MS - Pharmacology Rochet

Question 1

What drugs are used for acute attacks of MS?

Answer 1

Methylprednisolone
Prednisone
ACTH

Question 2

What are corticosteroids MOA?

Answer 2

Upregulating anti-inflammatory genes
Down-regulating inflammatory genes
Alleviating edema

Question 3

What are the interferons MOA?

Answer 3

Inhibit autoreactive lymphocytes

Inhibit BBB penetration via MMP

Question 4

What are ADEs of interferons?

Answer 4

Well-tolerated

Question 5

Interferons delay what?

Answer 5

Conversion of CIS to clinical MS

Question 6

T/F: Interferons have a risk for neutralizing antibodies

Answer 6

True

Question 7

What is the MOA of glatiramer acetate?

Answer 7

Inhibits autoreactive lymphocytes

Question 8

What are autoreactive lymphocytes?

Answer 8

DCs and T cells

Question 9

Glatiramer acetate delays what?

Answer 9

Conversion of CIS to MS

Question 10

T/F: Glatiramer acetate has a risk for neutralizing antibodies

Answer 10

False

Question 11

What type of structure is glatiramer acetate?

Answer 11

polypeptide

Question 12

Glatiramer acetate mimics antigenic properties of _________

Answer 12

myelin basic protein

Question 13

What is unique about fingolimod’s structure?

Answer 13

Lipid tail

Question 14

Fingolimod is a ______ receptor agonist

Answer 14

Sphingosine 1-phosphate

Question 15

What is fingolimod’s MOA?

Answer 15

Stimulate oligodendrocyte survival & remyelination

Interfere w/lymphocytes moving out of lymphoids

Question 16

T/F: Fingolimods are superior to IFN-Beta

Answer 16

True

Question 17

What are fingolimods side effects?

Answer 17

Cardiotoxicity
Fatal viral encephalitis
PML

Question 18

What is natalizumab’s MOA?

Answer 18

antibody against a4 integrin

Question 19

What does a4 integrin normally do? (MOA?)

Answer 19

Pair with B1 integrin to make VLA-4, which binds to VCAM-1 to get B and T cells into periphery

Question 20

T/F: Natalizumab has superior effects compared to first-line DMDs

Answer 20

True

Question 21

Side effects of natalizumab?

Answer 21

Allergic reactions (from neutralizing antibodies)
PML!!!!

Question 22

Mitoxantrone has what MOA?

Answer 22

Cytotoxic - causes DNA strand breaks and delays DNA repair

Question 23

How doe mitoxantrone delay DNA repair?

Answer 23

Inhibition of topoisomerase II

Question 24

T/F: Mitoxantrone is used to treat SPMS

Answer 24

True

Question 25

What are mitoxantrone's side effects?

Answer 25

Cardiotoxicity | Malignancy

Question 26

Which drug can be used as induction therapy initially?

Answer 26

Mitoxantrone

Question 27

Teriflunomide has what MOA?

Answer 27

Cytotoxic - inhibits pyrimidine biosynthesis

Question 28

What enzyme does teriflunomide inhibit?

Answer 28

Dihydroorotate dehydrogenase

Question 29

Teriflunomide's ADEs?

Answer 29

Hepatotoxicity | Teratogenicity

Question 30

How does teriflunomide affect MS?

Answer 30

Reduces relapse rates | MRI endpoints

Question 31

Demithyl fumurate structure?

Answer 31

two esters attached by double bound (esterified carboxylic acid)

Question 32

Dimethyl fumarate MOA?

Answer 32

Metabolized by esterases to active Nrf2 antioxidant responses Promotes remyelination Suppresses activated T cells and DCs

Question 33

Side effects of dimethyl fumarate?

Answer 33

- PML | - Lymphocytopenia

Question 34

What is the Nrf2 antioxidant response pathway?

Answer 34

Nrf2 normally degraded by Keap1 (ubiquitylation) Keap1 modified during oxidative stress - inhibited Nrf2 accumulates, enters nucleus, activates transcription of antioxidant response element (ARE) genes Genes under ARE make glutathione and detoxify

Question 35

Nrf2 activates genes regulated by what element ?

Answer 35

ARE - antioxidant response element

Question 36

Keap1 is covalently modified on what residues by oxidative stress?

Answer 36

Cysteine residues

Question 37

How is Nrf2 normally inactivated?

Answer 37

ubiquitylation by Keap1

Question 38

Genes under control of ARE are part of what response?

Answer 38

Phase II

Question 39

What is neutrophin?

Answer 39

Antioxidant released by glial cells (astrocytes)

Question 40

Nrf2 pathway increases ____ in astrocytes which travels to _____ and interacts with _____

Answer 40

Increases GSH; travels to neurons; interacts with ROS and RNS

Question 41

Alemtuzumab targets ____

Answer 41

CD52

Question 42

Alemtuzumab is effective in early phase or degenerative phase of MS?

Answer 42

early phase

Question 43

Rituximab targets ___ on ___

Answer 43

CD20 on B cells

Question 44

Rituximab stops ___MS and may be effective for ___ MS

Answer 44

RRMS may be PPMS

Question 45

Daclizumab targets ____

Answer 45

CD25

Question 46

Firategrast MOA?

Answer 46

a4 integrin - B and T cells can't get into CNS

Question 47

T/F: Firategrast reduces MRI Gd lesions

Answer 47

True

Question 48

T/F: Firategrast reduces relapse rates

Answer 48

False - little effect on relapse rates

Question 49

Amiloride MOA

Answer 49

Antagonizes ASIC-1 channel -- calcium channel

Question 50

Amiloride is used in patients with ___MS

Answer 50

PPMS

Question 51

Laquinimod MOA

Answer 51

Up-regulates BNDF --> neuroprotection | Immunomodulatory effects

Question 52

LINGO-1 Antagonist MOA

Answer 52

Interfers with LINGO-1, negative regulator of OPC differentiation

Question 53

Cladribine structure

Answer 53

Like DNA

Question 54

Cladribine MOA

Answer 54

Phosphorylated to 2-chloro-dATP, which damages DNA and interfers with DNA metabolism--> lymphocyte depletion

Question 55

What cells is cladribine converted to 2-chloro-dATP in?

Answer 55

Lymphocytes, monocytes

Question 56

What ROA does cladribine have?

Answer 56

Oral

Question 57

What cells does daclizumab binding affect?

Answer 57

T cells (via CD25 on IL-2 receptor)

Question 58

How does daclizumab affect MS?

Answer 58

Decrease in relapse and new lesions

Question 59

Daclizumab ROA?

Answer 59

SC q month

Question 60

Contraindication to daclizumab?

Answer 60

Hepatotoxicity | Infections, skin rash

Question 61

Ocrelizumab MOA

Answer 61

Targets CD20 - on mature B cells only

Question 62

T/F: Ocrelizumab does not affect disease progessio in PPMS

Answer 62

FALSE - decrease progression of PPMS!

Question 63

T/F: Ocrelizumab increases relapse rate in RRMS

Answer 63

False - Decrease relapse rate!

Question 64

Ocrelizumab MOA?

Answer 64

Infusion