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Pharmacy Stage 3 > Pathophysiology of Rheumatoid Arthritis > Flashcards

Pathophysiology of Rheumatoid Arthritis Flashcards

1
Q

what is rheumatoid arthritis?

A

A chronic, systemic inflammatory condition that develops progressively

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2
Q

what joints are affected 1st?

A

Interphalangeal joints of fingers and wrist

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3
Q

what is felt and seen at the affected joints?

A

heat, swollen, redness, increased extracellular fluid

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4
Q

what effect does the extracellular fluid have on the joints?

A

causes stiffness particularly in the morning

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5
Q

what other diseases does rheumatoid arthritis increase the risk of?

A
  1. Cardiovascular disease
  2. Inflammation around lungs and heart
  3. Systemic symptoms e.g. malaise / weight loss
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6
Q

what happens to the bone and cartilage around the joint in RA?

A

they become destroyed

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7
Q

what is septic arthritis?

A

when there is an infection in the joint causing inflammation

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8
Q

what is post-traumatic arthritis?

A

inflammation at joint brought about by physical injury

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9
Q

is RA an autoimmune condition?

A

yes

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10
Q

Is the rheumatoid factor specific for RA?

A

nope

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11
Q

what causes autoantibody formation in RA?

A

Citrullinated proteins/peptides

so we get Anti-citrullinated peptide antibodies formed which are what cause the self-harm in autoimmunity

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12
Q

what is citrulline?

A

an amino acid related to arginine that is NOT used in protein synthesis

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13
Q

what is citrullination?

A

a mechanism that converts arginine into citrulline

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14
Q

what enzyme catalyses the reaction of citrullination?

A

peptidylarginine deiminases (PAD)

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15
Q

what does peptidylarginine deiminases do?

A
  • PAD destabilizes proteins and makes them more prone to proteolyisis.
  • if there are cells that don’t accept the new proteins containing the citrulline, then they are classed as intolerant so B-cells and T-cells come along
  • this is what causes the immunological intolerance at the start of RA development/pathogenesis
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16
Q

what makes up the joint capsule?

A

`Synovial membrane and fibrous layer

17
Q

what does PAD2 and PAD4 do in the synovial fluid?

A

they are enzymes that citrullinate unknown proteins in the joint capsule
-this would stimulate an autoimmune reaction when the antictrullinated protein antibodies enter the fluid and cause inflammation

18
Q

what initiates RA?

A

joint damage e.g. wound or infection

-this induces inflammation in the joint causing further activation of PAD

19
Q

why is vascular permeability important in RA?

A
  1. it is important in the inflammatory response

2. also allows the antictrullinated protein antibodies to enter the joint capsule

20
Q

what do CD4T cells differentiate into?

A

TH-17 and TH-1

21
Q

what does TH-17 do?

A

releases IL17 and recruits neutrophils and monocytes

22
Q

what does TH-1 do?

A

releases IFN-γ and activates macrophages

23
Q

Which antibody is specific for RA disease?

A

Anti-citrullinated protein antibody (ACPA)

24
Q

Which mediator is actively involved in osteoclast activation?

A

RANKL

25
Q

what are the 4 classes of rheumatoid arthritis therapy?

A
  1. NSAIDS
  2. Glucocorticoids
  3. DMARDs
  4. Biologics
26
Q

what do glucocorticoids do?

A

Reduce development of joint damage as the damage to the joint is permanent so can only slow the process of progression

27
Q

What do DMARDS do?

A

produce long term depression of the inflammatory response

28
Q

how does methotrexate work?

A
  • methotrexate is a DMARD
  • Suppresses neutrophil adhesion to blood vessels and so prevents entry to site of inflammation
  • Suppresses cytokine production
  • Reduces macrophage function
29
Q

how does sulfasalaine work?

A

-suppress signalling pathways involved in synthesis of pro-inflammatory cytokines

30
Q

how does hydroxychloroquinine work?

A
  • enters lysosomes inside cell and disturbs pH
  • Macrophages depend upon acid protease for digestion of intracellular protein
  • Altered pH inside lysosome may alter processing of peptide antigens
  • Reduces activity of other immune cells
31
Q

how does leflunomide work?

A
  • Inhibits enzyme involved in synthesis of uridine monophosphate (UMP)
  • also Inhibits tyrosine kinases
  • both of these effects suppress the expansion of autoimmune lymphocytes
  • this suppresses autoimmunity
32
Q

what do biologics do?

A

-they target specific aspects of the immune system that are important in the inflammation associated with RA

33
Q

Give examplesof Biologics?

A
  1. Anti-TNF
  2. Anakinra
  3. Tocilzumab
34
Q

Give 4 examples of Anti-TNF drugs?

A
  1. Adalimumab
  2. Golimumab
  3. Etanercept
  4. Infliximab
35
Q

how do Anti-TNF drugs work?

A

They are antibodies against tumour necrosis factor α (TNF), which is an important mediator of the inflammatory response

36
Q

how does Anakinra work?

A

It is an antibody against IL-1 receptor. IL-1 is a proinflammatory cytokine released from activated macrophages

37
Q

How does Tocilzumab work?

A

It is an antibody that acts as a competitive antagonist against the IL-6 receptor which works as a pro-inflammatory cytokine

Pharmacy Stage 3 (51 decks)

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