Intravenous Conivaptan
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Am J Cardiovasc Drugs 2008; 8 (5): 349 1175-3277/08/0005-0349/$48.00/0 © 2008 Adis Data Information BV. All rights reserved.
Intravenous Conivaptan A viewpoint by Steven R. Goldsmith Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
Hyponatremia is an extremely common electrolyte disorder. It is associated with poor clinical outcomes, perhaps most particularly in patients with congestive heart failure (CHF). Severe hyponatremia may be life-threatening, but even mild or moderate hyponatremia may be associated with significant neurocognitive deficits. Hyponatremia may be associated with volume depleted states, but is more commonly seen in patients who are either euvolemic or hypervolemic, and correction of serum sodium levels is much more difficult in these patients. In euvolemic and hypervolemic states, a relative or absolute increase in body water due to excess antidiuretic hormone arginine vasopressin secretion is the principal and sometimes sole cause of hyponatremia. Until now there have been no direct methods of inhibiting either arginine vasopressin secretion or effect. Treatment has therefore depended on the manipulation of body water and salt levels via water restriction or the administration of hypertonic saline. Unfortunately, water restriction is not effective unless very strict, and consequently is not well tolerated. Hypertonic saline administration, with or without furosemide, is useful only for the treatment of acute symptomatic hyponatremia and is not practical under other circumstances, especially in hypervolemic states such as CHF. Directly inhibiting the secretion of arginine vasopressin, or antagonizing the effect of arginine vasopressin to retain water, would therefore represent a major advance in the treatment of hyponatremia in patients with normal or expanded blood volume.
Conivaptan is one of a family of new agents that directly and effectively antagonize the V2 receptors (the renal receptor that mediates the effect of arginine vasopressin to retain water). Recent data from clinical trials indicate that conivaptan is highly effective compared with placebo in correcting hyponatremia in patients with either normal or expanded blood volume. Conivaptan also blocks the effects of arginine vasopressin at the V1A receptor (the receptor on blood vessels, platelets, and myocardium). For the patient with CHF, relief of vasoconstriction by blocking the V1A receptor would potentially be an additional benefit, but clinical data in CHF patients without hyponatremia are limited at this time. The main advantage of using conivaptan to treat hyponatremia therefore derives from its ability to block the V2 receptor. In addition, the availability of conivaptan in an intravenous formulation makes it attractive for use in acutely ill patients. As noted, its V1A blocking effects may also be useful for the patient with CHF. Disadvantages of this agent include cytochrome P450 interactions, which may render long-term use of the oral formulation impractical, and the possibility that the V1
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