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PT2 Neuro 10-11 and Pain 1-4 > MS therapeutics > Flashcards

MS therapeutics Flashcards

1
Q

multiple sclerosis

A

autoimmune, inflammatory, demyelinating disease of the CNS

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2
Q

risk factors for MS

A
  • female
  • scandinavian ancestry
  • further from equator
  • age 15-45
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3
Q

the pathophysiologic response in MS

A
  • t-cells activated in the periphery
  • permeability of the BBB is increased, immune cells easily enter CNS
  • In CNS more immune and inflammatory cells activated against myelin
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4
Q

the end result of demyelination

A

eventual transection of axons and permanent disability

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5
Q

symptoms of MS

A
  • vary based on damage location*
  • visual disturbances
  • mental changes
  • depression
  • muscle spasms
  • limb weakness
  • incontinence
  • loss of sensation
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6
Q

relapsing-remitting MS

A

stable with acute relapses

85% initially

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7
Q

secondary progressive MS

A

gradual progression after a period of RRMS

-50% develop in 10 years, 90% w/i 25 years

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8
Q

primary-progressive MS

A

gradual progression from onset

15%

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9
Q

progressive-relapsing MS

A

gradual progression with intermittent relapses

-rarest

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10
Q

benign course MS

A

-progression doesn’t occur

10-20% have this

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11
Q

gold standard for MS diagnosis

A

MRI, looking for lesions separated in space and time

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12
Q

treatment goals of acute attacks

A
  • shorten duration

- decrease severity

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13
Q

treatment goals of disease modifying therapies (DMT)

A
  • alter course

- diminish progressive disability

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14
Q

main goal of therapy

A

maintain quality of life

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15
Q

relapse definition

A
  • worsening of symptoms lasting >24 hours
  • at least 30 days after previous relaps
  • absence of infection and fever
  • EDSS increased by 1 point from baseline
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16
Q

expanded disability status scale (EDSS)

A

point scale that measures the level of a persons disability

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17
Q

when to treat a patient

A

when they have functional disability

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18
Q

corticosteroid use in MS

A
  • mainstay of treatment
  • effective in 75%
  • reduce severity and length of relapse
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19
Q

corticosteroid MoA in MS

A
  • reduce edema in demyelination areas
  • restore BBB integrity
  • reduce cytokine release
  • exact MoA unknown*
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20
Q

typical corticosteroid dosing in MS

A
  • methylprednisolone 500-1000 mg IV qd for 3-10 days

- may be followed by prednisone taper for 1-3 weeks

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21
Q

corticosteroid side effects

A
  • mood changes
  • N/V
  • hyperglycemia
  • exacerbation of infection
  • decreased bone density
  • changes in taste or flushing during infusion
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22
Q

first line disease modifying therapy injections

A
  • interferon beta

- glatiramer acetate

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23
Q

oral second line disease modifying therapy injections

A
  • fingolimod (Gilenya)
  • teriflunomide (Aubagio)
  • dimethyl fumarate (Tecfidera)
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24
Q

IV second line disease modifying therapy injections

A
  • natalizumab (Tysabri)
  • mitoxantrone (Novantrone)
  • alemtuzumab (Lemtrada)
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25
Q

what to use asap after RRMS diagnosis

A

interferon beta or glatiramer (copaxone)

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26
Q

interferon beta MoA

A
  • exact is unknown
  • alters antigen presentation
  • interferes with t-cell proliferation
  • inhibits cytokine release
  • prevents inflammatory cells crossing BBB
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27
Q

interferon beta RRMS efficacy

A
  • 30% reduction in relapse rate

- 50-75% reduction in MRI disease activity

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28
Q

interferon beta efficacy in PPMS or SPMS

A

not effective without relapses

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29
Q

interferon beta side effects

A
  • flu-like symptoms

- depression

30
Q

glatiramer acetate MoA

A
  • exact is unknown
  • may divert immune destruction of myeline
  • Th2 cells that promote release of anti-inflammatory cytokines are produced
31
Q

glatiramer efficacy in relapsing MS

A
  • 30% reduction of relapse rate
  • 30% reduction in MRI activity
  • reduce disability progression
32
Q

glatiramer efficacy in CIS

A
  • delays time to second relapse

- reduces risk of clinically definite MS

33
Q

interferon efficacy in CIS

A
  • reduce risk of new activity on MRI
  • prolong time to 2nd relapse
  • reduce progression to clinically definite MS
34
Q

glatiramer side effects

A

-transient systemic post injection reaction that may feel like a heart attack

35
Q

Interferon beta IM injection

A

Avonex

36
Q

how to avoid flu-like symptoms with beta interferon

A
  • titrate dose
  • pre/post treat with NSAID or tylenol
  • inject before bedtime
  • often subsides over time
37
Q

fingolimod use

A

relapsing forms of MS

-oral

38
Q

fingolimod MoA

A

inhibits t-cells and lymphocytes migration out of lymph nodes

39
Q

fingolimod side effects

A
  • first dose bradycardia

- infection

40
Q

fingolimod monitoring

A

lots more than 1st line

  • vaccinations
  • CBC
  • LFTs
  • opthalmic
  • first dose monitoring
41
Q

teriflunomide MoA

A
  • suppression of pyrimidine synthesis (immune response)

- reduces T and B cell proliferation

42
Q

teriflunomide side effects

A

increased LFTs

43
Q

interferon beta monitoring

A

CBC
LFTs
efficacy after 6-12 months

44
Q

glatiramer monitoring

A

efficacy after 6-12 months

45
Q

teriflunomide monitoring

A
  • negative TB test prior to initiation

- teratogenicity and hepatotoxicity

46
Q

dimethyl fumarate MoA

A
  • induces apoptosis of activated T-cells
  • activation of antioxidant response elements
  • decreased inflammatory cells in CNS
47
Q

dimethyl fumarate side effects

A
  • lymphopenia

- elevated LFTs

48
Q

dimethyl fumarate monitoring

A
  • CBC

- signs of infection

49
Q

natalizumab use

A

recommended for patients w/ inadequate response to or intolerance of first line treatment

50
Q

natalizumab withdrawn due to

A

progressive multifocal leukoencephalopathy (PML)

-serious brain infection with high mortality

51
Q

natalizumab MoA

A

activated lymphocytes can’t cross BBB

52
Q

natalizumab efficacy in RRMS

A
  • 42% reduction of progression
  • 68% reduction relapse rate
  • 83% MRI lesion recdution
53
Q

natalizumab side effects

A
  • allergic reaction to infusion
  • neutralizing antibodies to medication
  • fatigue
  • infection
  • PML
54
Q

mitoxantrone use

A

clinically worsening of RRMS, SPMS, and PRMS

55
Q

mitoxantrone MoA

A
  • inhibits topoisomerase II
  • reduce inflammatory cytokines
  • inhibit T, B cell, and macrophage proliferation
56
Q

mitoxantrone dosing

A

max 140 mg/m^2 in a lifetime due to cardiotoxicity

57
Q

mitoxantrone

A

ECHO every month for cardiotoxicity

58
Q

mitoxantrone efficacy

A

for RRMS and SPMS

  • 60-70% reduction in relapse rate
  • reduced disability progression
59
Q

mitoxantrone side effects

A
  • chemotherapy side effects

- cardiotoxicity

60
Q

alemtuzumab use

A

RRMS and inadequate response to two or more drugs

61
Q

alemtuzumab MoA

A

-apoptosis of T cells

62
Q

alemtuzumab efficacy

A
  • 40% reduction in disability progression

- 51% reduction in relapse rate

63
Q

alemtuzumab side effects

A
  • rash
  • headache
  • nasopharyngitis
64
Q

alemtuzumab monitoring

A

CBC
skin exams
TSH
infections

65
Q

treatment for ambulation problems in MS

A

dalfampridine

66
Q

dalfampridine MoA

A

blocks K channels in CNS

67
Q

treatment for fatigue in MS

A

stimulants (amantadine, modafinil, methylphenidate)

68
Q

treatment for spasticity in MS

A

baclofen

69
Q

treatment for urinary urgency in MS

A

anticholinergic

70
Q

treatment for urinary retention in MS

A

catheter

alpha blocker

PT2 Neuro 10-11 and Pain 1-4 (5 decks)

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