Treating chronic inflammatory illness

Question 1

COX 1

Answer 1

Stomach lining and GI system - GI s/e of non-specific COX

Question 2

COX 2

Answer 2

Produced by stimulus of inflammation and infection

Question 3

What chemicals are responsible for inflammation?

Answer 3

Prostaglandins

Question 4

Arachidonic acid pathway

Answer 4

Phospholipase A2 -> arachidonic acid -> (COX) prostaglandins

Question 5

What do steroids target?

Answer 5

Phospholipase A2

Question 6

NSAIDs with greater affinity to COX 1

Answer 6

Aspirin, ibuprofen, naproxen

Question 7

NSAIDs with greater affinity to COX 2

Answer 7

Diclofenac, celecoxib

Question 8

NSAID used for patients with cardiovascular issues

Answer 8

Aspirin

Question 9

Types of steroid

Answer 9

Sex hormones and adrenal corticosteroids (hydrocortisone and cortisol) and mineralocorticoids

Question 10

Steroid moa

Answer 10

• Steroids have intracellular receptor
• Receptor is attached to heat shock protein
• Receptor and steroid enter nucleus to steroid receptor element at promoter region of gene of interest
• Up or down regulate transcription to change protein concentration
  Enter nucleus

Question 11

How does methotrexate work?

Answer 11

• Inhibits DNA expression = reduced RNA synthesis → limited protein production
• Folate competitor - people need to take folate supplements (alternate days of methotrexate and folic acid)

Question 12

How does hydroxychloroquine work?

Answer 12

• Antimalarial
• Reduced presentation of antigens by increasing pH inside macrophage lysosome
• Reduced T helper and macrophage presenting antigen
• COVID: reducing antigen on macrophage surface = less inflammation as response = fewer s/e

Question 13

How do anti-TNF molecules work?

Answer 13

• TNF stimulates inflammation
• 2 receptors: one is widely presented and the second in the immune system
• SC or IV
• T1/2 of 5-20 days
• Endosomal degradation

Question 14

RA treatment

Answer 14

• NSAIDs or steroids needed
• DMARD takes 3 months to take effect - methotrexate + folic acid or methotrexate + sulfasalazine/leflunomide/hydroxychloroquine
• Stop steroids after 6 months due to s/e
• Biologics if NSAIDs/steroids fail but are more expensive
• NSAIDs are good for pain and stiffness but no effect on long term outcome
• Ibuprofen (shorter half life - works quicker) and naproxen