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POTASSIUM-SPARING DIURETICSDuring the last several decades Post Date: Tue, 14 Oct 2008 14:04:41 +0000 In edematous patients with advanced renal insuffi-ciency, aldosterone antagonists may induce signifi-cant hyperkalemia even if administered concurrently with a thiazide.Competitive aldosterone antagonists, as well as potassium-retaining agents, are also useful in boththe diagnosis and the management of those rare metabolic and renal diseases associated with hypo-kalemia and potassium depletion {see Liddle, 1966).POTASSIUM-SPARING DIURETICSDuring the last several decades, the intro-duction of new natriuretic agents has been accompanied by parallel studies on the se-cretion of potassium. Autor of the post: Undefined TRIAMTERENEChemistry Post Date: Tue, 14 Oct 2008 13:46:36 +0000 These have established (1) that potassium excretion is achieved by distal tubular secretion, (2) that excessive potassium losses may constitute an unfavorable consequence of diuretic action, (3) that the excretion of potassium can be influenced by steroids with mineralocorticoid activity, and (4) that the loss of potassium may also be influenced by drugs that act directly on the distal nephron independently of adrenal steroids. While it is true that triamterene and amiloride possess moderate natriuretic activity, nevertheless their major importance lies in their effect on potassium excretion (Baer and Beyer, 1972).TRIAMTERENEChemistry. Autor of the post: Undefined In another series of pteridine Post Date: Tue, 14 Oct 2008 13:33:18 +0000 Triamterene has the following struc-tural formula: TriamtereneIt is a pteridine compound, related chemically to folic acid. The diuretic activity of closely related homologs of triamterene has been examined, but no specific structural requirements have been estab-lished (Maass and Wiebelhaus, 1967). In another series of pteridine compounds, it is possible to dem-onstrate natriuretic activity with agents that have no potassium-retaining action (Rosenthale and Osdene, 1966). Autor of the post: Undefined Triamterene is relatively insoluble in water Post Date: Tue, 14 Oct 2008 13:22:04 +0000 Triamterene is a weak competitive inhibitor of folic acid in vitro, but it has no significant antifolic activity in vivo (Maass et al, 1967).Absorption, Distribution, and Excretion.Triamterene is relatively insoluble in water and is administered only by the oral route. Autor of the post: Undefined It is probable Post Date: Tue, 14 Oct 2008 13:11:26 +0000 It is rapidly absorbed from the gastrointestinal tract and is then excreted in the urine, with a peak in renal excretion within 1 to 2 hours after oral ingestion. From 10 to 88%of the oral dose can be recovered from the urine within 24 hours. It is probable that this wide range of values is a reflection of variable intestinal absorption. Autor of the post: Undefined Mechanism of Diuretic Action Post Date: Tue, 14 Oct 2008 12:55:16 +0000 In the plasma, triamterene is about two-thirds bound to protein. Renal excretion is accomplished both by filtration and tubular secretion (Lassen and Nielsen, 1963).Mechanism of Diuretic Action. Autor of the post: Undefined Compared to acetazolamide, this latter Post Date: Tue, 14 Oct 2008 12:39:41 +0000 Triamter-ene has no significant pharmacological actions other than those on the kidney. As indicated in Table 39-1, diuresis is characterized by an increase in the excretion of sodium, mostly accompanied by chloride as the anion, and under some circumstances by slight alkalinization of the urine. Compared to acetazolamide, this latter effect is quantitatively of little importance as far as extracellular electrolyte balance is concerned. Autor of the post: Undefined Under normal circumstances, diuresis Post Date: Tue, 14 Oct 2008 12:27:58 +0000 Triamterene is not an inhibitor of carbonic anhydrase. The exact mechanisms by which it slightly alkalinizes the urine remain unexplained. Under normal circumstances, diuresis is accompanied either by no increase in potassium excretion or by only a slight increase. Autor of the post: Undefined The action of triamterene Post Date: Tue, 14 Oct 2008 12:15:30 +0000 However, the effect of triamterene on potassium excretion may be greatly modified by pharmacological means, and a sharp re-duction in potassium output is then observed. This is particularly noted when other natriuretic agents are given simultaneously, and when there is an excessive amount of mineralocorticoids, either by pretreatment or by spontaneous production {see Wiebelhaus et al, 1967). The action of triamterene is not significantly altered by alkalosis or acidosis. Autor of the post: Undefined This effect is achieved Post Date: Tue, 14 Oct 2008 12:05:01 +0000 Originally considered a nonsteroidal com-petitive antagonist of aldosterone, triamterene has subsequently been shown to have a natriuretic effect in the adrenalectomized animal that is not significantly different from that in the normal It is presumed, therefore, that the action of triamterene is directly on tubular transport and is independent of aldosterone. The reduced rate of potassium excretion results from an inhibition of the secretion of potassium in the distal nephron. This effect is achieved by a primary reduction in sodium reabsorption, which in turn leads to a drop in the transtubular electrical-potential difference. 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