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Flashcards in Multiple Sclerosis - GK Deck (107):
1

An immunologic disorder marked by chronic inflammation of the central nervous system (CNS) 

 

What disease is this? 

Multiple Sclerosis

2

In MS, mononuclear cells infiltrate the _______ space between arteries and veins and the pia mater, axons are _______ and destroyed, and immunoreactive changes in ______ cells result in the formation of ______ in multiple areas of the CNS. 

perivascular 

demyelinated

glial 

plaques

3

what is the key to the diagnosis of MS? 

dissemination of these plaques in time and space

4

What are the 4 types of MS? 

1. relapsing-remitting RR

2. primary-progressive PP

3. secondary-progressive SP 

4. progressive-relapsing or primary progressive with activity PR/PP

5

MS tx falls into what 3 categories? 

1. exacerbations: corticosteroids

2. Disease modifying therapies DMT

3. symptomatic therapies for spasticity, bladder and sensory sx, fatigue. 

6

What are the 5 FDA approved 1st gen agents used to tx MS? 

1. Avonex

2. Rebif

3. Interferon-B1b

4. Pegylated Interferon-B1b

5. Glatiramer acetate 

7

8

MOA: alters expression and response to surface antigens enhancing immune cell activities 

Dosage: IM

 

Avonex (Interferon-B1a) 

9

MOA: alters expression and response to surface antigens enhancing immune cell activities 

Dosage: SQ

 

Rebif (Interferon B-1a) 

10

MOA: 

•Augments suppressor cell function and reduce IFN-γ secretion by activated lymphocyte

Macrophage-activating effect

Down regulates the expression of IFN-γ–induced class II MHC gene products on antigen-presenting glial cells

•IFN suppresses T-cell proliferation and may decrease blood–brain barrier permeability

Dosage: SQ

 

Interferon B-1b

 

 

11

MOA: alters expression and response to surface antigens enhancing immune cell activities 

Dosage: SQ

 

Pegylated Interferon-B-1a

12

MOA: mimics antigenic properties of myeling binding protein (MBP) and inhibits binding of MBP peptides to T-cell receptor complexes. 

Dosage: SQ

 

Glatiramer acetate

13

Indication and Dose: relapsing, orally

MOA: sequesters circulating lymphocytes into secondary lymphoid organs & reduces infiltration of T-lymphocytes & macrophages into the CNS. 

 

Fongolimod

sequesters like a cowboy

14

 

MOA: inhibits dihydroorotate dehydrogenase = prevent proliferation of peripheral lymphocytes (T&B cells). Reduces activation of lymphocytes in CNS, reduces inflammation and demyelination. 

Dose & Indication: relapsing, orally

Which drug? 

Teriflunomide 

15

Dose & Indication: relapsing, orally

MOA: Unknown-invitro nicotinic acid receptor agonist, invitro activator of Nrf2 pathway involved in cellular response to oxidative stress 

 

Dimethyl Fumarate

 

"When you are di-ing, you need Oxygen and you fume if you don't get it"

AKA

cellular response to oxidative stress

 

 

16

Dose & Indication: RRMS, 1st dose: IV for 5 days 2nd dose: IV for 3 days. Administer 2nd dose 12 mo after 1st tx. 

Which drug? 

Alemtuzumab

17

What kind of MS would you use Ocrelizumab for? 

relapsing or progressive

18

ADE: depression, flu-like sx, leukopenia, injection site rxn

Monitor: electrolytes, CBC, [LFT's at baseline, 1 mo, and every 3 mo for a year, and every 6 mo thereafer],  thyroid function, LVEF. 

What drug is this? 

Avonex (Interferon-B1a) 

19

Indication: Relapsing form of MS

**low potency 

**avoid use in untreated severe depression**

What drug is this? 

Avonex (Interferon B-1a) 

20

ADE: depression, flu-like sx, leukopenia, injection site rxn

 

Monitor: electrolytes, CBC, [LFT's at baseline, 1 mo, and every 3 mo for a year, and every 6 mo thereafer],  thyroid function, LVEF. 

 

Rebif (Interferon-B-1a) 

21

Indication: Relapsing form of MS

**high potency 

**avoid use in untreated severe depression**

 

What drug is this? 

Rebif (Interferon-B1a) 

22

ADE: depression, flu-like sx, leukopenia, injection site rxn

 

Monitor: more frequent injection site rxns reported 

What drug is this? 

Interferon B-1b

23

Indication: Relapsing form of MS

**high potency, pregnancy category C

 

What drug is this? 

IFN Beta 1b

24

ADE: depression, flu-like sx, leukopenia, injection site rxn

 

Monitor: electrolytes, CBC, [LFT's at baseline, 1 mo, and every 3 mo for a year, and every 6 mo thereafer],  thyroid function, LVEF. 

What drug is this? 

Pegylated IFN Beta 1a

25

Indication: Remitting-Relapsing

**avoid use in untreated severe depression**

Can premedicate or concurrently use an antipyertic/analgesic for flu-like sx

 

What drug is this? 

Pegylated IFN B 1a

26

ADE: hypersensitivity, chest tightness, urticaria

 

Monitor: MRI, tissue necrosis

What drug is this? 

Glatiramer Acetate

27

Indication: CIS, RRMS

Pregnancy category B

 

What drug is this? 

Glatiramer acetate

28

ADE: macular retinal edema, lymphocytopenia, AV block, infection, headache

Monitoring: CBC, ECG, Varicella zoster antibody, BP, opthalmic exam, LFTs 

What drug is this? 

Fingolimod

Sequesters like a cowboy

29

Which drug requires 1st dose observation

 

Fingolimod 

sequesters like a cowboy

30

Contraindications for which drug? 

DO NOT USE IN pts receiving class I & III antiarrhythmic drugs & those with recent cardiac dz, 2nd & 3rd degree AV block. 

Fingolimod 

sequesters like a cowboy

31

ADE for which drug? 

Steven-Johnson Syndrome, liver failure, neutropenia, respiratory infection, TB activation, alopecia, neuropathy

Teriflunomide 

32

Which drug would you monitor the following? 

CBC, LFTs, BO, pregnancy, TB test

Teriflunomide 

33

_________ is an active metabolite of leflunomide. 

Teriflunomide

34

________ is contraindicated in severe hepatic impairment.

Teriflunomide

35

What is the main adverse effect of Teriflunomide

Stevens-Johnson syndrome 

**begins with flu-like symptoms, followed by a painful red or purplish rash that spreads and blisters. The top layer of the skin then dies and sheds. 

36

Which medication carries a pregnancy category X rating

Teriflunomide

37

Which medication as an active metabolite and what is the name of the active metabolite and the medication? 

Medication: Leflunomide

Active Metabolite: Teriflunomide

38

ADE: flushing, rash, pruiritis, GI discomfort, lymphocytopenia, inc LFTs, albuminuria

Monitoring: CBC, LFTs

 

Dimethyl Fumarate

39

How do you minimize the flushing associated with dimethyl fumarate

Take the medication with food 

40

MOA: monoclonal antibody that causes depletion of CD52-expressing T, B, natural killer cells and monocytes. 

Which drug?

Alemtuzumab

41

ADE: nasopharyngitis, UTI, URI, herpes viral infection, autoimmune dz, thyroid dz, purpura, goodpastures syndrome

Monitoring: CBC, thyroid fxn, antibodies to VZV, TB prior to tx, urinalysis

 

Aletuzumab

42

Premedicate w/high dose corticosteroid immediately prior to infusion for 1st 3 days

You would do this before starting which drug? 

Aletuzumab 

43

Administer herpes viral prophylaxis 1st day of tx & continue for atleast 2 mos after completion of tx or until CD4+ count atleast 200 cells/microliters

You would do this for which drug? 

Ateluzumab

44

Use birth control during tx & for 4 months following each tx course. 

 

You would do this for which drug? 

Alezutumab

45

Which drug is contraindicated with HIV infection? 

Alezutumab

46

Premedicate with methylprednisolone and diphenhydramine 30-60 min prior to each infusion before using this drug. 

 

Which drug? 

Ocrelizumab

47

ADE:

infusion rnx

Infections: 

- nasopharyngitis

- UTI

- URI 

- Herpes viral infection

- skin infections

- neutropenia


Which drug? 

Ocrelizumab

48

Which ADEs does Alemtuzumab have that separates it from Ocrelizumab

autoimmune disorders

thyroid disorders

purpura

goodpastures syndrome

49

What would you screen for in a patient who is taking Ocrelizumab

HBV, CNS changes

50

What drug is contraindicated in pts with HBV? 

Ocrelizumab

51

Which drug has a risk for progressive multifocal leukoencephalopathy (PML)

Ocrelizumab

52

MOA: recombinant human anti-CD20 monoclonal antibody that binds to the CD20 epitope 

(different binding region on CD20 than rituximab) 

Which drug is this? 

Ocrelizumab

53

Which drug is designed to optimize B cell depletion by modification of the Fc region, which enhances antibody-dependent cell-mediated cytotoxicity & reduces complement-dependent cytotixicity compared with rituximab? 

Ocrelizumab

54

MOA: Inhibits RNA and DNA synthesis 

**used in oncology for leukemias**

 

Which drug is this? 

Mitoxantrone

55

ADE: bone marrow suppression, neutropenia, cardiotoxicity, AML, nausea, vomiting, diarrhea, alopecia

Which drug? 

Mitoxantrone

56

What should you monitor for Mitoxantrone? 

CBC, ECG, LVEF, LEFTs

57

There is a lifetime maximum dose to this drug due to the associated cardiac toxicity

 

Which drug? 

mitoxantrone

58

What types of MS is mitoxantrone indicated for? 

SPMS, PRMS, worsening RRMS

59

MOA for which drug? 

activated lymphocytes are denied entry past the blood-brain barrier

Natalizumab

60

MOA for which drug? 

attaches to VLA-1 and blocks its interaction with its ligand on CNS endothelium vascular cell adhesion molecule (VCAM-1) 

Natalizumab

61

ADE: PML, depression, fatigue, respiratory infection, arthralgia, hepatotoxicity 

Which drug? 

Natalizumab

62

What should you monitor in a patient taking Natalizumab? 

JCV antibody

infection

MRI

LFT

63

Which drug has a risk of IRIS when discontinued due to PML? 

Natalizumab

64

a first episode of neurologic sx that lasts atleast 24 hrs

CIS (clinically isolated syndromes)

65

What is the "safety; tried & true" approach for relapsing-remitting MS? 

injection therapy with: 

IFN B-1a (Avenox or Rebif) 

OR

IFN B-1b

 OR

glatiramer

66

What is the "convenience" approach for relapsing-remitting MS? 

oral therapy with dimethyl fumarate, teriflunomide or fingolimide 

67

What is the "efficacy" approach to relapsing-remitting MS? 

Infusion monotherapy with natalizumab or ocrelizumab

68

Exacerbations are the hallmark of early ______

RRMS

69

Relapses are based on ____ or ________ symptomatic presentations

mono or poly

70

What are signs of a relapse? 

  • Localization to the optic nerve, spinal cord or brainstem
  • functional limitations affecting daily life
  • sx that continue to worsen over 2 weeks 

 

71

Exacerbations are treated with _______

high dose glucocorticoids

72

What high dose glucocorticoid is used to treat exacerbations? What is the response time of this drug? 

methylprednisolone IV

3 to 5 days

73

MOA: unknown but thought to improve recovery by decreasing edema in the area of demyelination

corticosteroids (methylprednisolone) 

74

T/F: Corticosteroids have been shown to definitively affect dz progression

FALSE; they have NOT been shown to definitively affect dz progression. 

75

When would you initiate methylprednisolone? 

Within 2 weeks of sx onset

76

What are short term use ADE's of corticosteroids? 

sleep disturbance

metallic taste 

77

What are ADE's of corticosteroids that would occur in pts with DM or those who have a predilection to DM? 

elevation of blood sugar: would require the use of insulin

78

ADEs of longer durations of IV methylprednisolone

acne

fungal infections

mood alteration

Rare: GI hemorrhage

79

Which drug is also used for RA? 

teriflunomide

80

If the pt declines oral therapy, what therapy option might provide the pt with a safer alternative

IFN-Beta 1a/1b

Galtiramer

81

What are the 1st line therapies for MS? 

self-injected medications

IFN-Beta1a/1b

(Avonex, Rebif) 

Glatiramir Acetate

82

1st line therapies decrease annualized relapse rate by about ______%

30

83

first line therapies decrease the formation of new _________

white matter lesion

84

Are first line DMT immediately efficacious for sx? 

 

NO

 

85

When is efficacy of first line DMTs noted? 

1-2 years after starting therapy

86

All IFNs exert their actions in the ______ and at the ______ level

periphery and blood-brain barrier

87

What is the overall purpose of IFNs? 

to balance the expression of pro and anti-inflammatory agents in the brain, and reduce the # of inflammatory cells that cross the blood brain barrier

88

This drug is a mixture of 4 amino acids which is antigenically similar to myelin basic protein 

L: 

alanine

glutamic acid

lysine

tyrosine

glatiramer acetate

89

This drug induces Th2 lymphocytes (bystander suppression @ site of MS lesion) 

glutiramer acetate

90

This drug reduces inflammation, demyelination and axonal damage

glutiramer acetate

91

Recent studies suggest that this drug may be associated with a neuroprotective effect by inducing BDNF

gultiramer acetate

92

Which medication has an indication for CIS and RRMS? 

glutiramer acetate

93

Which interferon is considered a low potency medication? 

Avonex

94

Which drug is category B pregnancy? 

Glutiramer acetate

95

Our pt reports a PMH of depression. Which meds would be considered a possible contraindication? 

IFN-Beta 1a & 1b

96

What is appropriate monitoring parameters for the IFN meds? 

electrolytes, CBC, LFT, thyroid fxn, LVEF, depression

97

Chest tightness can occur along with flusing with which med? 

Glatiramer acetate

98

When would you use fingolimod, natalizumab, alemtuzumab and mitoxantrone

MANF

cases of inadequate response or intolerance to 1st line agents

MANF

99

What are the limitations of mitoxantrone

life time limit dosage of 140 

preggo category D

secondary leukemia

100

When is fingolimod contraindicated? 

pts receiving class I and III antiarrhythmuc drugs and those with recent cardiac disease, 2nd & 3rd degree AV block

101

What is PML and what is the dz process? 

Progressive multifocal leukoencephalopathy

A viral infection that targets cells that make myelin: material that insulates nerve cells (neurons) 

 

102

When is John Cunninhgham virus activated? 

When a person's immune system is compromised

103

When is mitoxantrone indicated? 

SPMS

PRMS

worsening RRMS

104

Describe the drug interaction of fingolimod and ketoxonazole

ketoxconazole increases fingolimod serum concentration (3A4 inhibition)

105

What are possible starting treatments for RRMS? 

IFN

glatiramer acetate

fingolimod

teriflunomide

dimethyl fumarate

106

Pt has experienced 3 exacerbations in the last 9 months and the sx are worsening with each exacerbation and his recovery is taking longer. 

What option is available if this pt is wanting a regimen that is convenient? 

Teriflunomide or dimethyl fumarate (BG-12) 

Can be taken ORALLY 

107