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Pharm 3 Exam > Multiple Sclerosis > Flashcards

Multiple Sclerosis Flashcards

1
Q

2 characteristics of Multiple sclerosis

A

CNS demyelination and axonal damage

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2
Q

How does MS develop?

A

genetically susceptible individuals are exposed to random/environmental factors triggering immune mediated CNS damage

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3
Q

What are the 4 T helper cell subtypes and their clinical significance?

A

Th1 and Th17 = pathogenic pro-inflammatory
Th2 = anti-inflammatory
Treg = preventive of autoimmunity

  • mutual suppression b/t Th1 and Th2
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4
Q

Examples of favorable and unfavorable prognostic indicators for MS

A

Favorable –> relapsing/remitting, optic neuritis or sensory sxs, women

Unfavorable –> progressive course, motor or cerebellar sxs, polysymptomatic, men

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5
Q

What is MS?

A

immunologic disorder marked by chronic inflammation of the CNS

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6
Q

The key to the dx of MS is –>

A

the dissemination of these plaques in time and space

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7
Q

What are the 4 types of MS?

A
  1. RRMS – relapsing-remitting
  2. PPMS – primary-progressive
  3. SPMS – secondary-progressive
  4. PRMS – progressive-relapsing (or PR w/activity)
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8
Q

What are the 3 broad Tx categories for MS?

A
  • Tx of exacerbations = corticosteroids
  • DMT’s - disease modifying therapies
  • Symptomatic therapy for spasticity, bladder sxs, sensory sxs, & fatigue
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9
Q

Name 5 First-Generation DMT’s

A 
IFN = "BEAR" 
Betaseron
Extavia
Avonex
Rebif

non-IFN = Glatiramer acetate

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10
Q

What are First-Generation DMT’s?

A

self injected meds that decrease annualized relapse rates by 30%

decrease formation of new white matter lesion

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11
Q

How long is efficacy noted after starting therapy of First-Generation DMT’s?

A

1 to 2 years

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12
Q

Name some of the Second-Generation DMT’s for relapsing forms of MS.

A

“D-FANTOM”

Natalizumab
Alemtuzumab
Ocrelizumab
Fingolimod
Mitoxantrone
Teriflunomide
Dimethyl fumarate
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13
Q

2nd-Generation DMT w/an FDA indication for progressive or worsening MS?

A

Mitoxantrone

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14
Q

When is Mitoxantrone indicated?

A

SPMS, PRMS, and worsening RRMS

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15
Q

When is Fingolimod contraindicated?

A 
pt receive class I & III anti-arrhythmic drugs recent heart dz
2nd and 3rd degree AV block
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16
Q

Describe the limitations of Mitoxantrone

A

Lifetime limit of dose is 140
pregnancy category D
secondary leukemia

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17
Q

Which medications could be considered a possible Contraindicated if the pt has a PMHx of depression?

A

Interferons Beta 1a and 1b

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18
Q

What are the monitoring parameters for the interferon medications?

A

Electrolytes, CBC, LFT’s, thyroid, LVEF, depression

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19
Q

Chest tightness and flushing can occur w/ which medication?

A

Glatiramer acetate

20
Q

Which medication has an indication for CIS and RRMS?

A

Glatiramer acetate

21
Q

Which of the interferon medications is considered a LOW potency medication?

A

Interferon beta 1

22
Q

Describe the drug interaction of Fingolimod and Ketoconazole

A

Ketoconazole increases Fingolimod serum concentration (3A4 inhibitor)

23
Q

What is PML and the cause?

A

Progressive Multifocal leukoencephalopathy

  • viral infection that targets cells that make myelin
  • John Cunningham’s virus activated when a person’s immune system is compromised
24
Q

Which DMT is classified as pregnancy category X?

A

Teriflunomide

25
Q

Which 2nd-generation DMT must you administer herpes viral prophylaxis on the first day of Tx?

A

Alemtuzumab

26
Q

Adverse drug Rxn’s of Interferon medications

A

depression

flu-like sxs

27
Q

Adverse drug Rxn’s of Mitoxantrone

A

cardiotoxicity

AML

28
Q

Which DMT should you monitor JCV antibodies? why?

A

Natalizumab

Adverse drug rxn = PML

29
Q

How can you reduce the incidence of flushing while taking Dimethyl fumarate?

A

taking it w/food

30
Q

Adverse drug Rxn’s of Teriflunomide

A 
Steven-Johnson syndrome
liver failure
activation of TB
Neutropenia
lymphocytopenia
31
Q

Which drug is contraindicated w/ HBV?

A

Ocrelizumab

32
Q

What is the Tx for MS exacerbations and when can the pt expect to see improvement?

A

IV injection of high dose corticosteroids (Methylprednisolone) initiated w/in 2 weeks of onset

improvement w/in 3-5 days

33
Q

MOA for corticosteroids in MS

A

speculated to improve recovery by decreasing edema in the area of demyelination

34
Q

Short-term use ADEs of Corticosteroids

A

sleep disturbance

metallic taste

35
Q

Long duration of IV methylprednisolone can lead to –>

A

acne
fungal infections
mood alteration
rarely GI hemorrhage

36
Q

MOA of Teriflunomide (Aubagio)

A

inhibits dihyroorotate dehydrogenase –> prevents proliferation of peripheral lymphocytes (T & B cells) –> reduces activation of lymphocytes in the CNS –> reduces inflammation and demyelination

37
Q

MOA of Dimethyl fumarate

A

unknown – involved in cellular response to oxidative stress

in vitro nicotinic acid receptor agonist
in vivo activator of Nrf2 pathway

38
Q

ADE’s of Dimethyl fumarate

A

Flushing - give w/food
Rash, pruritis
GI discomfort
Increased LFT’s

39
Q

Which medication has an active metabolite and the name of this substance?

A

Teriflunomide

Leflunomide

40
Q

If you prescribe Teriflunomide, which labs should you monitor for adverse effects?

A 
pregnancy test
TB (reactivation)
LFT's 
CBC (lymphocytopenia, neutropenia)
Blood pressure
41
Q

If a pt declines oral therapy, what option might provide the pt w/ a safer alternative?

A

Interferons beta 1a or 1b

Glatiramer

42
Q

In general, all IFNs do what 3 things?

A
  • proposed MOA’s in periphery and at the blood-brain barrier level
  • balances expression of pro- and anti-inflammatory agent in the brain
  • reduce number of inflammatory cells that cross blood brain barrier
43
Q

MOA of Glatiramer acetate?

A

antigenically similar to myelin basic protein (MBP) –> inhibits MBP from binding to T-cell receptor complexes

induces Th2 (anti-inflamm) –> reduction of inflammation, demyelination, and axonal damage

Neuroprotective effect

44
Q

What is the 1st line Tx for MS? and what additional therapies can be used if pt has inadequate response or intolerance?

A

1st line = 1st-generation DMT’s

2nd generation DMTs

45
Q

MOA of Mitoxantrone

A

inhibits RNA and DNA synthesis (use in oncology-leukemias)

46
Q

MOA of Natalizumab

A

activated lymphocytes are denied entry past the blood-brain barrier

47
Q

MOA of Fingolimod

A

exhibits immunosuppressant properties by sequestering circulating lymphocytes

reduces the infiltration of T lymphocytes and macrophages into the CNS

Pharm 3 Exam (3 decks)

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