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3922 > 14 - Multiple Sclerosis > Flashcards

14 - Multiple Sclerosis Flashcards

1
Q

What is MS

A

Inflammatory disease in which the myelin sheath surrounding axons is damaged

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2
Q

What do lesions most commonly affect (4)

A

White matter of the optic nerve, brain stem, basal ganglia and spinal cord

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3
Q

What results from recurring episodes of MS

A

Scars to appear as a result of the breakdown of the myelin

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4
Q

What is a diagnostic tool for MS

A

Plaques/lesions in the brain

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5
Q

Are there curative drugs for MS

A

No

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6
Q

What are some current therapies aimed at reducing the severity and frequency of symptoms

A

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

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7
Q

What are beta interferons

A

Naturally occurring cytokines secreted by immune cells

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8
Q

What do beta interferons do (3)

A

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

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9
Q

What are some side-effects of beta interferons

A 
Live function abnormalities
Leukopenia
Thyroid disease
Depression
Flu-like symptoms
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10
Q

MOA of fingolimod (4)

A

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

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11
Q

What is fingolimod like

A

Comparable or better than beta-interferons

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12
Q

What are common adverse effects of fingolimod

A

1) Headache
2) Elevated liver enzymes
3) Influenza viral infections
4) Diarrhoea
5) Back pain

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13
Q

What is a myelin basic protein mimic

A

Glatiramer acetate

Copolymer polypeptide mixture consisting of L-glutamic acid, L-lysine, L-alanine and L-tyrosine

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14
Q

What do glatiramer acetate activate

A

Specific supressor T-cells are linked and activated in the periphery

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15
Q

What are glatiramer acetates used in

A

Patients who cannot tolerate beta interferons

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16
Q

What does glatiramer acetate do

A

Reduce inflammation

17
Q

What is dalfampridine used for

A

Improving walking in patients with MS

Improve the nerve conduction in fibres whose insulating myelin coating has been damaged by MS

18
Q

MOA of 4-aminopyridine

A

Blocks potassium channels

19
Q

What does an overdose of 4-aminopyridine do

A

Cause seizures

20
Q

What does mitoxanthrone do (4)

A
  • 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
21
Q

What is natalizumab

A

Humanised monoclonal IgG4 antibody

22
Q

What is MOA of natalizumab (3)

A
  • 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
23
Q

What does natalizumab do

A

Delay the progression of physical disability and reduce the frequency of relapse

24
Q

What is the risk of natalizumab

A

Progressive multifocal leukoencephalopathy, an opportunistic viral infection of the brain that usually leads to death or severe disability

25
Q

Which immunosuppressants are used for MS treatment

A

Azathiopurine and methotrexate
Cyclophosphamide
Mycophenolate Mofetil and cladribine

26
Q

What are some humanised monoclonal antibodies used against immune cell markers for MS treatment

A

Alemtuzumab - CD52 target
Daclizumab - CD25a of IL-2 receptor
Rituximab and ocrelizumab against CD20 antigen

27
Q

What did immunoablation treatment for aggresive MS involve

A

Immunosuppression followed by autologous haemopoietic stem-cell transplantation

28
Q

What occurs to the BBB in Alzheimer’s disease

A

The BBB is compromised
Elevated Igs and T-cells have been reported
Chronic inflammation

29
Q

What is rheumatoid arthiritis

A

Chronic inflammatory condition of the joints

30
Q

What is one of the therapies used to treat RA

A

Anti-TNF

31
Q

What are some symptoms of chronic fatigue syndrome (7)

A

1) Malaise after exertion
2) Unrefreshing sleep
3) Widespread muscle and joint pain
4) Sore throat
5) Headaches
6) Cognitive difficulties
7) Severe exhaustion

32
Q

What drug has been used against CFS in studies

A

Rituximab

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