PHARM: DMARDs + gout

Question 1

3 examples of DMARDs

Answer 1

• sulfasalazine
• methotrexate (most hepatotoxic)
• infliximab

Question 2

best Tx for RA and when must this be done?

Answer 2

• NSAIDs + corticosteroids provide rapid symptomatic relief
• DMARDs (combination therapy) to slow progression
• must do it within 3 years of onset otherwise loss of function can be permanent

Question 3

what are DMARDs?

Answer 3

• disease-modifying anti-rheumatic drugs
• disease modifying = slows progression of RA
• have diff MOAs, usually decrease WBC turnover or function
• take weeks or months to become effective > combination therapy recommended
• potent, usually toxic

Question 4

methotrexate: MOA

Answer 4

• 1st line Tx for RA - ‘rapid’ onset (1-3 months)
• MOA: inhibits DHF reductase and purine/pyrimidimine synthesis, therefore blocking DNA synthesis and proliferation in immune cells to prevent inflammation

Question 5

leflunomide MOA

Answer 5

• DMARD
• blocks pyrimidine synthesis to inhibit DNA synthesis and replication of immune cells = decreased inflammation

Question 6

sulfasalazine MOA

Answer 6

• DMARD that reduces lymphocyte function

Question 7

hydroxychloroquine MOA

Answer 7

• DMARD
• may decrease immune response
• also an anti-malarial
• major side effect: retinopathy

Question 8

advantages of DMARDs

Answer 8

• slow disease progression by interfering w/ inflammatory process
• decrease pain (analgesics still often required)

Question 9

possible DMARD combinations

Answer 9

• methotrexate combined with any of these:
• sulfasalazine + hydroxychloroquine
• cyclosporine
• leflunomide

Question 10

unmet needs in RA therapy

Answer 10

• maintaining an acceptable safety profile
• controlling disease activity in a large proportion of Pts (diff DMARDs will work differently for diff ppl b/c diff MOA)

Question 11

which inflammatory cytokines are relevant in RA?

Answer 11

• TNF-a
• IL-1B

Question 12

2 examples of biologic agents (new DMARDs)

Answer 12

• infliximab: TNF-a inhibitor - suppression of downstream cytokines
• rituximab: B-cell inhibitor

Question 13

what is gout and when does it require Tx?

Answer 13

• hyperuricaemia: overproduction or impaired removal of uric acid crystals, causing intermittent arthritis when they deposit in synovium
• no Tx required unless symptoms evident e.g. obesity, diabetes, HTN

Question 14

3 drugs used to treat gout + their functions

Answer 14

• allopurinol (competitive xanthine oxidase inhibitor = inhibit uric acid synthesis - CHRONIC GOUT)
• probenecid (inhibit reabsorption @ PCT to increase uric acid excretion)
• colchicine (bind to microtubules to inhibit migration of leukocytes into joint, but doesn’t actually decrease WBC = decrease swelling - ACUTE GOUT)

Question 15

OA vs RA

Answer 15

• RA (autoimmune - chronic inflammation of synovium): morning stiffness for 1 hr or more, pain improves w/ activity but returns @ rest. Due to low levels of cortisol @ night
• OA (repeated movements degrade articular cartilage): morning stiffness for 30 mins or less, pain after activity but better @ rest, crepitus