Nursing Pharmacology Chapter 26:  Renal Pharmacology

Thiazides:  nephrogenic diabetes insipidus

• Diabetes insipidus: impaired renal water conservation, caused by:

  • Inadequate vasopressin secretion (Central or cranial diabetes insipidus)

  • Insufficient kidney response to vasopressin (nephrogenic diabetes insipidus)

  • Induction of diabetes insipidus:

    •  Hypercalcemia

    •  Hypokalemia

    •  Postobstructive renal failure

    •  Lithium (incidence: as high as 33%)

    •  Demeclocycline (Declomycin)

  • Familial nephrogenic diabetes insipidus: X-linked, typically,recessive)

• Thiazides are central in treatment of nephrogenic diabetes insipidus, reducing urine volume by up to 50%.

• Other drugs:

  • Amiloride: by blocking lithium uptake by the sodium channel in the collecting duct, amiloride is the drug of choice for lithium-induced nephrogenic diabetes insipidus.

• Mechanism of action:

  • Decrease in volume promotes increased proximal tubule reabsorption.

    •  Decreased extracellular fluid volume results in compensatory mechanisms that increase NaCl reabsorption in the proximal tubule thus reducing the volume delivered to the distal tubule.

      •  As a result, less free water is formed and polyuria is decreased

  • Since the effectiveness of thiazide diuretics in treating nephrogenic diabetes insipidus follows the extent of natriuresis, the effectiveness may be enhanced by decreasing sodium intake.

Jackson, E.K. Diuretics In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp. 685- 713

Jackson, E.K. Vasopressin and Other Agents Affecting the Renal Conservation of Water In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.715-732