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.