Multiple Sclerosis Flashcards
2 characteristics of Multiple sclerosis
CNS demyelination and axonal damage
How does MS develop?
genetically susceptible individuals are exposed to random/environmental factors triggering immune mediated CNS damage
What are the 4 T helper cell subtypes and their clinical significance?
Th1 and Th17 = pathogenic pro-inflammatory
Th2 = anti-inflammatory
Treg = preventive of autoimmunity
- mutual suppression b/t Th1 and Th2
Examples of favorable and unfavorable prognostic indicators for MS
Favorable –> relapsing/remitting, optic neuritis or sensory sxs, women
Unfavorable –> progressive course, motor or cerebellar sxs, polysymptomatic, men
What is MS?
immunologic disorder marked by chronic inflammation of the CNS
The key to the dx of MS is –>
the dissemination of these plaques in time and space
What are the 4 types of MS?
- RRMS – relapsing-remitting
- PPMS – primary-progressive
- SPMS – secondary-progressive
- PRMS – progressive-relapsing (or PR w/activity)
What are the 3 broad Tx categories for MS?
- Tx of exacerbations = corticosteroids
- DMT’s - disease modifying therapies
- Symptomatic therapy for spasticity, bladder sxs, sensory sxs, & fatigue
Name 5 First-Generation DMT’s
IFN = "BEAR" Betaseron Extavia Avonex Rebif
non-IFN = Glatiramer acetate
What are First-Generation DMT’s?
self injected meds that decrease annualized relapse rates by 30%
decrease formation of new white matter lesion
How long is efficacy noted after starting therapy of First-Generation DMT’s?
1 to 2 years
Name some of the Second-Generation DMT’s for relapsing forms of MS.
“D-FANTOM”
Natalizumab Alemtuzumab Ocrelizumab Fingolimod Mitoxantrone Teriflunomide Dimethyl fumarate
2nd-Generation DMT w/an FDA indication for progressive or worsening MS?
Mitoxantrone
When is Mitoxantrone indicated?
SPMS, PRMS, and worsening RRMS
When is Fingolimod contraindicated?
pt receive class I & III anti-arrhythmic drugs recent heart dz 2nd and 3rd degree AV block
Describe the limitations of Mitoxantrone
Lifetime limit of dose is 140
pregnancy category D
secondary leukemia
Which medications could be considered a possible Contraindicated if the pt has a PMHx of depression?
Interferons Beta 1a and 1b
What are the monitoring parameters for the interferon medications?
Electrolytes, CBC, LFT’s, thyroid, LVEF, depression
Chest tightness and flushing can occur w/ which medication?
Glatiramer acetate
Which medication has an indication for CIS and RRMS?
Glatiramer acetate
Which of the interferon medications is considered a LOW potency medication?
Interferon beta 1
Describe the drug interaction of Fingolimod and Ketoconazole
Ketoconazole increases Fingolimod serum concentration (3A4 inhibitor)
What is PML and the cause?
Progressive Multifocal leukoencephalopathy
- viral infection that targets cells that make myelin
- John Cunningham’s virus activated when a person’s immune system is compromised
Which DMT is classified as pregnancy category X?
Teriflunomide
Which 2nd-generation DMT must you administer herpes viral prophylaxis on the first day of Tx?
Alemtuzumab
Adverse drug Rxn’s of Interferon medications
depression
flu-like sxs
Adverse drug Rxn’s of Mitoxantrone
cardiotoxicity
AML
Which DMT should you monitor JCV antibodies? why?
Natalizumab
Adverse drug rxn = PML
How can you reduce the incidence of flushing while taking Dimethyl fumarate?
taking it w/food
Adverse drug Rxn’s of Teriflunomide
Steven-Johnson syndrome liver failure activation of TB Neutropenia lymphocytopenia
Which drug is contraindicated w/ HBV?
Ocrelizumab
What is the Tx for MS exacerbations and when can the pt expect to see improvement?
IV injection of high dose corticosteroids (Methylprednisolone) initiated w/in 2 weeks of onset
improvement w/in 3-5 days
MOA for corticosteroids in MS
speculated to improve recovery by decreasing edema in the area of demyelination
Short-term use ADEs of Corticosteroids
sleep disturbance
metallic taste
Long duration of IV methylprednisolone can lead to –>
acne
fungal infections
mood alteration
rarely GI hemorrhage
MOA of Teriflunomide (Aubagio)
inhibits dihyroorotate dehydrogenase –> prevents proliferation of peripheral lymphocytes (T & B cells) –> reduces activation of lymphocytes in the CNS –> reduces inflammation and demyelination
MOA of Dimethyl fumarate
unknown – involved in cellular response to oxidative stress
in vitro nicotinic acid receptor agonist
in vivo activator of Nrf2 pathway
ADE’s of Dimethyl fumarate
Flushing - give w/food
Rash, pruritis
GI discomfort
Increased LFT’s
Which medication has an active metabolite and the name of this substance?
Teriflunomide
Leflunomide
If you prescribe Teriflunomide, which labs should you monitor for adverse effects?
pregnancy test TB (reactivation) LFT's CBC (lymphocytopenia, neutropenia) Blood pressure
If a pt declines oral therapy, what option might provide the pt w/ a safer alternative?
Interferons beta 1a or 1b
Glatiramer
In general, all IFNs do what 3 things?
- proposed MOA’s in periphery and at the blood-brain barrier level
- balances expression of pro- and anti-inflammatory agent in the brain
- reduce number of inflammatory cells that cross blood brain barrier
MOA of Glatiramer acetate?
antigenically similar to myelin basic protein (MBP) –> inhibits MBP from binding to T-cell receptor complexes
induces Th2 (anti-inflamm) –> reduction of inflammation, demyelination, and axonal damage
Neuroprotective effect
What is the 1st line Tx for MS? and what additional therapies can be used if pt has inadequate response or intolerance?
1st line = 1st-generation DMT’s
2nd generation DMTs
MOA of Mitoxantrone
inhibits RNA and DNA synthesis (use in oncology-leukemias)
MOA of Natalizumab
activated lymphocytes are denied entry past the blood-brain barrier
MOA of Fingolimod
exhibits immunosuppressant properties by sequestering circulating lymphocytes
reduces the infiltration of T lymphocytes and macrophages into the CNS
