MS
chronic inflammatory autoimmune disorder
- loss of the myelin sheath and axons which slows transmission
What cells are affected with MS
white and gray matter of the brain and spinal cord
Neuronal char of MS
inflammation, demyelination, scar dev (Gliosis)
cause of MS
unknown
- genetic predis, autoimm, enviro
known risks for MS
20-40Y, women, moderately cool climate (N. US), Caucasian, fam hx
possible risk fx for MS
smoking, vit D def. obese, infx (Epstein-Barr)
How does MS affect men?
Get worse and more prog sx
MS patho
- autoimm against myelin sheath
- T lymph to CNS cross the BBB, causing inflam
- antigen-antibody rxn in CNS–inflam
- axon demyelination
- plaque/sclerosis forms
- axons are destroyed and die
Neuronal effects of MS (early vs late)
Dec nerve fxn and transmission can cause eventual damage to the axons
- early–fiber not affected, impulse still transmitted, weakness
- late–axon destroyed, impulse blocked, perm loss of fxn
benign MS
no prog loss of fxn and very few exac that are weak
relapsing-remitting MS
- most common
- long remissions w/o exac and minimum prog weakness
Primary progressive MS
steady prog w/o remissions
Secondary progressive MS
initial relapse and remission then progressive decline w/o remissions
Progressive relapsing MS
Gradual progressive decline w/o many remissions
CM of MS
tingling, numbness, paresthesia in face, trunk, and legs, weakness and loss of fxn, vision loss, impaired gait, incontinence, sz, cog fog, depression, fatigue, pain (acute/chronic, burn/stab), bowel/blad (esp constipation), sexual probs, muscle stiffness/spasm, vertigo and falls
Goals of MS pharm
Improve fxn, limit lesions, dec exac
- modify disease process
tx of acute MS relapse
- pulse dose of IV glucocorticoids (v high dose for 3-5d)–avoid long-term/freq use
- IV gamma globulin–for pt intolerant to glucocort
- ACTH (acthar gel)–prolonged ACTH release; for intolerant to steroids
- plasmapheresis–take plasma out and replace it with donor plasma
Drugs to tx MS symptoms
- anticholinergics and cholinergic for urine freq/retention
- bulk form lax
- amantadine for fatigue and longer rest
- muscle relaxants for muscle spasms
- donepezil for cog fog
Interferon beta-1a/b class and MOA
- Naturally occurring sub
- Inhibit pro-inflam WBCs T-cells from crossing BBB
Interferon beta-1a/b SE and NC
- Flu-like, liver tox, bone marrow supp, dep, drug intx
- dec relapse rate by 30%
Glatiramer acetate MOA
Inc prod anti-inflam T cells that cross BBB and supp inflam
Glatiramer acetate SE and NC
- IJ site rxn, IJ rxn–flush, palpitations, chest pain, rash, laryngeal constriction
- IJ rxn usually last 15-20 min and tx not necessary
- sim efficacy to other drug
fingolimod
Retain lymphocytes in lymph nodes, prevent from migrating to BBB–dec inflam
- for RRMS
- oral
Dimethyl fumarate
- Inhibit immune cells and may have antioxidant properties
- oral
