Thiazide diuretics diabetes insipidus

The answer is a. (Katzung, pp 255-256.) Thiazide diuretics can be used in the treatment of nephrogenic diabetes insipidus. Its other uses include the treatment of hypertension, CHF, and nephrolithiasis due to idiopathic hypercalcuria. 

Lithium reduces the kidney s ability to concentrate urine and may cause a nephrogenic diabetes insipidus with low urine specific gravity and low osmolality polyuria (urine volume greater than 3 L/day). This may be treated with loop diuretics, thiazide diuretics, or triamterene. If a thiazide diuretic is used, lithium doses should be decreased by 50% and lithium and potassium levels monitored. 

Nephrogenic diabetes insipidus is due to resistance to action of vasopressin, and therefore DDAVP is not indicated, but some benefit may be gained by using thiazide diuretics or chlorpropamide. The syndrome of inappropriate antidiuretic hormone (SIADH) can be treated by using the antibiotic derivative demeclocycline to induce a state of vasopressin resistance and partial nephrogenic diabetes insipidus. 

A second unusual action of this class of diuretics is their utility in treating nephrogenic diabetes insipidus. Patients who have an adequate supply of ADH but whose kidneys fail to respond to ADH excrete large volumes of very dilute urine, not unlike those who have an ADH deficiency. The thiazides reduce glomerular filtration modestly and decrease positive free water formation (Ch2o), that is, production of dilute urine. These actions combine to cause patients with nephrogenic diabetes insipidus to excrete a somewhat reduced urine volume with increased osmolality. 

Both drugs are used in conjunction with other diuretics like thiazide or loop diuretics to augment natriuresis and reduce loss of potassium. Triamterene may be used in the treatment of congestive heart failure, cirrhosis and the edema caused by secondary hyperaldosteronism. Amiloride is also useful in lithium induced diabetes insipidus. 

See Table 15-5. The major indications for thiazide diuretics are (1) hypertension, (2) heart failure, (3) nephrolithiasis due to idiopathic hypercalciuria, and (4) nephrogenic diabetes insipidus. Use of the thiazides in each of these conditions is described in Clinical Pharmacology of Diuretic Agents. 

If serum Na+ is not monitored closely, ADH antagonists can cause severe hypernatremia and nephrogenic diabetes insipidus. If lithium is being used for a psychiatric disorder, nephrogenic diabetes insipidus can be treated with a thiazide diuretic or amiloride. 

Nephrogenic diabetes insipidus, which occurs less often than central diabetes insipidus, is characterized by the inability of the kidneys to reabsorb water into the bloodstream. Treatment with thiazide or potassium-sparing diuretics can help maintain a fluid and electrolyte balance in some individuals with diabetes insipidus. 

There are two types of disturbances in vasopressin secretion. In central diabetes insipidus, vasopressin secretion is reduced it can be treated by giving vasopressin or desmopressin, which has a longer half-life, by mouth or intranasally. In nephrogenic diabetes insipidus, the plasma vasopressin concentration may be normal but the kidney fails to respond. The latter type of diabetes insipidus does not respond to vasopressin therapy but, paradoxically, can be managed by giving a thiazide diuretic, for example chlortalidone, at a maintenance dose of 50 mg daily. 

In the absence of ADH or when the nephron is unresponsive to ADH, only hypotonic urine can be produced. Large volumes of dilute urine are produced, a condition called diabetes insipidus. This condition can be treated with thiazide diuretic agents. 

Nephrogenic diabetes insipidus secondary to lithium led to severe dehydration in two patients who required intravenous rehydration followed by a thiazide diuretic to reduce urine volume (382). One patient had persistent polyuria (6.7 1/day) 57 months after stopping lithium (296). 

Desmopressin replacement therapy is the first choice. Thiazide diuretics (and chlortalidone) also have paradoxical antidiuretic effect in diabetes insipidus. That this is not due to sodium depletion is suggested by the fact that the nondiuretic thiazide, diazoxide (see Index), also has this effect. It is probable that changes in the proximal renal tubule result in increased reabsorption and in delivery of less sodium and water to the distal tubule, but the mechanism remains incompletely elucidated. Some cases of the nephrogenic form, which is not helped by antidiuretic hormone, may be benefited by a thiazide. 

Patients with congenital nephrogenic diabetes insipidus are often treated with a combination of a thiazide and a potassium-sparing diuretic, without consensus on the preferred potassium-sparing diuretic. A Japanese adult was systematically studied to determine the renal effects of hydrochlorothiazide plus amiloride and hydrochlorothiazide plus triamterene (1). The combination with amiloride was superior to that with triamterene in preventing excessive urinary potassium loss, hjrpokalemia, and metabolic alkalosis. These results suggest that amiloride is the preferred add-on therapy to hydrochlorothiazide in nephrogenic diabetes insipidus. 

Thiazide diuretics are used in the management of edema, the management of hypertension, the treatment of nephrogenic diabetes insipidus, and the prophylaxis of renal calculus formation. 

Trade names Aprinox Berkozide Centyl Corzide (Monarch) Naturetin (Bristol-Myers Squibb) Naturine Neo-Naclex Pluryle Indications Edema, diabetes insipidus, hypertension Category Diuretic, thiazide Half-life 8.5 hours... 

The thiazide diuretics can reduce free water formation in patients with diabetes insipidus, in whom large amounts of free water are eliminated. 

Thiazide diuretics, which reduce urinary excretion of Ca, sometimes are employed to treat calcium nephrolithiasis and may be useful for the treatment of osteoporosis see Chapter 61). Thiazide diuretics also are a mainstay for treatment of nephrogenic diabetes insipidus, reducing urine volume by up to 50%. The mechanism of this paradoxical effect remains unknown. Since other hahdes are excreted by renal processes similar to those for Cl", thiazide diuretics may be useful for the management of Br" intoxication. 

B. Effects and Clinical Uses ADH and desmopressin reduce urine volume and increase its concentration. ADH and desmopressin are useful in pituitary diabetes insipidus. They are of no value in the nephrogenic form of the disease, but salt restriction, thiazides, and loop diuretics may be used. These therapies reduce blood volume, a very strong stimulus to proximal tubular reabsorption. The proximal tubule thus substitutes— in part— for the deficient concentrating function of the collecting tubule. 

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