod, pzanimod, ponesimod
-dimethyl fumarate, monometyl fumarate, diroximel fumarate
What are MS drugs that act at the blood-brain barrier?
interferon-B, natalizumab, ATL1102
What MS drugs act via a cytotoxic effect?
mitoxantrone, teriflunomide, cladribine
What MS drugs increase the risk of PML?
-fingolimod, natalizumab
-dimetyl fumarate, monomethyl fumarate, diroximel fumarate
What MS drugs may have limited effectiveness due to neutralizing antibodies?
-interferon-B, natalizumab, rituximab (ocrelizumab)
What MS drugs can be used to treat PPMS?
rituximab (ocrelizumab)
How are acute attacks of MS treated?
methylprednisolone & prednisone
-work by up-regulating anti-inflammatory genes & down-regulating pro-inflammatory genes and alleviating edema in demyelinated areas
What are the first line drugs for MS?
1st line: interferon B1a, B1b, glatiramer acetate, fingolimod
What are the new drugs for MS?
teriflunomide, dimethyl fumarate, cladribine
What are the 2nd line drugs for MS?
natalizumab, mitoxantrone
What is the MOA of Interferon B1a & b?
-acts in periphery to inhibit T cells & dendritic cells
-acts to inhibit BBB penetration by decreasing matrix metalloproteinase (MMP)
What is the MOA of glatiramer acetate?
mimics myelin basic protein and therefore modulates antigen-presenting cells such as dendtritic cells leading to decreased T cell activation
What is the MOA of fingolimod (and all other -imods)?
-works in the periphery to interfere with lymphocyte movement out of lymphoid organs
-works in the CNS to stimulate oligodendrocyte survival and remyelination
What is the MOA of Natalizumab?
-mab specific for a4 intergrin which works with B1-integrin to inhibit VLA-4 which interferes with B and T cell movement into the CNS
What is the MOA of Mitoxantrone?
-cytotoxic effect that reduces lymphocytes by causing DNA strand breaks via intercalation and delaying DNA repair via inhibition of topoisomerase II
What is the MOA of teriflunomide?
-cytotoxic agent that inhibits proliferation of peripheral lymphocytes (activated B and T cells)
What is the MOA of Dimethyl fumarate (and Diroximel fumarate, monomethyl fumarate) ?
-acts in the CNS by activating Nrf2-mediated cellular antioxidant responses and anti-inflammatory pathways; may promote remyelination
-acts in the periphery by suppressing activated T cells, dendritic cells in the periphery
What is the MOA of Cladribine?
prodrug (2-chloro-dATP) with cytotoxic effect that interferes with DNA metabolism which results in cell death and lymphocyte depletion
What is the MOA of Rituximab/Ocrelizumab?
-human monoclonal antibody that targets CD20 (B cell marker)
What are important counseling points for Dimethyl fumarate + derivatives?
-monitor LFTs and CBC w/differential
-associated with PML
-can cause flushing, can take aspirin to avoid this
What are important counseling points for Sphingosine-1-phosphate receptor modulators?
-CI w/arrhythmias
-discontinuing can worsen MS
*Siponimod requires CYP2C9 genotype testing
*Ozanimod avoid use with MAOi
What are important counseling points for Glatiramer Acetate?
-may experience chest pain 4-8 hours after injection
-reject injection sites due to lipoatrophy
*preferred in pregnancy
What are important counseling points for interferon?
-monitor LFTs and TSH
-depression, suicidal thinking
-flu-like symptoms post injection; can use NSAIDS/tylenol
What is the only FDA approved drug for PPMS?
Ocrelizumab
What medication is FDA approved for walking speed?
Dalfampridine (Ampyra)
-IR dosage form CI w h/o seizures
