Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conivaptan [YM 087], a benzazepine derivative, belongs to a series of highly potent, orally active arginine vasopressin V1 and V2 receptor antagonists that are being developed by Yamanouchi. Yamanouchi licensed conivaptan to Warner-Lambert for co-development and marketing in the Americas, Europe and Africa. In return, Yamanouchi has rights to market atorvastatin in Japan. In June 2000, Warner-Lambert merged with Pfizer. The resulting company retained the Pfizer name. However, Yamanouchi and Pfizer discontinued the co-development and marketing agreement for conivaptan. Yamanouchi is continuing the independent development of conivaptan in the US and Europe. Yamanouchi is developing an oral drug delivery formulation of conivaptan for administration in patients with chronic heart failure. The company has initiated the ADVANCE (A Dose evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise) trial, a double-blind, multicentre trial in which 345 patients with heart failure will receive placebo or one of three doses of conivaptan for 12 weeks and their functional capacity will be assessed. Conivaptan demonstrated a potent diuretic effect in animal studies.
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PMID:Conivaptan: YM 087. 1529 69

Despite diuretics being used to relieve the fluid retention/congestion associated with heart failure (HF), patients with HF are commonly hospitalised due to progressive volume retention with an increase in body weight and the deterioration of symptoms. Arginine vasopressin acts at vasopressin V2 receptors in the kidney as an antidiuretic. Tolvaptan is an orally-active selective V2-receptor antagonist. In the Acute and Chronic Therapeutic Impact of a Vasopressin antagonist in Congestive Heart Failure trial of patients hospitalised with HF, tolvaptan 30 mg/day increased urine volume and induced a weight loss of 3.3 kg at discharge (placebo; 1.9 kg). In post hoc analyses, mortality was lower with tolvaptan in patients with renal impairment and severe congestion, compared to placebo. Thus, it seems that tolvaptan is an advancement in the treatment of severely decompensated HF.
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PMID:Is vasopressin-receptor antagonism an advancement in the treatment of heart failure? 1511 14

We review the diuretics regarding the mechanism of action, way of clinical use and their adverse effects. Recent progress of molecular biology revealed the molecular target of diuretics and thereby, the molecular mechanism of diuretic action became clear to understand. Loop diuretics and thiazides are the most widely used diuretics and the physiologic adaptation to their prolonged use are mentioned. Carbonic anhydrase inhibitors are not used as diuretics but for correction of metabolic alkalosis and treatment of glaucoma. Potassium-sparing diuretics have modest natriuresis but the combination with loop diuretics or thiazides results in strong natriuresis. Adenosine type 1 receptor antagonist has been developed for treatment of edema in chronic heart failure. Vasopressin type 2 receptor antagonists are developed for a new type of diuretics to increase the free water clearance in cases of chronic heart failure and SIADH. The recombinant atrial natriuretic polypeptide is recently used as diuretics in acute heart failure. Knowledge of pharmacological action of diuretics could help the appropriately clinical use of diuretics, in particular the diuretics-resistant edema.
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PMID:[Diuretics; their characteristics and future development]. 1567 32

Vasopressin is a potent vasoconstrictor and plays a significant role in the regulation of volume homeostasis. Several non-peptide vasopressin receptor antagonists (vaptans) have emerged as promising drugs in the management of acute heart failure. Results of early trials with tolvaptan (selective vasopressin subtype 2 receptor antagonist) and conivaptan (dual vasopressin subtypes 1a and 2 receptor antagonist) have demonstrated improvement in the fluid status, osmotic balance and haemodynamic profile in patients with heart failure presenting with signs and symptoms of decompensation. Nevertheless, their comparative long-term safety and efficacy remains to be determined in large-scale clinical trials.
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PMID:Vasopressin receptor antagonists in the management of acute heart failure. 1592 66

Vasopressin antagonists are a class of neurohormonal antagonists with applications in both the short-term and long-term management of patients with acute decompensated heart failure (ADHF). The pharmacologic effects of vasopressin antagonists include changes in fluid balance and hemodynamics that may improve symptoms and outcomes in patients hospitalized with ADHF. With chronic therapy, vasopressin antagonists offer the potential to improve outcomes through a variety of mechanisms, including more effective treatment of congestion, preservation or improvement of renal function, or a reduction in the use of concomitant loop diuretic therapy. Several vasopressin antagonists are currently in advanced clinical trials for the treatment of ADHF, chronic stable heart failure, and hyponatremia.
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PMID:Role of vasopressin antagonists in the management of acute decompensated heart failure. 1613 49

Acute heart failure syndromes (AHFS) are among the most frequent causes of hospitalizations in the United States and Europe. Despite current therapies, patients with AHFS have high readmission and mortality rates. The randomized, controlled clinical trial is the standard by which contemporary therapies are evaluated, yet this tool of clinical science only recently has been rigorously applied to the development of novel therapies for patients with AHFS. This review briefly discusses some of the challenges presented in designing a clinical trial of therapies for AHFS and to describe some of the recent trials with respect to these issues in established drugs (such as milrinone, dobutamine, nitroglycerin, nitroprusside, and nesiritide) that have been approved by the US Food and Drug Administration (FDA). Recent trials of current investigational agents, such as levosimendan (the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy Versus Placebo in the Short-Term Treatment of Decompensated Heart Failure [REVIVE], the Calcium Sensitizer or Inotrope or None in Low-Output Heart Failure [CASINO] study, and the Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support [SURVIVE] trial), tezosentan (the Randomized Intravenous Tezosentan [RITZ] study and the Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure Studies [VERITAS]), and tolvaptan (the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure [ACTIV-CHF] study), are also discussed.
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PMID:Overview of randomized clinical trials in acute heart failure syndromes. 1618 24

Vasopressin is an endogenous peptide hormone with the antidiuretic and vasoactive action. Its mechanisms of action on vasal smooth muscles and kidney collective tubules are well known. This hormone also plays a role in the central nervous system and influences smooth muscles of the gastrointestinal tract. The recent research results indicated much more extensive effects of endogenous vasopressin action on the circulation than appeared from the water-electrolyte balance regulation only. The use of this hormone is actually an alternative for catecholamine in treatment of the shock. This paper presents short review of vasopressin action, actual clinical use and perspectives in use of vasopressin antagonists in the heart failure.
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PMID:[Use of vasopressin analogues and antagonist in clinical practice]. 1627 29

Patients with worsening heart failure (HF) requiring hospitalization commonly have a history of progressive fluid retention, decreased renal function, and hyponatremia. For these patients, diuretics have traditionally been the mainstay of treatment, but they are associated with electrolyte abnormalities and impaired renal function. Previous studies have shown that levels of the endogenous arginine vasopressin (AVP) hormone are elevated in patients with HF and may be the contributing factor to fluid retention and hyponatremia, and probably progression of HF. Vasopressin antagonists represent a unique class of therapeutic agents because of their potential role in both the short- and long-term treatment of patients hospitalized with worsening HF. As "aquaretics," AVP antagonists offer the possibility of added efficacy in relieving congestion and improving symptoms with minimal adverse effects in combination with standard medical therapy. Some AVP receptor antagonists have shown promising results in animal studies and small-scale clinical trials. The purpose of this review was to update the current status of studies with the available AVP antagonists.
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PMID:Overview of vasopressin receptor antagonists in heart failure resulting in hospitalization. 1639 90

Hyponatremia as it occurs in the heart failure patient is a multifactorial process. The presence of hyponatremia in the heart failure patient correlates with both the severity of the disease and its ultimate outcome. The therapeutic approach to the treatment of hyponatremia in heart failure has traditionally relied on attempts to improve cardiac function while at the same time limiting fluid intake. In more select circumstances, hypertonic saline, loop diuretics, and/or lithium or demeclocycline have been used. The latter two compounds act by retarding the antidiuretic effect of vasopressin but carry with their use the risk of serious renal and/or cardiovascular side effects. Alternatively, agents that selectively block the type 2 vasopressin receptor increase free water excretion without any of the adverse consequences of other therapies. Conivaptan, lixivaptan, and tolvaptan are three such aquaretic drugs. Vasopressin receptor antagonists will redefine the treatment of heart failure-related hyponatremia and may possibly evolve as adjunct therapies to loop diuretics in diuretic-resistant patients.
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PMID:Hyponatremia and heart failure--treatment considerations. 1647 95

Hyponatraemia is a common clinical finding in cardiac failure, complicating the management of these patients. Vasopressin plays a fundamental role in the physiopathology of the hyponatraemia of cardiac failure and binds to two distinct specific receptors, receptor V1a and V2. The V2 receptors, situated in the renal collecting duct, control the resorbtion of free water. The V1a receptors, present everywhere, are responsible for the vasoconstrictive effect of vasopressin. Specific antagonists of vasopressin receptors are being evaluated in pathologies associated with hyponatraemia. The preliminary results in patients with cardiac failure are encouraging and mortality studies are underway.
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PMID:[Hyponatraemia, antagonists of the antidiuretic hormone and cardiac failure]. 1661 24


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