Multiple Sclerosis - Low/Med Priority Flashcards by Jordan Cyr

What is gait?

the way a person walks

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What is MS?

a chronic neurologic disease in which the bodys immune system damages its own nerve cells and connections between the brain and spinal cord

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What is myelin?

a fatty protective layer that covers the axon fibers, that protects the nerves in the brain and spinal cord

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Describe the pathophysiology of MS.

the triggers of MS are not fully understood, but a postulated theory is:

body has an immune response to a foreign molecule similar in structure to myelin
local inflammation occurs
demyelination of axons occurs

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What are the risk factors for MS?

female sex (2-3x more likely)
viral infections (Epstein-Barr, measles, human herpes)
smoking
family history in 1st degree relative
changes in gut microbiome
obesity
variations in HLA genes
deficiencies of vitamin D
certain autoimmune diseases

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Describe the clinical presentation of MS.

highly variable and patient-specific:
-vision issues (including possible vision loss)
-dizziness
-bladder and/or bowel dysfunction
-dyesthesias
-numbness and weakness of limbs
-ataxia
-neuropathic pain
-tremors
-Lhermittes Phenomenon
-Uhthoff Phenomenon

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What might mimic symptoms of MS?

B12 deficiency

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Which drugs are associated with an increased risk of MS?

TNF-alpha inhibitors

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What are the 4 subtypes of MS?

clinically isolated syndrome
relapsing-remitting
secondary progressive
primary progressive

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Describe CIS.

first episode of neurologic sx that lasts at least 24 hrs
pt reported sx that suggest MS w/o confirmed diagnosis
sx may include:
-unilateral optic neuritis, partial myelopathy, or focal syndromes

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Describe RRMS.

consists of clearly defined worsening of sx, called relapses, followed by partial or full improvement of sx
relapses can last days to weeks
remission periods can last weeks to years

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Which subtype of MS is most common?

RRMS

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What is the goal of DMT?

keep pts in remission and to avoid relapses
-reduce relapses and delay progression of disease

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Describe SPMS.

progressive course that follows RRMS
sx slowly worsen with variable remission and relapses
65% of pts convert 15-20 yrs after disease onset

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Describe PPMS.

10-15% at onset
neurologic disability that steadily worsens from onset
no distinct periods of remission or relapse
diagnosis can only be made from disease hx
avg age of onset: 40 yrs old

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What are the goals of therapy for MS?

reduce number, severity, and duration of relapses
slow disease progression
improve QoL

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What is the cure for MS?

there is currently no cure for MS

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What is the role for non-pharm measures in MS?

provide symptomatic improvement

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What are the non-pharm measures for MS?

exercising:
-can improve balance, coordination, muscle tone, strength
avoid excessive heat or cold exposure
physiotherapy, massage, stretching:
-relief for spasticity and gait improvement

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How do DMTs work?

reducing inflammation associated with relapse periods

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In which subtypes of MS do DMTs have less utility?

PPMS and SPMS

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Which therapy is approved for PPMS?

ocrelizumab

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Which therapy is approved for SPMS?

siponimod

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What are the 1st line DMTs?

interferon beta
glatiramer acetate
dimethyl fumarate
teriflunomide
siponimod
ozanimod
ponesimod
ocrelizumab (PPMS)

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What are the 2nd line DMTs?

alemtuzumab cladribine fingolimod ocrelizumab (RRMS) natalizumab ofatumumab ublituximab

Which 1st line DMTs are administered via injection?

interferon beta glatiramer acetate

Which 1st line DMTs are administered orally?

dimethyl fumarate teriflunomide siponimod ozanimod ponesimod

What are the significant differences between dimethyl fumarate and glatiramer acetate?

no significant differences

Which oral 1st line DMT has a favourable safety profile?

teriflunomide

Which 1st line DMT has no known cases of PML reported?

teriflunomide

What are the impacts of teriflunomide on fertility?

can affect sperm and cause teratogenic effects -may last for 2 yrs after stopping

What is a CI of siponimod?

pts with CYP 2C9*3*3 genotype

What is a key drug interaction of ozanimod?

cannot be used in combination with MAOIs and pts should avoid tyramine-rich foods due to risk of hypertensive crisis

Which 2nd line DMTs are administered via infusion?

alemtuzumab ocrelizumab natalizumab ublituximab

What is alemtuzumab typically reserved for?

very active disease

Which 2nd line DMTs are administered orally?

cladribine fingolimod

Which 2nd line DMTs are administered by injection?

ofatumumab

How long is cladribine given for?

very short courses over 2 yrs, then pt stops

What is fingolimod typically reserved for?

very active disease -precautions needed for serious adverse drug events

What is the risk with natalizumab?

higher PML risk -reserved for very active disease

What is the risk of PML with ofatumumab?

no cases of PML reported during trials but still labeled as a risk

What is the role for fampridine?

improves walking ability -walking speed and ambulatory function

How are MS flares managed?

corticosteroids -methylpred 1g IV x 3-5 days +/- po prednisone taper -prednisone 1250 mg daily x 3-5 days +/- taper

What is the role for corticosteroids in MS?

used to control inflammation causing relapses, they no have no effect on the course of the disease

How is neuropathic pain managed in MS?

gabapentin, pregabalin

How is MS-fatigued managed?

modafinil amphetamine MPH lisdexamfetamine

How are spasms managed in MS?

baclofen (oral or intrathecal) cyclobenzapine tizanidine nabiximols BZDs

How are bladder symptoms managed in MS?

oxybutynin mirabegron botox (into bladder)

Describe the treatment algorithm for MS.

CIS/RRMS with abnormal brain MRI DMT not desired/feasible OR pt pregnant/breastfeeding OR pt planning to become pregnant? -yes --> monitor clinical status and imaging - treat if needed -no -- start 1st line DMT 1st line DMT: -adequate response and well tolerated --> continue -inadequate response --> consider 2nd line DMT -adequate response but not well tolerated --> change to another 1st line DMT new 1st line DMT adequate response and well tolerated? -yes --> continue -no --> consider 2nd line DMT

How long do DMTs take to show effect?

6-12 months -full effect may take 1-2 yrs

When should a pt be switched DMTs?

if a pt has 2 or more relapses after 6-12 months on a DMT

When should immunomodulators be d/c in relation to conception?

2-6 months prior to conception

Which agents are not recommended in pregnancy?

immunosuppressive or immunomodulator treatment is NOT recommended -teriflunomide, cladribine, and sphingosine 1-phosphate receptor modulators are CI

If a pt is taking teriflunomide and planning pregnancy, what should occur?

washout period with cholestyramine prior to conception

How is therapy managed during breastfeeding?

breastfeeding may reduce the risk of relapse thus immunomodulator tx are typically d/c during this time -avoid teriflunomide, cladribine -no significant risks have been reported regarding maternal immunomodulator use during breastfeeding

What are some side effects of dimethyl fumarate?

flushing rare risk of PML proteinuria

What are some side effects of interferons?

elevated liver enzymes flu-like sx HTN/tachycardia

What are some side effects of ocrelizumab?

URTIs infusion rxns PML (rare)

What is given prior to ocrelizumab infusion?

methylpred 100 mg IV 30 min prior to infusion antihistamine antipyretic

Which vaccines should be avoided in pts taking DMTs?

live vaccines

What should be assessed prior to starting ocrelizumab?

hep B status

What are some side effects of teriflunomide?

elevated liver enzymes (serious liver toxicity risk) alopecia neutropenia

What is a key monitoring parameter of teriflunomide?

hepatic enzymes at baseline and monthly x 6 months

What are some side effects of the "-mods"?

bradyarrhythmias QT prolongation increased BP increased liver enzymes rare PML

What are the key monitoring parameters for "-mods"?

baseline ECG, CBC, liver enzymes monitor HR for 6h following 1st dose hep B

What are CI to the "-mods"?

pts with CYP 2C9*3*3 genotype prior MI, unstable angina, or stroke/TIA, class 3/4 HF pregnant or wishing to become pregnant liver impairment

What are some side effects of natalizumab?

PML (rare but fatal) increased liver enzymes infection

What are some side effects of alemtuzumab?

autoimmunity (thyroid, hepatitis) infections infusion rxns PML (rare but fatal)

What should be given with alemtuzumab infusion?

pre-medicate with corticosteroids for first 3 days of tx

What should be given for minimum 1 month with alemtuzumab?

antiviral prophylaxis

What are some side effects of cladribine?

lymphopenia herpes zoster infection

What needs to be ensured before starting cladribine?

lymphocyte count must be normal before initiaing and >= 800 cells/mm3 before initiating in year 2

What is key with administration of cladribine?

separate all other oral meds by minimum of 3 hrs from cladribine

What are some side effects of ofatumumab?

URTI injection-site reactions hep B reactivation

What are CI to ofatumumab?

active infections malignancies hep B severely immunocompromised

What does fampridine increase the risk for?

seizures (dose-related)

When should fampridine be avoided?

renal impairment history of seizures

What are some side effects of fampridine?

balance disorders headache nausea paraesthesia UTI

How should fampridine be taken?

not to take doses less than 12 hrs apart with glass of water, do not take with food missed doses should not be taken late omit missed dose and resume with next scheduled dose

When should f/u occur with fampridine?

assess walking ability after 4 wks -if no benefit, d/c the drug

What should all MS pts be supplemented with?

vitamin D (min 1000 IU/day)

Multiple Sclerosis - Low/Med Priority Flashcards

(81 cards)