Hyponatremia is a very common electrolyte abnormality. Dilutional hyponatremia is very difficult to treat effectively due to the complications of conventional treatment. Arginine-vasopressin (AVP) plays an integral role in circulatory and water homeostasis. AVP is a hormone released in response to increases in plasma tonicity or decreases in plasma volume in an attempt to maintain the plasma osmolality between 284 and 295 mOsm/L. AVP receptor antagonists or “vaptans” are a new class of drugs that allow for the safe and efficacious treatment of dilutional hyponatremia. Conivaptan, a mixed V1a/V2 receptor antagonist, and tolvaptan, a selective V2 receptor antagonist, are the only 2 vaptans approved by the US Food and Drug Administration.
UpadhyayAJaberBLMadiasNE. Epidemiology of hyponatremia. Semin Nephrol. 2009;29:227–238.
2.
KraftMDBtaicheIFSacksGS. Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health Syst Pharm. 2005;62:1663–1682.
3.
HawkinsRC. Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta. 2003;337:169–172.
4.
ZilberbergMDExuzidesASpaldingJ. Epidemiology, clinical and economic outcomes of admission hyponatremia among hospitalized patients. Curr Med Res Opin. 2008;24:1601–1608.
5.
GheorghiadeMAbrahamWTAlbertNM. OPTIMIZE-HF Investigators and Coordinators. Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry. Eur Heart J. 2007;28:980–988.Epub February 19, 2007. PubMed PMID: 17309900.
6.
PorcelADíazFRendónP. Dilutional hyponatremia in patients with cirrhosis and ascites. Arch Intern Med. 2002;162:323–328.
7.
AndersonRJChungHMKlugeR. Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med. 1985;102:164–168.
8.
AdroguéHJMadiasNE. Hyponatremia. N Engl J Med. 2000;342(21):1581–1589.
9.
KhannaAMenonMC. The use of vasopressin receptor antagonists in hyponatremia. Curr Opin Investig Drugs. 2010;11(9):1007–1014. Review.
10.
LiamisGMilionisHElisafM. A review of drug-induced hyponatremia. Am J Kid Dis. 2008;52:144–153.
11.
BankirL. Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2-receptor mediated effects. Cardiovasc Res. 2001;51:372–390.
12.
JacksonEKVasopressin and other agents affecting the renal conservation of water. In: BruntonLLazoJSParkerKL eds. Goodman and Gilaman’s the Pharmacologic Basis of Therapeutics. 11th ed.New York, NY: McGraw-Hill; 2006:771–788.
13.
RingRH. The central vasopressinergic system; examining the opportunities for psychiatric drug development. Curr Pharm Des. 2005;11:205–225.
14.
DecauxGSouportAVassartG. Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet. 2008;371:1624–1632.
15.
FergusonJWTherapondosGNewbyDE. Therapeutic role of vasopressin receptor antagonism in patients with liver cirrhosis. Clin Sci (Lond). 2003;105:1–8.
TaharaASaitoMSugimotoT. Pharmacological characterization of YM087, a potent, nonpeptide human vasopressin V1A and V2 receptor antagonist. Naunyn Schmeidebergs Arch Pharmacol. 1998;357:63–69.
18.
GoldsmithSR. Current treatments and novel pharmacologic treatments for hyponatremia in congestive heart failure. Am J Cardiol. 2005;95:14B–23B.
19.
GhaliJKorenMTaylorJ. Efficacy and safety or oral conivaptan: A V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab. 2006;91:2145–2152.
20.
AnnaneDDecauxGSmithN. Efficacy and safety of oral conivaptan, a vasopressin-receptor antagonist, evaluated in a randomized, controlled trial in patients with euvolemic or hypervolemic hyponatremia. Am J Med Sci. 2009;337:28–36.
21.
ZeltserDRosanskySVan RensburgH. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol. 2007;27:447–457.
22.
NaidechAPaparelloLeiblingS. Use of conivaptan (vaprisol) for hyponatremic neuro-icu patients. Neurocrit Care. 2010;13:57–61.
23.
GlezermanIG. Successful treatment of ifosfamide-induced hyponatremia with AVP receptor antagonist without interruption of hydration for prevention of hemorrhagic cystitis. Ann Oncol. 2009;20:1283–1285.[Letter].
YamamuraYNakamuraSItohS. OPC-41061, a highly potent human vasopressin V2-receptor antagonist: pharmacological profile and aquaretic effect by single and multiple oral dosing in rats. J Pharmacol Exp Ther. 1998;287:860–867.
26.
Costello-BoerrigterLCBoerrigterGBurnettJC. Pharmacology of vasopressin antagonists. Heart Fail Rev. 2009;14:75–82.
27.
GheorghiadeMGottliebSUdelsonJ. Vasopressin V2 receptor blockade with tolvaptan versus fluid restriction in the treatment of hyponatremia. Am J Cardiol. 2006;97:1064–1067.
28.
U.S. Food and Drug Administration. FDA approves Samsca to treat hyponatremia [press release]. May22, 2009.
29.
SchrierRWGrossPGheorghiadeM. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355:2099–2112.
30.
JosiassenRCGoldmanMJessaniM. Double-blind, placebo-controlled, multicenter trial of a vasopressin V2-receptor antagonist in patients with schizophrenia and hyponatremia. Biol Psychiatry. 2008;64:1097–1100.
31.
BerlTQuittnat-PelletierFVerbalisJG. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010;21:705–712.
32.
KonstamMAGheorghiadeMBurnettJC. Effects of oral tolvaptan in patients hospitalized for worsening heart failure. The EVEREST outcome trial. JAMA. 2007;297:1319–1331.
33.
FrancisGSBenedictCJohnstoneDE. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 1990;82:1724–1729.
34.
Red Book August 2009 Update. Montvale, NJ: Thomson Healthcare; 2009.
35.
Otsuka Pharmaceutical Co.OAPI Patient Assistance Program for SAMSCA (Tolvaptan) Brochure. Tokyo, Japan; 2009.
36.
GreenbergALehrichRW. Treatment of chronic hyponatremia: now we know how, but do we know when or if?. J Am Soc Nephrol. 2010;21:552–555.
