406 E2: multiple sclerosis

Question 1

MS definition

Answer 1

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

Question 2

MS characteristics

Answer 2

-inflammation of the white matter of brain and spinal cord
-demyelination of the nerve fibers
-development of scar tissue (gliosis)

Question 3

MS etiology

Answer 3

unknown but autoimmune so likely a genetic predisposition that was triggered

Question 4

MS risk factors

Answer 4

age: 20-40
gender: women
location: moderately cool climate
race: caucasian
genetics: fam hx

Question 5

possible risk factors for MS

Answer 5

smoking
vit D deficiency
obesity
infection (including epstein-barr)

Question 6

MS pathogenesis

Answer 6

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

Question 7

loss of myelin…

Answer 7

disrupts nerve conduction & w/ subsequent death of neurons and brain atrophy

Question 8

neurons in early disease

Answer 8

-nerve fiber not affected
-impulses still transmitted
-may notice weakness

Question 9

neurons in a more progressed disease

Answer 9

-axons are destroyed
-impulses are totally blocked
-permanent loss of function

Question 10

MS subtypes: benign

Answer 10

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

Question 11

MS subtypes: relapsing - remitting

Answer 11

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

Question 12

MS subtypes: primary - progressive

Answer 12

a gradual progression of symptoms without periods of remission

Question 13

MS subtypes: secondary - progressive

Answer 13

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

Question 14

MS subtypes: progressive - relapsing

Answer 14

there is a gradual progression of symptoms and also exacerbations and they have fewer remissions

Question 15

what is the most common initial symptoms of MS

Answer 15

-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

Question 16

symptoms to monitor w/ MS

Answer 16

-cognitive problems (cog fog)
-vision problems
-depression
-fatigue
-pain (acute, chronic, burning, stabbing)
-bowel/bladder
-weakness
-sexual issues
-muscle stiffness/spasm
-walking/balance

Question 17

cog fog

Answer 17

difficulty thinking clearly and concentrating
not a memory thing

Question 18

is there a cure to MS

Answer 18

no

Question 19

goals of therapy for MS

Answer 19

-slow disability
-reduce frequency of relapses
-reduce new brain lesions

Question 20

drugs for MS are used to

Answer 20

-modify the disease process
-treat an acute relapse
-manage symptoms

Question 21

how do we modify the disease process

Answer 21

-interferon beta (injectable)
-glatiramer acetate (injectable)

Question 22

interferon beta

Answer 22

-avonex (1a)
-betaseron (1b)
-extavia (1b)
-plegridy (pegylated 1a)
-rebif (1a)
natural occur in body

Question 23

glatiramer acetate

Answer 23

-copaxone
-glatopa

Question 24

interferon beta MOA

Answer 24

inhibit pro-inflammatory WBCs from crossing BBB
decrease relapse rate by up to 30%

Question 25

interferon beta SE

Answer 25

-flu like -liver toxicity -bone marrow suppression -depression -drug interaction

Question 26

glatiramer acetate MOA

Answer 26

increased production of anti inflammatory T cells which cross the BBB and suppress inflammation

Question 27

glatiramer acetate SE

Answer 27

-injection site reactions -post injection reactions -flushing, palpitations, chest pain, rash, laryngeal constriction (lasts 15-20 mins, **treatment not necessary**)

Question 28

oral MS medications

Answer 28

-fingolimod -dimethyl fumarate

Question 29

infusion MS drugs

Answer 29

natalizumab

Question 30

fingolimod

Answer 30

retain lymphocytes in the lymph nodes, preventing them from crossing the BBB -> decreasing inflammation **helps w/ RRMS**

Question 31

dimethyl fumarate

Answer 31

thought to inhibit immune cells and may have anti oxidant properties

Question 32

natalizumab MOA

Answer 32

prevents circulating T cells from leaving the vasculature and crossing blood brain barrier

Question 33

natalizumab therapeutic uses

Answer 33

-MS (reduces relapse by 68%), relapsing form -Crohn's disease **monotherapy only**

Question 34

natalizumab SE

Answer 34

**headache & fatigue** -progressive mutlifocal leukoencephalopathy (fetal, **to be on this drug need to be in program that is very regulated**) -hepatotoxicity -hypersensitivity

Question 35

what increases the risk of PML while on natalizumab

Answer 35

use of other immunosuppressants in combo w/ it (steroids)

Question 36

alemtuzumab

Answer 36

reserved for patients w/ poor response to 2 or more MS meds

Question 37

mitozantrone

Answer 37

-secondary progressive -progressive relapsing -worsening RRMS (w/o complete remission)

Question 38

treating an acute relapse: preferred treatment

Answer 38

high does IV glucocorticoid **short term**

Question 39

treating an acute relapse: non preferred

Answer 39

-IV gamma globulin -> used if pt is intolerant to glucocorticoids -ACTH (H.P. acthar gel) which prolongs the release of ACTH after injection

Question 40

managing sx drugs to use for: urinary frequency / retention

Answer 40

anticholinergic / cholinergic

Question 41

managing sx drugs to use for: constipation

Answer 41

bulking forming laxative

Question 42

managing sx drugs to use for: fatigue

Answer 42

amantadine

Question 43

managing sx drugs to use for: muscle spasms

Answer 43

muscle relaxants

Question 44

managing sx drugs to use for: cognitive dysfunction

Answer 44

donepezil