DRUGS THAT MODIFY WATER EXCRETION Mechanisms Antidiuretic hormone (vasopressin) and its se

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DRUGS THAT MODIFY WATER EXCRETION Mechanisms * Antidiuretic hormone (vasopressin) and its semisynthetic derivative, desmopressin (DDAVP) act in the collecting duct of the nephron to in- crease its permeability to water and thereby increase the reabsorption of water. They act at specific receptors to increase the synthesis of cAMP in the cell. They are of no value in the treatment of nephrogenic diabetes insipidus since the defect in this condition lies distal to the ADH receptor. * The thiazides reduce diluting ability of the kidney by the mechanism de- scribed in Section I.A.; loop diuretics decrease diluting ability by reducing the osmotic gradient set up in the medulla of the kidney. Fur- thermore, diuretic-induced reduction in blood volume stimulates sodium and water retention in the proximal tubule. These agents can therefore reduce the volume of urine produced in diabetes insipidus; in nephrogenic diabetes insipidus they constitute, along with sodium restriction, the major mode of therapy. (PgDn key for more text) * Lithium and certain antibiotics, notably demeclocyline, inhibit the ac- tion of ADH in the kidney at some point distal to the generation of cAMP, and produce a drug-induced nephrogenic diabetes insipidus. This is usually an undesired effect, but in the syndrome of inappropriate ADH secretion (SIADH), demeclocyline can be used to ameliorate the ex-

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