36-39 Pharmacology of MS drugs Flashcards
3 categories of MS treatment
1) treatment of ___ attacks
2) disease ___ therapies
3) ___ therapies
1) acute
2) modifying
3) symptomatic
treatment of acute attacks (3)
- methylprednisolone
- prednisone
- adrenocorticotropic hormone (ACTH)
ACTH is expensive (rarely used)
disease modifying therapies
reduce ___ rates, may slow the ___ of disability
- generally used to treat ___ rather than ___ forms of MS
relapse, progression
- relapse, progressive
disease modifying therapies - examples
1st line (4)
- interferon B1a
- interferon B1b
- glatiramer acetate
- fingolimod
disease modifying therapies - examples
2nd line (2)
- natalizumab
- mitoxantrone
disease modifying therapies - examples
new drugs (3)
teriflunomide
dimethyl fumarate
cladribine
primary corticosteroids for acute attacks
MOA:
- up-regulating anti - ___ genes
- down-regulating ___ -inflammatory genes
- alleviating ___ in ___ areas
- inflammatory
- pro
- edema, demyelinated
interferon B1a and B1b drugs
first line drugs
MOA: act in the ___ and at the ___
- inhibition of ___ lymphocytes - T cells, dendritic cells
- inhibition of BBB penetration by ____ matrix metalloproteinase
clinical features
- delay conversion of ___ to clinical MS
- efficacy reduced by neutralizing ___
periphery, BBB
- autoreactive
- decreasing
- CIS
- antibodies
lymphocytes - T cells and dendritic cells
interferon B1a drugs (2)
Avonex
Rebif
interferon B1b drugs (2)
Betaseron
Extavia
Glatiramer acetate (Copaxone)
first line
MOA: ___ polypeptide, mimics ___ properties of myelin basic protein
- modulation of APCs such as dendritic cells, leading to decreased ___ activation
clinical features
- delay conversion of ___ to clinical MS
synthetic, antigenic
- T cells
- CIS
fingolimod (Gilenya)
first line
MOA: ___ receptor ___
- stimulation of ___ survival, remyelination
- interference with ___ movement out of lymphoid organs
clinical features
- first oral drug approved for RRMS, superior to IFN-B
- SE: cardiotoxicity, fatal viral encephalitis (HSV or Varicella-Zoster), and progressive multifocal ___ (PML), a potentially lethal brain infection
sphingosine-1-phosphate (S1P), agonist
- oligodendrocyte survival
- lymphocyte
- leukoencephalopathy
natalizumab (Tysabri)
second line
MOA: monoclonal antibody specific for ___ integrin
- ___ integrin pairs with ___ integrin to produce very late antigen (VLA-4)
- inhibition of VLA-4 binding to its ligand ( ___ on CNS vascular endothelium) and interferes with ___ and ___ cell movement into the CNS
clinical features
- superior effects vs first line DMDs
- SE: development of ___
- induces the development of ___ antibodies leading to ___ reactions
a4
- a4, B1
- VCAM-1, B, T
- PML
- neutralizing, allergic
mitoxantrone (Novantrone)
second line
MOA: antracenedione with ___ activity
reduces lymphocyte numbers by
- causing DNA stand ___ via ___
- delaying DNA ___ via inhibition of ___ II
clinical features
- first ___ drug licensed for SPMS
- SE: cardiotoxicity and malignancies (mutagenic activity)
- can be used as ___ therapy and then replaced with IFN-B or GLAT
cytotoxic
- breaks, intercalation
- repair, topoisomerase
- cytotoxic
- induction
teriflunomide (Aubagio)
MOA: ___ agent that inhibits dihydroorotate dehydrogenase, an enzyme involved in de novo ___ biosynthesis
- inhibition proliferation of peripheral ___
clinical features
- reduces ___ rates, MRI endpoints
- primary risks are hepatotoxicity and ___
cytotoxic, pyrimidine
- lymphocytes
- relapse
- teratogenicity