Ghali Jalal K, Farah Jareer O, Daifallah Suleiman, Zabalawi Hassan A, Zmily Hammam D
Detroit Medical Center, Harper University Hospital, 3990 John R., Detroit, MI 48201, USA.
Drug Des Devel Ther. 2009 Dec 29;3:253-68. doi: 10.2147/dddt.s4505.
Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with increased morbidity and mortality. The recognition of the central role that arginin vasopressin plays in the pathogenesis of hyponatremia and the discovery that its actions are mediated by stimulation of V(1A) and V(2) receptors have led to the development of a new class of drugs, the arginin vasopressin antagonists. Conivaptan is a nonselective V(1A) and V(2) receptors antagonist that was the first of this class to be approved by the FDA for the management of euvolemic and hypervolemic hyponatremia. Its short-term safety and efficacy for the correction of hyponatremia have been established by multiple double-blind, randomized, controlled studies. Blocking the effects of arginin vasopressin on V(2) receptors produces aquaresis--the electrolyte-sparing excretion of water--an ideal approach to correct hypervolemic hyponatremia. The nonselectivity of conivaptan offers a theoretical advantage for its use in heart failure that may merit further exploration.
低钠血症是住院患者中最常见的电解质紊乱,与发病率和死亡率增加相关。精氨酸加压素在低钠血症发病机制中所起的核心作用得到认识,且其作用是由V(1A)和V(2)受体的刺激介导的,这促使了一类新型药物——精氨酸加压素拮抗剂的研发。考尼伐坦是一种非选择性V(1A)和V(2)受体拮抗剂,是该类药物中首个获美国食品药品监督管理局批准用于治疗等容性和高容性低钠血症的药物。多项双盲、随机对照研究已证实其纠正低钠血症的短期安全性和有效性。阻断精氨酸加压素对V(2)受体的作用可产生利水作用——即不伴有电解质丢失的排水作用——这是纠正高容性低钠血症的理想方法。考尼伐坦的非选择性为其在心力衰竭中的应用提供了理论优势,值得进一步探索。