40-41 Pharmacotherapy of MS Flashcards
diagnosis of MS requires having at least __ demyelination related episodes separated by ___ and ___
2, time, space
2017 McDonald Diagnostic Criteria Revision
Dissemination in Time (DIT) - ___ between evidence of new lesions in subsequent MRIs (30 days)
- damage that has happened more than ___
time
once
2017 McDonald Diagnostic Criteria Revision
Dissemination in Space (DIS) - need for > ___ T2 lesion appearing in at least two of four MS typical CNS regions - cortical, periventricular, infratentorial, and spinal cord
- damage that is in more than one ___
one
place
Types of MS
Clinically ___ Syndrome (CIS)
- descriptor of the ___ demyelinating event
- most will develop MS in 20 years
Isolated
first
Types of MS
Relapsing Remitting MS (RRMS)
- most ___
- consists of relapses with partial or complete ___ between relapses
- most will become ___ over time
- common
- remission
- progressive
Types of MS
Secondary Progressive MS (SPMS)
- ___ % of RRMS patients will progress to SPMS
- ___ relapses with continuing disability
- 80%
- fewer
Types of MS
Primary Progressive MS (PPMS)
- 10-15% of patients
- progressive form from onset with ___ improvements or periods of ___
- more common in patients disagnosed in ___ years (> 50 years of age)
- minor, stability
- later
Types of MS
Progressive Relapsing MS (PRMS)
- ___ common
- ___ worsening disease from onset with later, clear, acute relapses
- may be some recovery from acute attacks, but no ___ between relapses
- least
- steadily
- remission
disease modifying drug therapy is focused in the ___ type of MS, based upon current drug target of ___ vs neurodegeneration
RRMS, inflammation
Treatment of Acute Attacks
high dose ___ treatment is the first choice
- oral or intravenous treatment based on setting
most patients will be inpatient
corticosteroid
Treatment of Acute Attacks
methylprednisolone ___ - ___ mg IV daily for 3-7 days, with or without taper over 1-3 weels
500 - 1000 mg
Treatment of Acute Attacks
if outpatient:
- oral prednisone ____ mg every other day for 5 doses without need for taper
1250 mg
oral medications and brand names
cladribine
dimethyl fumurate
diroximel fumarate
monomethyl fumerate
fingolimod
ozanimod
ponesimod
siponimod
teriflunomide
Mavenclad
Tecfidera
Vumerity
Bafiertam
Gilenya, Tascenso ODT
Zeposia
Ponvory
Mayzent
Aubagio
injectable medications and brand names
interferon B1a
Peginterferon B1a
interferon B1b
glatiramire acetate
ofatumumab
Avonex, Rebif
Plegridy
Betaseron, Extavia
Copaxone
Kesimpta
infusion medications and brand names
alemtuzumab
mitoxantrone
natalizumab
ocrelizumab
ublituximab-xiiy
Lemtrada
Mitoxantrone
Tysabri
Ocrevus
Briumvi
progressive multifocal leukoencephalopathy
- rare adverse event caused by reactivation of dormant JCV
- causes myelin producing cells to break down, looks simialr to MS relapse
- 50-80% or adults have antibodies to JCV, risk reactivation with some immunotherapies
- ___ % mortality rate
- **patients must be tested for JCV ___ ***
JCV = Human polyomavirus 2
50%
antibodies
vaccines
- ___ vaccines preferred
- ___ , attenuated vaccines are not recommended because the ability to cause the disease is weakened, but not eliminated
- ____ - no live virus vaccines
- ___ vaccine should be considered by people with MS who have ___ had chicken pox, especially if they may start a MS medication that suppresses cell mediated immunity ( ___ and ___ )
- inactivated
- live
- alemtuzumab
- varicella, never, fingolimod, alemtuzumab
dimethyl, diroximel, and monomethyl fumarate
- capsule should not be opened
- monitor ___ and CBC with differential ( ___ )
- assocaited with ___
- can cause ___, may take ASA 30 min prior to dose
- LFTs, neutropenia
- PML
- flushing
S1P receptor modulators
4 drugs:
- CI with past ___ diagnosis (or MI, unstable angina, stroke/TIA, class III-IV HF within past 6 months)
- D/C can result in significant ___ of MS symptoms
- ___: avoid use with an MAO inhibitor
- ___: CYP2C9 genotype testing required before prescribing
- must be monitored 6 hours after first dose, monitor CBC
if they fail one, they fail all
fingolimod, ozanimod, ponesimod, siponimod
- arrhythmia
- worsening
- ozanimod
- siponimod
glatiramer acetate
- injection SE: flushing, sweating, dyspnea, chest pain, anxiey, itching
- ___ may occur at injection site that is likely permanent, rotate
- ___ may occur outside of injection, usually not clinically significant
- may be preferred if treatment is necessary in ___ (teratogenic effects are unknown)
- lipoatrophy
- chest pain
- pregnancy
interferons
- can be dosed SC or IM every other day to every 2 weeks depending
- ___ like symptoms can occur after injection (can pretreat with APAP or NSAID)
- psychiatric SE: depression and ___ thinking
- elevated liver function tests and thyroid dysfunction - monitor ___ and ___
- flu
- suicidal
- LFT, TSH
monoclonal antibodies
alemtuzumab
- ___ program
- possible fatal infusion reactions and autoimmune conditions
- associated with increased risk of ___
- CI in ___ infection - prolonged decreased CD4 count
- REMs
- malignancies
- HIV
monoclonal antibodies
natalizumab
- ___ program
- significant association with ___
- REMs
- PML
monoclonal antibodies
ocrelizumab
- only drug FDA approved for ___
- CI in active ___
- associated with increased risk of ___
- PPMS
- hepatitis B
- malignancies
monoclonal antibodies
- complete vaccinations at least ___ weeks before starting treatment
- can premedicate with steroid, antihistamine, APAP prior to dose
6
Pregnancy
teriflunomide
- ** ___ **
- accelerated elimination via activated charcoal /cholestyraline for 11 days
mitoxantrone
- contraception required and ___ before each infusion
cladribine
- contraception + barrier method for at least ___ months after D/C
- CI in ___
- CI
- pregnancy test
- 6, breastfeeding
toxic, not just teratogenic
Pregnancy
contraception required during treatment
- fingolimod: ___ months after D/C
- ozanimod: ___ months after D/C
- ponesimod: ___ days after D/C
- siponimod: ___ days after D/C
- ocrelizumab: ___ months after D/C
2
3
7
10
6
pregnancy
- rates of relapse ___ during pregnancy, increase for first ___ months post-partum, then return to normal pre-pregnancy rate
- MS therapy should be D/C prior to conception
- not advised to ___ if treatment is restarted
- decrease, 3
- breastfeed
pseudobulbar affect
inappropriate episodes of crying, laughing, both unrelated to actual mood
- ___ (dextrimethorphan/quinidine) used for this
Neudexta
- DM = sigma-1 receptor agonist; supress release of excitatory neurotransmitters, NDMA receptor antagonist
Gait abnormalities/Walking speed
___ (Ampyra)
MOA: blocks ___ channels and prevents ___ of cell, causing prolonged action potentials and nerve impulse transmission
- improve 25 foot walking speed by ___ seconds
- ___ dosage form assocaited with seizures; CI in patients with history of seizures
- ___ formulation preferred (SE: UTIs, insomnia, dizziness, headache, nausea)
dalfampridine
- K, repolarization
- 3
- IR
- ER
symptomatic management
- ___ for bladder dysfunction may worsen cognitive function
- ___ is indicated for treatment of spasticity
- anticholinergics
- baclofen
marijuana in MS
Spasticity: OCE/THC decreased patient reported scores, but not ___ scores
Pain: ___ effective for central pain, ___ probably effective to decrease painful spasms
Tremor, bladder dysfunction: OCE and THC probably ineffective
objective
OCE, THC
