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Principles of Heart Failure Pharmacotherapy
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Erika L. Hellenbart, Stephanie Dwyer Kaluzna, Robert J. DiDomenico
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
Physiology of the Pituitary Gland
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Mária Hérincs, Karen Young, Márta Korbonits
Central DI is managed by administering an exogenous AVP analogue. The analogue used in clinical practice is desmopressin, which, with its strong antidiuretic but relatively low vasopressive effect, is a good therapeutic option not only in central DI but also as treatment for enuresis in children. In nephrogenic DI, thiazide diuretics can be beneficial (inhibiting reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl− symporter as well as increasing calcium reabsorption at the distal tubule). In contrast, the syndrome of inappropriate antidiuretic hormone (SIADH or Schwartz-Bartter syndrome) is characterized by excessive release of AVP from the posterior pituitary gland or from neuroendocrine tumours, typically small-cell carcinoma of the lung. This is treated using V2R antagonists, which block the V2R receptors in the collecting duct and therefore result in aquaresis (excretion of water that is free of electrolytes). V2R blockers must be used cautiously since rapid reversal of hyponatraemia carries a risk of severe central nervous system complications.
Urine output
Published in Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor, 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.
Current and emerging treatment options to prevent renal failure due to autosomal dominant polycystic kidney disease
Published in Expert Opinion on Orphan Drugs, 2020
Gopala K. Rangan, Aarya Raghubanshi, Alissa Chaitarvornkit, Ashley N. Chandra, Robert Gardos, Alexandra Munt, Mark N. Read, Sayanthooran Saravanabavan, Jennifer Q.J. Zhang, Annette T.Y. Wong
Due to off-target suppression of water reabsorption in the distal nephron, the universal adverse effect of tolvaptan is aquaresis resulting in massive polyuria, pollakiuria, nocturia, thirst and polydipsia. In ADPKD clinical studies, the split-dose twice daily dosing of tolvaptan (90/30 mg) in patients with CKD Stage 1 or 2, caused a mean total daily volume of 7 liters (or a 4 liter increase above baseline urine output), and in Stage 4 patients, this was lower at 5 liters per day (or a 2 liter increase above baseline urine output). The aquaresis requires chronic adaptation in fluid intake behavior to avoid dehydration and may be tolerated in the long-term by up to 60–75% of motivated patients (e.g, those enrolled in clinicals) [94,95]. In addition, in the TEMPO 3:4 trial, 4.9% of ADPKD patients treated with tolvaptan developed clinically important idiosyncratic hepatic toxicity (ALT levels> 3 times the upper limit of normal) compared to 1.2% in the placebo [89]. All episodes were reversible (up to 4 months later) with interruption or drug withdrawal; unlikely to result in chronic hepatocellular injury; and occurred during the first 3 to 18 months of treatment [89,96]. A post-hoc analysis of the TEMPO and REPRISE trials showed that there was a small increased risk for liver function test abnormalities when statins are concurrently prescribed with tolvaptan [97].
Vasopressin receptor antagonists: a patent summary (2018-2022)
Published in Expert Opinion on Therapeutic Patents, 2023
Ferenc Baska, Éva Bozó, Tamás Patócs
In recent years, Bayer has published ribuvaptan (BAY 86–8050, 12) and pecavaptan (BAY1753011, 13, Figure 4) which are structurally different from other members of the „vaptan” family [56,57]. Pecavaptan (13) showed almost the same affinity for the human V1a (Ki: 0.5 nM) and V2 (Ki: 0.6 nM) receptors and it was quite potent (hV1a IC50: 3.6 nM and hV2 IC50: 1.7 nM) in the cell-based assays as well [57]. Further preclinical studies revealed that 13 not only effectively induced aquaresis but was also able to compensate for the AVP-mediated deterioration of the cardiovascular system [58]. Having identified and characterized 13, Bayer initiated clinical trials in patients with congestive heart failure [59,60].
Pharmacological management of hyponatremia
Published in Expert Opinion on Pharmacotherapy, 2018
Theodosios Filippatos, Moses Elisaf, George Liamis
ADH acts through V2 receptors causing free-water reabsorption leading to increased water retention [46–48]. Specifically, the binding of ADH to the V2 receptors located in the renal collecting duct activates adenylyl cyclase, generates cAMP and activates protein kinase A, resulting in translocation of aquaporin-2 water channels from endosomes to the apical membrane of collecting duct cells and increased water reabsorption [49]. Vaptans (V2 receptor antagonists) are aquaretics as they correct hyponatremia by producing a selective water diuresis without affecting sodium and potassium excretion [50].