Reversal of Thiazide-Induced Transient Hyperuricemia by Uricosuric Agents

Smilo, Renata P.; Beisel, William R.Lieutenant Colonel; Forsham, Peter H.

doi:10.1056/nejm196212132672403

Cited by 21 publications

(6 citation statements)

References 18 publications

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“…Indeed, the natriuretic effect of mercurials in chickens (26) and of furosemide in mongrel dogs (27) is markedly reduced by the administration of probenecid. Although this possibility has not been examined extensively in man, zoxazolamine (28) and probenecid (29) are said have no effect on the natriuretic effect of the chlorothiazides in man.…”

Section: Diureticsmentioning

confidence: 99%

Effects of Drugs on Uric Acid in Man

Kelley¹

1975

Annu. Rev. Pharmacol.

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In this review the drugs capable of increasing or lowering the serum urate concentration are considered with regard to mechanism of action and significance of the effect, where known. Several hypouricemic agents, probenecid, sulfinpyrazone, and allopurinol, are considered in further detail because of their major clinical importance. No effort has been made, however, to summarize the relative clinical indications for each agent. In addition, in those cases where specific details could not be included because of limitation of space, the appropiate reference has been given.

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Section: Diureticsmentioning

confidence: 99%

Effects of Drugs on Uric Acid in Man

Kelley¹

1975

Annu. Rev. Pharmacol.

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“…If diuretic-induced hyperuricemia is due partially to diminished net urate secretion (24), the uricosuric response to probenecid might be subnormal in that condition. Although previous data have suggested that probenecid is effective at ameliorating chronic diuretic-inducing hyperuricemia, no comparisons of uricosuric responses in normals and hyperuricemic patients were made (31).…”

Section: Resultsmentioning

confidence: 99%

Origins of the Uricosuric Response

Steele¹,

Boner²

1973

J. Clin. Invest.

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A BaS T R A C T The acute effects of intravenous (i.v.) probenecid and chlorothiazide on renal urate handling were investigated in paired studies in normal men. Uricosuric responses to these agents were compared in the same subjects, both without and with pyrazinamide (PZA) pretreatment. Assuming that PZA selectively inhibits the tubular secretion of urate and that uricosuric agents act by increasing the excretion of filtered urate, then the uricosuric responses (the increment in urate excretion or clearance) should have been unaffected by PZA. Defined in this manner, however, uricosuric responses to probenecid and chlorothiazide were significantly decreased after PZA pretreatment. In order to determine whether PZA diminished other renal actions of chlorothiazide, changes in sodium and inorganic phosphorus excretion were examined. Chlorothiazide produced equivalent natriuretic and phosphaturic responses after PZA pretreatment, indicating that PZA does not interfere with at least some of the renal actions of chlorothiazide. In separate studies, PZA depressed urate excretion by at least 68% during the maintenance of chlorothiazide-induced natriuresis and phosphaturia, suggesting that chlorothiazide does not diminish the antisecretory action of PZA.The results suggest that probenecid and chlorothiazide may derive their uricosuric properties by facilitating the excretion of both filtered and secreted urate. Possibly, increased excretion of secreted urate might occur through modulation of urate reabsorption at a site distal to tubular secretion, rather than by the direct acceleration of secretory transport. However, PZA-induced interference with the actions of probenecid and chlorothiazide on renal urate transport mechanisms cannot be excluded as a possible explanation for the present results. INTRODUCTIONThe mechanism of action of uricosuric agents has been a matter of considerable theoretical and practical interest,

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“…With prolonged oral administration, the associated hyperuricemia may signify more than just decreased renal clearance of urate; it may be the result of thiazide influence on the synthesis of purine nucleotides and hence not be entirely due to action on the renal tubules. Uricosuric agents (5, 6) reverse the thiazide effect. Acute gouty episodes have been reported (5, 7, 8).…”

Section: Newer Diureticsmentioning

confidence: 99%