Northwestern University Medical School, Chicago, IL 60611, USA.
Nat Rev Endocrinol. 2011 Mar;7(3):151-61. doi: 10.1038/nrendo.2010.229. Epub 2011 Feb 1.
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.
缬肽类药物属于新型治疗药物，可用于治疗高容量性和等容量性低钠血症。这类药物是非肽类血管加压素拮抗剂，通过竞争性结合肾脏中的 V2 受体，干扰激素的抗利尿作用。这种阻断作用导致水排泄（利尿），如果没有增加液体摄入来抵消，会降低身体的水分含量并提高血浆钠水平。可能由于血浆钠升高，口渴和血浆血管加压素浓度增加，潜在地限制了血管加压素拮抗剂的作用。尽管如此，缬肽类药物在治疗与严重充血性心力衰竭或慢性肝功能衰竭相关的高容量性低钠血症时特别有用，因为目前可用的其他治疗方法，如液体限制和利尿剂，作用缓慢且效果有限。缬肽类药物也可用于治疗与抗利尿激素不适当分泌综合征（SIADH）相关的等容量性低钠血症，至少在慢性和/或轻度症状时是如此。然而，由于它们对每个患者的作用不可预测，因此在急性、严重和有症状的低钠血症的情况下，它们不如高渗盐水输注有用。低血容量性低钠血症（总体液减少）患者绝对禁用缬肽类药物治疗，并且对由 V2 受体组成性激活突变引起的非血管加压素依赖性不适当利尿无效。
