Diuretics diabetes insipidus

In nephrogenic diabetes insipidus the kidney s ability to respond to AVP is impaired by different causes, such as drugs (e.g. lithium), chronic disorders (e.g. sickle cell disease, kidney failure) or inherited genetic disorders (X-linked or autosomal NDI). This type of diabetes insipidus can not be treated by exogenous administration of AVP or AVP analogues. Instead, diuretics (hydrochlorothiazide combined or not with amiloride) and NSAI (indomethacin) are administrated to ameliorate polyuria. 

The answer is c. (Katzung, p 493.) Lithium treatment frequently causes polyuria and polydipsia. The collecting tubule of the kidney loses the capacity to conserve water via anti diuretic hormone. This results in significant free-water clearance, which is referred to as nephrogenic 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. 

Anti-diuretic hormone is a small peptide shown as Figure 8.9, which is secreted by the pituitary gland located at the base of the brain. The cellular actions of ADH are mediated by activation of a G-protein linked receptor generating cAMP as second messenger. Absence of ADH or a functional defect in the action of ADH-stimulated water reabsorption in the collecting duct results in the condition diabetes insipidus, characterized by the passing of large volumes (= diabetes) of dilute (= insipidus) urine. 

VLc. Diabetes Insipidus and Vasopressin (Anti-diuretic Hormone)... 

Deficiency of pituitary vasopressin (arginine vasopressin or AVP, also termed anti-diuretic hormone, ADH) causes the syndrome of polyuria, thirst and polydipsia termed cranial diabetes insipidus. It is... 

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. 

Also known as water diabetes, diabetes insipidus (DI) is a rare chronic disease that causes excessive urination. If not properly treated, it can result in electrolyte imbalance and dehydration. It may be caused by a number of factors, including lithium use (a psychiatric drug used for bipolar disorder), neurological disease, or an inadequate amount of ADH (anti-diuretic hormone, or vasopressin, which is produced by the pituitary gland). DI caused by insufficient ADH is called central diabetes insipidus. 

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). 

The most common disease state related to anti-diuretic hormone is diabetes insipidus. This condition can arise from either of two simations ... 

The major indication of either type of diabetes insipidus is excessive urine production as much as 161 of urine per day. If adequate water is available for consumption, the disease is rarely fife-threatening. Hypothalamic diabetes insipidus can be treated with exogenous anti-diuretic hormone. 

Nephrogenic diabetes insipidus, paradoxically, may respond to diuretics which, by contracting vascular volume, increase salt and water reabsorption in the proximal tubule, and thus reduce urine volume. 

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. 

Volume resuscitation is the cornerstone of management of lithium toxicity (Table 3) [124, 125]. Patients with underlying lithium-induced diabetes insipidus may initially present with volume depletion. It must be borne in mind, however, that hypernatremia [125] is a potential complication, especially in those with underlying diabetes insipidus. Forced saline diuresis is expected to increase lithium clearance by decreasing proximal tubular reabsorption. With normal renal function, lithium can be cleared at a rate of 10-40 mL/min [125]. The excretion of lithium can be further increased acutely by using acetazolamide and/or loop diuretics [124,125]. 

Lithium carbonate 0.9-1.2gq.24hr Renal 100% 50-75% 25-50% Nephrotoxic adverse effects include nephrogenic diabetes insipidus, nephrotic syndrome, renal tubular acidosis, and interstitial fibrosis acute toxicity when serum levels > 1.2 mEq/L serum levels should be measured periodically 12 hr after dosing half life does not reflect extensive tissue accumulation plasma levels rebound after dialysis toxicity enhanced by volume depletion, NSAIDs, and diuretics Dose after dialysis NC Dose for GFR 10-50 ml/min... 

Many drugs and other chemicals can adversely affect renal function by directly or indirectly affecting the reabsorption of electrolytes and water in the kidney. Chlorpropamide can enhance the secretion of ADH and promote the water conservation actions of the hormone, while lithium use can lead to a nephrogenic diabetes insipidus. NSAIDs block the formation of renal prostaglandins, which can result in hyperkalemia. Hyperkalemia may also result from the use of beta blockers, potassium-sparing diuretics, and cyclosporine. 

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... 

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