Multiple Sclerosis

Question 1

What happens to the brain with the natural course of MS?

Answer 1

brain atrophy

Question 2

What is most likely responsible for disability in MS?

Answer 2

Axonal involvement

Question 3

Diagnosis of MS depends on demonstrating what?

Answer 3

attacks of neurologic dysfunction disseminated in time and space

Question 4

Most patients with MS begin as what type?

Answer 4

Relapsing- Remitting

Question 5

Untreated pts w/ RRMS typically progress to what type of MS?

Answer 5

Progressive

Question 6

Name four interferons used for MS treatment.

Answer 6

Avonex, Rebif, Betaseron, Extavia

Question 7

Name three treatments for acute MS

Answer 7

Corticosteroids, plasmaphoresis, ACTH

Question 8

What is the MOA of interferons in MS

Answer 8

inhibit T cell activation, shift from Th1 to Th2 (non-inflammatory), inhibit lymphocyte movement into CNS, apoptosis of T cells, IFN antagonism

Question 9

What interferons are high dose, low dose?

Answer 9

Avonex - low dose

Rebif, Extavia, Betasteron- high dose

Question 10

What are added benefits of Rebif over other interferons?

Answer 10

reduces disability

Question 11

What two interferons work on IFN beta-1a?

Answer 11

Rebif, Avonex

Question 12

What two interferons work on IFN beta-1b?

Answer 12

Extavia, Betasteron

Question 13

Of the interferons what has the greatest likelihood of causing Neutralizing antibodies?

Answer 13

Betasteron

Question 14

SE of avonex

Answer 14

lesser than other corticosteroids because lesser dose
mild anemia, elevated LFTs, hypothyroid
monitor LFTs every 6 months

Question 15

SE of Rebif, Betasteron, Extavia

Answer 15

anemia, leukopenia, elevated LFTs, hypothyroid, menstrual irregularities, depression
monitor LFTs every 3 months

Question 16

What are interferons used to treat?

Answer 16

RRMS

Question 17

What is MOA of glatiramer acetate (Copaxone)?

Answer 17

causes T cell apoptosis, induces anti-inflammatory Th2 cells, induces regulatory T cells

Question 18

What problem occurs with NAB caused by use of an IFN?

Answer 18

All IFNs can no longer be used to treat because of cross reactivity

Question 19

When should you begin treating MS?

Answer 19

EARLY, before diagnosis with MS but high risk of developing MS by MRI criteria

Question 20

SE of glatiramer acetate (copaxone)?

Answer 20

mild injection site reaction

Anxiety-like reactions- chest tightness, SOB (Not related to heart problem)

Question 21

What isglatiramer acetate (copaxone) used to treat?

Answer 21

RRMS

Question 22

What is Natalizumab used to treat?

Answer 22

RRMS, considered 3rd line now with oral agents in use

Question 23

What are the SE of natalizumab?

Answer 23

PML (jc virus)
acute uticaria
systemic hypersensitivity reaction

headache, dizziness, fatigue, arthralgia, rigors

More common in pts with NAB

Question 24

When would you use ACTH?

Answer 24

treat acute MS attack in person with allergy to corticosteroids or poor IV access

Question 25

MOA of Natalizumab?

Answer 25

Binds VLA4 inhibiting leukocyte migration across BB barrier

Question 26

What is fingolimod used to treat?

Answer 26

RRMS

Question 27

Fingolimod MOA?

Answer 27

prodrug, sequesters circulating lymphocytes in secondary lymphoid organs via internalization of receptors on lymphocytes

Question 28

SE of Fingolimod?

Answer 28

``` Bradycardia and heart block (EKG for 6 hrs) Macular edema (eye exam before treatment adn at 3 months)--> don't use in Diabetics ``` Reduced FEV1, increased LFTs, lymphopenia, leukopenia, asthenia, back pain, blurred vision, headache dizziness, infections

Question 29

What must a patient be immune to before prescription of Fingolomid?

Answer 29

VZV

Question 30

What is teriflunomide (Aubagio) use to treat?

Answer 30

RRMS

Question 31

MOA of teriflunomide (Aubagio)?

Answer 31

Selective dihydro-orotate dehydrogenase inhibitor | blocks de-novo pyramidine synthesis, reducing T and B cell proliferation and function in response to autoantigens

Question 32

SE of teriflunomide (Aubagio)?

Answer 32

hepatotoxicity, teratogenicity, nausea, decreased hair density

Question 33

Dimethyl fumarate MOA?

Answer 33

activates Nrf2 pathway and induces antioxidant enzyme production (decreases oxidative stress) Induces TH1--> Th2 shift

Question 34

SE of dimethyl fumarate?

Answer 34

N/V/D, stomach pain, flushing

Question 35

What are SE of corticosteroid use?

Answer 35

ST: insomnia, mood changes, fluid retention, epigastric pain, hypertension LT: osteoporosis, cushingoid, secondary malignancies

Question 36

In regards to MS what does a Gd+ lesion and a T2 lesion represent?

Answer 36

Gd+ lesions are new lesions that convert to Th2 after 2 months

Question 37

Name four immunosuppressants used to treat SPMS?

Answer 37

Azathioprine, Methotrexate, Cyclophosphamide, Mycophenolate mofetil

Question 38

SE of immunosuppressants?

Answer 38

Systemic toxicity, monitor for blood changes

Question 39

What is Mitoxantrone used to treat?

Answer 39

SPMS and RRMS (2nd line)

Question 40

SE of Mitoxantrone?

Answer 40

Cardiac toxicity- decreased LVEF and irreversible CHF, risk increases w/ cumulative dosing Acute leukemia N/V, alopecia, increased infection risk, menstrual irregularities

Question 41

MOA of Mitoxantrone?

Answer 41

Broad immune suppression of macrophages, B & T cells. Reduces disease progression and disability.