<s>[INST] context: ESSENTIAL of medical PHARMACOLOGY SEVENTH EDITION KD TRIPATHI Page:215 URICOSURIC DRUGS Probenecid It is highly tipid-soluble organic acid developed In 1951 to inhibit renal tubular secretion of Penicillin so that its duration of action could be Prolon ged. It competitively blocks active transpo Organic acids by OATP at all sites; that in renal Tubules being the mostprominent. This transpo bidirectional: net effect depends on whether secretion or reabsorption of the paicular organic acid is quantitatively more impoant, e.g.: (a) Penicillin is predominantly secreted by the proximal tubules, its reabsorption is minimal. Net effect of probenecid is intLibition of excretion; more sustained blood levels are achieved. (b) Uric acid is largely reabsorbed by active transpo, while less of it is secreted; only I / 10th of filtered load is excreted in urine. Probenecid, therefore, promotes its excretion and reduces its blood level. Probenecid does nothave any other significant pharmacological action; it is neither analgesic nor antiinflammatory. lnteractions 1. In addition to penicillins, probenecid inhibits the urinary excretion of cephalosporins, sulfona- mides, Mtx and indomethacin. 2. It inhibits biliary excretion of rifampicin. Pyrazinamide and ethambutol may interfere with uricosuric action of probenecid. 3. Probenecid inhibits tubular secretion of nitrofurantoin which may not attain antibacterial concentration in urine. 4. Salicylates block uricosuric action of pro- benecid. Pharmacokinetics Probenecid is completely absorbed orally; 90% plasma protein bound: paly conjugated in liver and excreted by the kidney; plasma tT/z is 8-10 hours. Adverse effects Probenecid is generally well tolerated. Dispepsia is the most common side effect (upto 25% incidence with high doses). It should be used cautiously in peptic ulcer patients. Rashes and other hypersensitivity phenomena are rare. Toxic doses cause convulsions and respiratory failure. Uses :chronic gout and hyperurecimia To prolong ampicillin and penicillin action [/INST] question: Drug not causing hyperuricemia: | options: A: Probenecid B: Thiazide C: Pyrazinamide D: Ethambutol | answer: A </s>