Nursing Pharmacology Chapter 26:  Renal Pharmacology

Chlorpropamide (Diabinese) and clofibrate (Abitrate, Atromid-S) : Central (Cranial) Diabetes Insipidus

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

  • Inadequate vasopressin secretion (Central or cranial diabetes insipidus)

  • Inadequate kidney response to vasopressin (nephrogenic diabetes insipidus)

• Clinical Presentations

  • Large volumes of dilute (200 mOsm/kg) urine excreted

  • With normal thirst, polydipsia is present

  • By contrast with diabetes mellitus, the urine in diabetes insipidus is tasteless.

  • Central or cranial diabetes insipidus can be discriminated from nephrogenic diabetes insipidus by administration of desmopressin (DDAVP).

    •  Urine osmolality will

      •  Increase following desmopressin administration in patients with central diabetes insipidus

      •  Have limited effect or no effect in patients with nephrogenic diabetes insipidus.

• Causes of central diabetes insipidus

  • Head injury (near the pituitary and/or hypothalamus

  • Hypothalamic or pituitary tumor

  • Cerebral aneurysms

  • CNS ischemia

  • CNS infections

  • Central diabetes insipidus: idiopathic or familial

    • Familial: autosomal dominant (chromosome 20)

      • Point mutations in the signal peptide and VP-neurophysin-- causing defects in synthesis, processing, and preprohoromone transport.

• Treatment

  • Primary treatment: (antidiuretic peptides): desmopressin (DDAVP)

  • Patients intolerant of desmopressin: chlorpropamide (Diabinese) (oral sulfonylurea)

    • Mechanism of action -- chlorpropramide

      •  Potentiates effects of residual, circulating vasopressin (reduces urine volume in more than 50% of patients)

      •  Antidiuretic mechanisms of carbamazepine (Tegretol), clofibrate, chlorpropamide (Diabinese) have not been definitively determined.

  • If polyuria is insufficiently reduced by chlorpropramide, a thiazide diuretic may be added.

  • For short-term management, the combination of carbamazepine (Tegretol) and clofibrate (Abitrate, Atromid-S) will also decreased polyuria in central diabetes insipidus:

    •  Serious, adverse effects associated with prolonged use of this combination are limiting.

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) The McGraw-Hill Companies, Inc.,1996, pp.715-732.