406 E2: multiple sclerosis Flashcards
MS definition
chronic, inflammatory autoimmune disorder that targets both the white and gray matter of the spinal cord and involves the degeneration of CNS myeline or loss of myelin sheath w/ scarring
MS characteristics
-inflammation of the white matter of brain and spinal cord
-demyelination of the nerve fibers
-development of scar tissue (gliosis)
MS etiology
unknown but autoimmune so likely a genetic predisposition that was triggered
MS risk factors
age: 20-40
gender: women
location: moderately cool climate
race: caucasian
genetics: fam hx
possible risk factors for MS
smoking
vit D deficiency
obesity
infection (including epstein-barr)
MS pathogenesis
T lymphocytes migrate to the CNS and cross the blood brain barrier -> antigen antibody reaction in CNS initiates an inflammatory response -> axons are de myelinated & plaques / sclerosis forms -> axons are destroyed
axon is the nerve itself
loss of myelin…
disrupts nerve conduction & w/ subsequent death of neurons and brain atrophy
neurons in early disease
-nerve fiber not affected
-impulses still transmitted
-may notice weakness
neurons in a more progressed disease
-axons are destroyed
-impulses are totally blocked
-permanent loss of function
MS subtypes: benign
there is an exacerbation of symptoms but after the flare subsides, there is a return to baseline
they recover and there is no loss of function once they are back at baseline
MS subtypes: relapsing - remitting
most common form
long periods of remission w/ few exacerbations, the pt is stable between exacerbations and there is minimal disability or progression of the disease
won’t necessarily return to their baseline & may have some permanent deficits, will be weaker than baseline and each time there is a flare they do not recover all the way
MS subtypes: primary - progressive
a gradual progression of symptoms without periods of remission
MS subtypes: secondary - progressive
there is an initial relapsing or exacerbation followed by remission w/ some loss of function with each exacerbation but changes course and loses the periods of remission
MS subtypes: progressive - relapsing
there is a gradual progression of symptoms and also exacerbations and they have fewer remissions
what is the most common initial symptoms of MS
-paresthesia of the face, trunk or limbs d/t nerves no longer innervating the muscles
-loss of muscle function
-numbness
-tingling
-optic neuritis / unilateral vision loss
-impaired gait
-urinary incon
-seizures
symptoms to monitor w/ MS
-cognitive problems (cog fog)
-vision problems
-depression
-fatigue
-pain (acute, chronic, burning, stabbing)
-bowel/bladder
-weakness
-sexual issues
-muscle stiffness/spasm
-walking/balance
cog fog
difficulty thinking clearly and concentrating
not a memory thing
is there a cure to MS
no
goals of therapy for MS
-slow disability
-reduce frequency of relapses
-reduce new brain lesions
drugs for MS are used to
-modify the disease process
-treat an acute relapse
-manage symptoms
how do we modify the disease process
-interferon beta (injectable)
-glatiramer acetate (injectable)
interferon beta
-avonex (1a)
-betaseron (1b)
-extavia (1b)
-plegridy (pegylated 1a)
-rebif (1a)
natural occur in body
glatiramer acetate
-copaxone
-glatopa
interferon beta MOA
inhibit pro-inflammatory WBCs from crossing BBB
decrease relapse rate by up to 30%
interferon beta SE
-flu like
-liver toxicity
-bone marrow suppression
-depression
-drug interaction
glatiramer acetate MOA
increased production of anti inflammatory T cells which cross the BBB and suppress inflammation
glatiramer acetate SE
-injection site reactions
-post injection reactions
-flushing, palpitations, chest pain, rash, laryngeal constriction (lasts 15-20 mins, treatment not necessary)
oral MS medications
-fingolimod
-dimethyl fumarate
infusion MS drugs
natalizumab
fingolimod
retain lymphocytes in the lymph nodes, preventing them from crossing the BBB -> decreasing inflammation
helps w/ RRMS
dimethyl fumarate
thought to inhibit immune cells and may have anti oxidant properties
natalizumab MOA
prevents circulating T cells from leaving the vasculature and crossing blood brain barrier
natalizumab therapeutic uses
-MS (reduces relapse by 68%), relapsing form
-Crohn’s disease
monotherapy only
natalizumab SE
headache & fatigue
-progressive mutlifocal leukoencephalopathy (fetal, to be on this drug need to be in program that is very regulated)
-hepatotoxicity
-hypersensitivity
what increases the risk of PML while on natalizumab
use of other immunosuppressants in combo w/ it (steroids)
alemtuzumab
reserved for patients w/ poor response to 2 or more MS meds
mitozantrone
-secondary progressive
-progressive relapsing
-worsening RRMS (w/o complete remission)
treating an acute relapse: preferred treatment
high does IV glucocorticoid short term
treating an acute relapse: non preferred
-IV gamma globulin -> used if pt is intolerant to glucocorticoids
-ACTH (H.P. acthar gel) which prolongs the release of ACTH after injection
managing sx drugs to use for: urinary frequency / retention
anticholinergic / cholinergic
managing sx drugs to use for: constipation
bulking forming laxative
managing sx drugs to use for: fatigue
amantadine
managing sx drugs to use for: muscle spasms
muscle relaxants
managing sx drugs to use for: cognitive dysfunction
donepezil
