View source for Uricosuric Agent

==General==
*Indications: Chronic [[Gout]] (prevention), Hyperuricemia, Adjunct to antibiotic therapy (specific agents only)
*Mechanism: Increases renal excretion of uric acid
*Common Agents:
{{#ask:[[Is DrugClass::Uricosuric Agent]] |format=ul }}

*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  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 Stone]]
*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)

==References==
<references/>

[[Category:Pharmacology]] [[Category:Rheumatology]] [[Category:Renal]]