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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
RRMS: convenience approach
oral dimethyl fumarate, teriflunomide or fingoliod
26
RRMS: efficacy approach
IV natalizumab or ocrelizumab
27
What is the hallmark of early RRMS?
exacerbations
28
Exacerbations: treatment
high dose glucocorticoid (IV methylprednisolone) clinical response in 3-5 days
29
Corticosteroids: MOA
improve recovery by dec edema in area of demyelination no affect on disease progression
30
Corticosteroids: ADEs
short term: - sleep disturbance - metallic taste (IV) long term: - acne - fungal infections - mood alteration - GI hemorrhage diabetics: -significant elevation of blood sugar
31
Teriflunomide
immunomodulatory agent prevents proliferation of peripheral lymphocytes (T and B cells) reduces activation of lymphocytes --> reduces inflammation, demyelination
32
Dimethyl Fumerate
involved in cellular response to oxidative stress
33
Which medication carries a pregnancy category X rating?
teriflunomide female or male
34
Which medication has an active metabolite and the name of this substance?
teriflunomide leflunomide
35
What labs would be appropriate to monitor for adverse effects?
``` pregnancy test TB test LFT CBC blood pressure ```
36
How do you minimize the flushing associated with dimethyl fumarate?
Take the medication with food
37
What therapy option is a safer alternative for a patient that declines oral therapy?
interferon or glatiramer acetate screen for depression
38
First Line Therapies
self injected medications - interferons, glatiramer acetate dec relapse rate dec formation of new white matter lesion not immediately efficacious (1-2 years)
39
Interferon Beta 1alpha: MOA
alters expression/response to surface antigens --> enhanced immune cell activites
40
Interferon Beta 1beta: MOA
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
Interferons
balance the expression of pro and anti inflammatory agents in the brain reduce the number of inflammatory cells that cross the BBB
42
Glatiramer: MOA
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
Which medication has an indication for CIS and RRMS?
glatiramer acetate
44
Which interferon medication is considered a low potency medication?
avonex
45
Which agent is a pregnancy category B?
glatiramer acetate
46
If the patient reports a history of depression, which medications would possibly be contraindicated?
interferons
47
What are the appropriate monitoring parameters for the interferon medications?
``` electrolytes CBC LFTs thyroid function LVEF depression (PHQ9) ```
48
Which medication might cause chest tightness and flushing?
glatiramer acetate
49
Medications used when inadequate response or intolerance to first line agents
fingolimod natalizumab alemtuzumab mitoxantrone
50
What are the limitations of mitoxantrone?
Life time limit of dose of 140 pregnancy category D secondary leukemia
51
When is fingolamod contraindicated?
patients receiving class I and III antiarrhythmic drugs patients with recent cardiac disease, 2nd and 3rd degree AV block
52
What is PML and what is the cause?
progressive multifocal leukoencephalopathy viral infection that targets myelin making cells john cunningham virus (activated when a person's immune system is compromised)
53
When is mitoxantrone indicated?
SPMS PRMS worsening RRMS
54
Describe the drug interaction of fingolimod and ketoconazole.
ketoconazole inc fingolamod serum concentration (3A4 inhibition)
55
Last ditch effort of treatment (end of the algorithm)
switch to IVIG add IV pulse methylprednisolone IV pulse cyclophosphamide + pulse methylprednisolone
56
If the patient wants to treat exacerbations acutely, rather than daily treatment, what would our plan be?
corticosteroids

PHA 550 (26 decks)

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