Wolff: Gout

Question 1

What are the 3 recommended potent NSAIDs for treating acute gout and the selectivity of each?

Answer 1

• Naproxen (non-selective)
• Indomethacin (COX 1 > COX 2)
• Celecoxib (COX-2, high dose, if others not tolerated)

Question 2

Using NSAIDs for acute gout is most effective if treatment is initiated when?

Answer 2

≤48 hours of onset

Question 3

If NSAIDs and colchicine are contraindicated, which drugs can be used for acute gout?

Answer 3

Glucocorticoids (betamethasone + methylprednisone + triamcinolone)

Question 4

What is the MOA of Colchicine used for gout?

Answer 4

• Diffuses into cells to bind to tubulin, blocks formation of microtubules
• Leads to inhibition of leukocyte migration and phagocytosis

Question 5

What are the clinical indications for using Colchicine for gout?

Answer 5

• Used in pt’s with NSAID intolerance or absolute contraindication to NSAIDs

Question 6

Use of Colchicine for gout is contraindicated in whom?

Answer 6

Pt’s w/ advanced renal or hepatic impairment

Question 7

If pt with gout is an underexcreter with good GFR and no tophi or stones, which drugs can be used?

Answer 7

Urate lowering therapy w/ allopurinol, febuxostat or uricosuric agent

Question 8

What is the MOA of Allopurinol?

Answer 8

• Metabolite acts as competitive inhibitor of xanthine oxidase
• W/o conversion to urate, hypoxanthine and xanthine are excreted

Question 9

What is a noteworthy serious AE of Allopurinol?

Answer 9

Stevens-Johnson Syndrome (epidermal necrolysis) –> ↑ risk if HLA-B*5801

Question 10

What is the MOA of Febuxostat used for gout?

Answer 10

• Non-purine inhibitor of xanthine oxidase –> blocks conversion to urate
• Hypoxanthine and xanthine are excreted

Question 11

What is the clinical indication for using Febuxostat for gout?

Answer 11

Typically well-tolerated by those who cannot tolerate allopurinol

…but it is expensive

Question 12

What is the MOA of the gout drug, Pegloticase?

Answer 12

• Recombinant mammalian uricase, covalently attached to methoxy polyethylene glycol –> prolongs ciruclating half-life and diminished immunogenic response
• Converts uric acid to the far more soluble allantoin

Question 13

What is the clinical indication for using Pegloticase?

Answer 13

Tx of chronic gout in those refractory to conventional therapy

Question 14

Which AE’s are associated with Pegloticase and how can they be managed?

Answer 14

• Infusion rxns i.e., fever, chills, rash, angioedema, bronchospasm, hypo- or HTN
• Need to premedicate w/ glucocorticoids and anti-histamines

Question 15

What is the MOA of Probenecid and Sulfinpyrazone used for gout?

Answer 15

• Organic acid that acts at anionic transport sites of renal tubule in manner that blocks urate reabsorption more than urate secretion
• ↑ the fractional excretion of urate –> ↓ plasma [urate]

Question 16

What is the clinical inidication for using Probenecid for gout?

Answer 16

• Used in underexcreters w/ GFR >60 mL/min and no stones to ↓ body pool of urate in pt’s with:
• Hyperuricemia
• Frequent attacks
• Tophi (?)… some say OK, others say no

Question 17

Why is low-dose aspirin not a good choice for gout?

Answer 17

Aspirin promotes urate reabsorption

Question 18

What are some of the AE’s associated with Probenecid and Sulfinpyrazone used for gout; strategies for minimizing these effects?

Answer 18

• Acutely ↑ risk of kidney stones (both uric acid and calcium oxalate) –> minimize by keeping well-hydrated and urine pH >6
• May cause gouty arthritis flare
• Sulfur-containing drug, may cause hypersensitivity