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MJ- Pharm Exam 3 > Multiple Sclerosis - GK > Flashcards

Multiple Sclerosis - GK Flashcards

1
Q

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

What disease is this?

A

Multiple Sclerosis

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2
Q

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.

A

perivascular

demyelinated

glial

plaques

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3
Q

what is the key to the diagnosis of MS?

A

dissemination of these plaques in time and space

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4
Q

What are the 4 types of MS?

A
  1. relapsing-remitting RR
  2. primary-progressive PP
  3. secondary-progressive SP
  4. progressive-relapsing or primary progressive with activity PR/PP
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5
Q

MS tx falls into what 3 categories?

A
  1. exacerbations: corticosteroids
  2. Disease modifying therapies DMT
  3. symptomatic therapies for spasticity, bladder and sensory sx, fatigue.
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6
Q

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

A
  1. Avonex
  2. Rebif
  3. Interferon-B1b
  4. Pegylated Interferon-B1b
  5. Glatiramer acetate
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7
Q
A
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8
Q

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

Dosage: IM

A

Avonex (Interferon-B1a)

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9
Q

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

Dosage: SQ

A

Rebif (Interferon B-1a)

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10
Q

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

A

Interferon B-1b

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11
Q

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

Dosage: SQ

A

Pegylated Interferon-B-1a

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12
Q

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

Dosage: SQ

A

Glatiramer acetate

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13
Q

Indication and Dose: relapsing, orally

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

A

Fongolimod

sequesters like a cowboy

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14
Q

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?

A

Teriflunomide

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15
Q

Dose & Indication: relapsing, orally

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

A

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

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16
Q

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?

A

Alemtuzumab

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17
Q

What kind of MS would you use Ocrelizumab for?

A

relapsing or progressive

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18
Q

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?

A

Avonex (Interferon-B1a)

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19
Q

Indication: Relapsing form of MS

**low potency

**avoid use in untreated severe depression**

What drug is this?

A

Avonex (Interferon B-1a)

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20
Q

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.

A

Rebif (Interferon-B-1a)

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21
Q

Indication: Relapsing form of MS

_**high potency_

_**avoid use in untreated severe depression**_

What drug is this?

A

Rebif (Interferon-B1a)

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22
Q

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

Monitor: more frequent injection site rxns reported

What drug is this?

A

Interferon B-1b

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23
Q

Indication: Relapsing form of MS

**high potency, pregnancy category C

What drug is this?

A

IFN Beta 1b

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24
Q

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?

A

Pegylated IFN Beta 1a

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25
Q

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?

A

Pegylated IFN B 1a

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26
Q

ADE: hypersensitivity, chest tightness, urticaria

Monitor: MRI, tissue necrosis

What drug is this?

A

Glatiramer Acetate

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27
Q

Indication: CIS, RRMS

Pregnancy category B

What drug is this?

A

Glatiramer acetate

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28
Q

ADE: macular r_etinal edema_, lymphocytopenia, AV block, infection, headache

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

What drug is this?

A

Fingolimod

Sequesters like a cowboy

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29
Q

Which drug requires 1st dose observation?

A

Fingolimod

sequesters like a cowboy

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30
Q

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.

A

Fingolimod

sequesters like a cowboy

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31
Q

ADE for which drug?

Steven-Johnson Syndrome, l_iver failure_, neutropenia, respiratory infection, TB activation, alopecia, neuropathy

A

Teriflunomide

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32
Q

Which drug would you monitor the following?

CBC, LFTs, BO, pregnancy, TB test

A

Teriflunomide

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33
Q

_________ is an active metabolite of leflunomide.

A

Teriflunomide

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34
Q

________ is contraindicated in severe hepatic impairment.

A

Teriflunomide

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35
Q

What is the main adverse effect of Teriflunomide?

A

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.

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36
Q

Which medication carries a pregnancy category X rating?

A

Teriflunomide

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37
Q

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

A

Medication: Leflunomide

Active Metabolite: Teriflunomide

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38
Q

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

Monitoring: CBC, LFTs

A

Dimethyl Fumarate

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39
Q

How do you minimize the flushing associated with dimethyl fumarate?

A

Take the medication with food

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40
Q

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

Which drug?

A

Alemtuzumab

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41
Q

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

A

Aletuzumab

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42
Q

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

You would do this before starting which drug?

A

Aletuzumab

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43
Q

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?

A

Ateluzumab

44
Q

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

You would do this for which drug?

A

Alezutumab

45
Q

Which drug is contraindicated with HIV infection?

A

Alezutumab

46
Q

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

Which drug?

A

Ocrelizumab

47
Q

ADE:

infusion rnx

Infections:

  • nasopharyngitis
  • UTI
  • URI
  • Herpes viral infection
  • skin infections
  • neutropenia

Which drug?

A

Ocrelizumab

48
Q

Which ADEs does Alemtuzumab have that separates it from Ocrelizumab?

A

autoimmune disorders

thyroid disorders

purpura

goodpastures syndrome

49
Q

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

A

HBV, CNS changes

50
Q

What drug is contraindicated in pts with HBV?

A

Ocrelizumab

51
Q

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

A

Ocrelizumab

52
Q

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

(different binding region on CD20 than rituximab)

Which drug is this?

A

Ocrelizumab

53
Q

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?

A

Ocrelizumab

54
Q

MOA: Inhibits RNA and DNA synthesis

**used in oncology for leukemias**

Which drug is this?

A

Mitoxantrone

55
Q

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

Which drug?

A

Mitoxantrone

56
Q

What should you monitor for Mitoxantrone?

A

CBC, ECG, LVEF, LEFTs

57
Q

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

Which drug?

A

mitoxantrone

58
Q

What types of MS is mitoxantrone indicated for?

A

SPMS, PRMS, worsening RRMS

59
Q

MOA for which drug?

activated lymphocytes are denied entry past the blood-brain barrier

A

Natalizumab

60
Q

MOA for which drug?

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

A

Natalizumab

61
Q

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

Which drug?

A

Natalizumab

62
Q

What should you monitor in a patient taking Natalizumab?

A

JCV antibody

infection

MRI

LFT

63
Q

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

A

Natalizumab

64
Q

a first episode of neurologic sx that lasts atleast 24 hrs

A

CIS (clinically isolated syndromes)

65
Q

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

A

injection therapy with:

IFN B-1a (Avenox or Rebif)

OR

IFN B-1b

OR

glatiramer

66
Q

What is the “convenience” approach for relapsing-remitting MS?

A

oral therapy with dimethyl fumarate, teriflunomide or fingolimide

67
Q

What is the “efficacy” approach to relapsing-remitting MS?

A

Infusion monotherapy with natalizumab or ocrelizumab

68
Q

Exacerbations are the hallmark of early ______

69
Q

Relapses are based on ____ or ________ symptomatic presentations

A

mono or poly

70
Q

What are signs of a relapse?

A
  • Localization to the optic nerve, spinal cord or brainstem
  • functional limitations affecting daily life
  • sx that continue to worsen over 2 weeks
71
Q

Exacerbations are treated with _______

A

high dose glucocorticoids

72
Q

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

A

methylprednisolone IV

3 to 5 days

73
Q

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

A

corticosteroids (methylprednisolone)

74
Q

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

A

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

75
Q

When would you initiate methylprednisolone?

A

Within 2 weeks of sx onset

76
Q

What are short term use ADE’s of corticosteroids?

A

sleep disturbance

metallic taste

77
Q

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

A

elevation of blood sugar: would require the use of insulin

78
Q

ADEs of longer durations of IV methylprednisolone

A

acne

fungal infections

mood alteration

Rare: GI hemorrhage

79
Q

Which drug is also used for RA?

A

teriflunomide

80
Q

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

A

IFN-Beta 1a/1b

Galtiramer

81
Q

What are the 1st line therapies for MS?

A

self-injected medications

IFN-Beta1a/1b

(Avonex, Rebif)

Glatiramir Acetate

82
Q

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

83
Q

first line therapies decrease the formation of new _________

A

white matter lesion

84
Q

Are first line DMT immediately efficacious for sx?

85
Q

When is efficacy of first line DMTs noted?

A

1-2 years after starting therapy

86
Q

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

A

periphery and blood-brain barrier

87
Q

What is the overall purpose of IFNs?

A

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
Q

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

L:

alanine

glutamic acid

lysine

tyrosine

A

glatiramer acetate

89
Q

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

A

glutiramer acetate

90
Q

This drug reduces inflammation, demyelination and axonal damage

A

glutiramer acetate

91
Q

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

A

gultiramer acetate

92
Q

Which medication has an indication for CIS and RRMS?

A

glutiramer acetate

93
Q

Which interferon is considered a low potency medication?

94
Q

Which drug is category B pregnancy?

A

Glutiramer acetate

95
Q

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

A

IFN-Beta 1a & 1b

96
Q

What is appropriate monitoring parameters for the IFN meds?

A

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

97
Q

Chest tightness can occur along with flusing with which med?

A

Glatiramer acetate

98
Q

When would you use fingolimod, natalizumab, alemtuzumab and mitoxantrone?

MANF

A

cases of inadequate response or intolerance to 1st line agents

MANF

99
Q

What are the limitations of mitoxantrone?

A

life time limit dosage of 140

preggo category D

secondary leukemia

100
Q

When is fingolimod contraindicated?

A

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

101
Q

What is PML and what is the dz process?

A

Progressive multifocal leukoencephalopathy

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

102
Q

When is John Cunninhgham virus activated?

A

When a person’s immune system is compromised

103
Q

When is mitoxantrone indicated?

A

SPMS

PRMS

worsening RRMS

104
Q

Describe the drug interaction of fingolimod and ketoxonazole

A

ketoxconazole increases fingolimod serum concentration (3A4 inhibition)

105
Q

What are possible starting treatments for RRMS?

A

IFN

glatiramer acetate

fingolimod

teriflunomide

dimethyl fumarate

106
Q

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?

A

Teriflunomide or dimethyl fumarate (BG-12)

Can be taken ORALLY

MJ- Pharm Exam 3 (17 decks)

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