Vasopressin Receptor Antagonists in Hyponatremia: Uses and Misuses

Abstract

Decreases in the concentration of sodium in plasma constitute hyponatremia, the commonest electrolyte disorder in clinical medicine. It is now well established that its presence conveys an increased mortality risk even when the decrement is mild. In addition, recent evidence suggests that chronic and apparently asymptomatic hyponatremia is associated with increased morbidity including neurocognitive deficits and bone fractures. Furthermore, hyponatremia is associated with higher health care-related expenses. Consequently, exploring new therapeutic strategies that increase plasma sodium in a safe and effective manner is of paramount importance. In this regard, there are scant data to support the use of traditional management strategies for hyponatremia (fluid restriction, salt tablets, loop diuretics, and normal saline). Furthermore, data from a large hyponatremia registry reveal the limited efficacy of these therapies. More recently vasopressin receptor antagonists provide a promising treatment for hyponatremia by targeting its most common mechanism, namely, increased vasopressin activity. However, uncertainty still lingers as to the optimal indications for the use of vasopressin receptor antagonists in hyponatremia and a few reports have described complications resulting from their misuse. This review summarizes the appropriate and inappropriate uses of vasopressin receptor antagonists in the treatment of hyponatremia.

Diagnosis and Management of Hyponatremia

“…Uncertainty about the presence of hypovolemic hyponatremia can be addressed by infusing 1 L to 2 L of saline and assessing urine flow and the serum sodium level. Vaptans can worsen both hypovolemia and hemodynamics and should be avoided . In patients with thiazide-induced hyponatremia, drug replacement with loop diuretics (rarely associated with hyponatremia) may be required.…”

Clinical Implications, Evaluation, and Management of Hyponatremia in Cirrhosis

“…These included excessive day time micturition, polyuria, thirst, dry mouth and fatigue in up to 10% of patients (123). Rarely, life threatening adverse events including ODS due to rapid correction of hyponatremia, AKI and gastrointestinal hemorrhage have also been reported (124). Following use of tolvaptan in patients with Polycystic Kidney disease serious adverse events including markedly J o u r n a l P r e -p r o o f elevated transaminases and acute liver failure were reported.…”

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective

“…Vasopressin receptor antagonists (VRAs) drugs that block AVP receptors used in the treatment of hyponatremia as in SIADH, heart failure and liver cirrhosis [75] . VRAs might be non-selective like conivaptan, which block V1 and V2 receptors, V1 A receptor antagonist like relcovaptan, V1 B receptor antagonist like nelivaptan, and selective V2 receptor antagonist like tolvaptan [76] .…”