14 - Multiple Sclerosis Flashcards
What is MS
Inflammatory disease in which the myelin sheath surrounding axons is damaged
What do lesions most commonly affect (4)
White matter of the optic nerve, brain stem, basal ganglia and spinal cord
What results from recurring episodes of MS
Scars to appear as a result of the breakdown of the myelin
What is a diagnostic tool for MS
Plaques/lesions in the brain
Are there curative drugs for MS
No
What are some current therapies aimed at reducing the severity and frequency of symptoms
1) B interferons
2) Sphingosine-1-phosphate receptor modulator
3) Myelin basic protein mimic
4) K+ channel blockers
5) Chemotheraputic agents
6) Immunosupressants
7) Human immunoglobins
What are beta interferons
Naturally occurring cytokines secreted by immune cells
What do beta interferons do (3)
Inhibit viral replication via a variety of immunomodulating and antiviral activities
Perform regulatory functions in the immune system and are anti-inflammatory
Restrict lymphocytes crossing BBB, limit immune response
What are some side-effects of beta interferons
Live function abnormalities Leukopenia Thyroid disease Depression Flu-like symptoms
MOA of fingolimod (4)
1) Metabolised by sphingosine kinase to active metabolite fingolimod phosphate
2) Ligand enters via cell membrane
3) Causes internalisation of the receptor and is functional antagonist
4) Prevents the migration of lymphocytes from lymph nodes, reducing number of lymphocytes in peripheral blood
What is fingolimod like
Comparable or better than beta-interferons
What are common adverse effects of fingolimod
1) Headache
2) Elevated liver enzymes
3) Influenza viral infections
4) Diarrhoea
5) Back pain
What is a myelin basic protein mimic
Glatiramer acetate
Copolymer polypeptide mixture consisting of L-glutamic acid, L-lysine, L-alanine and L-tyrosine
What do glatiramer acetate activate
Specific supressor T-cells are linked and activated in the periphery
What are glatiramer acetates used in
Patients who cannot tolerate beta interferons
What does glatiramer acetate do
Reduce inflammation
What is dalfampridine used for
Improving walking in patients with MS
Improve the nerve conduction in fibres whose insulating myelin coating has been damaged by MS
MOA of 4-aminopyridine
Blocks potassium channels
What does an overdose of 4-aminopyridine do
Cause seizures
What does mitoxanthrone do (4)
- Suppress activity of T-cells, B-cells and macrophages that attack the myelin sheath
- Impairs antigen presentation as well as the secretion of interferon gamma, TNF-a and IL2
- Intercalates into DNA and RNA
- Potent inhibitor of topoisomerase II
What is natalizumab
Humanised monoclonal IgG4 antibody
What is MOA of natalizumab (3)
- Bind to a4 subunit of of a4b1 and a4b7 integrins expressed on the surface of leukocytes
- Inhibits a4-mediated adhesion of leukocytes
- Prevents lymphocyte migration across the BBB
What does natalizumab do
Delay the progression of physical disability and reduce the frequency of relapse
What is the risk of natalizumab
Progressive multifocal leukoencephalopathy, an opportunistic viral infection of the brain that usually leads to death or severe disability
Which immunosuppressants are used for MS treatment
Azathiopurine and methotrexate
Cyclophosphamide
Mycophenolate Mofetil and cladribine
What are some humanised monoclonal antibodies used against immune cell markers for MS treatment
Alemtuzumab - CD52 target
Daclizumab - CD25a of IL-2 receptor
Rituximab and ocrelizumab against CD20 antigen
What did immunoablation treatment for aggresive MS involve
Immunosuppression followed by autologous haemopoietic stem-cell transplantation
What occurs to the BBB in Alzheimer’s disease
The BBB is compromised
Elevated Igs and T-cells have been reported
Chronic inflammation
What is rheumatoid arthiritis
Chronic inflammatory condition of the joints
What is one of the therapies used to treat RA
Anti-TNF
What are some symptoms of chronic fatigue syndrome (7)
1) Malaise after exertion
2) Unrefreshing sleep
3) Widespread muscle and joint pain
4) Sore throat
5) Headaches
6) Cognitive difficulties
7) Severe exhaustion
What drug has been used against CFS in studies
Rituximab
