Uricosuric Agent

General

• Type: Uricosuric Agent
• Indications: Chronic Gout (prevention), Hyperuricemia, Adjunct to antibiotic therapy (specific agents only)
• Mechanism: Increases renal excretion of uric acid
• Common Agents:
  • Probenecid (Prototype)
  • Sulfinpyrazone
  • Benzbromarone (Not available in all regions)
• Secondary Agents (Off-label/Minor effect):
  • Losartan
  • Fenofibrate
  • Atorvastatin

Emergency Medicine Clinical Pearls

• Acute Gout Flares: Do NOT initiate uricosuric agents during an acute gout attack; mobilizing urate stores can worsen or prolong the flare.
• Complications: The rapid increase in urinary uric acid can precipitate Nephrolithiasis (Uric Acid Stones). Patients must maintain high fluid intake (2-3L/day).
• ASA Interaction: Salicylates (like Aspirin) antagonize the uricosuric action of these drugs.
• Biphasic Effect: Sub-therapeutic doses may inhibit tubular secretion without inhibiting reabsorption, paradoxically increasing serum uric acid levels.

Pharmacology

Mechanism of Action

• Acting primarily at the Proximal Convoluted Tubule (PCT) of the kidney.
• Inhibits URAT1 (Urate Transporter 1) and OAT4 (Organic Anion Transporter 4) on the apical membrane.
• Blocks the active reabsorption of uric acid from the urine back into the blood, resulting in a net increase in uric acid excretion.

Pharmacokinetics

• Absorption: generally well-absorbed orally.
• Protein Binding: High (85-95%).
• Metabolism: Hepatic.
• Excretion: Renal/Biliary.

Adverse Reactions

Acute

• Nausea and Vomiting (GI intolerance is common)
• Rash / Hypersensitivity
• Nephrolithiasis (Renal Colic) due to uricosuria
• Paradoxical precipitation of acute Gout arthritis

Serious

• Nephrotic Syndrome
• Hepatic Necrosis (rare, associated with Benzbromarone)
• Bone Marrow Suppression / Aplastic Anemia
• Hemolytic Anemia (in patients with G6PD Deficiency)

Contraindications

Absolute

• History of Uric Acid Kidney Stones
• Hypersensitivity to the specific agent
• Children < 2 years (specifically Probenecid)
• High-grade renal insufficiency (CrCl < 30 mL/min) – drugs rely on renal flow to work effectively

Relative

• Acute Gout Attack (wait until attack resolves before initiating)
• Peptic Ulcer Disease (specifically Sulfinpyrazone)
• Concomitant use with drugs dependent on renal excretion (see Interactions)

Drug Interactions

• Note: This class (especially Probenecid) is notorious for inhibiting the renal excretion of other organic acids.
• Increased Toxicity Risk:
  • Methotrexate (can be fatal)
  • Ketorolac and other NSAIDs
  • Penicillin / Cephalosporins (often used therapeutically to boost levels, but can lead to toxicity if unplanned)
  • Sulfonylureas (Risk of Hypoglycemia)
• Decreased Efficacy:
  • Salicylates (Aspirin) > 325mg/day block the uricosuric effect.

See Also

• Gout
• Probenecid
• Nephrolithiasis
• Hyperuricemia
• Allopurinol (Xanthine Oxidase Inhibitor - distinct class)