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Medical Pharmacology Chapter 26: Renal Pharmacology
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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.
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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) TheMcGraw-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 Pharmacologial 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
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