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The actions of the thiazides Post Date: Sun, 12 Oct 2008 14:52:44 +0000 Other potent natri-uretic agents, such as ethacrynic acid, have also been successfully employed (Brown et at, 1966). The chemistry, pharmacology, available preparations, and usual therapeutic applications of these natriuretic agents are discussed in Chapter 39.The actions of the thiazides in diabetes insipidus differ from those of ADH in two important ways. Autor of the post: Undefined However, the change Post Date: Sun, 12 Oct 2008 14:42:41 +0000 First, they are effective in diabetes insipidus of nephrogenic as well as pituitary origin. Second, a negative free-water clearance is rarely induced by these agents alone. However, the change from a copious polyuria to the excretion of a smaller volume of urine can reduce or eliminate the handicap of the patient in the pursuit of daily activities. Autor of the post: Undefined Most investigators agree thatthe natriuretic Post Date: Sun, 12 Oct 2008 14:24:31 +0000 In infants with diabetes insipidus resistant to ADH, the anti-diuretic effect may be of more crucial importance since the uncontrolled polyuria may exceed the child's capacity to imbibe and absorb fluids.The mechanism of the antidiuretic effect is not yet completely understood. Most investigators agree thatthe natriuretic action of the thiazides plays an im-portant role. Autor of the post: Undefined It has been proposed that Post Date: Sun, 12 Oct 2008 14:12:45 +0000 When these agents are given continu-ously to nonedematous subjects, an initial loss of sodium, chloride, and water during the first 2 days is followed by a sustained, moderate state of electrolyte depletion and reduction of extracellular volume. A small reduction in filtration rate may occur, but this is not always observed. It has been proposed that, under these conditions, a significant increase in the fraction of glomerular filtrate reabsorbed in the proximal tubule leads to delivery of reduced amounts of sodium chloride and, most importantly, potential free water to the distal tubule (see Earley and OrlofF, 1964). Autor of the post: Undefined Also, it has been observed Post Date: Sun, 12 Oct 2008 13:53:10 +0000 Thus, a fluid smaller in volume and less dilute escapes the distal tubule. This explanation is supported by the fact that reduction of filtration rate by dehydration or by drug-induced hypotension has a similar antidiuretic effect in diabetes insipidus. Also, it has been observed that restricted salt intake enhances, and high salt intake antagonizes, the antidiuretic effect of the thiazides. Autor of the post: Undefined The degree to Post Date: Sun, 12 Oct 2008 13:33:28 +0000 The common denominator among these effects is felt to be the reduction of the amount of filtered water reaching the distal segment (see Earley and Orloff, 1962).It is also believed that the collecting ducts are never completely impermeable to water and that any procedure that reduces the rate of flow of collecting-duct urine allows an increased opportunity for the abstraction of water and the elevation of osmotic pressure of the luminal contents (Berliner and Davidson, 1957). The degree to which the perme-ability of this segment may be influenced by the thiazides awaits more complete experimental eval-uation. Autor of the post: Undefined Chlorothiazide and its con-geners Post Date: Sun, 12 Oct 2008 13:21:39 +0000 However, a number of observations suggest that the thiazides may influence the excretion of free water by actions other than salt depletion (Heine-man et al, 1959; Dies et al, 1963).Therapeutic Use. Chlorothiazide and its con-geners are less effective than vasopressin in the treat-ment of pituitary diabetes insipidus but are invalu-able for patients who experience undesirable side effects or allergic reactions after vasopressin and for those who have nephrogenic diabetes insipidus. Autor of the post: Undefined Reduction of urine volume Post Date: Sun, 12 Oct 2008 13:02:33 +0000 Since their antidiuretic effects appear to parallel their ability to cause natriuresis, they are given in doses similar to those used for the mobilization of edema fluid. Chlorothiazide, 1,0 to 1,5 g, or hydro-chlorothiazide, 50 to 150 mg, in daily divided doses, have been most frequently employed. Reduction of urine volume to 50% or less of pretreatment volumes is considered to be a good response. Autor of the post: Undefined Among the most common Post Date: Sun, 12 Oct 2008 12:46:37 +0000 Moderate re-striction of sodium chloride intake has been shown to enhance the antidiuretic effect. Representative clinical studies in adults are described by Havard and Wood (1961) as well as by Earley and Orloff (1962); in infants, by Schotland and associates (1963).Among the most common of the side effects encountered is potassium depletion. Autor of the post: Undefined Other untoward effects of the thiazides Post Date: Sun, 12 Oct 2008 12:32:24 +0000 It is essential,therefore, that the patient maintain a high dietaryintake of this ion. It is sometimes necessary to administer supplementary oral potassium chloride.Other untoward effects of the thiazides are describedin Chapter 39. 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