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p3 year :) > MS > Flashcards

MS Flashcards

1
Q

corticosteriod MoA

A

stimulates body to make own hormone to improve immune system –> suppress mirgration of polymorphonuclar leukocytes AND dec capillary permeability –> decrease inflammation –> dec myelin destruction

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2
Q

corticosteriod options

A

1st: methylprednisolone iv
2nd: corticotropin acthar gel IM or SQ

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3
Q

methylprednisolone dose

A

1g IV qd x3-5 days
**follow with oral prednisone taper if needed

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4
Q

methylprednisolone additional needs

A
  1. H2RA or PPI for ulcer prophylaxis
  2. monitor blood glucose nd infection
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5
Q

corticosteriod acute effects

A
  • insomnia
  • mood change
  • inc energy
  • inc irritability
  • inc infection risk
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6
Q

corticotropin acthnar gel MoA

A

adrenocroticotropic hormone –> stimulate adren cortex –> secrete adrenal steriods such as cortisol –> androgenic and aldosteronic

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7
Q

corticotropin acthar gel dose

A

IM or SQ 80-120U/day x2-3 weeks

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8
Q

classes of disease modifying drugs

A
  1. ABCR-injectables
  2. mAb
  3. immunomodulators
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9
Q

ABCR injectable drugs

A

interferon beta 1a
- Avonex
- Rebif

interferon beta 1b
- Betaseron

glatiramer acetate
- Capaxone

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10
Q

ABCR injectable dosage forms

A

autoinjectors
or
vial and needle

  • rotate injection site
  • injection technique
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11
Q

interferon impact on liver

A

(Avonex, Rebif, Betaseron)
**inc LFT’s, therefore need…
- monitoring
- NSAID instead of APAP for pre-medication
- caution alcohol (also inc LFTs)

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12
Q

interferon beta MoA

A

interferon-induced proteins and mechanisms –>
- inc supporessor T cell function
- dec interferon gamma
- dec macrophage activation
- dec expression of major histocompatibility complex
- supress T cell proliferation
- dec BBB permeability

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13
Q

interferon beta indication

A
  • CIS
  • RRMS
  • active SPMS
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14
Q

interferon beta-1a in pregnancy

A

DONT USE

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15
Q

interferon beta 1a options

A
  • Avonex
  • Rebif
  • Plegridy
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16
Q

Avonex dose

A
  • IM qweek
  • titrate
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17
Q

Rebif dose

A
  • SQ three times a week
  • titrate
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18
Q

Plegridy dose

A
  • SQ q 2 weeks
  • titrate

**pegylated (PEG) –> therefore act for longer in body

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19
Q

interferon beta-1b options

A
  • Betaseron
  • Extavia
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19
Q

Betaseron dosing

A
  • SQ qod
  • titrate
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20
Q

interferon beta AE

A

***flu-like symptoms!!!
- fever
- chills
- HA
- chest pain

**injection site reactions

*depression

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21
Q

interferon beta overcoming flu like symptoms

A

*pre-medicate
- before injection and day after injection
- APAP or NSAID
*if worried about LFTs use NSAID

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22
Q

when to not use interferon beta

A

if depression uncontrolled or pt predisposed

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23
Q

glatiramer acetate options

A
  • Capaxone
  • Glatopa
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24
Q

glatiramer acetate MoA

A

alter T cell activation and differentiation
- inc suppressor T cells
- mimic antigens of myseling basic protien
- bind major histocompatbility complex
- dec inflammation, demyelination, axon damage

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25
Q

Capaxone dose

A
  • SQ qd or TIW (different doses)
  • NO titrate
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26
Q

capaxone and pregnany

A

**SAFE for patients who may become pregnant

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27
Q

general rule of treating MS in pregnancy

A
  • have certain agents that are safe in pregancy that can be used when patients may become pregnant
  • generally don’t treat during pregnancy bc MS usually gets better during preg anyway –> protective effect
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28
Q

copaxone indication

A

CIS, RRMS, active SPMS

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29
Q

copaxone AE

A

***injection site reactions
- induration/mass/welt
- pain
- redness
- inflammaiton
- uritcaria
*lasts for days after

can occur anytime –> FEELS LIKE HEART ATTACK
- flushing
- vasodilation
- chest tightness
- palpitations
- throat constriction

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30
Q

types of monoclonal antibodies

A
  • murine: fully mouse
  • chimaeric: mouse antigen binding site and complement sequence
  • humanized: mouse complement sequence
  • human: fully human
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31
Q

monoclonal antibody options

A
  • natalizumab
  • alemtuzimab
  • daclizumab
  • ocrelizumab
  • ofatunumab
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32
Q

natalizumab MoA

A

antagonize alpha-4 integrin that activates leukocytes –> inhibits adhesion of leukocytes to receptors –> inhibitis migration of leukocytes acorss BBB

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33
Q

natalizumab indication

A
  • CIS
  • RRMS
  • active SPMS
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34
Q

natalizumab dose

A
  • 300mg IV q 4 weeks
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35
Q

natalizumab and pregnancy

A

no use

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36
Q

natalizumab AE

A

***PML (progressive multifocal leukoencephalopathy)!!! –> fatal viral opportunistic infection

  • infusion reactions
  • RTI
  • UTI
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37
Q

what is PML?

A

fatal viral opportunistic infection
- from latent john cunningham polyomavirus –> reactivated when immunocompromised
- massive brain inflammation –> acute neurologic s/s

  • demyelinating disease –> in PML, myelin CANNOT BE REGAINED
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38
Q

which factors increase PML risk?

A
  • positive JCV antibodies
  • prior use of immunsuppressants
  • use natalizumab for > 2 years
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39
Q

requirements for natalizumab prescribing

A

*TOUCH prescribing program –> need to register to monitor for PML
- similar to REMS

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40
Q

alemtuzumab (Lemtrada) MoA

A

taregts CD52 on T and B lymphocytes, NK cells, macrophage, monocytes –> long term reduction in circulating T cells!
**blatent wipe out of immune system –> reset button

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41
Q

alemtuzumab indication

A

RRMS SPMS
**ONLY if inadequte response to 2+ other therapies —> not first line, bc huge wipe out and serious AEs

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42
Q

alemtuzumab dose

A
  • 12mg IV qd over 4 hours x 5 days
    THEN AFTER 12 MONTHS
  • 12mg IV qd over 4 hours x 3 days
    THEN IF NEEDED AFTER ANOTHER 12 MONTHS
  • 12mg IV qd over 4 hours x 3 days
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43
Q

alemtuzumab and pregnancy

A

no use

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44
Q

alemtuzumab infusion meds and monitoring

A
  • observe for 2 hours after infusion

**PREMEDICATE
1. methylprednisolone
- before first 3 days of treatment
2. antihistamines
3. antipyretics
4. antiviral prophylaxis
- day of treatment and 2 months after until CD4 >200

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45
Q

alemtuzumab AE

A

***DEVELOPMENT OF AUTOIMMUNE THYROID DISORDERS –> graves disease –> required thyroid ablation
- monitor TSH baseline, q 3 months, until 48 months after last dose

  • rash
  • HA
  • fever
  • infection

**very serious AEs

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46
Q

alemtuzumab BBW

A
  • fatal autoimmune conditions
  • life-threatening infusion reactions
  • malignancy
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47
Q

alemtuzumab monitoring

A
  • TSH (thyroid)
  • CBC, SCr, urinalysis
  • anaphylaxis for 2 horus after infusion
  • skin exams
  • ECG
  • HPV
  • PML
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48
Q

alemtuzumab CI

A

live vaccines –> give live then wait 6 weeks before give alemtuzumab

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49
Q

ocrelizumab MoA

A

binds to CD20 on surface of B cells –> depletes B cells from circulation
- inc cytotoxic effects
- less immunogenic

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50
Q

ocrelizumab dose

A

300mg IV day 1 –> 300mg IV 2 weeks later –> 600mg IV q6months

**continued benefit up to 18 months after D/C

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51
Q

ocrelizumab AEs

A

**infusion reactions –> premedicate!
- rash, uricaria, redness, bronchospas, flushing, N)
- more common with: higher doses, first infusion

  • UTI
  • URI
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52
Q

ocrelizumab premedication

A
  1. steroid – methylprednisolone
  2. antihistamine – dyphenhydramine
  3. antipyretic – APAP
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53
Q

ocrelizumab CI

A
  • life threatening infusion reaction
  • HBV infection (herpes)
  • herpes infection
  • malignancy
  • PML (theorhetically)
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54
Q

ocrelizumab monitoring

A
  • HBV screening
  • herpes screening
  • *Infection –> delay treatment until resolved
  • breat cancer screening
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55
Q

ofatunumab MoA

A

binds to CD20 molecule on B cells –> cell lysis and cell toxicity in B cells

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56
Q

oftanumuab dose

A

20mg SQ qweek x 3 doses –> 20mgSQ qmonth

administer: abdomen, thigh, outer upper arm

**first injection monitored with HCP!!!

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57
Q

ofatunumab storage

A

unopened: fridge
before admin: reach room temp

58
Q

ofatnumuab CI

A
  • live vaccines (4 weeks before dose)
  • non-live vaccines (2 weeks before dose)
  • HBV
  • TB
  • low immunoglobulins + infection
  • PML
  • need effective contraception –> CI preg
59
Q

ofatnumuab monitoring

A
  • HBV
  • TB
  • serum immunoglobulins
  • first dose observe!!
60
Q

ofatunumab AE

A
  • URI
  • UTI
  • *injectin reactions –> premed with steroid, antihistamine, APAP
  • PML
  • HA
61
Q

immunomodulator options

A

chemo
non chemo

62
Q

chemo options

A
  • mitoxantrone
  • cladribine (mavenclad)
63
Q

why do chemo drugs work in MS

A

overactive immune system –> keeping immune system in check

64
Q

mitoxantrone MoA

A

intercalates with DNA –> causes DNA breaks –> inhibitis DNA repair ——> targets rapidly dividing cells and immune system –> antigen presentation, cytokine expression, dec leukocyte migration

immunosupressant

65
Q

mitoxantrone dose

A

12mg/m2 IV q3months –> lifetime max dose 100mg/m2 (8 doses)

bc of cardiotoxicity

66
Q

mitoxantrone and pregnancy

A

NO
also no breastfeeding

67
Q

mitaxantrone indication

A
  • SPMS
  • PRMS
  • RRMS worsening to reduce disbaility or relapse rate

NOT PPMS

**restrict use for refractory disease

68
Q

mitoxantrone AE

A

***cardiotoxicity – hence lifetime dose limit
- bone marrow supression (chemo agent)
- alopecia
- N/V

69
Q

mitoxantrone monitoring

A
  • Hgb levels
  • WBC
  • plateley

**before each infusion

70
Q

cladribine (Mavenclad) MoA

A

purine nucleoside analog, prodrug –> incorporates into DNA, breaks DNA, no DNA synthesis or repair –> deplete ATP –> cell cycle nonspecific

shut down DNS synthesis –> cytotoxic B and T lymphocyte effects –> lymphocyte depletion

71
Q

cladribine (Mavenclad) indication

A

RRMS, active SPMS –> inadqeuate response

**NOT CIS

72
Q

cladribine dose

A

10mg tab

3.5mg/kg over 2 years –> 1.75mg/kg per year
- 2 cycles of 4-5 days per year

after 2 year treatment CANNOT GIVE MORE UNTIL 2 MORE YEARS HAVE PASSED

missed doses –> extend the days per cycle

**lymphocytes must be >800 before each dose, if not, delay and if still not D/C

separate from other meds by 3 hours

hazardous drug –> gloves, compounding controls

73
Q

cladribine BBW

A
  • malignancy
  • teratogenicity –> pregnancy, child bearing potential (men and women)
  • bone marrow supression
  • infection
  • PML
  • vaccines
    -GVHD (graft versus hsot disease)
  • hepatoxicity
  • cardiotoxicity
74
Q

cladribine CI

A
  • current malignancy
  • **need contraception during and 6 months after each treatment course
  • hypersensitivity
  • HIV
  • chronic infection
  • pregnancy and breast feeding
  • live vaccines (4-6 weeks)
75
Q

cladribine monioring

A
  • cancer screening
  • CBC
  • HIV, TB, HBV, HCV
  • VZV
  • pregnancy test
  • LFT
  • MRI
  • infection
76
Q

cladribine DDI

A
  • BCRP/ABCG2 inducer/inhib
  • echinacea (dec efficacy)
  • cladribine dec efficacy contraception –> add barrier method
  • cladribine dec vaccine efficacy
77
Q

cladribine AE

A
  • HA
  • nausea
  • lymphocytopenia
  • uri
  • fever
78
Q

non chemo options

A
  • S1P receptor drugs
  • teriflunomide
  • fumarate derivatives
79
Q

s1P receptor drug options

A
  • fingolimod
  • siponimod
  • ozonimod
80
Q

fingolimod MoA

A

activates S1P1 and S1P3-5 receptors on lymphocytes –> depletes CD4 and CD8 T lymphocytes IN BLOOD STREAM by 75% –> inhibits lymphocyte release from lymph nodes –> dec circulating numeber

**still in the bodt reserved in the lymph nodes –> but not mount response —-> WILL NOT SHOW UP ON BLOOD TESTS BUT THEY ARE STILL THERE IF NEEDED FOR INFECTION

81
Q

fingolimod dose

A

0.5mg qd –> oral

high F

82
Q

fingolimod indication

A

CIS
RRMS
active SPMS
patients > 10 years

83
Q

what do we consider in this drug class

A

first dose monitoring

84
Q

fingolimod AE

A
  • HR decrease on day 1, improves overtime –> bc S1P receptors on cardiac tissue too –> dec by 10bpm –> this is what we need to monitor
  • dec in FEV1 at high doses
85
Q

fingolimod first dose monitoring

A
  1. ECG at baseline (check QTc, bradycardia,…)
  2. bloodwork (check varicella VZV antibodies, vaccinate prn)
  3. baseline eye exam and 304 months after (macular edema)
  4. vitals (for HR baseline and BP)

low risk: monitor for 6 hours post first dose –> if <45 or at lowest point, keep monitoring

high risk: monitor for 24 hours overnight
- high risk if: prolonger QTc, taking drugs with risk of torsades

REPEAT 1st dose monitoring if 1 day in first 2 weeks, etc, –> body will lose tolerance to HR effects

86
Q

fingolimod CI

A
  • recent MI
  • unstable angina
  • TIA
  • HF
  • AV block
  • sick sinus syndrome
  • baseline QTc > 500
  • treatment with antiarrhythmic drugs
  • pregnancy
87
Q

fingolimod AE

A
  • HA
  • lymphopenia, leukopenia (apparent)
  • FEV1 change
  • LFT inc
  • dose dependent HR dec, BP, macular edema
  • PML
88
Q

siponimod MoA

A

S1P1 and S1P5 modulator/activator –> blocks lymphocyte ability to emerge from lymph node –> cannot cross BBB to CNS –> reduce central inflammation

89
Q

siponimod indication

A

CIS
RRMS
active SPMS

90
Q

siponimod dose

A

0.25mg or 2mg po qd
**titration

91
Q

siponimod storage

A

unopened: fridge, room temp for 3 months
open: room temp or 3 months

92
Q

siponmiod genetic consideration

A

**MUST DO GENOTYPE TEST FOR CYP 2C9

normal dose:
1/1
1/2
2/2

reduced dose
1/3
2/3

contradindicated
3/3

if miss doses –> restart titration and first dose monitoring

93
Q

siponimod first dose monitoring

A

low risk: none
high risk: 6 hours
- preexisiting cardiac conditions
- bradycardia (HR<55)

94
Q

siponimod CI

A
  • CYP 2C9 3/3
  • recent cardiovascular conditions (MI, unstable angina, stroke, TIA, HF, …)
95
Q

siponimoid warnings

A
  • infection
  • immunization
  • PML
  • macular edema
  • bradycardia (occur after 3-4 horus vs 6)
  • AV conduction delays
  • QT prolongation
  • CV disease
  • respiratory –> FEV1
  • hepatic –> LFT
  • HTN
  • neurotoxicity (PRES)
  • malignancy
  • rebound syndrome with worse s/s when stop –> caution starting another drug within 3-4 weeks of last dose
96
Q

siponimod DDI

A
  • CYP2C9 inducer/inhibit
  • immunosupressants
  • impact bradycardia, av block, qt prolong
  • echinaeca dec effect
97
Q

siponimod AE

A
  • HTN
  • HA
  • falling
  • peripheral edema
  • lymophcytopenia (apparent)
  • macular edema
  • dec fev1
98
Q

siponimod and pregnancy

A

no
need effective contraception

99
Q

siponimod monitoring

A
  • cbc
  • LFTs
  • ECG baseline
  • eye exams
  • fev1
  • BP
  • infection
  • PML/PRES
  • skin lesions
  • infection
  • severe inc in disability after d/c therapy
100
Q

what is a qt prolongation agent that you can’t take a patient off of if used for things other than htn and therefore would force the pt to stay for 6 hour monitoring?

A

beta blockers

101
Q

ozonimod MoA

A

S1P1 and S1P5 –> block ability of lymphocytes ot leave lymoh nodes –> apparent dec lymphocytes

102
Q

ozonimod dose

A

0.23mg-0.92mg po qd
-*titrate!!

103
Q

ozonimod CI

A
  • heart conditions
  • **CONCOMINANT MAOI USE!! – bc this drug may have some MAOi activity
  • tyramine containing foods >150mg (meat, cheese) –> bc of maoi activity –> htn emergency
104
Q

ozonimod warning

A
  • AV block
  • bradycardia (smallest drop)
  • hepatotoxic
  • HTN
  • infection opportunistic
  • lymphopenia (apparent)
  • macular edema
  • neurotoxicty PRES
  • PML
  • respirstory – fev1
  • VZV vaccine
  • CV
  • rebound syndrome
  • pregnancy –> effecive contraception –> need to wait 3 months***
105
Q

ozonimod AE

A
  • infection
  • uri
  • htn
  • orthostatic hypotension
  • uti
  • lymopenmia apparaent
106
Q

ozonimod DDI

A
  • BCRP/ABCG2
  • 2C8
  • MAOI (HTN effect), SNRI (htn)
  • smoking
  • vaccines
107
Q

ozonimod monitoring

A
  • cbc
  • hepatic
  • ecg
  • eye exams
108
Q

ozonimod PKPD

A

active metabolites for 11 days –> hence why need contraception wash out period

109
Q

teriflunomide (Aubagio) MoA

A

blocks pyrimidine synthesis in rapidly dividing cells –> inhibit protein tyroine kinase and COX2 –> dec ability of antigen to activate t cells

*is the active metabolite of leflunomide –> antiproliferation, antiinflammatory –> cytostatic(inhibitory) effect on proliferating t and b lymphocytes in periphery –> reduce b lmyphocyte proliferation

110
Q

teriflunomide indication

A

RRMS
SPMS

111
Q

terifluonmide dose

A

7mg or 14mg po qd
- food delays absorption

112
Q

teriflunomide half life

A

long!! 10-12 days
- enterohepatic cycling
- BCRP
- 3A4, 2C9, N-cetyltransferase

113
Q

terifluonmide DDI

A
  • inc ethinyl estradiol and levonorgestrel concentration
114
Q

teriflunomide AE

A
  • nasopharngitis
  • URI
  • alopecia
  • inc LFT
  • diarrhea
  • neuropathy
  • kidney issues
  • hyper k
  • HTN
  • breathing problems
  • dec WBC
115
Q

terifluonmide monitroing

A
  • CBC
  • LFT
  • latent TB
116
Q

terfilunomide BBW

A
  • hepatoxicity
  • teratogenic (pregnancy) –> need male contraception too (dec sperm count)
117
Q

how to eliminate terifluonamide more quickly

A
  1. cholestyramine 4-8g q8hr x 11 days
  2. activated charcoal 50mg q12h x 11days

** to dec AE, allow for pregnancy

alone – takes 8mon-2years

118
Q

terilfunomide DDI

A
  • inc exposure to ethinyl estradiol and levorngestrel
  • rosuvastatin NOT > 10mg
  • dec INR in patients taking warfarin
119
Q

fumarate derivative options

A
  • dimethyl fumarate
  • diroximel fumarate
  • monomethyl fumarate
120
Q

dimethyl fumarate MoA

A

induce T-helper cytokines –> activated T cell apoptosis, down regulate adhesion molecules -> reduce migratoin of lymphocytes

DMF (dimethyl) —-> MMF (monomethyl) active metabolite
*activate nuclear factor Nrf2 pathway –> oxidative stress response

121
Q

dimethyl fumarate dose

A

DR –> do not crush
120mg bid x7 days –> 240mg bid
*tid no additional benefit

122
Q

dimethyl fumarate AE

A
  • **GI symptoms –> may dec if high fat high protein food
    *flushing, N, cramping, diarrhea
  • **flushing –> apsirin nonenteric coated 325mg 30 min prior
  • inc lft
  • esosinophilia
  • lymphpenua
  • PML
  • urinayalsi s
123
Q

dimethyl fumuarate CI/ d/c

A
  • flushing tolerance
  • hepatic injury
  • low lymphocytes
  • infection
124
Q

diroximel fumerate moa

A
  • bioequivalent to DMF
  • converts to MMF in body
125
Q

diroximel fumerate benefitd

A

**less GI irritation

126
Q

diroximel fumerate dose

A

321mg bid x7 days –> 462mg bid

127
Q

diroximel fumerate ae

A
  • flushing –> aspirin

**if GI or flushing AE not tolerated –> can dec to 321mg for 4 weeks –> if cannot redose at 462mg d/c!

128
Q

diroximel fumerate food effect

A
  • dec concentration and MMF active metabolite

*limit fat and calories
* limiti alcohol ( dec peak)

129
Q

monomethyl fumarate MoA

A
  • bioequvalent to DMF
130
Q

monomethyl fumarate benefits

A

**need lower doses –> therefore fewer GI AEs

131
Q

monomethyl fumerate dose

A

95mg bid x7 days –> 190mg bid

if cannot tolerate maintenance dose, dec 4 weeks, need to inc back or else d/c

132
Q

monomethyl fum ae

A
  • flushing –> asa
  • gi
133
Q

monomethyl fum storage

A
  • unopen: fridge, do not freeze , room temp up ot 3 months
134
Q

what is pseudobulbar affect (PBA)

A

uncontrollable crying. laughing in MS or PD or ….

135
Q

PBA treatment

A

Neudexta ((dextromethrophan and quinidine)

136
Q

Neudexta mOa

A

DXM: inhibit glutamate at NMDA and sigma 1 –> dec excitatory

quinidine: block DXM metabolism (2D6) –> inc DXM concentrations –> therefore quinidine used as much lower dose than therapeutics

137
Q

neudexta dose

A

1 cap po qd x7 days –> 1 cap po bid

138
Q

dalfampridine moa

A

broad spectrum potassium channel blocker –> inc AP conduction in demyelinated axxons –> inc ability to walk

139
Q

dalfampridine CI

A
  • mod sev renal impair
  • hx seizure
140
Q

dalfampridine AE

A
  • asthenia
  • balance
  • paresthsia
  • nasopharyngitis
  • constiptation
  • uti
  • back pain
  • n
141
Q

dalfampridine dose

A

10mg bid –> do not crush, chew

142
Q
A

p3 year :) (5 decks)

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