Pharmacotherapy of Gout & Hyperuricemia

Pharmacotherapy of Gout & Hyperuricemia

1. Definition, epidemiology & disease overview

• Gout is a metabolic disorder characterized by recurrent episodes of acute arthritis caused by deposition of monosodium urate (MSU) crystals in joints and cartilage, with uric-acid renal calculi, tophi, and interstitial nephritis as additional manifestations (Katzung 16e Ch.36, p.695).
• It results from precipitation of urate crystals in tissues and the subsequent inflammatory response; acute gout typically causes painful distal monoarthritis and can lead to joint destruction, subcutaneous tophi, renal calculi and renal damage (G&G 14e Ch.42, p.847).
• Hyperuricaemia is the biochemical prerequisite — normal plasma urate ~5 mg/dL (≈0.3 mM) in G&G; KDT quotes normal plasma urate 2–6 mg/dL. Urate at these levels already approaches the limit of solubility (G&G 14e Ch.42, p.847; KDT 8e Ch.15, p.230).
• Hyperuricaemia is necessary but not sufficient — it does not inevitably lead to gout; most individuals with hyperuricaemia never develop a clinical urate-crystal event (G&G 14e Ch.42, p.847; Katzung 16e Ch.36, p.695).
• Gout affects ~3% of the adult population of Western countries (G&G 14e Ch.42, p.847).
• Risk factors: male sex, diuretic use, alcohol intake, obesity, hypertension, and consumption of sweetened beverages, red meat and certain seafood (G&G 14e Ch.42, p.847).
• Adverse cardiovascular outcomes are increasingly recognised as associated with gout (Katzung 16e Ch.36, p.695).