Therapeutics Neuro/psych Exam 2- Ms

Front 1

properties of MS (including diagnosis, cause, disease duration, etc.) (5)

Back 1

•Chronic, unpredictable disease of the CNS
•Variable from patient to patient
•Lifelong disease (does not kill the patient or shorten life but pt may die of co-morbidities)
•Exact cause of disease still unknown
•Diagnosis of exclusion!!!

Front 2

4 subsets of MS and incidence relatively

Back 2

1) most are relapsing-remitting- attacks then fine (flat line/periods of stability- never go back to baseline)
2) then primary progressive (aggressive/no recovery)
3) Secondary progessive disease (1/2 pts with relapsing/remitting will go on to this type of disease- turns into progressive disease)
4) then progressive relapsing

Front 3

age of onset of MS
gender (2)

Back 3

20-50 yo (child bearing age)
female > male
but male more disabling (primary progressive

Front 4

genetics/triggers of MS (3)

Back 4

Multiple genes involved
•Plus virus
•Plus environmental factor

Front 5

risk factors/helpful factors of MS (6)

Back 5

•Sunlight exposure and vitamin D decrease risk
•Vitamin D intake
•Cigarette smoking- worsens
•Dietary fat- worsens
•Dietary antioxidants- slows progression
•Sex hormone- estrogen worsens progression

Front 6

latitude and MS

Back 6

higher latitudes = higher prevalence...might be due to sunlight

if kids...born in northern latitude move to texas or w/e they adopt risk of texas

Front 7

viruses and MS patients titres (2)

Back 7

Peripheral blood antibody titers to many viruses are elevated in MS
•Sometimes detected in CSF

Front 8

5 viruses linked to MS

Back 8

Varicella zoster
•Vaccinia
•Rubella
•Epstein-Barr
•Human herpes virus 6 (HHV-6)

Front 9

pathophys of MS (5)

Back 9

1.Autoimmune response to trigger
2.Myelin seen as foreign antigen
3.T cells cross blood brain barrier → attack myelin → additional T-cell activation
4.Cytokines released, causing myelin and axonal damage
5) signal interrupted as it goes down damaged mylein

Front 10

2 "components" to the pathophys damage of MS and what characteristics of MS they coincide with

Back 10

•Inflammatory component- Coincides with relapsing features of the disease
•Neurodegenerative component (axons and neurons)- coincides with Progressive, slow, worsening of disease

Front 11

damage to CNS with MS (5) types of dmg i guess

Back 11

•Permanent damage accumulates
•If patient stable but untreated, damage continues to build
•Macroscopic and microscopic damage
•White inflammatory lesions on MRI scan
•Up to 70% of brain tissue is abnormal (microscopic dmg)

Front 12

sx of MS starting with highest incidence (6)
typical presentation in a pt

Back 12

Variable:
Fatigue- most common
Difficulty walking
stiffness/spasms
cognitive
bladder
pain (paresthesia, neuralgia)
mood problems
vision problems (inflamed optic neuritis)
just...anything nerve related
(see list)

Front 13

what is the EDSS? describe the scoring a little

used for what

Back 13

EDSS- disability status scale
0-4 = no disability/normal/not much difference
6 = assistance required to walk
7 = wheelchair
9 = highest...confined to bed
10 = death

done in neuro clinic to guide therapy

Front 14

tx goals of MS (5)

Back 14

•Reduce number of relapses
•Prevent disability progression
•Minimize new MRI lesions
•Manage symptoms
•Restore functions
•Maintain or improve quality of life

Front 15

definition of acute relapse (4) + sx type, duration, frequency

Back 15

•IS a Exacerbation or attack
•with new or recurring symptoms
•Lasting more than 24 hours
•Separated by 1 month

Front 16

what is NOT rec'd for acute relapse (2)

Back 16

•Low-dose oral steroids not recommended- not effective
•Chronic daily corticosteroids not rec'd; does not affect rate of relapse

Front 17

regimen for acute relapse/drug/route

another more conservative approach

Back 17

•Methylprednisolone 500-1000 mg IV q24h x 3-5 days ± prednisone taper x 1-3 weeks

•another approach is to Wait and see if minor relapse (just sensory sx, not physical disability)

Front 18

main 3 AE with IV methylpred (for acute relapse)

Back 18

•Adverse effects: GI distress, hyperglycemia is big, mood swings

Front 19

what is optic neuritis
relationship to MS

Back 19

inflammation of optic nerve
"hallmark" sx of MS??

Front 20

ONTT trial- what was it measuring, what were the arms, what did it show

Back 20

ONTT (optic neuritis trial)
tx'd with low dose pred oral (1mg/kg/day)
methyl pred IV
placebo

6 month visual assesssments-

primary endpoints: visual field and contrast sensitivity

found oral pred same as placebo- only beneficial was IV high dose methylpred

Front 21

doses of methylpred used in ONTT trial

Back 21

Methylprednisolone 1 g/day IV x 3 days, then prednisone 1 mg/kg/day po x 11 days

Front 22

ONTT iv HD steroids results

Back 22

•Visual function recovered faster with IV therapy
•At 6 months- improved BETTER
•Improved visual fields
•Improved contrast sensitivity
•Improved color
•Visual acuity same

Front 23

in ONT if steroids ineffective? what to do? (evidence and frequency/number of tx)

Back 23

Consider plasma exchange (PLEX)
•Small studies show benefit1-2
•Faster symptom resolution in relapsing forms of MS
•Typically q48h x 7 treatments

Front 24

1st line Disease Modifying Therapies- type of drug

Back 24

Immunomodulators in relapsing-remitting MS

Front 25

clinical benefits of DMTs (6)

Back 25

•↓ number of relapses, severity
•↑ time between relapses
•↑ number of patients relapse-free
•↓ disability and worsening on neuro exam
•↑ quality of life
•↓ MRI lesion formation, size, and severity

Front 26

4-5 DMTs for MS

Back 26

interferons

enter rest

Front 27

what are interferons? (2)

Back 27

Family of naturally occurring proteins
•Respond to viral infection and other biologic agents

Front 28

3 groups of interferons

Back 28

IFN-1a/b??
IFN-2 (gamaa)

Front 29

what does interferon beta do (4)

Back 29

•Enhances of suppressor T-cell activity
•Reduces proinflammatory cytokine production
•Downregulates antigen presentation
•Inhibits lymphocyte migration into CNS

Front 30

idk...list of FDA approved meds for MS...

Back 30

betaseron- now has generic (oldest)
avonex
copaxone
rebif
tysabri
gilenya
aubagio
extavia** idk this is betaseron as a generic...or something

Front 31

interferon beta-1b: name of drug

contains what

made from what

Back 31

betaseron/extavia

•Recombinant DNA from E. coli

•Contains human albumin- NO JENOVAS WITNESS

Front 32

beta(b1)seron- dosing and route

Back 32

•Dose = 0.25 mg SQ q48h

Front 33

6 ADR from betaseron

1 ADR that applies to all interferons

Back 33

•Most common ADRs: Injection site reaction/necrosis (lipoatrophy), lymphopenia, asthenia (weakness), flu-like symptom complex, headache, and pain
•All interferons have increased risk of depression and suicide

Front 34

names for interferon beta 1a (2 of them)

similarity to human IFN-b, and contains what

what is it made from

Back 34

Rebif/avonex (not bioequivalent)
•Recombinant DNA from genetically engineered from chinese hamster ovary cells!!
•Identical to natural human IFN-β

has human albumin

Front 35

6 most common ADR with IFN-b-1a

Back 35

•Injection site reactions (most problematic with 1a), fatigue, flu-like illness, headache, abnormal LFTs, depression

Front 36

IFN-b-1a routes of admin (2)

Back 36

•Rebif SQ
•Avonex IM

Front 37

monitoring for IFN-b-1a/1b

Back 37

CBC with platelets and LFTs at baseline, at 1 month, then q3months x 1 year, and q6months thereafter

due to transaminitis (2/3 of pt with elevated LFTs)
most common with betaseron and rebif but also with avonex
Thyroid too must be monitored (can cause hypothyroid)
watch for immunogenecity (neutralizing ab that make drug ineffective)

Front 38

IFN b 1a/1b pregnancy category

Back 38

C

Front 39

IFN b 1a/1b DDIs?

Back 39

DDIs: no formal drug interaction studies conducted...body has interferons so probably not?

Front 40

counseling points

and storage (betaseron, avonex, rebif)

Back 40

SQ or IM injection technique
•Storage
•Betaseron & Extavia: room temp.
•Avonex: refrigerator, good for 7 days at room temp.
•Rebif: refrigerator, good for 30 days at room temp.

Front 41

INCOMIN study: type of study, studying what type of MS

Arms

duration

Back 41

Prospective, randomized, multicenter study
•Relapsing-remitting MS

duration 2 years

arms- betaseron vs. avonex (1a)

Front 42

INCOMIN study primary endpoints (2)

Back 42

Proportion of patients free from relapses
•Free from new proton density lesions on MRI

Front 43

results of INCOMIN

Back 43

proportion of pts relapse free: betaseron looks better...

pts remaining lesion free: same

Front 44

EVIDENCE trial: type of trial, arms, duration

Back 44

Randomized, controlled, multicenter trial for relapsing/remit MS comparing rebif to avonex for 24 weeks (both 1a)

Front 45

EVIDENCE primary endpoint

Back 45

Proportion of patients who were relapse free at 24 weeks

Front 46

results of EVIDENCE (2)

Back 46

avonex worse than rebif for recurrence of relapses

HOWEVER rebif more portent...more adverse effects

Front 47

2 effects of neutralizing ab on interferons

Back 47

Reduce bioavailability and clinical efficacy of interferons

Front 48

betaseron, avonex, rebif and incidence of creating neutralizing antibodies

Back 48

betaseron has highest risk of neutralizing antibodies- avonex lowest risk

Front 49

what is copaxone (generic name and structure)

Back 49

Random polymer of 4 amino acids

glatiramer acetate

Front 50

MoA of copaxone (3)

Back 50

•Mechanism of action not fully understood
•Modifies immune processes
•Induces and activates suppressor T cells

Front 51

dosing of copaxone

Back 51

20 mg sq q24h

Front 52

storage of copaxone
how long is it good for

Back 52

Store in refrigerator
•Good for 1 month at room temperature

Front 53

advantages of copaxone (3)

Back 53

•No routine laboratory monitoring
•Pregnancy category B
•Useful in patients with depression (not an interferon)

Front 54

disadvantages of copaxone (3)

Back 54

•first dose usually given in clinic: ~ 10% of patients experience a one-time, transient (less than 20 minute) reaction consisting of chest tightness, flushing, and dyspnea beginning several minutes after injection (heart attack-y)
•Lipoatrophy may occur at injection site
•Immunogenicity potential

Front 55

copaxone: DDIs, renal function

Back 55

•No formal drug interactions studies conducted
•Not tested in patients with impaired renal function

Front 56

AE of copaxone (9) 2 main ones

Back 56

injection site reactions**, chest pain with first dose

vasodilatation, infection, pain, nausea, arthralgia, anxiety, and hypertonia (these might just be related to disease state)

Front 57

4 first line agents for MS

Back 57

avonex
betaseron
rebif
copaxone

Front 58

trial comparing all 4 first line agents- type of study

primary endpoint

Back 58

Retrospective, open-label study

reduction of relapse rates at 24 months

Front 59

first line agents- WHICH WAS BEST?? in trial..

Back 59

copaxone won

Front 60

newer first line? agent for MS
route

Back 60

Teriflunomide (Aubagio)
oral- ONLY ORAL AGENT

Front 61

what is teriflunomide (structure)

Back 61

Active metabolite of lefluonomide

Front 62

teriflunomide- dosing used in trials

results of trials

Back 62

Teriflunomide 7 or 14 mg po daily vs. placebo x 2 years
•30% decrease in annual relapse rate

Front 63

AE of teriflunomide (3)

monitoring

Back 63

N/V/D, ↑ LFTs, alopecia
•Monthly LFTs for at least 6 months

Front 64

teriflunomide- preg cat
issues with pregnancy (how long dose it last?)

drug you can give to help clear drug

Back 64

Pregnancy category X for both men and women
•Detectable up to 2 years after last use
•Cholestyramine can increase CL

Front 65

2nd line therapy for MS

used only as...

Back 65

Natalizumab (Tysabri)
Monotherapy only with REMS program

Front 66

why was tysabri pulled off market

Back 66

toxicity: PML- posterior multifocal L..? when used as dual therapy

attack of the body against neurons (viral?)

Front 67

what is natalizumab (2)

Back 67

•Recombinant humanized monoclonal antibody to α4 integrin
•Adhesion molecule expressed on leukocytes that allows the binding to blood vessels and penetration into body organs

Front 68

MoA of natalizumab (2)

Back 68

•Specific MOA not fully defined
•Thought to prevent leukocytes from crossing blood brain barrier

Front 69

AE of natalizumab: long ass list

Back 69

Headache, fatigue, arthralgia, UTI, lower respiratory tract infection

gastroenteritis, vaginitis, depression (not to same extent as interferon)

didn't talk about these: pain in extremity, abdominal discomfort, diarrhea, and rash

Front 70

AFFIRM Trial (2)

Back 70

natalizumab 300 mg IV q4weeks for 2 years

reduced relapse by 68%!!!

Front 71

natalizumab storage

Back 71

Refrigerate

Front 72

dosing of natalizumab

administer within how long
infusion time
monitor for what

Back 72

300 mg IV q4weeks

•Administer within 8 hours of preparation
•Infuse over 1 hour
•Monitor for infusion reaction

Front 73

natalizumab monitoring (2)

Back 73

infusion reaction
LFTs monthly

Front 74

major precautions of natalizumab (2)

must be enrolled in what program

Back 74

•Increased risk for infection
•BBW: Risk of progressive multifocal leukoencephalopathy (PML)
•Must be enrolled in Tysabri Outreach: Unified Commitment to Health (TOUCH) program- pt, prescriber and parmacy must be enrolled

Front 75

tysabri only to be used for...
assess risk for what before giving

CI with what drug

Back 75

•For use in relapsing MS in patients with inadequate response or intolerance to other therapies
•Assess for risk of PML
•Contraindicated with immunosuppressants

Front 76

tysabri only to be dispensed where?
who must be enrolled

Back 76

Only dispensed at registered infusion centers
•Doctors, pharmacies, and patients must be enrolled

Front 77

what is gilenya (generic, and what is it) (3)

Back 77

Fingolimod

•Sphingosine analogue
•Modulates sphingosine-1-phosphate receptor to alter lymphocyte migration
•Lymphocytes sequestered in lymph nodes and can't get into CNS

Front 78

gilenya route of admin

Back 78

oral!

Front 79

TRANFORMS trial

Back 79

gilenya- showed it halved relapse rate compared to IF

Front 80

common AE of gilenya (6)

Back 80

headache, influenza, diarrhea, back pain, LFTs, cough

Front 81

gilenya- must get baseline what? (4) and their assoc. AEs

Back 81

CBC (leukopenia) /LFT/ocular exam (macular edema)/EKG (bradycardia/AV block)

Front 82

5 CIs to gilenya

Back 82

if ACS or TIA/CVA within 6 months, HF, QTc prolongation, preexisting 2nd-3rd degree heart block or antiarrhythmic use

Front 83

why gilenya sucks

Back 83

TOO MANY AEs

Front 84

infections and gilenya- 2 you have to worry about, and one...other...not infection..thing

how to prevent..

Back 84

Tumor development
Varicella- someone died in trial from this
•Zoster vaccination > 1 month BEFORE starting fingolimod
•PML

Front 85

Mitoxantrone (Novantrone) line of therapy

Back 85

2nd-line therapy in relapsing forms of MS

Front 86

mitoxantrone- what is it? (type of...class..of drug)

MoA (3)

Back 86

Anthracycline- CHEMO WOO
•Inhibits B-cell, T-cell, and macrophage proliferation
•Impairs antigen presentation
•Decreases IFN-γ, TNF-α, and IL-2

Front 87

ok mitoxantrone is an anthracycline...remember the major dose limiting shit with this drug?

Back 87

Lifetime maximum of 140 mg/m² due to cardiotoxicity which can occur at any time but significantly increased with increased cum dose

so..never really caught on. pretty last line.

Front 88

cardiotox issues with mitoxantrone- what happens?

assess for what at baseline

avoid if...

Back 88

•Heart failure months to years after stopping
•Assess for cardiovascular problems with baseline EKG and LVEF
•Avoid if EF < 50%

Front 89

how is mitoxantrone dosed

Back 89

5-15 minute infusion q3months- so cheaper

Front 90

AE of mitoxantron 7

Back 90

chemo! so...

Nausea, alopecia, infections, EKG abnormalities, diarrhea, back pain, headache

Front 91

5 precautions with mitoxantrone
what must you monitor

Back 91

HF, CV disease, LVEF < 50%, blood abnormalities, liver disease (how it's cleared)

Monitor LFTs

Front 92

consensus algorithm for MS (4 steps and when you would give each drug)

Back 92

consensus for MS (2008)

1) start with IFN beta or copaxone (either is fine)
2) initiate if definite dx of relapse/remit MS (remember dx of exclusion) or if high risk pt with first attack (optic neuritis)
3) then natalizumab if inadequate response/unable to tolerate 1st line
4) reserve mitoxantrone for worsening disease despite tx or secondary progressive MS

Front 93

other drugs that have been studied in MS (6)

Back 93

•Alemtuzumab
•Azathioprine- feh
•Cyclophosphamide
•Daclizumab- pulled off market
•Rituximab- quasi decent data

Front 94

Dalfampridine (Ampyra™) what dis (moa...what it for)

Back 94

Potassium-channel blocker which increases conductivity of demyelinated nerve fibers → increased walking speed

Front 95

dosing of dalfampridine

Back 95

Extended-release 10 mg tablet po bid

Front 96

CI of dalfampridine (2)

Back 96

•CrCl < 50 mL/min
•History of seizures

Front 97

dalfampridine availability

Back 97

Available March 2010 via specialty pharmacies

Front 98

economic burden of ms- how much per pt per year

what components make up this cost (3)

Back 98

47000$ per patient per year
50% due to direct med/non-med costs
loss of productivity makes up a third of it
10% on informal care

Front 99

insurance barriers for MS (5)

Back 99

most formularies only have 1 or 2 DMTs- with financial penalties for not using preferred agent

many insurances don't have coverage of injectable drugs

some require pt to go on drug holiday periodically to demonstrate need for drug...

some require documentation of continued attack- if absence of attacks they make you stop it..which makes no sense

arbitrary restrictions

ceiling on cost of tx? idk what this means she didn't talk about it

Front 100

some arbitrary restriction placed on MS pt by insurance (4)

Back 100

ambulatory! so no coverage!
full recovery after attack = no more drug
age- not old enough
requiring 2 relapses in past year before drug is covered