Principles of Heart Failure Pharmacotherapy
Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler in Heart Failure, 2023
In select patients hospitalized for ADHF with evidence of volume overload, refractory hyponatremia, or presence of risk factors for hyponatremia-related cognitive symptoms, the short-term use of vasopressin antagonists may be considered.6,9 Conivaptan is a non-selective IV vasopressin antagonist of both V1A and V2 receptors with greater affinity for the V2 receptors (10:1).46,47 Tolvaptan is a selective V2 receptor antagonist. Through inhibition of V2 receptors, both drugs prevent water reabsorption via aquaporin 2 channels in the collecting ducts of the kidney, resulting in aquaresis.46,47 Blockade of peripheral V1A receptors by conivaptan counteracts vasopressin-induced vasoconstriction, improves hemodynamic indices, and may prevent myocardial hypertrophy.46–48
Urine output
Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor in Manual of Neuroanesthesia, 2017
ADH receptor antagonists, such as conivaptan and lixivaptan, inhibit the binding of ADH to renal receptors. They have been shown to be effective in small clinical trials by inducing aquaresis, the electrolyte-sparing excretion of free water.
New drugs on the horizon for cerebral edema: what’s in the clinical development pipeline?
Published in Expert Opinion on Investigational Drugs, 2020
Stephanie M. Robert, Benjamin C. Reeves, Seth L. Alper, Jinwei Zhang, Kristopher T. Kahle
Vaptans, small-molecule vasopressin receptor inhibitors, can modestly ameliorate cerebral edema. Administration of the AVP A1A/A2 receptor inhibitor, conivaptan, demonstrated reduction of brain edema in a rodent model [28], and is now being investigated in an ongoing phase 1 clinical trial (ClinicalTrials.gov Identifier: NCT03000283). However, while conivaptan effects on renal water excretion have been well characterized, the drug’s mechanism of action in the brain remains poorly understood, warranting further molecular and clinical research. Furthermore, the side effect profile of conivaptan includes hypernatremia, dehydration, and infusion site reaction. Conivaptan may also precipitate renal failure and ischemic organ damage; thus, given the aforementioned considerations, it is classified as a category C drug in pregnancy, and it is contraindicated in lactating women. These risks will need to be taken into account if proven effective for cerebral edema in a clinical setting [29].
Vasopressin receptor antagonists: a patent summary (2018-2022)
Published in Expert Opinion on Therapeutic Patents, 2023
Ferenc Baska, Éva Bozó, Tamás Patócs
The last part of our review focuses on dual-acting V1a/V2 antagonists. Because treatment options for euvolemic and hypervolemic hyponatremia were limited earlier and the majority of the applied therapies were not well tolerated, additional therapeutic opportunities were of high demand. Conivaptan (11, Figure 4) is a marketed drug approved by the FDA in 2005 for the treatment of hyponatremia and it was the first vasopressin antagonist which has achieved this milestone [41,51,52].
Pharmacological management of hyponatremia
Published in Expert Opinion on Pharmacotherapy, 2018
Theodosios Filippatos, Moses Elisaf, George Liamis
Conivaptan (a dual V1a/V2 receptor antagonist) is given intravenously as a loading dose of 20 mg administered over 30 min, followed by continuous infusion at a rate of 20 mg/24 h (which may be increased up to 40 mg/24 h) for 2–4 days. Conivaptan is contraindicated in cirrhosis, because blockage of V1a receptor effects may increase portal blood flow and precipitate variceal bleeding [67]. Conivaptan has not been specifically associated with elevation of liver enzymes.
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