- Uricosuric agents act directly on renal tubule → increased uric acid renal excretion;
- They can also alter plasma binding, distribution & renal excretion of other organic acids;
- Uric acid in man generally demonstrates net reabsorption in most instances with about 10% of filtered uric acid being excreted, although net secretion is possible;
- This net reabsorption is via an inhibitable specific transporter which allows luminal uric acid to be exchanged with cellular anions (incl. PAH); The uric acid then exits cell via a different transporter on basolateral membrane not involving PAH;
- Uricosuric agents when present in lumen, compete with urate for the brush border transporter, thus decreased urate reabsorption;
- Probenecid also inhibits a specific PAH transporter on basolateral memb. → decreased i/cell. PAH & thus causing decreased PAH secretion;
- Biphasic effects on urate excretion are usually present depending on the concentration of the uricosuric agent.
- Low doses usually cause decreased excretion presumably due to extreme sensitivity of urate secretion transporter to these drugs at the lower dose → decreased secretion & no effect on reabsorption;
- Higher doses usually increased excretion as inhibition of reabsorption » inhibition of secretion;
Interactions between uricosuric agents:
- one drug may decrease tub. secret. of another drug → decreased luminal  → decreased inhibition of urate reabsorption.
- inhibition of urate secretion by one drug may counter the inhibition of reabsorption by another;
- high doses of vitamin C supplementation
uricosurics.txt · Last modified: 2023/07/20 11:40 by gary1