Chapter 22: Drugs for Multiple Sclerosis Flashcards
What country has the highers rate of MS in the world?
Canada - 1/340
What is MS and its characteristics?
Autoimmune disease of the CNS
Attacks Myelin - Oligodenderocytes
Type IV Hypersensitivity - Cell-Mediated\
Onset 17-35 Yrs of Age
3Female: 1MAle
What is the mechanism of Multiple Sclerosis?
- T Cell crosses BBB
- Gets activated by Myelin (Unkown Cause; Possible Viral Infection)
- Activated T-cell can upregulate more receptors for circulating immune cells. (To cross BBB)
- Produce and release cytokines (IL-1, IL-6, TNF-alpha, INF-gamma) - Dilates Blood Vessels
- Recruit B cells for antibody production and macrophages for destruction/clearance.
- Results in plaque (sclera) formation that an be obseved on MRI scans.
What are the 4 types of Multiple Sclerosis?
- Relapsing-Remitting MS (85%)
- Secondary-Progressive MS (?)
- Primary-Progressive MS (10%)
- Progressive-Relapsing (5%)
What are symptoms of MS?
- Charcot’s Neurologic Triad
- Nystagmus
- Intention Tremor
- Unclear Speech
- Plaques in sensory pathways.
- Numbness
- Pins&Needles
- Paresthesias (Tingling, itching, burning)
- Lhermitte’s Sign
- An electrical sensation that runs down the back, neck and into the lumbs by stretching the spine.
- Plaques in ANS
- Bowel and Bladder Symptoms
- Sexual Disfunction
- Higher order activites
- Poor concentration and critical thinking
- Depression & Anxiety
- Uhthoff’s Phenomenon
- Worsening of Symptoms in heat
- Increases in body temperature can slow or block impulse conduction in demyelinated nerves.
MS suspected when symptoms spread over____and ____.
MS suspected when symptoms spread over space and time.
What are the different Acute treatment methods?
Methylprednisolone - Immunosupressive
Plasma Exchange Therapy **
- Plasma is separated and discarded *(containing autoantibodies)
- Replaced with donor plasma or *albumin/saline.
The aim of acute treatment is to stop the current inflammatory event.
What is the aim of Disease Modifying Therapies when treating MS?
Decrease risk of relapses (drive new lesions on MRI) with goal of slowing disability progression.
What are the first line DMT Immunomodulating therapies in treating MS?
Interferon-B
- 30% reduction in MS relapses
- Reduces antigen presentaiton and T-cell proliferation
- Balance pro and anti inflammatory agents
- Safe profile
Glatiramer Acetate (Does not cross BBB)
- Mixture of random sized peptides composed of the four amino acids found in myelin basic protein.
- Decoy for attacking immune cells
- Shifts proinflammatory Th1 T-cells to anti inflammatory th2 T-cells
Fingolimod (Crosses BBB)
- 54% reduction in MS relapses
- First oral DMT for MS approved in Canada 2011
- Prevents lymphocytes entering CNS for relapse
- CB1 antagonist and ceramide synthase inhibitor
What is the second line in DMT immunomodulating therapy?
Natalizumab
- **Anti a4 Integrin **(Blood Vessel receptor that allows immune cells to cross BBB)
- 68% reduction in MS relapses
- Prevents binding and crossing BBB
Alemtuzumab (Targets CD52 mature Lymphocytes)
- Tagged lymphocytes are destroyed
- Rapid and prolonged depletion requiring reconstitution.
Ocrelizumab (Target CD20 - B cells)
- First drug approved for PPMS
- Immunosuppressive
- Kills B cells (overlaps with rituximab epitope)
Daclizumab
- Approved first for kidney transplants
- Bloxks IL-2 slpha subunit for net reduction in T-cell responses
- Generally well tolerated with adverse events manageable
MABS
Orelizumab more immunosupressive than alemtuzumab.
How can you treat the symptom of difficulty walking in MS?
Dalfampridine
K channel antagonist - Prevents current leakage (through K channels) in demyelination. Increases conductance.
How to treat the symptom of spasticity in MS?
Tizanidine
- a2 andregenic agonist
- muscle relaxant
- more tolerable than baclofen and diazepam (these drugs affect GABA)
- may cause hypotension.
Botulinum Toxin
- blocks vesicle docking
- injected locally to affect small areas
- specific to Ach containing nerves
- After taken up and activated it claves SNARE proteins - Long lasting
- Leads to paralysis.
Nabiximols (Cannabis sativa L extract)
1:1 THC:CBD
