Effects of Drugs on Uric Acid in Man

Abstract

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.

The influence of allopurinol on urinary purine loss after repeated sprint exercise in man

“…2). Our inability to measure a decrease in basal urinary uric acid excretion with allopurinol is in contrast to previous research [31]. The increase in basal xanthine excretion confirms the data of Klinenberg et al [34] who reported that approximately half of the increase in basal oxypurine excretion after allopurinol treatment was attributed to xanthine.…”

“…As mentioned above, the metabolic stress is likely to be similar in both trials, and hence, the magnitude of purine base efflux across the sarcolemma is probably the same after exercise. However, consistent with the inhibitory effect of allopurinol [31], the inhibition of xanthine oxidase influenced the mix of the circulating purines and resulted in greater rises in plasma inosine (Fig. 1A) and Hx (Fig.…”

“…2) [17,31]. Sprint exercise increased ( P b .05) plasma inosine, Hx, and uric acid concentrations during recovery in both trials (Fig.…”

De novo synthesis of purine nucleotides in human peripheral blood leukocytes. Excessive activity of the pathway in hypoxanthine-guanine phosphoribosyltransferase deficiency.

“…These conversions have a combined inhibitory effect on the glutamine-PRPP amidotransferase: by consumption of its substrate, PRPP, and by feedback inhibition on this enzyme by the formed ribonucleotides (17). A similar mechanism has been suggested for the purine analogues allopurinol and oxipurinol (18), whereas orotic acid is presumed to decrease purine production by depleting cellular PRPP only (19). Azaserine, an analogue of glutamine, competitively inhibits the glutamine requiring enzymes, glutamine-PRPP amidotransferase and phosphoribosyl-formylglycineamidine synthetase, which catalyze the first and fourth reactions, respectively, in the de novo purine synthesis pathways (20).…”

Management of Hyperuricemia and Gout

“…Allopurinol is a competitive inhibitor of xanthine oxidase since its structure is almost identical to the natural substrate of this enzyme, hypoxanthine [ 620 ] . Allopurinol is a much more potent inhibitor of xanthine oxidase activity ( fi veto ten-fold) than oxypurinol in vitro, but this mechanism may not be operative in vivo since oxypurinol appears to be the major xanthine oxidase inhibitor on the basis of its prolonged halflife (>25 h) [ 621 ] . In addition to the decrease in uric acid synthesis via the xanthine oxidase pathway, these hypouricemic agents also inhibit de novo purine biosynthesis presumably as a result of a combination of feedback inhibition by adenine and guanine nucleotides on the fi rst irreversible step in de novo purine biosynthesis (phosphoribosylpyrophosphate amidotransferase) and the depletion of its substrate phosphoribosylpyrophosphate (PRPP) [622][623][624] .…”