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
2
Q
corticosteriod options
A
1st: methylprednisolone iv
2nd: corticotropin acthar gel IM or SQ
3
Q
methylprednisolone dose
A
1g IV qd x3-5 days
**follow with oral prednisone taper if needed
4
Q
methylprednisolone additional needs
A
- H2RA or PPI for ulcer prophylaxis
- monitor blood glucose nd infection
5
Q
corticosteriod acute effects
A
- insomnia
- mood change
- inc energy
- inc irritability
- inc infection risk
6
Q
corticotropin acthnar gel MoA
A
adrenocroticotropic hormone –> stimulate adren cortex –> secrete adrenal steriods such as cortisol –> androgenic and aldosteronic
7
Q
corticotropin acthar gel dose
A
IM or SQ 80-120U/day x2-3 weeks
8
Q
classes of disease modifying drugs
A
- ABCR-injectables
- mAb
- immunomodulators
9
Q
ABCR injectable drugs
A
interferon beta 1a
- Avonex
- Rebif
interferon beta 1b
- Betaseron
glatiramer acetate
- Capaxone
10
Q
ABCR injectable dosage forms
A
autoinjectors
or
vial and needle
- rotate injection site
- injection technique
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)
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
13
Q
interferon beta indication
A
- CIS
- RRMS
- active SPMS
14
Q
interferon beta-1a in pregnancy
A
DONT USE
15
Q
interferon beta 1a options
A
- Avonex
- Rebif
- Plegridy
16
Q
Avonex dose
A
- IM qweek
- titrate
17
Q
Rebif dose
A
- SQ three times a week
- titrate
18
Q
Plegridy dose
A
- SQ q 2 weeks
- titrate
**pegylated (PEG) –> therefore act for longer in body
19
Q
interferon beta-1b options
A
- Betaseron
- Extavia
19
Q
Betaseron dosing
A
- SQ qod
- titrate
20
Q
interferon beta AE
A
***flu-like symptoms!!!
- fever
- chills
- HA
- chest pain
**injection site reactions
*depression
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
22
Q
when to not use interferon beta
A
if depression uncontrolled or pt predisposed
23
Q
glatiramer acetate options
A
- Capaxone
- Glatopa
24
glatiramer acetate MoA
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
25
Capaxone dose
- SQ qd or TIW (different doses)
- NO titrate
26
capaxone and pregnany
**SAFE for patients who may become pregnant
27
general rule of treating MS in pregnancy
- 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
28
copaxone indication
CIS, RRMS, active SPMS
29
copaxone AE
***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
30
types of monoclonal antibodies
- murine: fully mouse
- chimaeric: mouse antigen binding site and complement sequence
- humanized: mouse complement sequence
- human: fully human
31
monoclonal antibody options
- natalizumab
- alemtuzimab
- daclizumab
- ocrelizumab
- ofatunumab
32
natalizumab MoA
antagonize alpha-4 integrin that activates leukocytes --> inhibits adhesion of leukocytes to receptors --> inhibitis migration of leukocytes acorss BBB
33
natalizumab indication
- CIS
- RRMS
- active SPMS
34
natalizumab dose
- 300mg IV q 4 weeks
35
natalizumab and pregnancy
no use
36
natalizumab AE
***PML (progressive multifocal leukoencephalopathy)!!! --> fatal viral opportunistic infection
- infusion reactions
- RTI
- UTI
37
what is PML?
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
38
which factors increase PML risk?
- positive JCV antibodies
- prior use of immunsuppressants
- use natalizumab for > 2 years
39
requirements for natalizumab prescribing
*TOUCH prescribing program --> need to register to monitor for PML
- similar to REMS
40
alemtuzumab (Lemtrada) MoA
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
41
alemtuzumab indication
RRMS SPMS
**ONLY if inadequte response to 2+ other therapies ---> not first line, bc huge wipe out and serious AEs
42
alemtuzumab dose
- 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
43
alemtuzumab and pregnancy
no use
44
alemtuzumab infusion meds and monitoring
- 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
45
alemtuzumab AE
***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
46
alemtuzumab BBW
- fatal autoimmune conditions
- life-threatening infusion reactions
- malignancy
47
alemtuzumab monitoring
- TSH (thyroid)
- CBC, SCr, urinalysis
- anaphylaxis for 2 horus after infusion
- skin exams
- ECG
- HPV
- PML
48
alemtuzumab CI
live vaccines --> give live then wait 6 weeks before give alemtuzumab
49
ocrelizumab MoA
binds to CD20 on surface of B cells --> depletes B cells from circulation
- inc cytotoxic effects
- less immunogenic
50
ocrelizumab dose
300mg IV day 1 --> 300mg IV 2 weeks later --> 600mg IV q6months
**continued benefit up to 18 months after D/C
51
ocrelizumab AEs
**infusion reactions --> premedicate!
- rash, uricaria, redness, bronchospas, flushing, N)
- more common with: higher doses, first infusion
- UTI
- URI
52
ocrelizumab premedication
1. steroid -- methylprednisolone
2. antihistamine -- dyphenhydramine
3. antipyretic -- APAP
53
ocrelizumab CI
- life threatening infusion reaction
- HBV infection (herpes)
- herpes infection
- malignancy
- PML (theorhetically)
54
ocrelizumab monitoring
- HBV screening
- herpes screening
- *Infection --> delay treatment until resolved
- breat cancer screening
55
ofatunumab MoA
binds to CD20 molecule on B cells --> cell lysis and cell toxicity in B cells
56
oftanumuab dose
20mg SQ qweek x 3 doses --> 20mgSQ qmonth
administer: abdomen, thigh, outer upper arm
**first injection monitored with HCP!!!
57
ofatunumab storage
unopened: fridge
before admin: reach room temp
58
ofatnumuab CI
- 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
ofatnumuab monitoring
- HBV
- TB
- serum immunoglobulins
- first dose observe!!
60
ofatunumab AE
- URI
- UTI
- *injectin reactions --> premed with steroid, antihistamine, APAP
- PML
- HA
61
immunomodulator options
chemo
non chemo
62
chemo options
- mitoxantrone
- cladribine (mavenclad)
63
why do chemo drugs work in MS
overactive immune system --> keeping immune system in check
64
mitoxantrone MoA
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
mitoxantrone dose
12mg/m2 IV q3months --> lifetime max dose 100mg/m2 (8 doses)
bc of cardiotoxicity
66
mitoxantrone and pregnancy
NO
also no breastfeeding
67
mitaxantrone indication
- SPMS
- PRMS
- RRMS worsening to reduce disbaility or relapse rate
NOT PPMS
**restrict use for refractory disease
68
mitoxantrone AE
***cardiotoxicity -- hence lifetime dose limit
- bone marrow supression (chemo agent)
- alopecia
- N/V
69
mitoxantrone monitoring
- Hgb levels
- WBC
- plateley
**before each infusion
70
cladribine (Mavenclad) MoA
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
cladribine (Mavenclad) indication
RRMS, active SPMS --> inadqeuate response
**NOT CIS
72
cladribine dose
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
cladribine BBW
- malignancy
- teratogenicity --> pregnancy, child bearing potential (men and women)
- bone marrow supression
- infection
- PML
- vaccines
-GVHD (graft versus hsot disease)
- hepatoxicity
- cardiotoxicity
74
cladribine CI
- 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
cladribine monioring
- cancer screening
- CBC
- HIV, TB, HBV, HCV
- VZV
- pregnancy test
- LFT
- MRI
- infection
76
cladribine DDI
- BCRP/ABCG2 inducer/inhib
- echinacea (dec efficacy)
- cladribine dec efficacy contraception --> add barrier method
- cladribine dec vaccine efficacy
77
cladribine AE
- HA
- nausea
- lymphocytopenia
- uri
- fever
78
non chemo options
- S1P receptor drugs
- teriflunomide
- fumarate derivatives
79
s1P receptor drug options
- fingolimod
- siponimod
- ozonimod
80
fingolimod MoA
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
fingolimod dose
0.5mg qd --> oral
high F
82
fingolimod indication
CIS
RRMS
active SPMS
patients > 10 years
83
what do we consider in this drug class
first dose monitoring
84
fingolimod AE
- 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
fingolimod first dose monitoring
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
fingolimod CI
- recent MI
- unstable angina
- TIA
- HF
- AV block
- sick sinus syndrome
- baseline QTc > 500
- treatment with antiarrhythmic drugs
- pregnancy
87
fingolimod AE
- HA
- lymphopenia, leukopenia (apparent)
- FEV1 change
- LFT inc
- dose dependent HR dec, BP, macular edema
- PML
88
siponimod MoA
S1P1 and S1P5 modulator/activator --> blocks lymphocyte ability to emerge from lymph node --> cannot cross BBB to CNS --> reduce central inflammation
89
siponimod indication
CIS
RRMS
active SPMS
90
siponimod dose
0.25mg or 2mg po qd
**titration
91
siponimod storage
unopened: fridge, room temp for 3 months
open: room temp or 3 months
92
siponmiod genetic consideration
**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
siponimod first dose monitoring
low risk: none
high risk: 6 hours
- preexisiting cardiac conditions
- bradycardia (HR<55)
94
siponimod CI
- CYP 2C9 *3/*3
- recent cardiovascular conditions (MI, unstable angina, stroke, TIA, HF, ...)
95
siponimoid warnings
- 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
siponimod DDI
- CYP2C9 inducer/inhibit
- immunosupressants
- impact bradycardia, av block, qt prolong
- echinaeca dec effect
97
siponimod AE
- HTN
- HA
- falling
- peripheral edema
- lymophcytopenia (apparent)
- macular edema
- dec fev1
98
siponimod and pregnancy
no
need effective contraception
99
siponimod monitoring
- cbc
- LFTs
- ECG baseline
- eye exams
- fev1
- BP
- infection
- PML/PRES
- skin lesions
- infection
- severe inc in disability after d/c therapy
100
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?
beta blockers
101
ozonimod MoA
S1P1 and S1P5 --> block ability of lymphocytes ot leave lymoh nodes --> apparent dec lymphocytes
102
ozonimod dose
0.23mg-0.92mg po qd
-*titrate!!
103
ozonimod CI
- 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
ozonimod warning
- 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
ozonimod AE
- infection
- uri
- htn
- orthostatic hypotension
- uti
- lymopenmia apparaent
106
ozonimod DDI
- BCRP/ABCG2
- 2C8
- MAOI (HTN effect), SNRI (htn)
- smoking
- vaccines
107
ozonimod monitoring
- cbc
- hepatic
- ecg
- eye exams
108
ozonimod PKPD
active metabolites for 11 days --> hence why need contraception wash out period
109
teriflunomide (Aubagio) MoA
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
teriflunomide indication
RRMS
SPMS
111
terifluonmide dose
7mg or 14mg po qd
- food delays absorption
112
teriflunomide half life
long!! 10-12 days
- enterohepatic cycling
- BCRP
- 3A4, 2C9, N-cetyltransferase
113
terifluonmide DDI
- inc ethinyl estradiol and levonorgestrel concentration
114
teriflunomide AE
- nasopharngitis
- URI
- alopecia
- inc LFT
- diarrhea
- neuropathy
- kidney issues
- hyper k
- HTN
- breathing problems
- dec WBC
115
terifluonmide monitroing
- CBC
- LFT
- latent TB
116
terfilunomide BBW
- hepatoxicity
- teratogenic (pregnancy) --> need male contraception too (dec sperm count)
117
how to eliminate terifluonamide more quickly
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
terilfunomide DDI
- inc exposure to ethinyl estradiol and levorngestrel
- rosuvastatin NOT > 10mg
- dec INR in patients taking warfarin
119
fumarate derivative options
- dimethyl fumarate
- diroximel fumarate
- monomethyl fumarate
120
dimethyl fumarate MoA
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
dimethyl fumarate dose
DR --> do not crush
120mg bid x7 days --> 240mg bid
*tid no additional benefit
122
dimethyl fumarate AE
- **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
dimethyl fumuarate CI/ d/c
- flushing tolerance
- hepatic injury
- low lymphocytes
- infection
124
diroximel fumerate moa
- bioequivalent to DMF
- converts to MMF in body
125
diroximel fumerate benefitd
**less GI irritation
126
diroximel fumerate dose
321mg bid x7 days --> 462mg bid
127
diroximel fumerate ae
- flushing --> aspirin
**if GI or flushing AE not tolerated --> can dec to 321mg for 4 weeks --> if cannot redose at 462mg d/c!
128
diroximel fumerate food effect
- dec concentration and MMF active metabolite
*limit fat and calories
* limiti alcohol ( dec peak)
129
monomethyl fumarate MoA
- bioequvalent to DMF
130
monomethyl fumarate benefits
**need lower doses --> therefore fewer GI AEs
131
monomethyl fumerate dose
95mg bid x7 days --> 190mg bid
if cannot tolerate maintenance dose, dec 4 weeks, need to inc back or else d/c
132
monomethyl fum ae
- flushing --> asa
- gi
133
monomethyl fum storage
- unopen: fridge, do not freeze , room temp up ot 3 months
134
what is pseudobulbar affect (PBA)
uncontrollable crying. laughing in MS or PD or ....
135
PBA treatment
Neudexta ((dextromethrophan and quinidine)
136
Neudexta mOa
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
neudexta dose
1 cap po qd x7 days --> 1 cap po bid
138
dalfampridine moa
broad spectrum potassium channel blocker --> inc AP conduction in demyelinated axxons --> inc ability to walk
139
dalfampridine CI
- mod sev renal impair
- hx seizure
140
dalfampridine AE
- asthenia
- balance
- paresthsia
- nasopharyngitis
- constiptation
- uti
- back pain
- n
141
dalfampridine dose
10mg bid --> do not crush, chew
142
