Drugs for Gout

Question 1

• Indirectly inhibits the inflammatory process by inhibiting granulocyte infiltration
• Treatment for acute and chronic gout
  i. Acute: Reduces frequency of attacks; requires high doses (increasing toxicity (diarrhea); hence, NSAIDs are first line)
  ii. Chronic: Used prophylactically; Used as initiation therapy in conjunction with Allopurinol or Febuxustat to prevent paradoxical acute gouty attacks

Mech: Inhibits microtubule polymerization in granulocytes (neutrophils, eiosinophils, basophils, etc.) → impairs lamellipodia formation, impairing ability of granulocytes form invading the joint

• Reduces lactic acid production by granulocytes
• Inhibits release of proteolytic & inflammatory enzymes by granulocytes
• Decreases leukotriene B4 synthesis by granulocytes
• Does not change renal excretion of uric acid; only affects the inflammatory process

ADME: IV admin for acute; Biliary excretion, with extensive enterohepatic recirculation

Toxicity: GI (esp DIARRHEA, nausea, vomiting, abdominal pain); Leukopenia, aplastic anemia, alopecia
i. Acute poisoning: GI, hemorrhagic gastroenteritis, vascular damage, ascending paralysis, muscular depression, nephrotoxicity

Answer 1

Colchicine

Question 2

• Decreases inflammation
• Treatment of choice for acute gout

Adverse: Indomethacin can cause adverse CNS effect in the elderly; use naproxen or ibuprofen instead)

Answer 2

NSAIDs (Indomethacin)

Question 3

• Xanthine oxidase inhibitor (enzyme that metabolizes purine bases to uric acid) → Inhibits production of uric acid/urate (to reduce uric acid to

Answer 3

Allopurinol

Question 4

• Xanthine oxidase inhibitor → Inhibits production of uric acid/urate
• Treatment for chronic gout
• More effective than allopurinol, esp. in patients with renal impairment (no dose reductions needed)
• Does not cause hypersensitivity reactions

Adverse: increased risk of cardiovascular event (MI, anemia); requires co-admin with Colchicine for 6 months to prevent paradoxical gouty attacks

ADME: oral admin; CYP450 metabolism, followed by conjugation with glucuronic acid

Answer 4

Febuxustat

Question 5

• Uricosuric agent (increases the excretion of uric acid/urate to reduce uric acid to

Answer 5

Probenecid