Multiple Sclerosis Flashcards
what type of disorder is MS
a chronic, inflammatory demyelinating disorder
age of diagnosis for MS
15-45 yo, peak incidence 4th decade
which gender more commonly has MS
women
factors that may be linked to MS
genetic: MS susceptibility genes (HLA class II)
environmental: late onset/severe childhood infections, viral infections
what might be a protective factor for MS
increased vitamin D
describe the pathophysiology of MS
auto-reactive T-lymphocytes are activated, cross into the CNS, and attack the myelin sheath of neurons— damaged myelin forms scar tissue (sclerosis)
T cells induce pro-inflammatory response in which cytokines further activate B cells/macrophages
what is the role of the myelin sheath?
a fatty substance surrounding and insulating neurons, necessary for proper signal transduction in CNS
what are PRIMARY MS symptoms?
visual complaints, gait problems, paresthesias, pain, spasticity, weakness, ataxia, speech difficulty, psychological changes, cognitive changes, fatigue, bowel/bladder dysfunction, sexual dysfunction, tremor
what is the relationship of heat sensitivity and MS
many people with MS experience worsening of symptoms with increased body temperature: cooling may help (cooling vests, etc)
what are secondary and tertiary MS symptoms
secondary: recurrent UTI, urinary calculi, decubiti, muscle contractures, resp infections, poor nutrition
tertiary: financial problems, personal/social problems, vocational problems, emotional problems
4 different subtypes of MS
relapsing-remitting: relapses with full recovery
secondary progressive: (following relapsing-remitting) disease progresses with or without occasional relapses/remissions/plateaus
primary progressive: progressive from onset
progressive relapsing: progressive from onset with acute relapses– with or without full recovery– continuous progression between relapses
what factors indicate a favorable prognosis in MS?
<40 years at onset
female
initial symptoms: optic neuritis or sensory symptoms
low attack frequency in early disease
relapsing/remitting course of disease
which factors indicate an unfavorable prognosis in MS?
> 40 years at onset
male
motor or cerebellar initial symptoms
high attack frequency in early disease
progressive course of disease
diagnosis/assessment of MS?
MRI: demyelination present
CSF: CNS IgG is increased, serum IgG normal
Oligoclonal bands (OCBs) are present
CEDSS: expanded disability status scale
3 broad treatment categories for MS
treatment of acute attacks
disease-modifying therapies
symptomatic therapy
how are acute exacerbations treated in MS
methylprednisolone 500-1000 mg/day IV x 3-5 days
which disease modifying therapies are PO
teriflunomide
dimethyl fumarate
diroximel fumarate
fingolimod
siponimod
cladribine
which disease modifying therapies are INJECTABLES (SQ)
interferon beta
glatiramer
ofatumumab
which disease modifying therapies are INFUSIONS (IV)
alemtuzumab
mitoxantrone
natalizumab
ocrelizumab
teriflunomide brand name
aubagio
dimethyl fumarate brand name
tecfidera
diroximel fumarate brand name
vumerity
fingolimod brand name
gilenya
siponimod brand name
mayzent
cladribine brand name
mavenclad
glatiramer brand name
copoxone
ofatumumab brand name
kesimpta
alemtuzumab brand name
lemtrada
mitoxantrone brane name
novantrone
natalizumab brand name
tysabri
ocrelizumab brand name
ocrevus
what do you know about teriflunomide
pregnancy category X, teratogen
drug interactions:
-CYP2C8: inc exposure of repaglinide/pioglitazone
-CYP1A2: dec exposure of fluoxetine, tizanidine
-may dec INR w/ warfarin
what do you know about dimethyl fumarate
ADEs: flushing, GI effects
take w/ food for GI effects
take ASA 325 mg 30 minutes before dose for flushing
can cause lymphopenia: interrupt therapy if lymphocyte count <0.5 x 10^9 for 6+ months
what do you know about diroximel fumarate
rapidly converts to mono-methyl fumarate, the same active metabolite as dimethyl fumarate– lower rates of GI effects
what do you know about fingolimod
increased risk of life-threatening infections, tumor development: disseminated varicella zoster, herpes simplex encephalitis: BEFORE TREATMENT SHOULD HAVE VARICELLA SEROLOGY & ZOSTER VACCINE
less common but serious ADE: bradyarrhythmia, AV block
contraindicated in recent hx of MI, stroke, TIA, heart failure, second or third degree heart block, QTc>500 ms, use with class Ia or III antiarrhythmics (amiodarone/sotalol)
what do you know about siponimod
contraindicated for CYP2C93/3 genotype
first dose monitor for bradycardia/arrhythmias
monitor liver function, BP during treatment
contraindicated in recent MI, unstable angina, advanced HF, AV block
AEs: dose-dependent bradyarrhythmia
what do you know about cladribine
reserved for patients who do not tolerate or have inadequate response to other drugs for MS
lymphocyte counts should be monitored before, during, after treatment
each treatment course is two cycles of 4-5 days separated by 4 weeks
contraindicated in pregnancy, breastfeeding, women/men of reproductive potential (unless effective contraception for 6 months after)
what do you know about interferon beta
causes flu-like symptoms (fever, chills, myalgias)
contraindicated in severe depression
counsel women to use appropriate contraception
what do you know about glatiramer
causing transient chest tightness, flushing, dyspnea, if no hx CAD- self limited and benign
pregnancy category B
what do you know about ofatumumab
requires HBV and quantitative serum immunoglobulins screening prior to treatment
dosing is 20 mg SQ at weeks 0,1,2
subsequent dosing 20 mg monthly starting at week 4
contraindicated in active HBV infection
counsel females to use effective contraception during treatment and for 6 months after stopping Kesimpta
what do you know about alemtuzumab
due to safety profile, FDA recommends reserving for patients with inadequate response to two or more MS therapies
black box warnings for immune thrombocytopenia, serious & life-threatening infusion reactions, malignancies including thyroid cancer, melanoma, lymphoproliferative disorders
what do you know about mitoxantrone
have to monitor EF before each dose and monitor for symptoms of CHF
Counsel patients it may impart blue-green color to urine, bluish color to sclera
what do you know about natalizumab
it has a black box warning for increasing the risk of progressive multifocal leukoencephalopathy (PML): risk increases with number of infusions received
monitor JCV antibody every 3-6 months
what do you know about ocrelizumab
approved for PPMS
targets CD20 positive B cells
ADEs are infusion reactions and infections (upper and lower resp tract, skin infections)
counseling tips to tell your patients for injectables
-make sure the drug is at room or body temp before injecting
-ice the injection site before/after injecting drug
-never shake the vials
-rotate injection sites
-never inject the drug into an area that has a lump or a knot
when does the national MS society recommend starting therapy?
immediately after diagnosis
vitamin ____ deficiency is a common comorbidity with MS
D
consider obtaining a level and/or providing supplementation to every patient with MS
drug used to improve walking/gait in MS?
dalfampridine (Ampyra) CNS potassium channel blocker
what do you know about dalfampridine
take the tablets whole; do not crush, chew, etc
do not double or take extra dose due to seizure risk
contraindicated in history of seizures, moderate-severe renal impairment (CrCL<50)
drug interaction with metformin
what drugs are recommended for spasticity in MS
baclofen, tizanidine
what do you know about baclofen
GABA analog
must not be discontinued abruptly: hallucinations and seizure
KNOW THAT IT MUST BE TAPERED
what do you know about tizanidine
centrally acting alpha adrenergic agonist
ADEs include hypotension, dry mouth
what drugs are used for MS fatigue (“lassitude”)
amantadine (Symmetrel) 100 mg BID
Modafinil (Provigil) 100-400 mg daily
drugs used for tremor in MS
propranolol, primidone
drugs used for bowel/bladder issues in MS
hyperreflexic bladder (inability to store urine): oxybutynin, tolterodine
detrusor sphincter dyssynergia in men: alpha blockers (terazosin, doxazosin, tamsulosin)
constipation: fiber, laxatives, enemas
depression drugs in MS
SSRIs are reasonable
concurrent pain: duloxetine
fatigue: bupropion or fluoxetine
drugs for sensory symptoms in MS
DOC for chronic pain: carbamazepine
painful dysasthesias: TCAs, carbamazepine, gabapentin, SNRIs, pregabalin
drugs for sexual dysfunction in MS
sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra) in men; lubricants in women
alternative/complementary therapy for MS
oral cannabis; synthetic THC are probably effective for reducing patient-reported symptoms of spasticity and pain
