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Therapeutics > Multiple Sclerosis > Flashcards

Multiple Sclerosis Flashcards

1
Q

What is the effect of vitamin D in multiple sclerosis?

A

increased vitamin D may decrease disease activity

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2
Q

What are risk factors of MS?

A
  • smoking
  • women
  • Northern European descent living above 40 degrees latitude
  • 1st degree relative with MS
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3
Q

What is the effect of pregnancy in multiple sclerosis?

A

pregnancy is protective against relapses

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4
Q

What is required for MS diagnosis?

A

2 documented exacerbations & 2 distinct MRI lesions separated by time and space

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5
Q

What is clinically isolated syndrome (CIS)?

A
  • the first episode of neuro symptoms lasting greater than 24 h
  • 1 attack, 1 lesion
  • may or may not become MS
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6
Q

What is relapsing remitting MS (RRMS)?

A
  • most common MS
  • worsening or onset of new symptoms for greater than 48 hrs WITHOUT fever
  • contrasted by symptom free periods where symptoms partially or completely disappear
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7
Q

What is secondary progressive MS (SPMS)?

A

starts as RRMS and turns to progressive

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8
Q

What is primary progressive MS (PPMS)?

A
  • steady decline without relapses
  • meds are generally not effective
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9
Q

What is progressive relapsing MS (PRMS)?

A
  • steady progression with periods of exacerbation
  • can only treat relapses will still progress
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10
Q

What are the 2 options for acute MS relapse treatment?

A
  1. methylprednisolone IV x 3-5 days (+/- PO prednisone taper)
    AND H2RA/PPI for ulcer prophylaxis
  2. acthar gel IM or subQ for 2-3 weeks
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11
Q

What is PML (progressive multifocal leukoencephalopathy)?

A

fatal viral opportunistic infection caused by activation of latent John Cunningham polyomavrius and causes demyelinating diseases (like MS)

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12
Q

What are risk factors for PML?

A
  • testing + for JCV antibodies
  • prior use of immunosuppressive meds
  • using natalizumab for > 2 years
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13
Q

What are the interferon beta-1a agents that are used for MS?

A
  1. Avonex
  2. Rebif
  3. Plegridy (pegylated)
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14
Q

What is the indication for all interferon beta agents used in MS?

A

CIS, RRMS, active SPMS

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15
Q

What is the class ADR for interferon beta agents used in MS? (5)

A
  1. Flu like symptoms (pretreat w/ NSAID/APAP, improves overtime)
  2. injection site run
  3. depression
  4. abdominal pain
  5. increased LFTs
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16
Q

What is the interferon beta-1b agent used for MS?

A

Betaseron/Extavia

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17
Q

Which interferon beta is administered IM weekly in MS?

A

Avonex (beta-1a)

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18
Q

Which interferon beta is administered subQ TIW in MS?

A

Rebif (beta-1a)

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19
Q

Which interferon beta is administered subQ every 2 weeks in MS?

A

Plegridy (pegylated beta-1a)

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20
Q

Which interferon beta is administered subQ every other day in MS?

A

Betaseron/Extavia (beta-1b)

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21
Q

What is the indication for Glatiramer acetate (Copaxone, Glatopabiosimilar) in MS?

A

CIS, RRMS, active SPMS

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22
Q

How is Glatiramer acetate (Copaxone, Glatopabiosimilar) administered in MS?

A

subQ

either 20 mg daily or 40 mg TIW

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23
Q

What MS agent prevents transmigration of leukocytes across the endothelium via antagonizing alpha 4 integrin on VLA 4 of leukocytes?

A

Natalizumab (Tysabri, Tyrukobiosimilar)

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24
Q

Which MS agent has a BBW for PML & requires enrollment into the TOUCH program?

A

Natalizumab (Tysabri, Tyrukobiosimilar)

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25
Q

What is the indication for Natalizumab (Tysabri, Tyrukobiosimilar) in MS?

A

CIS, RRMS, active SPMS

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26
Q

How is Natalizumab (Tysabri, Tyrukobiosimilar) administed in MS?

A

IV infusion q4w

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27
Q

What MS agent targets CD52 on immune cells and reduces the number of circulating T cells?

A

Alemtuzumab (Lemtrada)

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28
Q

What is the indication for Alemtuzumab (Lemtrada) in MS?

A

RRMS or active SPMS

WITH inadequate response to 2 or more meds

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29
Q

What are 2 common ADR in patients on Alemtuzumab (Lemtrada) for MS?

A
  1. development of a thyroid disorder
  2. rash
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30
Q

What are the BBWs for Alemtuzumab (Lemtrada) in MS therapy?

A
  1. immune thrombocytopenia
  2. infusion reaction (pre med w/ steroids, 2 hour post injury monitoring)
  3. malignancy
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31
Q

How is Alemtuzumab (Lemtrada) administered in MS?

A

IV infusion

12 mg over 4 hours x 5 days

repeat 3 day course at 1 year

can do another 3 day course after another 12 mo

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32
Q

What MS agents bind CD20 on B cells & depletes them from circulation?

A
  1. Ocrelizumab (Ocrevus)
  2. Ublituximab (Biumvi)
  3. Ofantunumab (Kesimpta)
33
Q

What are the general indications across all CD20 binding mAbs used for MS?

Which CD20 agent ALSO has indication for PPMS???

A

CIS, RRMS, active SPMS

Ocrelizumab (Ocrevus)

34
Q

Which CD20 mAbs used in MS require the dose to be split for the 1st IV infusion and then given every 6 mo thereafter?

A
  1. Ocrelizumab (Ocrevus)
  2. Ublituximab (Biumvi)
35
Q

What are common ADR of the CD20 mAbs used for MS?

A

infusion reactions

UTI, URI

HA, nausea

PML

36
Q

Which CD20 mAb used for MS needs to have the 1st injection done under medical supervision?

A

Ofantunumab (Kesimpta)

37
Q

How is Ofantunumab (Kesimpta) administered in MS?

A

subQ
QW x 3 doses THEN QM

38
Q

What chemotherapy agents are used in MS?

A
  1. Mitoxantrone (Novantrone)
  2. Mavenclad (cladribine, 2-chloro deoxyadenosine)
39
Q

What is the indication for Mitoxantrone (Novantrone) in MS?

A

PRMS, SPMS & RRMS

reserved for rapidly advancing refractory MS

40
Q

How is Mitoxantrone (Novantrone) administered in MS?

A

IV based on BSA q3mo

MAX cumulative lifetime dose of 100 mg/m^2

41
Q

What are the BBWs for Mitoxantrone (Novantrone)?

A
  1. cardiotoxicity
  2. bone marrow suppression
42
Q

What is the indication for Mavenclad (cladribine, 2-chloro deoxyadenosine) in MS?

A

RRMS & active SPMS

WITH failure or CI to other therapies

43
Q

How is Mavenclad (cladribine, 2-chloro deoxyadenosine) administered in MS?

A

PO tab (separate from other meds by 3 hours)

given as 3.5 mg/kg over a 2 year treatment course (half of total dose each year)

split into 2 cycles/year that are 4-5 days and 23-37 days apart

2nd year has to be at least 43 weeks from previous cycles

can repeat another 2 year course; minimum of 2 years later

44
Q

What is required before the first course of Mavenclad (cladribine, 2-chloro deoxyadenosine) for MS?

What about for subsequent courses?

A

lymphocytes WNL

lymphocytes >/= 800 cells/mm^3

45
Q

What are the BBWs for Mavenclad (cladribine, 2-chloro deoxyadenosine)?

A
  1. malignancy
  2. teratogenicity (contraceptive during & 6 mo after)
46
Q

How long is contraception needed after Mavenclad (cladribine, 2-chloro deoxyadenosine) therapy is complete?

What is an additional pearl regarding hormonal contraceptives & Mavenclad?

A

6 months

Mavenclad decreased the effect of oral contraceptives

47
Q

What are MS agents that act on sphingosine-1-phosphate (S1P) recep and decreases overall number of lymphocytes in circulation?

A
  1. Fingolimod (Gilenya - PO, Tascensobiosimilar - ODT)
  2. Siponimod (Mayzent)
  3. Ozanimod (Zeposia)
  4. Ponesimod (Ponvory)
48
Q

What are the indications of S1P drugs for MS?

A

CIS, RRMS, active SPMS

49
Q

What is the frequency of dosing for all S1P drugs used for MS?

A

QD!

50
Q

Which S1P used in MS ALWAYS required 6 hour post dose BP monitoring?

A

Fingolimod (Gilenya - PO, Tascensobiosimilar - ODT)

51
Q

Which S1P’s require first dose monitoring ONLY if the patient has pre-existing cardiac conditions?

How many hours is needed for each?

A
  1. Siponimod (Mayzent) -> 6 hours
  2. Ponesimod (Ponvory -> 4 hours
52
Q

In what circumstance should 1st dose monitoring continue overnight for any of the S1Ps used for MS that require 1st dose monitoring?

A

if pt is high risk
- prolonged QT
- drugs w/ Torsades risk or that affect HR

53
Q

What S1P drug used for MS has dosing dependent on CYP2C9 genotyping?

What CYP2C9 genotype is contraindicated?

A

Siponimod (Mayzent)

3/3

54
Q

What MS agents are associated with rebound syndrome (severe increase in disability) upon D/C?

A

S1P drugs
1. Fingolimod (Gilenya - PO, Tascensobiosimilar - ODT)

  1. Siponimod (Mayzent)
  2. Ozanimod (Zeposia)
  3. Ponesimod (Ponvory)
55
Q

When does 1st dose monitoring need to be repeated in patients on Fingolimod (Gilenya - PO, Tascensobiosimilar - ODT) for MS?

A

1 days missed in 1st 2 weeks

7 days missed in a row in weeks 3-4

14 days missed after 1 mo

56
Q

When does 1st dose monitoring need to be repeated in patients on Siponimod (Mayzent) for MS?

A

1 day missed in initial regimen

4 days or more missed in maintence

57
Q

When does 1st dose monitoring need to be repeated in patients on Ponesimod (Ponvory) for MS?

A

4 days or more missed

58
Q

What MS agent produces a cytostatic effect on proliferating B & T cells in the periphery?

A

Teriflunomide (Aubagio)

59
Q

What is the indication for Teriflunomide (Aubagio) in MS?

A

CIS, RRMS, active SPMS

60
Q

How is Teriflunomide (Aubagio) administered in MS?

A

PO QD

food delays abs by 6h but can take w/ food

61
Q

What CI does Teriflunomide (Aubagio) have in MS?

A
  1. pregnancy
  2. breastfeeding
62
Q

What BBWs does Teriflunomide (Aubagio) have in MS?

A
  1. hepatotoxicity
  2. teratogenicity
63
Q

How long is a contraceptive needed after Fingolimod (Gilenya - PO, Tascensobiosimilar - ODT) therapy for MS is complete?

A

2 months

64
Q

How long is a contraceptive needed after Siponimod (Mayzent) therapy for MS is complete?

A

10 days

65
Q

How long is a contraceptive needed after Ozanimod (Zeposia) therapy for MS is complete?

A

3 months

66
Q

How long is a contraceptive needed after Ponesimod (Ponvory) therapy for MS is complete?

A

1 week

67
Q

Teriflunomide (Aubagio) has a very long t1/2 of 8mo-2y, what can be done to accelerate it’s elimination?

A

admin….

cholestyramine 4g q8h x 11 days

OR

activated charcoal 50g q12h x 11 days

68
Q

What is the MAX dose of rosuvastatin that can be given to a patient on Teriflunomide (Aubagio)?

A

10 mg

69
Q

What effect does Teriflunomide (Aubagio) have an INR?

A

may decrease INR in patients on warfarin (inc risk of clot)

70
Q

What MS agents belong to the fumurate class?

A
  1. Dimethyl Fumarate (Tecfidera)
  2. Diroximel Fumarate (Vulmerity)
  3. Monomethyl Fumarate (Bafiertam)
71
Q

What is the MOA of fumurates in MS?

A

induces T helper 2 like cytokines leading to decreased leukocyte migration & is involved in cell response to oxidative stress

72
Q

How are the fumurates dosed in MS?

A

PO BID

73
Q

Which fumurate needs to have its unopened bottle stored in the fridge?

A

Monomethyl Fumarate (Bafiertam)

74
Q

Which fumurate requires meals to have a MAX 30 g of fat and 700 calories?

A

Diroximel Fumarate (Vulmerity)

75
Q

What are fumurates indicated for in MS?

A

CIS, RRMS, active SPMS

76
Q

What are the common ADR for fumurates in MS?

How can they be minimized?

A

GI symptoms and flushing

take w/ high fat, hight protein meal

premed w/ non EC ASA 325 mg 30 min before

77
Q

What agent is used for pseudobulbar affect in MS?

A

Nudexta (dextromethorphan HBr & quinidine sulfate)

78
Q

What agent is used to walking/gait issues in MS?

A

Ampyra (dalfampridine)

79
Q

When is use of Ampyra (dalfampridine) contraindicated for walking/gait issues in MS?

A
  1. hx of seizures
  2. mod-severe renal impairment (CrCl < 50 mL/min)

Therapeutics (17 decks)

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