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Pharmacotherapy III > MS-Rochet > Flashcards

MS-Rochet Flashcards

1
Q

What is MS?

A

Immune-mediated disorder

Destroys myelin sheath of neurons

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2
Q

What is sclerosis?

A

Scars in white matter of MS patients

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3
Q

What are 3 key signs of MS - Charcot’s triad?

A

Nystagmus (eye problems)
Intention tremor
Telegraphic speech

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4
Q

MS is more common in men/women?

A

Women

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5
Q

What are common symptoms of MS?

A 
Visual problems
Numbness/tingling
Fatigue, motor weakness
Difficulty walking/gait problems
Pain
Spasms
Dizziness/vertigo
Sexual dysfunction
Bladder problems/constipation
Emotional changes/depression
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6
Q

The most prominent symptoms of an MS patient reflect what?

A

The regions of the brain with the most severe damage

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7
Q

Where is MS most prevalent in the world?

A

above the 37th parallel

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8
Q

There is an increased MS risk with decrease ____

A

Vit D levels

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9
Q

What are some risk factors of MS?

A 
Age (40's)
Decreased Vit D
Viral infections
Environmental insults
Cigarette smoking
genes
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10
Q

How can bacterial infections induce MS?

A

Activating autoreactive immune cells

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11
Q

MS patients have increased ___ synthesis in the CNS

A

IgG

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12
Q

MS patients have increased _______ to certain viruses

A

antibody titers

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13
Q

What virus might be involved with MS?

A

Epstein-Barr Virus (MONO)

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14
Q

Why would EBV be involved with MS?

A

Sequence similarities between self-peptides and EBV –> activation of immune cells against self

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15
Q

Does EBV cause MS?

A

Not directly

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16
Q

Risk distribution in families indicates a ____ mode of inheritance

A

Polygenic – >50 genomic regions involved

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17
Q

What proteins are linked to MS?

A

Major histocompatibility complex (HLA)
Interleukin 2a
Interleukin 7a

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18
Q

RRMS is ???

A

Relapsing Remitting MS, where symptoms come and go (remission and relapse)

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19
Q

RRMS usually eventually enters into ____

A

SPMS - secondary progressive MS, where symptoms don’t go away

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20
Q

What is PPMS?

A

Primary progressive MS - never has relapses/remission periods

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21
Q

Mean onset is later for PPMS or RRMS?

A

PPMS

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22
Q

What does CIS stand for?

A

clinically isolated syndrome

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23
Q

What is CIS?

A

First episode of MS symptoms lasting >24 hours

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24
Q

T/F: Most cases of CIS progress to MS

A

True

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25
Q

What is the Marburg variant of MS?

A

Aggressive MS involving inflammation- resembles brain tumor

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26
Q

What is the progressive phase?

A

Constantly occurring cytodegeneration (loss of myelin/oligodendrocytes)

27
Q

T/F: Progressive phase is faster with PPMS

A

FALSE: occurs at similar rate in all different forms of MS

28
Q

The relapse phases are more determined by ______

A

immune activity/inflammation

29
Q

What happens in autoimmune phase of MS?

A

Antigens released from CNS or foreign antigens that look like CNS activate aB and T cells
B and T cells migrate to CNS where they carry out immune functions at CNS sites

30
Q

What happens in the degenerative phase of MS?

  • CNS damage is triggered by ___
  • Antigens released from CNS ______ in the periphery
A
  • Triggered by activated B and T cells, or stroke/infection/etc
  • Further prime immune cells
31
Q

Does degenerative trigger autoimmune or autoimmune trigger degenerative?

A

Not clear

32
Q

So two theories of MS development are:

A
  • Inside-out: CNS antigens are entering periphery and activating immune cells
  • Outside in: Autoimmunity in periphery is developing and immune cells are entering CNS
33
Q

____ cells that present CNS antigens activate ___ in peripheral lymphoid tissue

A

Dendritic cells; activate T-cell responses

34
Q

What protein is important for B and T cells to get through the BBB into the CNS?

A

alpha-4-integrin!!

35
Q

CD8+T cells interact with ligands presented by ____ on MHC class __

A

Oligodendrocytes or neurons

Class I

36
Q

CD4+T cells interact with ligands presented by ___ on MHC class __ molecules

A 
Microglia
MHC class II
37
Q

T cell activation results in ___ release and ___ stimulation, leading to damage to the ________

A

cytokine release
macrophage stimulation
damage to myelin sheath

38
Q

How do CD8 T cells damage Oligodendrocytes?

A 
Release cytokines
IFN-gamma
TNF-alpha
perforin
granzyme
39
Q

How do antibodies damage oligodendrocytes?

A

Trigger complement activation –> pore formation

40
Q

How do macrophages damage oligodendrocytes?

A

Release toxic ROS/Nitrogen that harm oligodendrocytes

41
Q

How do macrophages damage the myelin sheath?

A

Phagocytosis

42
Q

In demyelinated axons, AP is faster/slower?

A

slower

43
Q

Normally, how are Na/K channels arranged?

A

Separated–
Na found in Nodes
K found under myelin sheath

44
Q

How are N/K channels arranged with MS?

A

Mixed together in areas of demyelination - Na channels move

45
Q

How can damaged neurons and oligodendrocytes be replaced?

A

Neuronal stem cells and oligodendrocyte progenitor cells migrate to the lesion!

46
Q

Why does remyelination usually fail in MS?

A

Lack of OPCs or failure of OPCs to differentiate to oligodendrocytes

47
Q

What is astroglisosis?

Invasions and propagation of ___ resulting in irreversible formation of ____

A

astrocytes

gliotic plaques/scars

48
Q

Demyelination activates __ and ___

A

Microglia and astrocytes

49
Q

What produces pro-migratory factors that recruits OPCs?

A

Activated microglia and astrocytes

50
Q

T/F: Myelin sheaths that result from remyelination are just as strong as the original sheaths

A

False: they are thinner and shorter

51
Q

Remyelination in MS fails because of ___

A

ongoing inflammation

52
Q

What target to prevent T cell binding/penetration of BBB?

A

a4-integrin antibodies

IFN-Beta

53
Q

What are the targets for MS treatment?

A
  • Immune system
  • Remyelination (OPC recruitment/differentiation)
  • Neurodegeneration
54
Q

What are the immune system targets for MS?

A

T cell binding/penetration
T cell/APC interactions
Cytokines

55
Q

What agent is used to visualize MS brain lesions w/MRI?

A

gadolinium

56
Q

Where does gadolinium penetrate?

A

Regions where BBB is compromised

57
Q

What are active lesions?

A

MS lesions that exhibit enhancement after gadolinium

58
Q

What is Guillain-Barre syndrome?

A

Inflammatory neuropathy

59
Q

What precedes Guillain-Barre syndrome?

A

GI or respiratory infection

60
Q

Symptoms of Guillain-Barre?

A
  • Weakness in distal muscles

- Can become total paralysis w/DEATH

61
Q

Pathophysiology of Guillain Barre?

A

Autoimmune attack on peripheral nerves –> DEMYELINATION

62
Q

Treatment of Guillain Barre?

A

Ventilation
Plasmapheresis (get rid of auto-abs)
IV Immunoglobulin administration

63
Q

How long does recovery from Guillain-barre take?

A

months to years

Pharmacotherapy III (12 decks)

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