Vaptans for the treatment of hyponatremia

The vaptans constitute a new class of pharmaceuticals developed for the treatment of the hypervolemic and euvolemic forms of hyponatremia. These agents are nonpeptide vasopressin antagonists that interfere with the antidiuretic effect of the hormone by competitively binding to V-2 receptors in the kidney. This blockade results in water diuresis (aquaresis) that, if not offset by increased fluid intake, reduces body water content and raises plasma sodium levels. Probably as a result of this rise in plasma sodium, thirst and plasma vasopressin concentration increase, potentionally limiting the effects of the vasopressin antagonists. Nonetheless, vaptans are particularly useful to treat hypervolemic hyponatremia associated with severe congestive heart failure or chronic liver failure, as the only other treatments currently available, such as fluid restriction and diuretics, are slow-acting and minimally effective. Vaptans are also useful for treating euvolemic hyponatremia associated with the syndrome of inappropriate antidiuretic hormone (SIADH), at least when it is chronic and/or minimally symptomatic. However, because their effects vary unpredictably from patient to patient, vaptans are less useful than hypertonic saline infusion in cases of acute, severe and symptomatic hyponatremia. Vaptan therapy is absolutely contraindicated in hypovolemic hyponatremia (in which total body water is reduced) and is ineffective in the vasopressin-independent form of inappropriate antidiuresis caused by constitutive activating mutations of V-2 receptors.