Pharmacology - Multiple Sclerosis

Question 1

For patients allergic to methylprenisolone, what is the second choice for treatment of acute attacks of MS?

Answer 1

Plasmaphoresis

Question 2

MOA: Interferon-beta

Answer 2

Inhibit T-cell activation;
Cytokine shifts from Th1 to Th2;
Inhibits lymphocyte migration into CNS;
Antiproliferative effect
Apoptosis of autoreactive T-cells
IFN-gamma antagonism;
Antiviral effect;
Does not cross BBB

Question 3

MOA: Glatiramer Acetate

Answer 3

Active in CNS, not systemically;
Causes T-cell apoptosis because it looks like myelin basic protein;
Induction of anti-inflammatory Th2 cells with shift from Th1 to Th2 cytokines;
Induces regulatory T cells with induction of anergy;
Possible neuroprotection

Question 4

Use: Interferon-beta

Answer 4

Treat MS, prevents relapse in 1/3 of patients

Question 5

Use: Glatiramer Acetate

Answer 5

Treat MS

Question 6

T/F: Higher and more frequent dosing of interferons and glatiramer acetate is better for treating MS, based on clinical studies.

Answer 6

True

Question 7

Which is the preferred treatment for MS, Rebif, Avonex, Copaxone or Betaseron?

Answer 7

Rebif (Interferon beta-1a)

Question 8

What drug carries a risk factor for developing PML?

Answer 8

Natalizumab

MRI every 6 months and JC virus antibody testing every 6 months

**Both fingolimod and dimethyl fumarate have caused PML as well, although risk is much lower.

Question 9

Use: Fingolimod

Answer 9

RRMS

oral

Question 10

MOA: Fingolimod

Answer 10

Prodrug;

Active form sequesters circulating lymphocytes in secondary lymphoid organs

Question 11

Side Effects: Fingolimod

Answer 11

Bradycardia, heart block
Macular edema;
Must have VZV antibodies;
increased risk of zoster

Question 12

Use: Teriflunomide

Answer 12

RRMS;

oral

Question 13

MOA: Teriflunomide

Answer 13

blocks dihydro-orate dehydrogenase –> blocks de novo pyrimdine synthesis, reducing T and B cell proliferation and function in response to autoantigens

Question 14

Side Effects: Teriflunamide

Answer 14

Decreased hair density, GI irritation, elevated liver enzymes

Hepatotoxicity, Teratogenicity

Question 15

MOA: Dimethyl fumarate (BG12)

Answer 15

Neuroprotective:
Activates Nrf2 pathway and induces antioxidant enzyme production;
Protects oligodendrocytes against free-radical induced cytotoxicity;
Increases neuronal survival and protects astrocytes against oxidative stress in vitro;
Preserves myelin, axons and neurons in EAE

Anti-inflammatory:
Inhibits expression of adhesion molecules and proinflammatory cytokines;
Induces Th1 to Th2 shift

Question 16

Side Effects: Dimethyl fumarte (BG12)

Answer 16

Diarrhea, nausea, flushing

Question 17

Use: Dimethyl fumarate (BG12)

Answer 17

RRMS

Question 18

What is a problem with the use of Alemtuzumab for MS?

Answer 18

Infusion reactions and some increased LFTs, and some new autoimmune diseases

**must do CBC every month to monitor for ITP

used as a 3rd line agent for RRMS

Question 19

What is a major side effect of Mitoxantrone for secondary progressive MS?

Answer 19

Cardiotoxicity;

Acute Leukemia

Question 20

What is the best way to treat MS

Answer 20

Start treatment at disease onset