Drugs Used in Gout and Hyperuricemia

Gout Basics & Acute Flare Fighters - Crystal Crisis Crew

Hyperuricemia (↑urate production / ↓excretion) → Monosodium Urate (MSU) crystal deposition in joints → inflammation.

• Acute Attack Drugs: Target inflammation & pain.
  • NSAIDs: (e.g., Indomethacin, Naproxen)
    • MOA: Inhibit COX → ↓prostaglandin synthesis.
    • AEs: GI upset (PUD), renal toxicity, CV risk. Use with caution.
  • Colchicine:
    • MOA: Inhibits tubulin polymerization → ↓neutrophil migration & activity.
    • Dose: Acute: 1.2mg stat, then 0.6mg 1hr later (max 1.8mg/24h). Prophylaxis: 0.6mg OD/BD.
    • AEs: Diarrhea (most common!), N/V. 📌 Mnemonic: "Colchicine: Can't Continue (Diarrhea)". Myelosuppression (rare, high dose).
    • Interactions: CYP3A4/P-gp inhibitors (e.g., clarithromycin, cyclosporine) → ↑toxicity.
  • Corticosteroids: (e.g., Prednisolone oral, Triamcinolone intra-articular/IM)
    • Use if NSAIDs/Colchicine C/I, severe/refractory attacks. Potent anti-inflammatory.

⭐ Exam Favourite: Colchicine's primary mechanism involves binding to tubulin, preventing its polymerization into microtubules. This impairs multiple inflammatory cell functions, including neutrophil chemotaxis and inflammasome activation.

Xanthine Oxidase Blockers - Purine Pathway Patrol

XOIs reduce uric acid production, cornerstone for CHRONIC gout management.

📌 Remember: Allopurinol for All, but Febuxostat if Failing or Forbidden (Allopurinol).

Urate Excretion & Enzyme Elixir - Flushing Foes

Uricosuric Agents: ↑ Urate Outflow

• MOA: Inhibit URAT1 (proximal tubule) → ↑ uric acid excretion.
• Probenecid:
  • Use: Gout.
  • AEs: GI upset, rash, stones (hydrate!).
  • Contra: Urolithiasis, CrCl <50 mL/min.
  • DIs: ↑ Penicillin, ↑ Methotrexate.
• Benzbromarone: Potent. Hepatotoxicity risk.
• Lesinurad: With XOI. URAT1 inhibitor. AEs: ↑SCr.

Uricase Agents (Enzyme Elixir): Urate Breakdown

• MOA: Convert uric acid → allantoin (soluble).
• Pegloticase:
  • Use: Refractory chronic gout. IV.
  • AEs: Infusion reactions, anaphylaxis (BBW), gout flares.
  • ⭐ > Pegloticase is contraindicated in G6PD deficiency due to risk of hemolysis and methemoglobinemia.
• Rasburicase:
  • Use: Tumor Lysis Syndrome.
  • AEs: Similar; methemoglobinemia, hemolysis (G6PD def.).

Gout Management Strategy - Long-Term Lockdown

• Overall Goal: Serum Urate (sUA) target <6 mg/dL (or <5 mg/dL for tophaceous gout).
• Initiate Urate-Lowering Therapy (ULT) if:
  • ≥2 gout flares/year
  • Presence of tophi
  • History of urate kidney stones
  • CKD stage ≥2 with hyperuricemia
• Prophylaxis during ULT Initiation:
  • Co-administer colchicine or NSAIDs for 3-6 months to prevent paradoxical gout flares.
• Lifestyle Modifications:
  • Limit purine-rich foods (e.g., red meat, seafood), alcohol, sugary drinks.
  • Encourage weight loss and adequate hydration.
• Management in Special Populations:
  • CKD: Dose adjustments needed; Allopurinol/Febuxostat preferred (monitor closely).
  • Tumor Lysis Syndrome (TLS): Prophylaxis with hydration, Allopurinol or Rasburicase.
• Monitoring: Regular sUA levels, monitor for adverse events (AEs).

⭐ The 'start low, go slow' principle for Allopurinol dosing is crucial to minimize hypersensitivity risk.

High‑Yield Points - ⚡ Biggest Takeaways

• Acute gout is managed with NSAIDs, colchicine, or corticosteroids.
• Allopurinol and febuxostat are xanthine oxidase inhibitors for chronic gout.
• Probenecid, a uricosuric, increases uric acid excretion; risk of renal stones.
• Colchicine inhibits microtubule polymerization; diarrhea is a key side effect.
• Allopurinol hypersensitivity (SJS/TEN) is associated with HLA-B*5801.
• Pegloticase is a recombinant uricase for severe refractory gout.
• Initiate urate-lowering therapy (ULT) with prophylactic colchicine/NSAID to prevent flares.