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PHA 550 > Multiple Sclerosis > Flashcards

Multiple Sclerosis Flashcards

1
Q

Multiple Sclerosis: features

A

visual compromise
stiffness
weakness

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2
Q

Multiple Sclerosis: pathology

A

autoimmune disease marked by chronic inflammation of the CNS

mononuclear cells infiltrate the perivascular space –> demyelinate and destroy axons –> formation of plaques due to changes in the glial cells

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3
Q

What is the key to diagnosis of multiple sclerosis?

A

dissemination of plaques in time and space

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4
Q

What are the 4 types of multiple sclerosis?

A

relapsing remitting MS (target of therapy)

primary progressive MS

secondary progressive MS

progressive relapsing MS (primary progressive w/ activity)

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5
Q

What are the 3 categories of treatment of multiple sclerosis?

A

Tx of exacerbation (corticosteroids)

disease modifying therapies

symptomatic therapies (spasticity, bladder sx, sensory sx, fatigue)

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6
Q

What virus status needs to be checked when deciding on treatment for multiple sclerosis?

A

John Cunningham virus

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7
Q

Disease Modifying Therapy: goals

A 
reduce annual relapse rate
lessen severity of relapses
slow progression of changes on MRI
slow progression of disability
slow cognitive decline
reduce second attack after CIS
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8
Q

Disease Modifying Therapy: First Generation

A

dec relapse rate
dec formation of new white matter lesion

takes 1-2 yrs to be efficacious

interferon
glatiramer acetate

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9
Q

DMT: Avonex

A

relapsing MS

interferon (alpha)

low potency

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10
Q

DMT: Rebif

A

relapsing MS

interferon (alpha)

high potency

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11
Q

DMT: Betaseron, Extavia

A

relapsing MS

interferon (beta)

high potency

pregnancy category C

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12
Q

DMT: Plegridy

A

RRMS

pegylated interferon (alpha) (long acting)

pregnancy category C

premedicate/concurrent use w/ antipyretic/analgesic for flu like sx

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13
Q

DMT: copaxone glatopa

A

CIS, RRMS

glatiramer acetate

pregnancy category B

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14
Q

DMT: Interfeon: ADEs

A

depression
flu like symptoms
leukopenia
injection site reaction

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15
Q

DMT: glatiramer acetate: ADEs

A 
injection site reaction
infection
hypersensitivity
chest tightness
urticaria
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16
Q

Disease Modifying Therapy: Second Generation

A 
Natalizumab 
Mitoxantrone 
Fingolimod 
Teriflunomide
Dimethyl fumarate 
Alemtuzumab
Ocrelizumab
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17
Q

DMT: Fingolimod

A

oral

relapsing MS

pregnancy category C

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

sequesters lymphocytes
reduces infiltration of T lymphocytes and macrophages into CNS

neuroprotective

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18
Q

DMT: Teriflunomide

A

oral

relapsing MS

pregnancy category X

ADE: Steven–Johnson syndrome, liver failure, neutropenia, respiratory infection, activation of TB, alopecia, neuropathy

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19
Q

DMT: Dimethyl Fumarate

A

oral

relapsing MS

pregnancy category C

ADE: flushing, rash, pruritus, GI discomfort, lymphocytopenia, increased LFTs, albuminuria

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20
Q

DMT: Natalizumab

A

IV

relapsing MS

pregnancy category C

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

activated lymphocytes denied entry past BBB

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21
Q

DMT: Alemtuzumab

A

IV

RRMS

premedicate w/ high dose corticosteroid

administer herpes viral prophylaxis

pregnancy category C

ADE: Infusion reactions, infections (nasophyaryngitis, UTI, URI, herpes viral infections), autoimmune disorders, thyroid disorders, immune-mediated thrombocytopenic purpura, Goodpasture syndrome

depletes T cells, B cells, NK cells, monocytes

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22
Q

DMT: Ocrelizumab

A

IV

relapsing or progressive MS

premedicate w/ methylprednisolone

ADE: Infusion reactions, infections (nasophyaryngitis, UTI, URI, herpes viral infections; skin infections; neutropenia

B cell depletion

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23
Q

DMT: Mitoxantrone

A

IV

SPMS, PRMS, worsening RRMS

lifetime dose should not exceed 140

pregnancy category D

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

secondary leukemia

inhibits RNA and DNA synthesis

24
Q

RRMS: safety, tried and true approach

A

interferon or glatiramer

25
Q

RRMS: convenience approach

A

oral

dimethyl fumarate, teriflunomide or fingoliod

26
Q

RRMS: efficacy approach

A

IV

natalizumab or ocrelizumab

27
Q

What is the hallmark of early RRMS?

A

exacerbations

28
Q

Exacerbations: treatment

A

high dose glucocorticoid (IV methylprednisolone)

clinical response in 3-5 days

29
Q

Corticosteroids: MOA

A

improve recovery by dec edema in area of demyelination

no affect on disease progression

30
Q

Corticosteroids: ADEs

A

short term:

  • sleep disturbance
  • metallic taste (IV)

long term:

  • acne
  • fungal infections
  • mood alteration
  • GI hemorrhage

diabetics:
-significant elevation of blood sugar

31
Q

Teriflunomide

A

immunomodulatory agent

prevents proliferation of peripheral lymphocytes (T and B cells)

reduces activation of lymphocytes –> reduces inflammation, demyelination

32
Q

Dimethyl Fumerate

A

involved in cellular response to oxidative stress

33
Q

Which medication carries a pregnancy category X rating?

A

teriflunomide

female or male

34
Q

Which medication has an active metabolite and the name of this substance?

A

teriflunomide

leflunomide

35
Q

What labs would be appropriate to monitor for adverse effects?

A 
pregnancy test
TB test
LFT
CBC
blood pressure
36
Q

How do you minimize the flushing associated with dimethyl fumarate?

A

Take the medication with food

37
Q

What therapy option is a safer alternative for a patient that declines oral therapy?

A

interferon or glatiramer acetate

screen for depression

38
Q

First Line Therapies

A

self injected medications - interferons, glatiramer acetate

dec relapse rate
dec formation of new white matter lesion

not immediately efficacious (1-2 years)

39
Q

Interferon Beta 1alpha: MOA

A

alters expression/response to surface antigens –> enhanced immune cell activites

40
Q

Interferon Beta 1beta: MOA

A

augments suppressor cell function, reduces IFN gamma secretion by activated lymphocyte

macrophage activating effect

down regulates IGN gamma induced class II MHC expression

suppresses T cell proliferation, dec BBB permeability

41
Q

Interferons

A

balance the expression of pro and anti inflammatory agents in the brain

reduce the number of inflammatory cells that cross the BBB

42
Q

Glatiramer: MOA

A

antigenically similar to myelin basic protein

mimics antigenic properties of MBP - inhibits binding of MBP peptides to T cell receptor complexes

induces antiinflammatory lymphocytes –> bystander suppression –>
reduces inflammation, demyelination, axonal damage

suppresses T cell activation

neuroprotective effect

43
Q

Which medication has an indication for CIS and RRMS?

A

glatiramer acetate

44
Q

Which interferon medication is considered a low potency medication?

A

avonex

45
Q

Which agent is a pregnancy category B?

A

glatiramer acetate

46
Q

If the patient reports a history of depression, which medications would possibly be contraindicated?

A

interferons

47
Q

What are the appropriate monitoring parameters for the interferon medications?

A 
electrolytes
CBC
LFTs
thyroid function
LVEF
depression (PHQ9)
48
Q

Which medication might cause chest tightness and flushing?

A

glatiramer acetate

49
Q

Medications used when inadequate response or intolerance to first line agents

A

fingolimod
natalizumab
alemtuzumab
mitoxantrone

50
Q

What are the limitations of mitoxantrone?

A

Life time limit of dose of 140

pregnancy category D

secondary leukemia

51
Q

When is fingolamod contraindicated?

A

patients receiving class I and III antiarrhythmic drugs

patients with recent cardiac disease, 2nd and 3rd degree AV block

52
Q

What is PML and what is the cause?

A

progressive multifocal leukoencephalopathy

viral infection that targets myelin making cells

john cunningham virus (activated when a person’s immune system is compromised)

53
Q

When is mitoxantrone indicated?

A

SPMS
PRMS
worsening RRMS

54
Q

Describe the drug interaction of fingolimod and ketoconazole.

A

ketoconazole inc fingolamod serum concentration (3A4 inhibition)

55
Q

Last ditch effort of treatment (end of the algorithm)

A

switch to IVIG

add IV pulse methylprednisolone

IV pulse cyclophosphamide + pulse methylprednisolone

56
Q

If the patient wants to treat exacerbations acutely, rather than daily treatment, what would our plan be?

A

corticosteroids

PHA 550 (26 decks)

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