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Therapeutics > Exam 3 lecture 3 > Flashcards

Exam 3 lecture 3 Flashcards

1
Q

Treatments for acute attacks of MS (relapses/exacerbations)

A

methylprednisolone
Prednisolone
Adrenocorticotropic hormone (ACTH)

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2
Q

What are DMDs for MS

A

Reduce relapse rates, may slow progression of disability (generally used to treat relapsing rather than progressive forms of MS)

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3
Q

1st line DMD for MS

A

Interferon B1a (avonex, rebixf)
Interferon B1b (betaseron, extavia)
Glatiramer acetate (copaxone)
Fingolimod (gilenya)

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4
Q

2nd line DMD for MS

A

Natalizumab (tysabri)
Mitoxantrone (novatrone)

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5
Q

New drugs for DMD of MS

A

Teriflumide (aubagio)
dimethyl fumarate (Tecfidera)
cladribine (mylinax)

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6
Q

What are primary corticosteroid treatments for acute attacks

A

Methylprednisolone (oral vs IV)
Prednisone (oral)
Adrenocorticotropic hormone (ACTH)

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7
Q

how do corticosteroids act

A

likely act by upregulating antiinflammatory genes downregulating pro inflammatroy and alleviating edema in demyelinating areas.

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8
Q

MOA of interferon B1a and interferon B1b for MS

A

acts in periphery and at BBB
Periphery- inhibition of autoreactive lymphocytes, T cells, Dendritic cells

BBB- Inhibition of BBB penetration by lowering matrix metalloprotenase (MMP)

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9
Q

clinical features of interferon B1a and B1b

A

first line
Efficacy reduced by neutralizing antibodies

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10
Q

Glatiramer acetate MOA for MS

A

synthetic polypeptide. mimics antigenic properties of myelin basic protein.

modulation of antigen-presenting cells such as dendritic cells, leading to lower T cell activation.

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11
Q

Clinical features of glatiramer acetate

A

1st line
delays the conversion of CIS to clinical MS

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12
Q

Name drugs that act only in periphery (including BBB)

A

Interferon-B
glatiramer acetate
natalizumab
mitoxantrone
teriflunomide
cladribine
rituximab
ATL 1102

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13
Q

drugs that act on periphery and CNS for MS

A

FIngolimod
siponimod
ozanimod
ponesimod
dimethyl fumarate
monomethyl fumarate

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14
Q

Drugs that act at BBB for MS

A

Interferon-B
Natalizumab
ATL 1102

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15
Q

What are drugs that act via a cytotoxic effect for MS

A

mitocantrone
Teriflunomide
Cladribine

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16
Q

Drugs that increase risk of PML for MS

A

Fingolimod
Natalizumab
dimethyl fumarate
Monomethyl fumarate
diroximel fumarate

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17
Q

Drugs that can be used to treat PPMS

A

Rituximab (ocrelizumab(

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18
Q

Drugs whos effectiveness may be limited by neutralizing antibodies

A

IF-B
Natalizumab
Rituximab

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19
Q

Recognize fingolimod structure

A

left long chain structure
attached to phenol ring
attached to two OH groups and an H2N group

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20
Q

MOA of fingolimod (MS)

A

sphingophosine-1-phosphate (s1P) receptor agonist

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21
Q

action of fingolimod on BBB (MS)

A

interference with lymphocyte movement out of lymphoid organs

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22
Q

action of fingolimod on periphery (MS)

A

stimulation of oligodendrocyte survival, remyelination

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23
Q

clinical features of fingolimod (MS)

A

first line

side effects include

progressive multifocal leukoencephalopathy
(PML), a potentially lethal brain infection

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24
Q

side effects of fingolimod

A

Could cause PML

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25
Q

what is PML

A

a potentially life threatening brain infection

progressive multifocal leukoencephalopathy

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26
Q

Natalizumab MOA (MS)

A

Monoclonal antibody specific for a-4 integrin

27
Q

Natalizumab effect on periphery (MS)

A

a-4 integrin pairs with B1 integrin to produce very late antigen (VLA-4)

28
Q

What does natalizumabs inhibition of VLA-4 lead to

A

inhibition of VLA-4 binding to its ligand leads to interference with B and T cell movement into CNS

29
Q

Clinical features of Natalizumab

A

2nd line
a key side effect is the development of PML
- induces the development of neutralizing antibodies → allergic reactions

30
Q

Mitoxantrone MOA (MS)

A

anthracenidone with cytotoxic activity

31
Q

effect of mitoxantrone on periphery (MS)

A

reduces lymphocyte numbers

32
Q

How does mitoxantrone reduce lymphocyte numbers

A

Cause DNA strand breakage by intercalation
delaying DNA repair via inhibition of topoisomerase II

33
Q

Clinical features of mitocantrone

A

2nd line

34
Q

Teriflunomide MOA (MS)

A

Cytotoxic agent that inhibits dihydroorotate dehydrogenase

35
Q

effect of teriflunomide on periphery (MS)

A

Inhibits proliferation of peripheral lymphocytes (activated and T cells)

36
Q

What are the fumarate drugs used to treat MS

A

Dimethyl fumarate
diroximal fumarate
monomethyl fumarate

37
Q

Dimethyl fumarate, diroximal fumarate,
monomethyl fumarate MOA

A

metabolized by esterases in GI tract, blood, tissues

38
Q

Dimethyl fumarate, diroximal fumarate,
monomethyl fumarate effects on periphery

A

activate Nrf2- mediated cellular antioxidant responses and anti-inflammatory pathways
suppresses activated T cells, dendritic cells in periphery

39
Q

Dimethyl fumarate, diroximal fumarate,
monomethyl fumarate effects on BBB

A

may promote remyelination

40
Q

side effects on Dimethyl fumarate, diroximal fumarate,
monomethyl fumarate

A

PML

41
Q

recognize dimethyl fumarate structure

A
42
Q

Recognize cladribine structure

A

(same as adenosine but has Cl attached)

43
Q

Siponimod, ozanimod, ponesimod MOA

A

S1P receptor agonist (same as fingolimod)

44
Q

Cladribine MOA

A
  • taken up in cells by purine nucleoside transporters
  • in cells with a high ratio of deoxycytidine kinase to deoxynucleotidase (e.g.
    lymphocytes, monocytes), cladribine is phosphorylated to the triphosphate
    form, 2-chloro-dATP.
  • 2-chloro-dATP damages DNA and interferes with DNA
    metabolism, resulting in cell death -> lymphocyte depletion
45
Q

What are antibody therapies for MS

A

Rituximab (ocrelizumab)

46
Q

Use of rituximab (ocrelizumab)

A

PPMS pts

47
Q

Rituximab (ocrelizumab) (MS) MOA

A
  • humanized monoclonal antibody that targets CD20, a marker of mature B-cells
  • doesn’t bind CD20 on stem cells or plasma cells, so that key immune functions
    are unperturbed.
  • decreased disease progression in PPMS (first example)
  • decreased relapse rate in RRMS
48
Q

What are some experimental MS drugs

A

Antisense oligonucleotide (ATL 1102)

49
Q

ATL 1102 MOA

A

ASO targeting VLA 4, predicted to have the same outcome as natalizumab

50
Q

Which drug is active in both peripher and CNS

A

dimethyl fumarate

51
Q

What is a single diagnostic feature or criteria to diagnose MS

A

No single feature or diagnostic criteria is sufficient to diagnose on clinical features or presentations

52
Q

What are other disorders to rule out when diagnosing MS

A

Neuromyelitis
Optica spectrum disorder

53
Q

What is DIT (!)

A

Dissemination in time

Time between evidence of new lesions in subsequent MRIs (30 days). Damage that has happened more than once.

54
Q

What is DIS (!)

A

Dissemination in space

Need for more than 1 lesion to appear in atleast 2 of the 4 MS typical CNS regions (damage is in more than one place)

In summary- 1 lesion is not enough, 2 lesions at different areas of brain in different times.

55
Q

What are the types of MS

A

CIS
RRMS
SPMS
PPMS
PRMS

56
Q

define CIS (!)

A

Clinically isolated syndrome
descriptor of a 1st demyelinating event involving the optic nerve, cerebrum, cerebellum, brainstem or spinal cord.

most will develop MS within 20 yrs

57
Q

Define RRMS (!)

A

most common (80-90% of diagnosis)

Consists of relapses with partial or complete remission between relapses.

most will become progressive over time

58
Q

Define SPMS (!)

A

80% of RRMS pts will progress to SPMS.

consists of fewer relapses with continuing disability

59
Q

Define PPMS (!)

A

10-15% of pts
progressive form from onset with minor improvements or periods of stability more common in patiets diagnosed in later years (greater than 50 years of age)

60
Q

Define PRMS (!)

A

least common form. steadily worsening disease from onset with later, clear, acute relapses;
may be some recovery from acute attacks, but no
remission between relapses

61
Q

treatment of acute attacks of MS (!)

A
  1. High dose corticosteroid treatment is 1st choice (oral vs IV setting)
  2. Methylprednisolone 500 mg-1000mg IV daily for 3-7 days, with or without an oral taper over 1-3 weeks
  3. If outpatient- oral prednisone 1250 mg every other day x 3 doses
62
Q

Oral medications for MS (!)

A

Dimethyl fumarate
Diroximel fumarate
Fingolimod
Ozanimod
Punesimod
Siponimod
Teriflunomide

63
Q

Injectible medications for MS (!)

A

interferon B 1a
Peginterferon beta-1 a
Interferon beta-1 b
glatiramer acetate

64
Q

Infusion medications for MS (!)

A

Alemtuzumab
Natalizumab
Ocrelizumab (only one approved for PPMS)

Therapeutics (38 decks)

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