Treatment of RA

Question 1

What is the first line for RA?

Answer 1

NSAIDs

Question 2

How do NSAIDs work?

Answer 2

They inhibit COX enzymes and therefore prostaglandin synthesis

Question 3

What is the main drawback to NSAID use?

Answer 3

Gastric Irritation

Increased Gastric bleeding and Ulceration
- Inhibiting COX enzymes causes reduced mucous secretion and thins the blood

Question 4

What is COX-1 mainly involved in?

Answer 4

Housekeeper functions

Question 5

What is COX-2 mainly involved in?

Answer 5

Involved more in inflammation

Question 6

What is the problem associated with selectively inhibiting COX-2?

Answer 6

Blood clots

Question 7

What is second line for RA?

Answer 7

DMARDs

• They modify and dampen down the disease process but do not eradicate it
• Do not alter disease progression?

Question 8

How does methotrexate work?

Answer 8

It reduces cellular proliferation
- Inhibits dihydrofolate reductase (therefore reduces DNA synthesis)

It is:

• Anti inflammatory
• Anti proliferative
• Immunosuppresive

It reduces endothelial cell production (required for angiogenesis)
It also suppresses IL-1 and IL-6

Question 9

What are the main side effects associated with methotrexate?

Answer 9

• Bone marrow suppression
• GI damage
• Skin lesions
• Kidney failure

Question 10

In the first year of treatment with DMARDs….

Answer 10

• 10% may enter remission
• Less than half would respond
• Many will stop due to toxicity/intolerance

Question 11

In the second year of treatment with DMARDs…

Answer 11

• Less than half would remain on the same drug

Question 12

How does Sulphasalazine (a DMARD) work in RA?

Answer 12

Mechanism of action in RA is uncertain

- May affect macrophage biochemistry to favour anti-inflammatory cytokine production

Question 13

How does Penicillamine (a DMARD) work in RA?

Answer 13

• Decreased joint swelling, rheumatoid factor and concentration of APP
• Prevents maturation of newly synthesised collagen

Question 14

How does Chloroquine (a DMARD) work in RA?

Answer 14

• Induces remission but doesnt retard progression of bone damage
• Reduces joint swelling and decreased rheumatoid factor
• Lysosomotrophic and inhibits PLA2
• Reduces cytokine transcription

Question 15

How does Leflunomide (a DMARD) work in RA?

Answer 15

• Inhibits orotate dehydrogenase, an enzyme involve in de novo pyrimidine synthesis
• Mechanism in RA uncertain!
• > May supress B cell activity, autoantibody, RF production

Question 16

What’s the third line used in RA?

Answer 16

Steroids (Glucocorticoids)

Question 17

What’s the 3rd/4th line used in RA?

Answer 17

Anti-TNF

Question 18

What are some examples of anti-TNF?

Answer 18

Infliximab and Adalimumab

Question 19

How do anti-TNF therapies work?

Answer 19

if TNF is eliminated, all the inflammatory processes downstream of TNF are also reduced (including e.g. COX)

• Biological antibodies designed to ‘mop-up’ excess TNF
• Etanercept is a soluble TNF receptor rather than an antibody that also ‘mops up’

Question 20

What is the main problem associated with Adalimumab?

Answer 20

Can increase the risk of re-occurrence of TB