Exam 3 neuro therapeutics -MS

Question 1

What MS drugs act only in the periphery (including the blood-brain barrier)?

Answer 1

-interferon-B, glatirimer acetate, natalizumab, mitoxantrone, teriflunomide, cladribine, rituximab (ocrelizumab), ATL1102(antisense oligonucleotide)

Question 2

What are MS drugs that act in the periphery and CNS?

Answer 2

-fingolimod, siponimod, pzanimod, ponesimod
-dimethyl fumarate, monometyl fumarate, diroximel fumarate

Question 3

What are MS drugs that act at the blood-brain barrier?

Answer 3

interferon-B, natalizumab, ATL1102

Question 4

What MS drugs act via a cytotoxic effect?

Answer 4

mitoxantrone, teriflunomide, cladribine

Question 5

What MS drugs increase the risk of PML?

Answer 5

-fingolimod, natalizumab
-dimetyl fumarate, monomethyl fumarate, diroximel fumarate

Question 6

What MS drugs may have limited effectiveness due to neutralizing antibodies?

Answer 6

-interferon-B, natalizumab, rituximab (ocrelizumab)

Question 7

What MS drugs can be used to treat PPMS?

Answer 7

rituximab (ocrelizumab)

Question 8

How are acute attacks of MS treated?

Answer 8

methylprednisolone & prednisone
-work by up-regulating anti-inflammatory genes & down-regulating pro-inflammatory genes and alleviating edema in demyelinated areas

Question 9

What are the first line drugs for MS?

Answer 9

1st line: interferon B1a, B1b, glatiramer acetate, fingolimod

Question 10

What are the new drugs for MS?

Answer 10

teriflunomide, dimethyl fumarate, cladribine

Question 11

What are the 2nd line drugs for MS?

Answer 11

natalizumab, mitoxantrone

Question 12

What is the MOA of Interferon B1a & b?

Answer 12

-acts in periphery to inhibit T cells & dendritic cells
-acts to inhibit BBB penetration by decreasing matrix metalloproteinase (MMP)

Question 13

What is the MOA of glatiramer acetate?

Answer 13

mimics myelin basic protein and therefore modulates antigen-presenting cells such as dendtritic cells leading to decreased T cell activation

Question 14

What is the MOA of fingolimod (and all other -imods)?

Answer 14

-works in the periphery to interfere with lymphocyte movement out of lymphoid organs
-works in the CNS to stimulate oligodendrocyte survival and remyelination

Question 15

What is the MOA of Natalizumab?

Answer 15

-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

Question 16

What is the MOA of Mitoxantrone?

Answer 16

-cytotoxic effect that reduces lymphocytes by causing DNA strand breaks via intercalation and delaying DNA repair via inhibition of topoisomerase II

Question 17

What is the MOA of teriflunomide?

Answer 17

-cytotoxic agent that inhibits proliferation of peripheral lymphocytes (activated B and T cells)

Question 18

What is the MOA of Dimethyl fumarate (and Diroximel fumarate, monomethyl fumarate) ?

Answer 18

-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

Question 19

What is the MOA of Cladribine?

Answer 19

prodrug (2-chloro-dATP) with cytotoxic effect that interferes with DNA metabolism which results in cell death and lymphocyte depletion

Question 20

What is the MOA of Rituximab/Ocrelizumab?

Answer 20

-human monoclonal antibody that targets CD20 (B cell marker)

Question 21

What are important counseling points for Dimethyl fumarate + derivatives?

Answer 21

-monitor LFTs and CBC w/differential
-associated with PML
-can cause flushing, can take aspirin to avoid this

Question 22

What are important counseling points for Sphingosine-1-phosphate receptor modulators?

Answer 22

-CI w/arrhythmias
-discontinuing can worsen MS
*Siponimod requires CYP2C9 genotype testing
*Ozanimod avoid use with MAOi

Question 23

What are important counseling points for Glatiramer Acetate?

Answer 23

-may experience chest pain 4-8 hours after injection
-reject injection sites due to lipoatrophy
*preferred in pregnancy

Question 24

What are important counseling points for interferon?

Answer 24

-monitor LFTs and TSH
-depression, suicidal thinking
-flu-like symptoms post injection; can use NSAIDS/tylenol

Question 25

What is the only FDA approved drug for PPMS?

Answer 25

Ocrelizumab

Question 26

What medication is FDA approved for walking speed?

Answer 26

Dalfampridine (Ampyra)
-IR dosage form CI w h/o seizures