M. Smith
Sep 1, 1950
Citations
0
Influential Citations
11
Citations
Journal
Journal of Pharmacy and Pharmacology
Abstract
SODIUM SALICYLATE is widely used in the treatment of acute rheumatic fever and usually controls the pain and swelling associated with the disease. It has been emphasised that adequate therapy with the drug demands a high plasma-salicylate level of between 30 and 40 mg. per 100 m1.'S2. Graham and Parker3 demonstrated that plasma-salicylate levels greater than 35 mg. per 100 ml. are associated with the well-known toxic effects of salicylates on (the gastro-intestinal tract and on the special senses. This must be considered one of the serious drawbacks of prolonged salicylate therapy. Normal adults excrete 4 to 8 per cent. of ingested salicylate as gentisic acid4 (2:5dihydroxybenzoic acid) and it has been reported that in patients with acute rheumatic fever this fraction is appreciably increased5. The action of salicylates may be due to formation of gentisate, the latter substance acting as an inhibitor of the enzyme hyaluronidase6. This enzyme depolymerises hyaluronic acid which acts as an interfibrillar cement in the tissues and it has been suggested that there is increased hyaluronidase activity in rheumatic disease'. The sodium salt of gentisic acid has been used in the treatment of rheumatic fever8 and seems to be at least as therapeutically active as sodium salicylate and has the advantage that it produces few, if any, toxic effects even in doses up to 18 g. per dayg. Sodium gentisate may (be administered orally as cachets or tablets or by intramuscular injection. Two independent methods of estimation of the substance in these preparations have been devised. One method is based on the photometric measurement of the (blue colour produced when gentisate reacts with an aqueous solution of the Folin-Ciocal,teu phenol reagent in alkaline solution. The colour production depends on the reduction of hexavalent molybdenum and tungsten in the reagent to coloured products of lower valency. The other method utilises the absorption given (by gentisate in the ultraviolet region. The ultraviolet spectra of aqueous solutions of sodium gentisate show a maximum at 3200A and the optical densities at this wavelength were found to be directly proportional to the concentration of gentisate ion. Gentisic acid has been estimated in urine, after a preliminary extraction with ether, by means of the blue colour it gives with ferric chloridee but this colour is too transient for accurate work. It has also been assayed by the reduction of alkaline cupric solutions, carried out according to the Shaffer-Hartmann method for blood sugar, and by a bromine