Multiple Sclerosis Flashcards
Multiple Sclerosis: features
visual compromise
stiffness
weakness
Multiple Sclerosis: pathology
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
What is the key to diagnosis of multiple sclerosis?
dissemination of plaques in time and space
What are the 4 types of multiple sclerosis?
relapsing remitting MS (target of therapy)
primary progressive MS
secondary progressive MS
progressive relapsing MS (primary progressive w/ activity)
What are the 3 categories of treatment of multiple sclerosis?
Tx of exacerbation (corticosteroids)
disease modifying therapies
symptomatic therapies (spasticity, bladder sx, sensory sx, fatigue)
What virus status needs to be checked when deciding on treatment for multiple sclerosis?
John Cunningham virus
Disease Modifying Therapy: goals
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
Disease Modifying Therapy: First Generation
dec relapse rate
dec formation of new white matter lesion
takes 1-2 yrs to be efficacious
interferon
glatiramer acetate
DMT: Avonex
relapsing MS
interferon (alpha)
low potency
DMT: Rebif
relapsing MS
interferon (alpha)
high potency
DMT: Betaseron, Extavia
relapsing MS
interferon (beta)
high potency
pregnancy category C
DMT: Plegridy
RRMS
pegylated interferon (alpha) (long acting)
pregnancy category C
premedicate/concurrent use w/ antipyretic/analgesic for flu like sx
DMT: copaxone glatopa
CIS, RRMS
glatiramer acetate
pregnancy category B
DMT: Interfeon: ADEs
depression
flu like symptoms
leukopenia
injection site reaction
DMT: glatiramer acetate: ADEs
injection site reaction infection hypersensitivity chest tightness urticaria
Disease Modifying Therapy: Second Generation
Natalizumab Mitoxantrone Fingolimod Teriflunomide Dimethyl fumarate Alemtuzumab Ocrelizumab
DMT: Fingolimod
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
DMT: Teriflunomide
oral
relapsing MS
pregnancy category X
ADE: Steven–Johnson syndrome, liver failure, neutropenia, respiratory infection, activation of TB, alopecia, neuropathy
DMT: Dimethyl Fumarate
oral
relapsing MS
pregnancy category C
ADE: flushing, rash, pruritus, GI discomfort, lymphocytopenia, increased LFTs, albuminuria
DMT: Natalizumab
IV
relapsing MS
pregnancy category C
ADE: PML, depression, fatigue, respiratory infx, arthralgia, hepatotoxicity
activated lymphocytes denied entry past BBB
DMT: Alemtuzumab
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
DMT: Ocrelizumab
IV
relapsing or progressive MS
premedicate w/ methylprednisolone
ADE: Infusion reactions, infections (nasophyaryngitis, UTI, URI, herpes viral infections; skin infections; neutropenia
B cell depletion
DMT: Mitoxantrone
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
RRMS: safety, tried and true approach
interferon or glatiramer
RRMS: convenience approach
oral
dimethyl fumarate, teriflunomide or fingoliod
RRMS: efficacy approach
IV
natalizumab or ocrelizumab
What is the hallmark of early RRMS?
exacerbations
Exacerbations: treatment
high dose glucocorticoid (IV methylprednisolone)
clinical response in 3-5 days
Corticosteroids: MOA
improve recovery by dec edema in area of demyelination
no affect on disease progression
Corticosteroids: ADEs
short term:
- sleep disturbance
- metallic taste (IV)
long term:
- acne
- fungal infections
- mood alteration
- GI hemorrhage
diabetics:
-significant elevation of blood sugar
Teriflunomide
immunomodulatory agent
prevents proliferation of peripheral lymphocytes (T and B cells)
reduces activation of lymphocytes –> reduces inflammation, demyelination
Dimethyl Fumerate
involved in cellular response to oxidative stress
Which medication carries a pregnancy category X rating?
teriflunomide
female or male
Which medication has an active metabolite and the name of this substance?
teriflunomide
leflunomide
What labs would be appropriate to monitor for adverse effects?
pregnancy test TB test LFT CBC blood pressure
How do you minimize the flushing associated with dimethyl fumarate?
Take the medication with food
What therapy option is a safer alternative for a patient that declines oral therapy?
interferon or glatiramer acetate
screen for depression
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)
Interferon Beta 1alpha: MOA
alters expression/response to surface antigens –> enhanced immune cell activites
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
Interferons
balance the expression of pro and anti inflammatory agents in the brain
reduce the number of inflammatory cells that cross the BBB
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
Which medication has an indication for CIS and RRMS?
glatiramer acetate
Which interferon medication is considered a low potency medication?
avonex
Which agent is a pregnancy category B?
glatiramer acetate
If the patient reports a history of depression, which medications would possibly be contraindicated?
interferons
What are the appropriate monitoring parameters for the interferon medications?
electrolytes CBC LFTs thyroid function LVEF depression (PHQ9)
Which medication might cause chest tightness and flushing?
glatiramer acetate
Medications used when inadequate response or intolerance to first line agents
fingolimod
natalizumab
alemtuzumab
mitoxantrone
What are the limitations of mitoxantrone?
Life time limit of dose of 140
pregnancy category D
secondary leukemia
When is fingolamod contraindicated?
patients receiving class I and III antiarrhythmic drugs
patients with recent cardiac disease, 2nd and 3rd degree AV block
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)
When is mitoxantrone indicated?
SPMS
PRMS
worsening RRMS
Describe the drug interaction of fingolimod and ketoconazole.
ketoconazole inc fingolamod serum concentration (3A4 inhibition)
Last ditch effort of treatment (end of the algorithm)
switch to IVIG
add IV pulse methylprednisolone
IV pulse cyclophosphamide + pulse methylprednisolone
If the patient wants to treat exacerbations acutely, rather than daily treatment, what would our plan be?
corticosteroids
