MS

Question 0

what do the IFNbeta’s do? (7 fncs)

Answer 0

1. inhibit Tcell activation, promotes its apoptosis
2. th1–> th2 via cytokines production switch
3. inhibits lymphocyte movmt into CNS
4. antiproliferative effect
5. anti-viral
6. IFN-g antagonism

Question 1

the 4 interferon betas (IFN-b) used to tx RRMS (relapsing remitting MS). indicate if they are 1a or 1b

Answer 1

IFN1a: avonex and rebif
IFN1b: betaseron and extavia

Question 2

what are considered high dose IFNb’s? (3)

Answer 2

rebif, betaseron, extavia

Question 3

1st line tx for RRMS

Answer 3

rebif

Question 4

IFNb that forms least Nab

Answer 4

avonex

Question 5

IFNb that forms most Nab

Answer 5

betaseron

Question 6

all ____ produce these SEs: flue like, minor irritation at injection site, anemia. which one produces TCP?

Answer 6

IFNb’s. rebif also has TCP

Question 7

anemia
inc LFT
hypothyroidism

Answer 7

all IFNb’s: avonex, rebif, betaseron, extavia

Question 8

1. which 2 IFNb’s decrease progression and disability?

2. which 2 IFNbs have no effect on disease progression?

Answer 8

1. avonex and rebif

2. betaseron and extavia

Question 9

myelin basic protein analog

Answer 9

glatiramer acetate

Question 10

used to also tx____; this is a mix of 4 myelin basic proteins (MBPs) that causes:

1. T cell apoptosis (looks like MBP)
2. induces Th2 from Th1 switch
3. induces Treg with induction of anergy
4. neuroprotection

Answer 10

glatiramer acetate

Question 11

only active in CNS; reduces relapse by 1/3 of used early, modest reduction in MRI lesion and reduce atrophy; no effect on dz progression

Answer 11

glatiramer acetate

Question 12

mild SE: injection site rx, anxiety attack like rx, chest tightness, SOB

Answer 12

glatiramer acetate

Question 13

monoclonal ab that binds VLA4 (integrin subunit) and inhibits leukocyte migration to BBB

Answer 13

natalizumab

Question 14

second line for RRMS

Answer 14

natalizumab

Question 15

natalizumab puts pt at risk for ____ infection, resulting in ____. also acute urticaria, HSR (infusion rxn)

Answer 15

JC virus; PML

Question 16

can induce ab’s to this drug, causing it to not work for RRMS

Answer 16

natalizumab

Question 17

prodrug that helps sequester circulation lymphocytes in secondary lymphoid organs via internalization of SIP receptors in lymphocytes (but have no effect on lymphocyte induction, prolif, memory fnc);;;;used for tx ___

Answer 17

fingolimod (sphingosine-1-P analog)

-RRMS

Question 18

major SE of fingolimod?

Answer 18

• brady, heartblock (EKG monitor first 6hrs)
• macular edema

also: reduced FEV1, inc LFTs, lymphopenia, leukpenia, asthenia, back pain, blurred vision/HA/dizz, infections

Question 19

to admin fingolimod, need to make sure pt is what?

Answer 19

VZV immune

Question 20

1. Immunomodulators (5)

2. immunosuppressants (5)

Answer 20

1. the IFNb’s, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate
2. teriflunomide, mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil

Question 21

immunomodulator that enhances the nrf2 pathway (which inc antiox enzymes to dec ox stress), and Th1–>Th2 shift

Answer 21

dimethylfumarate

Question 22

tx psorasis and dec progression of MS; SE: rash/flushing, n/v/d/pain

Answer 22

dimethyl fumarate

Question 23

IS that selective dihydro-orotate dehydrogenase inhibitor (blocks denovo pyramidine synthesis, reduces B+T prolif);

• func against autoag’s
• preserves replication and fnc of cells living on salvage pathway (hematopoietic cells, memory cells)

Answer 23

teriflunomide

Question 24

hepatotoxicity, teratogenicity in animals

Answer 24

teriflunomide

Question 25

first line injectables for RRMS

Answer 25

teriflunomide

Question 26

broad immune suppression of b,t,macrophages, dec relapses reduces progression and disability -SPMS (secondary progressive MS), RRMS (2nd line)

Answer 26

mitoxantrone

Question 27

dose-dependent cardiac toxicity (dec LVEF, irrev CHF), acute leukemia; -thus, have a life time limit (depends of LVEF)

Answer 27

mitoxantrone

Question 28

4 IS that tx SPMS (resistant, or as comb with other therapies)

Answer 28

1. azathioprine 2. methotrexante 3. cyclophosphamide 4. mycophenolate mofetil (AMcycMyc)

Question 29

all IS have systemic tox: 1. methotrexate 2. cyclophosphamide 3. mycophenolate mofetil 4. terflunomide

Answer 29

1. liver and pul fibrosis 2. hemorrhagic cystitis 3. PML, lymphomas, skin malign, RBC aplasia 4. hepatotox, teratogenicity

Question 30

corticosteroid for IS

Answer 30

methylprednisone

Question 31

unclear mech but may involve suppression of both B and T cells, may reduce cytokine release

Answer 31

methylprednisone

Question 32

used for acute MS attack, SPMS | shortens acute attack duration, speeds recovery

Answer 32

methylprednisone

Question 33

short term: insomnia, mood changes, fluid retention, epigastric pain, HTN long term: osteoporosis, cushingoid, secondary malign

Answer 33

methylprednisone

Question 34

give during acute MS attack if the pt is allergic to corticosteroids or have poor IV access; or if MTP doesnt work

Answer 34

ACTH

Question 35

use this during acute MS that's not responsive to MTP

Answer 35

plasmapharesis