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Tolvaptan

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https://www.readbyqxmd.com/read/28326667/the-v2-receptor-antagonist-tolvaptan-raises-cytosolic-calcium-and-prevents-aqp2-trafficking-and-function-an-in-vitro-and-in-vivo-assessment
#1
Grazia Tamma, Annarita Di Mise, Marianna Ranieri, Ari Geller, Roberto Tamma, Alberta Zallone, Giovanna Valenti
Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney...
March 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28321325/assessing-risk-of-disease-progression-and-pharmacological-management-of-autosomal-dominant-polycystic-kidney-disease-a-canadian-expert-consensus
#2
Steven Soroka, Ahsan Alam, Micheli Bevilacqua, Louis-Philippe Girard, Paul Komenda, Rolf Loertscher, Philip McFarlane, Sanjaya Pandeya, Paul Tam, Daniel G Bichet
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder worldwide. The disease is characterized by renal cysts and progressive renal failure due to progressive enlargement of cysts and renal fibrosis. An estimated 45% to 70% of patients with ADPKD progress to end-stage renal disease by age 65 years. Although both targeted and nontargeted therapies have been tested in patients with ADPKD, tolvaptan is currently the only pharmacological therapy approved in Canada for the treatment of ADPKD...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28302292/short-term-effects-of-tolvaptan-in-patients%C3%A2-with-acute-heart-failure-and%C3%A2-volume-overload
#3
Marvin A Konstam, Michael Kiernan, Arthur Chandler, Ravi Dhingra, Freny Vaghaiwalla Mody, Howard Eisen, W Herbert Haught, Lynne Wagoner, Divya Gupta, Richard Patten, Paul Gordon, Kenneth Korr, Russell Fileccia, Susan J Pressler, Douglas Gregory, Patricia Wedge, Douglas Dowling, Matthew Romeling, Jeremy M Konstam, Joseph M Massaro, James E Udelson
BACKGROUND: In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments. OBJECTIVES: It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response. METHODS: In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo...
March 21, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28295447/effectiveness-and-tolerability-of-conivaptan-and-tolvaptan-for-the-treatment-of-hyponatremia-in-neurocritically-ill-patients
#4
Caroline Der-Nigoghossian, Christine Lesch, Karen Berger
STUDY OBJECTIVE: To describe the effectiveness and tolerability of conivaptan and tolvaptan for the correction of hyponatremia in neurocritically ill patients. DESIGN: Retrospective cohort study. SETTING: Neurointensive care units at two academic medical centers. PATIENTS: Thirty-six adults admitted to the neurocritical care unit who received at least one dose of conivaptan (5 patients) or tolvaptan (31 patients) between June 2012 and May 2013...
March 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28288570/effect-of-tolvaptan-on-renal-water-and-sodium-excretion-and-blood-pressure-during-nitric-oxide-inhibition-a-dose-response-study-in-healthy-subjects
#5
Safa Al Therwani, Jeppe Bakkestrøm Rosenbæk, Frank Holden Mose, Jesper Nørgaard Bech, Erling Bjerregaard Pedersen
BACKGROUND: Tolvaptan is a selective vasopressin receptor antagonist. Nitric Oxide (NO) promotes renal water and sodium excretion, but the effect is unknown in the nephron's principal cells. In a dose-response study, we measured the effect of tolvaptan on renal handling of water and sodium and systemic hemodynamics, during baseline and NO-inhibition with L-NMMA (L-NG-monomethyl-arginine). METHODS: In a randomized, placebo-controlled, double blind, cross over study, 15 healthy subjects received tolvaptan 15, 30 and 45 mg or placebo...
March 13, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28286940/comparison-of-tolvaptan-treatment-between-patients-with-the-siadh-and-congestive-heart-failure-a-single-center-experience
#6
Gun Ha Park, Chang Min Lee, Jae Won Song, Moon Chan Jung, Jwa Kyung Kim, Young Rim Song, Hyung Jik Kim, Sung Gyun Kim
Background/Aims: Tolvaptan is a very effective treatment for hypervolemic or euvolemic hyponatremia. We compared the clinical efficacy of and response to tolvaptan in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and congestive heart failure (CHF). Methods: We retrospectively reviewed the medical records of 50 patients (SIADH, n = 30; CHF, n = 20) who were prescribed tolvaptan between July 2013 and October 2015. Tolvaptan was prescribed when the serum sodium level was < 125 mmol/L and the standard treatment failed...
March 13, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28282848/long-term-vaptan-treatment-of-idiopathic-siadh-in-an-octogenarian
#7
Stefan Büttner, Jürgen Bachmann, Helmut Geiger, Nicholas Obermüller
Hyponatremia is the most common and by far underestimated electrolyte disorder in clinical practice. Especially in elderly patients, treatment of symptomatic hyponatremia is challenging. Herein we describe the case of an octogenarian with recurrent symptomatic hyponatremia due to idiopathic syndrome of inappropriate antidiuretic hormone release (SIADH). Fluid restriction was insufficient to prevent repeated episodes of hyponatremia complicated by falls and coma. After introduction of a low-dose therapy with tolvaptan, serum sodium levels as well as the clinical condition were stable under vaptan therapy, without any relapse for more than six years now...
March 8, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28270885/does-accidental-overcorrection-of-symptomatic-hyponatremia-in-chronic-heart-failure-require-specific-therapeutic-adjustments-for-preventing-central-pontine-myelinolysis
#8
REVIEW
Renato De Vecchis, Michel Noutsias, Carmelina Ariano, Arturo Cesaro, Carmela Cioppa, Anna Giasi, Nicola Maurea
This review aims at summarizing essential aspects of epidemiology and pathophysiology of hyponatremia in chronic heart failure (CHF), to set the ground for a practical as well as evidence-based approach to treatment. As a guide through the discussion of the available evidence, a clinical case of hyponatremia associated with CHF is presented. For this case, the severe neurological signs at presentation justified an emergency treatment with hypertonic saline plus furosemide, as indicated. Subsequently, as the neurological emergency began to subside, the reversion of the trend toward hyponatremia overcorrection was realized by continuous infusion of hypotonic solutions, and administration of desmopressin, so as to prevent the very feared risk of an osmotic demyelination syndrome...
April 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28255808/euvolemic-hyponatremia-in-cancer-patients-report-of-the-hyponatremia-registry-an-observational-multicenter-international-study
#9
Volker Burst, Franziska Grundmann, Torsten Kubacki, Arthur Greenberg, Despina Rudolf, Abdulla Salahudeen, Joseph Verbalis, Christian Grohé
PURPOSE: Hyponatremia secondary to SIADH is frequent in cancer patients and potentially deleterious. The aim of this sub-analysis of the Hyponatremia Registry database is to analyze current diagnostic and therapeutic management practices in cancer patients with SIADH. METHODS: We analyzed 358 cancer patients who had serum sodium concentration ([Na(+)]) ≤ 130 mEq/L and a clinical diagnosis of SIADH from 225 sites in the USA and EU. RESULTS: Precise diagnostic testing was performed in only 46%...
March 2, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28251822/tolvaptan-use-in-cancer-patients-with-hyponatremia-due-to-the-syndrome-of-inappropriate-antidiuretic-hormone-a-post-hoc-analysis-of-the-salt-1-and-salt-2-trials
#10
Richard J Gralla, Fatima Ahmad, Jaime D Blais, Joseph Chiodo, Wen Zhou, Linda A Glaser, Frank S Czerwiec
Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer-related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT-1 (Study of Ascending Levels of Tolvaptan in Hyponatremia) and SALT-2 clinical trials. Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2-receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once-daily for 30 days...
March 2, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28229305/erratum-to-the-efficacy-and-safety-of-tolvaptan-in-patients-with-hyponatremia-a-meta-analysis-of-randomized-controlled-trials
#11
Benlei Li, Dong Fang, Cheng Qian, Hongliang Feng, Yanggan Wang
No abstract text is available yet for this article.
February 22, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28218410/pharmacokinetics-and-pharmacodynamics-of-tolvaptan-in-autosomal-dominant-polycystic-kidney-disease-phase-2-trials-for-dose-selection-in-the-pivotal-phase-3-trial
#12
Susan E Shoaf, Arlene B Chapman, Vicente E Torres, John Ouyang, Frank S Czerwiec
In the pivotal TEMPO 3:4 trial, the arginine vasopressin V2-receptor antagonist tolvaptan reduced the rate of kidney growth in patients with autosomal dominant polycystic kidney disease. Tolvaptan was initiated as daily morning/afternoon doses of 45/15 mg, and uptitrated weekly to 60/30 mg and 90/30 mg according to patient-reported tolerability. The current report describes 3 phase 2 trials in adult autosomal dominant polycystic kidney disease subjects that were the basis for the titrated split-dose regimen: a single ascending-dose trial (tolvaptan 15 to 120 mg; n = 11), a multiple split-dose trial (tolvaptan 15/15 mg, 30/0 mg, 30/15 mg, and 30/30 mg; n = 37), and an 8-week open-label safety and efficacy trial in 46 of the 48 subjects who participated in the prior 2 trials (tolvaptan 30/15 mg, 45/15 mg, 60/30 mg, and 90/30 mg)...
February 20, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28214374/a-systematic-review-of-known-interventions-for-the-treatment-of-chronic-non-hypovolaemic-hypotonic-hyponatraemia-and-a-meta-analysis-of-the-vaptans
#13
REVIEW
Sunil Bhandari, Alessandro Peri, Iain Cranston, Rachael McCool, Alison Shaw, Julie Glanville, Larisa Petrakova, Karl O'Reilly
International and national guidelines on the treatment of chronic non-hypovolaemic hypotonic hyponatraemia differ; therefore we have undertaken this systematic review and meta-analysis to investigate the efficacy and safety of interventions for the treatment of chronic non-hypovolaemic hypotonic hyponatraemia. Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomised and quasi-randomised controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic non-hypovolaemic hypotonic hyponatraemia...
February 18, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28202885/tolvaptan-reduces-the-risk-of-worsening-renal-function-in-patients-with-acute-decompensated-heart-failure-and-preserved-left-ventricular-ejection-fraction%C3%A3-prospective-randomized-controlled-study
#14
Shunsuke Tamaki, Yoshihiro Sato, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Tatsuhisa Ozaki, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Makoto Abe, Jun Nakamura, Masatake Fukunami
BACKGROUND: Although the mainstay of treatment for acute decompensated heart failure (ADHF) is decongestion by diuretic therapy, it is often associated with worsening renal function (WRF). The effect of tolvaptan, a selective V2 receptor antagonist, on WRF in ADHF patients with preserved left ventricular ejection fraction (LVEF) is unknown.Methods and Results:We enrolled 50 consecutive ADHF patients whose LVEF on admission was ≥45%. Patients were randomly assigned to either tolvaptan add-on (n=26) or conventional diuretic therapy (n=24)...
February 16, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28194742/predictability-of-tricuspid-annular-plane-systolic-excursion-for-the-effectiveness-of-tolvaptan-in-patients-with-heart-failure
#15
Toru Niwa, Katsuhisa Waseda, Tomofumi Mizuno, Yusuke Nakano, Kentaro Mukai, Hirokazu Wakabayashi, Atsushi Watanabe, Hirohiko Ando, Hiroaki Takashima, Tetsuya Amano
BACKGROUND: There is no echocardiographic predictor of the effectiveness of tolvaptan in patients with heart failure (HF). The aim of this study was to investigate the echocardiographic predictor of responders to tolvaptan in patients with HF. METHODS: This observational study consisted of 62 consecutive in-hospital patients with HF who received tolvaptan with volume overload despite standard therapies. The echocardiography data were obtained within 1 week before the administration of tolvaptan...
February 13, 2017: Journal of Echocardiography
https://www.readbyqxmd.com/read/28194574/tolvaptan-treatment-for-severe-neonatal-autosomal-dominant-polycystic-kidney-disease
#16
Rodney D Gilbert, Hazel Evans, Kazeem Olalekan, Arvind Nagra, Mushfequr R Haq, Mark Griffiths
BACKGROUND: Severe neonatal autosomal-dominant polycystic kidney disease (ADPKD) is rare and easily confused with recessive PKD. Managing such infants is difficult and often unsuccessful. CASE DIAGNOSIS/TREATMENT: A female infant with massive renal enlargement, respiratory compromise and hyponatraemia was treated with the arginine vasopressin receptor 2 antagonist tolvaptan. This resolved hyponatraemia, and there was no further increase in renal size. CONCLUSION: Tolvaptan may be a useful treatment for severe neonatal PKD...
February 13, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28194573/hyponatremia-and-cyst-growth-in-neonatal-polycystic-kidney-disease-a-case-for-aquaretics
#17
EDITORIAL
Detlef Bockenhauer
Hyponatremia is a common complication in neonatal polycystic kidney disease and is thought to be due to water retention. Aquaretics are drugs that promote free water excretion by blocking the arginine vasopressin receptor type 2 (AVPR2) in the collecting duct and thus impair urinary concentration. AVPR2 is also a key stimulant for cyclic AMP production in the collecting duct and in this way promotes cyst proliferation and pathologic kidney growth in autosomal dominant polycystic kidney disease (ADPKD). Consequently, the aquaretic tolvaptan is now used to slow down progression of ADPKD in adult patients...
February 13, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28166521/rationale-and-design-of-a-clinical-trial-investigating-tolvaptan-safety-and-efficacy-in-autosomal-dominant-polycystic-kidney-disease
#18
Vicente E Torres, Olivier Devuyst, Arlene B Chapman, Ron T Gansevoort, Ronald D Perrone, John Ouyang, Jaime D Blais, Frank S Czerwiec, Olga Sergeyeva
BACKGROUND: In TEMPO 3:4, the vasopressin V2-receptor antagonist tolvaptan slowed kidney growth and function decline in autosomal dominant polycystic kidney disease (ADPKD) patients with relatively preserved kidney function. METHODS: Prospective, phase 3b, multi-center, randomized-withdrawal, placebo-controlled, double-blind trial of tolvaptan in ADPKD patients with late stage 2 to early stage 4 chronic kidney disease (CKD). The primary endpoint was estimated glomerular filtration rate (eGFR) change from pre-treatment baseline to post-treatment follow-up...
2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28129975/the-role-of-quantitative-systems-pharmacology-modeling-in-the-prediction-and-explanation-of-idiosyncratic-drug-induced-liver-injury
#19
REVIEW
Jeffrey L Woodhead, Paul B Watkins, Brett A Howell, Scott Q Siler, Lisl K M Shoda
Idiosyncratic drug-induced liver injury (iDILI) is a serious concern in drug development. The rarity and multifactorial nature of iDILI makes it difficult to predict and explain. Recently, human leukocyte antigen (HLA) allele associations have provided strong support for a role of an adaptive immune response in the pathogenesis of many iDILI cases; however, it is likely that an adaptive immune attack requires several preceding events. Quantitative systems pharmacology (QSP), an in silico modeling technique that leverages known physiology and the results of in vitro experiments in order to make predictions about how drugs affect biological processes, is proposed as a potentially useful tool for predicting and explaining critical events that likely precede immune-mediated iDILI, as well as the immune attack itself...
November 21, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28123500/effects-of-low-dose-tolvaptan-on-electrolyte-abnormality-and-hemodynamic-parameters-in-a-liver-cirrhosis-associated-portopulmonary-hypertension-patient-a-case-report
#20
Yoshito Ogihara, Norikazu Yamada, Kaoru Dohi, Akimasa Matsuda, Satoshi Ota, Ken Ishikura, Mashio Nakamura, Masaaki Ito
The present study reported a case of portopulmonary hypertension (POPH) that was secondary to underlying liver cirrhosis in a 58-year-old woman, who was successfully treated with low-dose tolvaptan. The patient had suffered from refractory peripheral edema and electrolyte abnormalities, including severe hypokalemia, under the combination therapy of sildenafil, ambrisentan, furosemide and spironolactone. Subsequent to the initiation of low-dose tolvaptan at 3.75 mg/day with concurrent de-escalation of the dose of furosemide, the daily urine volume increased, peripheral edema improved and the serum potassium level increased immediately...
January 2017: Experimental and Therapeutic Medicine
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