L 36-39 Pharm of MS drugs Flashcards
what are the 3 categories of MS treatment
- treatment of acute attacks
- disease-modifying therapies
- symptomatic therapies
what are the three primary corticosteroids used for acute attacks
methylprednisolone and prednisone, adrenocorticotropic hormone (ACTH) is also an option but barely used becasue it is expensive
methylprednisolone dosage form(s) for acute attacks
iv and oral
dosage form(s) of prednisone for acute attacks
oral.
what is the likely MOA of corticosteroids in acute MS attacks? (3)
- up-regulating anti-inflammatory genes
- down-regulating pro-inflammatory genes
- alleviating edema in demyelinated areas
2 interferon β1a drugs
avonex and rebif
2 interferon β1b drugs
betaseron and extavia
where do the interferon drugs act?
periphery and at BBB
2 things listed under MOA of interferon drugs
- inhibition of autoreactive lymphocytes– T cells, dendritic cells
- inhibition of BBB penetration by decreasing matrix metalloproteinase (MMP)
highlighted clinical feature(s) for interferon drugs
efficacy is reduced by neutralizing antibodies
MOA for glatiramer acetate (copaxone) (2 things)
- synthetic polypeptide, mimics antigenic properties of myelin basic protein
- modulation of antigen-presenting cells such as dendritic cells, leading to decreased T cell activation
MOA of fingolimod (3 things)
- sphingosine-1-phosphate (S1P) receptor agonist
- stimulation of oligodendrocyte survival, remyelination
- interference with lymphocyte movement out of lymphoid organs
highlighted clinical feature of fingolimod
there was 1 side effect highlighted and it was progressive multifocal leukoencephalopathy (PML), a potentially lethal brain infection
where does fingolimod act?
CNS AND periphery to block movement of shit outside of lymphoid organs
3 MOA things for -zumabs (humanized monoclonal)
- monoclonal antibody specific for a4 integrin
- a4-integrin pairs with B1-integrin to produce ‘very late antigen’ (VLA-4)
- inhibition of VLA-4 binding to its ligand (VCAM-1 on CNS vascular endothelium) and interferes with B and T cell movement into CNS
2 highlighted clinical features for natalizumab
- a key side effect is the development of PML
- induces the development of neutralizing antibodies -> allergic reactions
MOA of mitoxantrone (novantrone) (2 things)
- anthracenedione with cytotoxic activity
- reduces lymphocyte numbers by causing DNA strand breaks via intercalation, and delaying DNA repair via inhibiting topoisomerase II
where does mitoxantrone work
periphery
MOA of teriflunomide (Aubagio) (2 things)
- cytotoxic agent that inhibits dihydroorotate dehydrogenase, an enzyme involved in de novo pyrimidine biosynthesis
- inhibits proliferation of peripheral lymphocytes (activated B and T cells)
3 fumarate drugs
-dimethyl fumarate (Tecfidera)
- diroximel fumarate (vumerity)
- monomethyl fumarate (bafiertam)
what are fumarates metabolized by? Where does this happen?
esterases in GI tract, blood, tissues
what do fumarates activate
Nrf2-mediated cellular antioxidant responses and anti-inflammatory pathways
what “may” dimethyl fumarate promote?
remyelination
what 2 things does dimethyl fumarate suppress?
activated T cells and dendritic cells in the periphery
highligthed clinical feature for fumarates
“apparently PML”
what is the dosage form for all fumarates
all oral and extended release
siponimod name
BAF312? and Mayzent
ozanimod name
zeposia
ponesimod name
ponvory
MOA of -imods
- sphingosine-1-phosphate (S1P) receptor agonists
- may stimulate oligodendrocyte survival, remyelination
- interference with lymphocyte movement out of lymphoid organs
what are Siponimod, Ozanimod, and. Ponesimod indicated for?
RRMS AND SPMS
Cladribine name
mylinax
how does cladribine (mylinax) get into cells?
it is taken up in cells by purine nucleoside transporters
in what scenario is cladribine (mylinax) phosphorylated? what does it turn into?
when cells have high ratio of deoxycytidine kinase to deoxynucleotidase (e.g. lymphocytes and monocytes). gets phosphorylated into. triphosphate form 2-chloro-dATP
what does 2-chloro-dATP do? (this is the thing cladribine (mylinax) turns into)?
damages DNA and interferes with DNA metabolism, resulting in cell death -> lymphocyte depletion
cladribine (mylinax) dosage form
oral
whats special about cladribine (mylinax)
it started as a chemo drug
rituximab names
rituxan, mabthera, zytux
what does Rituximab target?
CD20 (B cell marker) on surface of lymphocytes
what are the two off-label indications for rituximab?
non-hodgkin lymphomas and rheumatoid arthritis
what is rituximab also known as?
ocrelizumab.
Rituximab stops ______ and is effective for some _______
RRMS, PPMS patients
where does rituximab act>
periphery (on B cells)
Drug class that is in late stage clinical trials
Antisense oligonucleotides
what is ATL1102?
an ASO targeting VLA-4 -> predicted to have same outcome as natalizumab
