Uricosuric agent: Difference between revisions
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==Emergency Medicine Clinical Pearls== | ==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. | *'''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== | ==Pharmacology== | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
*Acting primarily at the Proximal Convoluted Tubule of the kidney. | *Acting primarily at the Proximal Convoluted Tubule of the kidney. | ||
*Inhibits | *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. | *Blocks the active reabsorption of uric acid from the urine back into the blood, resulting in a net increase in uric acid excretion. | ||
===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
* | *Absorption: generally well-absorbed orally. | ||
* | *Protein Binding: High (85-95%). | ||
* | *Metabolism: Hepatic. | ||
* | *Excretion: Renal/Biliary. | ||
==Adverse Reactions== | ==Adverse Reactions== | ||
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==Drug Interactions== | ==Drug Interactions== | ||
*''Note: This class (especially Probenecid) is notorious for inhibiting the renal excretion of other organic acids.'' | *''Note: This class (especially Probenecid) is notorious for inhibiting the renal excretion of other organic acids.'' | ||
* | *Increased Toxicity Risk: | ||
**[[Methotrexate]] (can be fatal) | **[[Methotrexate]] (can be fatal) | ||
**[[Ketorolac]] and other NSAIDs | **[[Ketorolac]] and other NSAIDs | ||
**[[Penicillin]] / [[Cephalosporins]] (often used therapeutically to boost levels, but can lead to toxicity if unplanned) | **[[Penicillin]] / [[Cephalosporins]] (often used therapeutically to boost levels, but can lead to toxicity if unplanned) | ||
**Sulfonylureas (Risk of [[Hypoglycemia]]) | **Sulfonylureas (Risk of [[Hypoglycemia]]) | ||
* | *Decreased Efficacy: | ||
**Salicylates (Aspirin) > 325mg/day block the uricosuric effect. | **Salicylates (Aspirin) > 325mg/day block the uricosuric effect. | ||
Latest revision as of 09:15, 22 March 2026
General
- Indications: Chronic Gout (prevention), Hyperuricemia, Adjunct to antibiotic therapy (specific agents only)
- Mechanism: Increases renal excretion of uric acid
- Common Agents:
- Secondary Agents (Off-label/Minor effect):
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)