Pharmacology of uricosuric drugs.

When the level of uric acid, primarily in the form of monosodium urate (Wilcox, Khalaf, Weinberger, Kippen, and Klinenberg, 1972), exceeds the point of maximum solubility, crystals of monosodium urate may then form, particularly in the joints and connective tissues. These crystals initiate attacks of acute gout (Buchanan, Klinenberg, and Seegmiller, 1965; Seegmiller, 1965; Weissmann, 1971), and tophaceous deposits may occur if the hyperuricaemia is allowed to persist. While the drugs colchicine and phenylbutazone are useful in treating the acute attack of gout owing to theiranti-inflammatory activity (Smyth, 1972), the most effective approach to the long-term treatment of hyperuricaemia involves reducing the urate level so that the gouty attacks gradually cease and the deposits of urate formed during the hyperuricaemic periods are gradually resorbed. Urate levels can be lowered by decreasing the rate of production of urate or increasing its rate of elimination. With respect to the first alternative, the drug allopurinol, which blocks the conversion of hypoxanthine and xanthine to uric acid, is now in widespread use either by itself or in combination with one of the uricosurics (Klinenberg, Goldfinger, and Seegmiller, 1965; Scott, Hall, and Grahame, 1966). However, the most common method of reducing urate levels is to use drugs which increase the rate of elimination of urate by the kidneys. The long and fascinating history of the development of uricosuric agents has been reviewed in detail by Gutman (1966).