Vasopressin Antagonism

Abstract

Hyponatremia is a common electrolyte disorder frequently associated with central nervous system (CNS) diseases, neurosurgical procedures, and the use of neurotropic drugs. The clinical manifestations of hyponatremia are attributable to an increase in brain water content that occurs in response to a decrease in serum osmolality. Hyponatremia triggers adaptive processes in the brain to limit this cerebral swelling, but a rapid fall in serum [Na(+)] may overwhelm this adaptive mechanism. Patients with hyponatremia for more than 48 hours are at risk for developing osmotic demyelination when overly rapid correction of hyponatremia restores serum osmolality before this adaptive process can be reversed. The infusion of hypertonic saline for the restoration of serum [Na(+)] should therefore be carefully controlled to avoid this potentially devastating complication. Other options currently available for the treatment of hyponatremia, including strict restriction of fluid intake, are limited by their inconsistent response, poor tolerability, and frequent adverse effects. Arginine vasopressin (AVP)-receptor antagonists promote aquaresis (electrolyte-sparing excretion of free water) by blocking the antidiuretic action of the hormone at the level of the collecting ducts. In clinical trials, AVP-receptor antagonists increased serum [Na] in patients with euvolemic or hypervolemic hyponatremia associated with various conditions, including syndrome of inappropriate antidiuretic hormone secretion (SIADH). Patients who have neurologic disease with SIADH-related hyponatremia may be good candidates for treatment with AVP-receptor antagonists. Careful assessment of intravascular volume status before initiation of therapy and strict monitoring of the serum [Na] during treatment are necessary to avoid complications.