Department of Medicine, University of Arizona, Arizona Kidney Disease and Hypertension Center, Tucson, Arizona, USA.
Ther Clin Risk Manag. 2008 Dec;4(6):1149-55. doi: 10.2147/tcrm.s3115.
Tolvaptan is a selective arginine vasopressin (AVP) V(2) receptor blocker used to induce free water diuresis in the treatment of euvolemic or hypervolemic hyponatremia. Currently the orally active medication is in the final stages prior to approval by the FDA for outpatient therapy. It appears to be safe and effective at promoting aquaresis and raising serum sodium levels in both short- and long-term studies. Tolvaptan is also effective for treatment of congestive heart failure (CHF) exacerbation, but whether there are long standing beneficial effects on CHF is still controversial. Prolonged use of tolvaptan leads to increased endogenous levels of AVP and perhaps over-stimulation of V(1A) receptors. Theoretically this activation could lead to increased afterload and cardiac myocyte fibrosis, causing progression of CHF. However, after 52 weeks of tolvaptan therapy there was no worsening of left ventricular dilatation. In addition, tolvaptan is metabolized by the CYP3A4 system; thus physicians should be aware of the potential for increased interactions with other medications. Tolvaptan is a breakthrough in the therapy of hyponatremia as it directly combats elevated AVP levels associated with the syndrome of inappropriate secretion of antidiuretic hormone, congestive heart failure, and cirrhosis of the liver.
托伐普坦是一种选择性的精氨酸血管加压素（AVP）V2 受体阻滞剂，用于诱导等容或高容性低钠血症的自由水利尿。目前，这种口服活性药物已进入 FDA 批准的最后阶段，可用于门诊治疗。它在短期和长期研究中均安全且有效地促进了水排泄和提高血清钠水平。托伐普坦也可有效治疗充血性心力衰竭（CHF）恶化，但它是否对 CHF 有长期的有益影响仍存在争议。托伐普坦的长期使用会导致内源性 AVP 水平升高，可能会过度刺激 V1A 受体。理论上，这种激活可能会导致后负荷增加和心肌细胞纤维化，导致 CHF 的进展。然而，在托伐普坦治疗 52 周后，左心室扩张并没有恶化。此外，托伐普坦由 CYP3A4 系统代谢；因此，医生应注意与其他药物相互作用增加的潜在风险。托伐普坦是治疗低钠血症的突破，因为它直接对抗与抗利尿激素分泌不当综合征、充血性心力衰竭和肝硬化相关的升高的 AVP 水平。
