Furosemide potency

Kirchner KA, Voelker JR, Brater DC. Binding inhibitors restore furosemide potency in tubule fluid containing albumin. Kidney Int 1991 40 418-424. 

Thiazide diuretics are not the drugs of choice in patients with renal insufficiency. In this situation, the loop diuretics furosemide and bumetanide are recommended they have greater intrinsic natriuretic potency than do the thiazides and do not depress renal blood flow. 

The most commonly used loop diuretics are furosemide. bumetanide, and erhacrynic acid. Newer agents available in some countries include torasemide and pirelanide. The potency ratio for furosemide ethacrymc acid torasemide pirelanide bumelanide is 1 1 2 4 40. 

Pathophysiology Non-potassium-sparing diuretics are the treatment of choice to reduce fluid retention and dyspnea. Acting at specific sites of nephrons, they inhibit sodium and water reabsorption. Loop diuretics act on the loop of Henle, producing a maximal diuretic effect equivalent to 20% to 25% of the filtered sodium load and promoting the free water clearance. Currently available loop diuretics include furosemide, bumetanide, torsemide, and ethacrynic acid. Because of their potency, they are generally effective in patients with advanced renal insufficiency (glomerular filtration rates <25 ml/min) (49). 

Wollam GL, Tarazi RC, Bravo EL, Dustan HP. Diuretic potency of combined hydrochlorothiazide and furosemide therapy in patients with azotemia. Am J Med 1982 72(6) 929-38. 

Piretanide is a close relative of furosemide, with diuretic and kinetic properties very similar to those of furosemide and bumetanide (1,2). Its potency lies somewhere between the two. As with some other diuretics, attempts have been made to show specific advantages for piretanide, for example that it is a potassium-stable diuretic. However, there is no good evidence that it has such advantages (SEDA-10,188) (SEDA-15, 213). 

Preliminary communications have described the diuretic activity of the 6-pteridinecarboxamide Wy-5256 (X, R =05115, R = r3 = 2-methoxy-ethyl). The renal pharmacology of Wy-5256,39 and the synthesis and structure-activity relationships of a series of 6-pteridinecarboxamides (x) including Wy-5256,nov have been published in detail. Wy-5256 has about the same diuretic potency as hydrochlorothiazide in rats and dogs. It probably acts directly on the renal tubule to promote the excretion of nearly equal amounts of sodium and chloride along with some potassium. It is interesting to note that Wy-5256, like furosemide and ethacrynic acid, produces an increase in total renal blood flow, Studies on the pteridinecarboxamides (x) have shown that R must be... 

Bumetanide is the most potent of the three, with five times the potency of torsemide. Torsemide, in turn, has 2 to 4 times the potency of furosemide. 

Bumetanide and torsemide both block chloride channels, to varying degrees. This results in a decrease in sodium and chloride reabsorption, and increased diuretic potency, as compared to furosemide, which does not appear to block chloride channels. 

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