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It has received clinical trial Post Date: Sun, 12 Oct 2008 12:12:49 +0000 OTHER DRUGS.Chlorpropamide, an oral hypoglycemic agent, has been reported to impair free-water excretion, and a number of cases of hyponatremia and water intoxi-cation have resulted from its use (Weissman et al, 1971). It has received clinical trial in diabetes in-sipidus. Autor of the post: Undefined Hypoglycemia is observed in some Post Date: Sun, 12 Oct 2008 11:53:18 +0000 Webster and Bain (1970) reported an aver-age reduction in urine volume of 70%, with urine becoming hypertonic during periods of low fluid intake. Inhibition of the antidiuretic effect by ethyl alcohol suggests enhancement of the deficient ADH formation or release, although it has been shown experimentally that the drug may also directly po-tentiate the renal response to ADH. Hypoglycemia is observed in some patients. Autor of the post: Undefined Two antineoplastic agents, vincristine and Post Date: Sun, 12 Oct 2008 11:43:06 +0000 The hypolipemic agent clofibrate appears to exert a similar effect in pituitary diabetes insipidus without the accompanying risk of hypoglycemia. For details, see Hays and Levine (1974).Two antineoplastic agents, vincristine and, in high doses, cyclophosphamide, have been reported to have caused hyponatremia with all the clinical features of inappropriate ADH secretion (Cutting, 1971; DeFronzo et al, 1973). Autor of the post: Undefined The observation that lithium therapy Post Date: Sun, 12 Oct 2008 11:24:14 +0000 ADH ANTAGONISTSAlthough many congeners of ADH have been synthesized, none has the property of blocking the actions of ADH. Such a compound would be useful in the treatment of the syndrome of inappropriate secretion of antidiuretic hormone. The observation that lithium therapy in manic patients is associated with a high incidence of nephrogenic diabetes in-sipidus has lead to studies on its mechanism of action and possible therapeutic application. Autor of the post: Undefined ) Although the ubiq-uitous actions Post Date: Sun, 12 Oct 2008 11:12:25 +0000 Presum-ably the ion interferes in the sequence of events by which ADH increases the permeability of the col-lecting tubule to water and urea. (See page 793 for further details and references.) Although the ubiq-uitous actions of lithium make it far from an ideal antagonist of ADH, convincing evidence of its clini-cal efficacy in this distressing syndrome would cer-tainly stimulate efforts to find a more selective agent to overcome the effects of an inappropriately high concentration of ADH in the circulation. Autor of the post: Undefined Many substances are now known Post Date: Sun, 12 Oct 2008 11:01:20 +0000 The previous chapters have considered those renal tubular functions related to the reabsorption and excretion of electrolytes and water. Of no less importance are the renal tubular transport systems concerned with the reabsorption and secretion of or-ganic compounds. Many substances are now known to influence the function of these sys-tems, usually by inhibition of transport. Autor of the post: Undefined Such inhibitors, if suffi-ciently selective Post Date: Sun, 12 Oct 2008 10:43:59 +0000 An inhibitor capable of retarding the active tu-bular reabsorption of an organic compound augments the renal excretion of that com-pound. Conversely, an inhibitor capable of depressing the active tubular secretion of a compound retards the urinary excretion of that compound. Such inhibitors, if suffi-ciently selective in action, can have useful applications as drugs. Autor of the post: Undefined Physiological Considerations Post Date: Sun, 12 Oct 2008 10:27:50 +0000 A number of organic acids and bases have been shown to undergo bidirectional active transport, and many are also subject to passive reabsorption that is influenced principally by the pKa and lipid solubility of the substance and by urine pH and flow rate (see introduction to Section VIII). The effective use of the inhibitors to be described depends on a clear under-standing of these complex variables.Physiological Considerations. Autor of the post: Undefined However, the concept that secretion Post Date: Sun, 12 Oct 2008 10:08:31 +0000 In connection with his classical morphological description of the kidney, Bowman speculated that the function of the renal tubular epithelium was the secretion of solutes found in urine. In 1874, 32 years later, Heidenhain carried out experiments that clearly pointed to the tubular secretion of indigo carmine, an organic acid dye. However, the concept that secretion was among the normal functions of the kidney, which was rejected by Ludwig in 1844 and later by Cushny in 1917, remained unpopular. Autor of the post: Undefined Marshall, Jr Post Date: Sun, 12 Oct 2008 9:52:31 +0000 This attitude prevailed when, in 1910, the rate of excretion of phenolsulfonphthal-ein (PSP) was first used, empirically, for the clinical evaluation of renal function. The great rapidity with which the kidney excreted PSP prompted a critical investigation in the laboratory of E. 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