Pediatric Diabetes Insipidus Medication

For central diabetes insipidus (DI), the treatment of choice is desmopressin (a synthetic antidiuretic hormone [ADH] analogue). It is available in parenteral, intranasal, and oral dosage forms. The doses widely vary depending on the preparation used, so take care to correctly calculate the dose. Other useful medications include chlorpropamide and thiazide diuretics. The latter 2 can result in a 25-75% reduction in urine volume and can be used in combination with each other.

Nephrogenic DI cannot be effectively treated with desmopressin, because the receptor sites are defective and the kidney is prevented from responding. Thiazide diuretics, amiloride, and indomethacin or aspirin are useful when coupled with a low-solute diet.

Class Summary

DI of central origin is due to absence of vasopressin secretion by the pituitary. Consequently, use of a synthetic vasopressin analogue (ie, desmopressin) is required. The natural compound vasopressin (ie, antidiuretic hormone [ADH]) may be used to diagnose nephrogenic DI. It has a very short natural half-life. This permits its safe use in distinguishing central DI from nephrogenic DI by obviating prolonged fluid accumulation in the former. As an aqueous preparation, it can be administered parenterally, intramuscularly (IM), or subcutaneously.

Desmopressin acetate (DDAVP)

Desmopressin is a synthetic analogue (1-[3-mercaptopropionic acid]-8-D-arginine vasopressin monoacetate trihydrate) of pituitary ADH. It increases the cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys.

Dosage must be individualized. The drug is supplied as parenteral (4 µg/mL), nasal (100 µg/mL rhinal tube), and oral (0.1- and 0.2-mg tab) preparations.

Vasopressin (Pitressin)

Vasopressin has vasopressor and ADH activity. It increases water resorption at the distal renal tubular epithelium (ADH effect) and promotes smooth muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects). However, vasoconstriction is also increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.

Use only the aqueous preparation, which has a short half-life. Vasopressin tannate in oil, which has a longer action, should not be used.

Class Summary

Certain antiepileptic drugs, such as carbamazepine, have proven helpful in DI.

Carbamazepine (Tegretol, Carbatrol, Equetro)

Carbamazepine ameliorates DI by releasing ADH. It is not useful in total DI and generally is not a first-line drug.

Class Summary

Thiazide diuretics impair sodium chloride reabsorption in the distal tubule, reducing the loss of free water to the collecting system and increasing urine concentration. The reduction in urine volume derives from a concomitant action on the proximal tubule, which causes enhanced reabsorption of isoosmotic sodium chloride from the glomerular filtrate, thus drawing additional water along. The net result of both processes is a smaller volume and a higher concentration of the urine.

Hydrochlorothiazide (Microzide)

Hydrochlorothiazide is a thiazide diuretic. The combination of decreased free water delivery to distal tubule and increased sodium chloride reabsorption in proximal tubule underlies its efficacy in DI therapy.

Amiloride (Midamor)

Amiloride is a potassium-sparing diuretic. It has a potassium-sparing effect, so the risk of hypokalemia is decreased in combination with hydrochlorothiazide. In addition, the 2 agents are synergistic with respect to antidiuresis.

Class Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) act synergistically with thiazides to diminish urine volume, although the precise mechanism is unknown.

Ibuprofen (Caldolor, Advil, Motrin)

Inhibition of prostaglandin synthesis reduces the delivery of solute to distal tubules, reducing urine volume and increasing urine osmolality. Ibuprofen is usually used in nephrogenic DI.

Indomethacin (Indocin)

Indomethacin is a nonsteroidal prostaglandin inhibitor with antipyretic properties.

Class Summary

Sulfonylurea compounds are an alternative therapy to desmopressin and can be used in combination with thiazide diuretics. Sulfonylurea compounds have the reported property of causing a syndrome identical to inappropriate ADH secretion.

Chlorpropamide

Chlorpropamide promotes renal response to ADH. In central DI, ADH secretion is absent, although ADH receptor sites remain present in the kidney. Thus, interaction of the receptors with sulfonylurea compounds can produce a physiologic antidiuresis.

Dosage must be individualized. The agent is available only in tab form.