MEDICAL USES AND PHARMACOLOGY OF CONIVAPTAN

Received: 06-Dec-2021 Published: 16-Feb-2022

Editorial

Conivaptan, commonly known as Vaprisol, is a non-peptide inhibitor of the anti-diuretic hormone receptor, also known as vasopressin. It was authorised for hyponatremia in 2004. (low blood sodium levels). Astellas identified and trademarked the chemical in 2006. Cumberland Pharmaceuticals, Inc. is currently in charge of marketing the medicine. Two of the three subtypes of the vasopressin receptor are inhibited by conivaptan (V1a and V2). Iatrogenic nephrogenic diabetes insipidus is the result. The American Food and Drug Administration has not authorized conivaptan for the treatment of decompensated congestive heart failure. In principle, though, vasopressin receptor antagonism would be very advantageous in this situation, and preliminary research suggests that it has some promise. ]

Conivaptan is a nonpeptide that inhibits both the V1A and V2 receptors for arginine vasopressin (AVP). AVP levels in the blood are important for maintaining water and electrolyte balance, and they are frequently high in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated via V2 receptors in the apical membrane of the kidney's collecting ducts, which are functionally linked to aquaporin channels. These receptors increase the permeability of the renal collecting ducts to water, which helps to keep plasma osmolality within normal limits.

Vasopressin, through its activities on vascular 1A receptors, also produces vasoconstriction. Conivaptan's most important pharmacodynamic impact in the treatment of hyponatremia is its V2 antagonism of AVP in the renal collecting ducts, which causes aquaresis, or the excretion of free water. Conivaptan's antagonist effect on V1A receptors can promote splanchnic vasodilation, which can lead to hypotension or variceal hemorrhage in cirrhotic individuals. Higher free water excretion (i.e., effective water clearance [EWC]) is often accompanied by increased net fluid loss, increased urine output, and lower urine osmolality as a pharmacologic consequence of conivaptan.

Medical uses

Conivaptan is most typically used in hospitals for euvolemic and hypervolemic hyponatremia, which are situations in which the blood salt level falls drastically below normal. Hyponatremia affects roughly 4% of hospitalized patients in the United States. Although many people are asymptomatic, severe instances can lead to brain enlargement, respiratory arrest, and even death. When the body's serum sodium levels fall below the total body water rise, hypervolemic hyponatremia occurs, resulting in edema. Congestive heart failure, liver illness, and renal failure are all linked to this

Pharmacology

In vitro, conivaptan hydrochloride is an arginine vasopressin (AVP) receptor antagonist having nanomolar affinity for human V1A and V2 receptors. Water and electrolyte balance are dependent on AVP levels in the blood. In vitro, conivaptan hydrochloride is an arginine vasopressin (AVP) receptor antagonist having nanomolar affinity for human V1A and V2 receptors. Water and electrolyte control and balance are dependent on AVP levels in the blood. V2 receptors control AVP levels in the collecting ducts of the kidneys and are linked to aquaporin channels in the collecting ducts.

Conivaptan hydrochloride causes aquaresis or water secretion via antagonising V2 receptors in the renal collecting ducts. The drug's typical pharmacodynamic effects include increased net fluid loss, increased urine output, and decreased urine osmolality. Conivaptan has non-linear pharmacokinetics, which means it suppresses its own metabolism in the body. Over the range of 10 ng/mL to 1000 ng/mL, 99 percent of conivaptan detected is bound to human plasma proteins. The drug's average halflife is 5 hours, and its average clearance is 15.2 L/hr.

Adverse effects

Most adverse reactions to conivaptan are found at the site of infusion. Other complications include blood and lymphatic system disorders, gastrointestinal disorders, metabolism and nutrition disorders, psychiatric disorders as well as vascular disorders. There is risk of too rapid correction of hyponatremia causing fatal osmotic demyelination syndrome.