3- MS Flashcards
What is Multiple Sclerosis
CNS demyelination and axial damage
What is the key to MS diagnosis
dissemination of plaques
What is the pathophys of MS
PMN infiltrate space between A&V and pia mater and demyelinate axons. Immune reactions form plaques in multiple areas of CNS
What gets MS
genetically susceptible people exposed to random environmental effects that trigger immune mediated CNS damage
What are th most common MS triggers
Vitamin D deficiency CMV EBV HHV6 Smoking High dietary sodium Circadian Disruption
What is the “theory” behind MS
T helper cells stick to vessels and create openings allowing them to cross BBB
In the CNS, T helper cells produce cytokines
Cytokines call other inflammatory cells and they all form an immune attack causing plaques
What are the cytokines involved in MS
Th1 and Th2: pro-inflammatory
Th17 anti-inflammatory
Treg regulatory
Name the most favorable prognosis patient with MS
<40 female presenting Sx of option neuritis or sensory Sx RRMS Low T1/T2 single lesions
What is unique about Th17 and Treg
They can change and become Th1 and Th2
What are indications for Treatment of MS exacerbation
Relapses localize to optic nerve, spinal cord, or brainstem
Sx affect daily living
Sx worsen over 2 weeks
What is your med tx of choice for exacerbations of MS
Corticosteroids; high dose IV Methylprednisone w/in 2 days of Sx
(improvement w/in 3-5 days)
How does Methylprednisone work
Improves recovery by decreasing edema around demyelination
BUT doesn’t affect disease progression
What are S/E of Methylprednisone
Sleep disturbance
Metallic taste
Increase BG in Diabetics
Long term: acne, fungal infections, mood changes
What should your RRMS treatment regimen be (steps)
Interferon Glatarimir acetate Fingolimode Teriflunomide Dimethyl fumarate
What is Terifluronimide
Oral DMT that (inhibits dihydroorotate dehydrogenase) prevents proliferation of peripheral T/B lymphocytes= lower inflammation and demyelination
Pregnancy X**
S/E of Teriflunomide include
Steven-Johnson syndrome (flu sx, then painful red and purple rash and blisters, then top layer of skin dies and sheds)
What is Leflunomide
active metabolite of Teriflunomide
What is Dimethyl Fumarate
Nicotinic receptor agonist
Nuclear factor pathway activator
-Involved in response to oxidative stress
What are S/E of Dimethyl fumarate
Flushing (give w/ food)
Lymphocyopenia
rash, pruritus, GI discomfort
What do you need to monitor if patient is taking Teriflunomide or Dimethyl fumarate
Pregnancy TB test LFT CBC BP (may increase)
When would you add Teriflunomide or Dimethyl fumarate
If Symptoms continue to worsen when already on corticosteroids
What are your First Line DMT
Interferons (IFN Beta 1a/1b) and Glatiramir acetate
What are the IFN Beta 1a
Avonex (low potency)
Rebif (high potency)
What are the IFN Beta 1b
Betaseron (high potency)
Extavia (high potency)
How long does it take for first line therapies to have effect
1-2 years, not immediately efficacious!
They are self injected meds that decrease relapse and new white matter lesions
How do IFN Beta 1a work
alter expression and response to surface antigen= enhanced (good) immune cell activity
How does IFN Beta 1b work (immunomodulator)
Increase suppressor cell fxn and reduce IFN-y secretion
Activates Macrophages
Surpasses T cell proliferation (less BBB permeability)
Increases CD56 NK cells and Treg
What do you have to monitor for if your pt is on IFN
Depression! (big S/E)
Electrolytes, CBC, LFT, Thyroid, LVEF
What is Glatiramir acetate
4 AA (Ala, Glut acid, Lys, Tyr) that mimic myelin basic protein (MBP)= No binding of MBP to T receptor cells
= reduced inflammation, demyelination, and axon damage
*Suppresses T cell activation
*Neuroprotective effect
What can glatiramir acetate be used for
PREGNANCY!! and CIS and RRMS
but S/E are chest tightening and flushing
What are your second line therapies (if 1st line don’t work)
Mitoxantrone Natalizumab Alemtuzumab Ocrelizumab Fingolimod
What is Mitoxantrone
inhibits RNA and DNA synthesis
BUT has a lifetime dose of 140 (because it can cause PML)
*pregnancy category D
What is Mitoxantrone indicated for
SPMS
PRMS
worsening RRMS
What is Natilizumab
attaches to VLA-1 and blocks it’s interaction with VCAM so activated lymphocytes can’t cross the BBB
What is Alemtuzumab
Depletes CD52 expressing T cells, B cells, NK cells and monocytes
What is Ocrelizumab
recombinant human anti-CD20 Ab that deletes B cells by modifying Fc region= enhanced Ab dependent cytotoxicity and reduced complement dependent cytotoxicity
What is Fingolimod
Sequesters circulating lymphocytes into 2-ary lymph organs
Reduces T cell and macrophage infiltration into CNS
Who should NOT take Fingolimod
Its on Class 1/3 anti-arrhythmics
recent cardiac disease
w/ 2/3 degree AV block
*If on Ketoconazole, fingolimod concentration will increase
What are common MS symptoms
Spasticity
Bladder Sx
Sensory Sx
Fatigue
What is the bottom line with MS
Don’t stop Tx, Tx is indefinite
No FDA approved drugs are approved for pregnant women, trying to become pregnant, or nursing
No response to IFN Beta or Glatiramir acetate, give
Natilizumab
If Sx worsen or pt with SPMS give
Mitoxantrone
Only FDA approved drugs are
IFN-B
Glatiramir acetate
Mitoxantrone
Natalizumab
