Evaluation and management of hyponatremia: an emerging role for vasopressin receptor antagonists

Abstract

Vasopressin-2 receptor antagonists, collectively known as the 'vaptans', provide a new approach to the treatment of hyponatremia; therefore, an updated Review of the pathophysiology of hyponatremia is particularly timely. After briefly defining hyponatremia and introducing its clinical aspects and complications, we present an approach to the diagnosis and evaluation of hyponatremia that is based primarily on the often-underused concept of free water clearance and, more specifically, the electrolyte-free water clearance. Then we review the use of vasopressin receptor antagonists in the management of hyponatremia from the standpoint of their pharmacology, their mechanism of action, and available efficacy data from clinical trials.

Pharmacology of vasopressin antagonists

“…Due to concerns about serious drug-drug interactions if used for long periods, the oral preparation of conivaptan is no longer being developed for clinical use [36]. Coadministration of conivaptan with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir, is contraindicated.…”

Hyponatremia and other electrolyte/ion disorders

“…A new family of drugs, known as vaptans (Table 18.1), which increase renal solute-free water excretion through the inhibition of the V2 receptors located in the principal cells of the collecting ducts, has recently been investigated in the management of hypervolemic hyponatremia associated with different conditions including cirrhosis [55][56][57]. Nevertheless, among the different compounds, only tolvaptan has been approved, limited to Japan and the United States, for the management of hyponatremia in cirrhosis.…”

Efficacy and safety of 30-minute infusions of conivaptan in euvolemic and hypervolemic hyponatremia

“…For more severe and acute cases, hypertonic saline infusion may be used. 2 The rate of SSC correction with hypertonic saline is unpredictable. Clinicians must limit correction to no more than 10 meq/L in any 24-hour period in order to minimize the risk of osmotic demyelination.…”

“…4,10 In both euvolemic and hypervolemic hyponatremia, arginine vasopressin (AVP), the key regulator of body water, may be paradoxically elevated despite the patient's hypoosmolar state. 2,5,12 The treatment of hyponatremia depends on whether symptoms are present and whether the electrolyte imbalance developed rapidly or over a period of more than 48 hours. Fluid restriction is the mainstay of treatment for chronic asymptomatic hyponatremia.…”

“…1,2 It has been estimated that as many as 30% of hospitalized patients have hyponatremia, with many cases being mild and asymptomatic. 3 Nonetheless, clinical neurologic symptoms, such as irritability, lethargy, and confusion, can occur at SSCs that are slightly below normal, and potentially life-threatening problems, such as intractable headaches, vomiting, seizures, and loss of consciousness, can develop with rapid or major decreases in SSC.…”