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.
  



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   * 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-