lecture 40/41 Flashcards
ott - pharmacotherapy of MS
what is DIT?
dissemination in Time
time between evidence of new lesions in subsequent MRIs (30 days)
damage that has happened more than once
what is DIS?
dissemination in Space
need for over 1T2 lesion appearing in at least two of four MS-typical CNS region (corticol, periventricular, infratentorial, spinal cord)
damage that is in more than one place
what are the types of MS?
clinically isolated syndrome (CIS)
relapsing remitting MS (RRMS)
secondary progressive MS (SPMS)
Primary progressive MS (PPMS)
progressive relapsing MS (PRMS)
what type of MS does DMT focus on?
disease modifying drug therapy is focused on RRMS with one exception for PPMS
what is the average EDSS score in pts with RRMS?
4.0 within 7 years of diagnosis
fully ambulatory without aid, self-sufficient, up and about 12 hours per day day despite relatively severe disability in one functional system OR combination of lesser disabilities that exceed previous scores
able to walk without aid or rest-500 meters
what are the goals of treatment in MS?
start early
use DMDs at CIS stage if possible to traget inflammation
increase QoL by treating other symptoms like fatigue, gait disturbances, and pain
treat acute attacks
how should a pt be treated with acute attacks of MS?
first line - high dose corticosteroid oral (outpatient) or IV (inpatient)
what is the dosing of IV methylpredniosolone?
used for treatment of acute attacks in an inpatient setting
500mg-1000mg IV daily for 3-7days with or without an oral taper over 1-3 weeks
what is the dosing of PO prednisone?
used for treatment of acute attacks in an outpatient setting
1250 mg every other day for 5 doses without need for taper
what are oral medications used to treat MS?
dimethyl fumarate (tecfidera)
diroximel fumarate (vumerity)
fingolimod (gilenya, tascenso ODT)
ozanimod (zeposia)
ponesimod (ponvory)
siponimod (mayzent)
teriflunomide (aubagio)
what are injectable medication used for MS?
interferon B1a (Avonex, rebif)
peginterferon B1a (plegridy)
interferon B1b (betaseron, extavia)
glatiramer acetate (copaxone)
what are infusion medications used for MS?
alemtuzumab (lemtrada)
natalizumab (tysabri)
ocrelizumab (ocrevus)
what is PML?
rare serious adverse event caused by reactivation of dormant JCV, pts must be tested for JCV antibodies
progressive multifocal leukoencephalopathy
what are the CP of dimethyl fumarate, diroximel fumarate, and monomethyl fumarate?
monitor LFTs (due to hepatotoxicity) and CBC with differential (due to neutropenia)
associated with PML
can cause flushing (may take ASA 30 minutes prior)
what drugs are S1P receptor modulators?
fingolimod
ozanimod
ponesimod
siponimod
when are S1P receptor modulators CI?
pts with past arrhythmias diagnosis
what is a good CP for S1P receptor modulators?
d/c can result in significant worsening of MS symptoms
what is unique about siponimod?
interacts with CYP2C9 so needs genotype testing before prescribing
what are SE of inject based glatiramer acetate?
immediately post-injection –> flushing, sweating dyspnea, chest pain, anxiety, itching
later on –> lipoatrophy at site, chest pay outside of injection
how are interferons administered?
either SQ or IM
what are SE of interferon drugs?
flu-like symptoms can occur after injection
psychiatric SE –> depression, suicidal thinking
what should be monitored when using interferons?
LFTs and TSH due to elevated liver and thyroid dysfunction
what drugs are monoclonal antibodies used for MS?
alemtuzumab
natalizumab
ocrelizumab
what are important CP related to alemtuzumab?
increased risk of malignancies
CI in HIV infection
complete vaccinations at least 6 weeks before starting treatment
what are important CP related to natalizumab?
significant association with PML
complete vaccinations at least 6 weeks before starting treatment
what are important CP of ocrelizumab?
FDA approved for PPMS, CIS, RRMS, SPMS
CI in active Hep B
Associated with increased risk of malignancies
complete vaccination at least 6 weeks before starting
what should a pregnant person do while taking teriflunomide?
d/c immediately
CI in pregnancy
what should a pregnant person do while taking mitoxantrone?
use a contraceptive during treatment
take a pregnancy test before each infusion
what are the parameters of taking a certain MS drug and using a contraceptive?
fingolimod - during and 2 months after d/c
ozanimod - during and 3 months after d/c
ponesimod - during and 7 days after d/c
siponimod - during and 10 days after d/c
ocrelizumab - during and 6 months after
when it comes to cladribine and pregnancy, what is unique?
contraceptive required and barrier method for at least 6 months after d/c
CI in breastfeeding
what is the pseudobulbar affect?
frequent and inappropriate episodes of crying, laughing, or both
unrelated to actual and due to unknown cause (may be associated with disruption of neural pathways from brainstem to cerebellum)
what drug can be used to treat pseudobulbar affect?
neudexta (dextromethorphan/quinidine)
how does dextromethorphan act in neudexta?
agonist at sigma-1 recepotrs
suppresses release of excitatory neurotransmitters
antagonist at NMDA receptors
P450 2D6 substrate
when metabolized to dextrophan, it does not cross BBB, stays in the periphery
how does quinidine act in neudexta?
P450 2D6 inhibitor that blocks the conversion of dextromethorphan to dextrorphan, allowing dextromethorphan to reach the CNS
what does dalfampridine (ampyra) target?
blocks K channels to prevent repolarization
may improve walking speed
what are CP of dalfampridine (ampyra)?
IR dosage form and dose escalation associated with seizures
CI in pt with a hx of seizures
