Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tolvaptan is a selective arginine vasopressin (AVP) V(2) receptor blocker used to induce free water diuresis in the treatment of euvolemic or hypervolemic hyponatremia. Currently the orally active medication is in the final stages prior to approval by the FDA for outpatient therapy. It appears to be safe and effective at promoting aquaresis and raising serum sodium levels in both short- and long-term studies. Tolvaptan is also effective for treatment of congestive heart failure (CHF) exacerbation, but whether there are long standing beneficial effects on CHF is still controversial. Prolonged use of tolvaptan leads to increased endogenous levels of AVP and perhaps over-stimulation of V(1A) receptors. Theoretically this activation could lead to increased afterload and cardiac myocyte fibrosis, causing progression of CHF. However, after 52 weeks of tolvaptan therapy there was no worsening of left ventricular dilatation. In addition, tolvaptan is metabolized by the CYP3A4 system; thus physicians should be aware of the potential for increased interactions with other medications. Tolvaptan is a breakthrough in the therapy of hyponatremia as it directly combats elevated AVP levels associated with the syndrome of inappropriate secretion of antidiuretic hormone, congestive heart failure, and cirrhosis of the liver.
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PMID:Tolvaptan and its potential in the treatment of hyponatremia. 1933 22

Tolvaptan is an orally administered, nonpeptide, selective arginine vasopressin V(2) receptor antagonist that increases free water clearance, thereby correcting low serum sodium levels. SALT-1 and -2, two identical, randomized, double-blind, placebo-controlled, multicentre trials, included patients with hypervolaemic or euvolaemic hyponatraemia (serum sodium <135 mmol/L) associated with heart failure, cirrhosis or the syndrome of inappropriate antidiuretic hormone secretion. In both trials, patients receiving (in addition to standard medical treatment) tolvaptan 15-60 mg once daily (titrated according to response) for up to 30 days (n = 95 and 118) experienced significantly greater improvements than those receiving placebo (n = 89 and 114) for the co-primary endpoints of the change in average daily area under the curve for the serum sodium level from baseline to day 4 and from baseline to day 30. This beneficial effect of tolvaptan on serum sodium levels in SALT-1 and -2 was observed in patients with mild (serum sodium <135 mmol/L) and in those with marked (serum sodium <130 mmol/L) hyponatraemia at baseline. Tolvaptan was also superior to placebo in increasing serum sodium levels from baseline to day 7 in a subgroup of 323 patients with hyponatraemia (serum sodium <134 mmol/L) in the randomized, double-blind, multicentre EVEREST trials, which included patients who were hospitalized for worsening heart failure. Tolvaptan was generally well tolerated in clinical trials. The most frequently reported adverse events were thirst and dry mouth, which result from the pharmacodynamic effects of the drug.
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PMID:Tolvaptan. 2020 86

The development of hyponatremia represents an ominous event in the progression of cirrhosis to end-stage liver disease. It usually develops in those with refractory ascites and is a manifestation of the non-osmotic release of arginine vasopressin (AVP). In the hospitalized cirrhotic patient, hyponatremia is associated with increased disease severity and mortality. In this article, we review the pathophysiology of hyponatremia, its clinical implications, evaluation, and treatment.
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PMID:Managing hyponatremia in cirrhosis. 2115 9

Hyponatremia in critically ill patients is a common and challenging problem. Increased levels of arginine vasopressin almost always contribute to the etiology. Inhibition of the vasopressin receptor with a vasopressin receptor antagonist (vaptan) is a novel approach to the treatment of hyponatremia. Vaptans are well suited to the treatment of chronic hyponatremia associated with syndrome of inappropriate anti-diuretic hormone secretion (SIADH) and hypervolemic states like cirrhosis or congestive heart failure. No data are available on the use of vaptans in acute hyponatremia, and they are not indicated in hypovolemic hyponatremia. The focus of this review is the treatment of critically ill patients with hyponatremia with vaptans and other measures.
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PMID:Hyponatremia and the use of vasopressin receptor antagonists in critically ill patients. 2157 54

Hyponatremia is an electrolyte disorder frequently observed in several clinical settings and common in hospitalized patients with decompensated heart failure (HF). It is caused by deregulation of arginine vasopressin (AVP) homeostasis associated with water retention in hypervolemic or in euvolemic states. While hypervolemic hypotonic hyponatremia is also seen in advanced liver cirrhosis, renal failure, and nephrotic syndrome, the bulk of evidence associating this electrolyte disorder to increasing morbidity and mortality can be found in the HF literature. Hospitalized HF patients with low serum sodium concentration have lower short-term and long-term survival, longer hospital stay and increased readmission rates. Conventional therapeutic approaches, ie, restriction of fluid intake, saline and diuretics, can be effective, but often the results are unpredictable. Recent clinical trials have demonstrated the effectiveness of nonpeptide AVP receptor antagonists (vaptans) in the treatment of hyponatremia. The vaptans induce aquaresis, an electrolyte-sparing excretion of free water resulting in the correction of serum sodium concentrations and plasma osmolality, without activation of the renin-angiotensin-aldosterone system (RAAS) or changes in renal function and blood pressure. Further prospective studies in a selected congestive HF population with hyponatremia, using clinical-status titrated dose of tolvaptan, are needed to determine whether serum sodium normalization will be translated into a better long-term prognosis. This review will focus on recent clinical trials with tolvaptan, an oral V(2) receptor antagonist, in HF patients. The ability of tolvaptan to safely increase serum sodium concentration without activating the RAAS or compromising renal function and electrolyte balance makes it an attractive agent for treating hyponatremic HF patients.
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PMID:Clinical utility of tolvaptan in the management of hyponatremia in heart failure patients. 2169 29

Tolvaptan is the first FDA-approved oral V(2) receptor antagonist for the treatment of euvolemic and hypervolemic hyponatremia, in patients with conditions associated with free water excess such as heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone secretion. Tolvaptan inhibits the binding of arginine vasopressin to the V(2) receptors on the collecting ducts of the kidneys resulting in aquaresis, the electrolytes sparing excretion of water. This article reviews the accumulated experience with tolvaptan and all the major clinical trials that were conducted to study its safety and efficacy and concludes by summarizing clinicians' views of its current application in clinical practice.
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PMID:Tolvaptan, hyponatremia, and heart failure. 2169 50

Sodium and water retention in cardiac failure and cirrhosis is pivotal in the morbidity and mortality of patients with these disorders. Moreover, the pathophysiology of these edematous disorders is quite similar. Both disorders have activation of the renin-angiotensin-aldosterone system, increased sympathetic activity, and nonosmotic stimulation of arginine vasopressin, which is initiated by unloading of the arterial baroreceptors; this occurs secondary to diminished cardiac output with heart failure and primary systemic arterial vasodilation with cirrhosis. With this common pathophysiology causing pulmonary congestion, ascites, and peripheral edema, diuretics are pivotal in the therapy of patients with heart failure and cirrhosis. Advanced cardiac failure and cirrhosis both show secondary hyperaldosteronism and impaired renal escape from the sodium-retaining effect of aldosterone. However, currently there are contradictory uses of mineralocorticoid-receptor antagonists in cardiac failure (non-natriuretic doses) versus cirrhosis (natriuretic doses). This disparity relates to the greater potential of hyperkalemia in cardiac failure patients receiving inhibitors of the renin-angiotensin-aldosterone system. This review discusses the beneficial and potentially deleterious effects of diuretic use in patients with cardiac failure and cirrhosis.
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PMID:Use of diuretics in heart failure and cirrhosis. 2209 7

Antidiuretic hormone (ADH), or arginine vasopressin (AVP), is primarily regulated through plasma osmolarity, as well as non-osmotic stimuli including blood volume and stress. Links between water-electrolyte and carbohydrate metabolism have also been recently demonstrated. AVP acts via the intermediary of three types of receptors: V1a, or V1, which exerts vasoconstrictive effects; pituitary gland V1b, or V3, which participates in the secretion of ACTH; and renal V2, which reduces the excretion of pure water by combining with water channels (aquaporin 2). Antidiuresis syndrome is a form of euvolaemic, hypoosmolar hyponatraemia, which is characterised by a negative free water clearance with inappropriate urine osmolality and intracellular hyper-hydration in the absence of renal, adrenal and thyroid insufficiency. Ninety percent of cases of antidiuresis syndrome occur in association with hypersecretion of vasopressin, while vasopressin is undetectable in 10% of cases. Thus the term "antidiuresis syndrome" is more appropriate than the classic name "syndrome of inappropriate ADH secretion" (SIADH). The clinical symptoms, morbidity and mortality of hyponatraemia are related to its severity, as well as to the rapidity of its onset and duration. Even in cases of moderate hyponatraemia that are considered asymptomatic, there is a very high risk of falls due to gait and attention disorders, as well as rhabdomyolysis, which increases the fracture risk. The aetiological diagnosis of hyponatraemia is based on the analysis of calculated or measured plasma osmolality (POsm), as well as blood volume (skin tenting of dehydration, oedema). Hyperglycaemia and hypertriglyceridaemia lead to hyper- and normoosmolar hyponatraemia, respectively. Salt loss of gastrointestinal, renal, cutaneous and sometimes cerebral origin is hypovolaemic, hypoosmolar hyponatraemia (skin tenting), whereas oedema is present with hypervolaemic, hypoosmolar hyponatraemia of heart failure, nephrotic syndrome and cirrhosis. Some endocrinopathies (glucocorticoid deficiency and hypothyroidism) are associated with euvolaemic, hypoosmolar hyponatraemia, which must be distinguished from SIADH. Independent of adrenal insufficiency, isolated hypoaldosteronism can also be accompanied by hypersecretion of vasopressin secondary to hypovolaemia, which responds to mineralocorticoid administration. The causes of SIADH are classic: neoplastic (notably small-cell lung cancer), iatrogenic (particularly psychoactive drugs, chemotherapy), lung and cerebral. Some causes have been recently described: familial hyponatraemia via X-linked recessive disease caused by an activating mutation of the vasopressin 2 receptor; and corticotropin insufficiency related to drug interference between some inhaled glucocorticoids and cytochrome p450 inhibitors, such as the antiretroviral drugs and itraconazole, etc. SIADH in marathon runners exposes them to a risk of hypotonic encephalopathy with fatal cerebral oedema. SIADH treatment is based on water restriction and demeclocycline. V2 receptor antagonists are still not marketed in France. These aquaretics seem effective clinically and biologically, without demonstrated improvement to date of mortality in eu- and hypervolaemic hyponatraemia. Obviously treatment of a corticotropic deficit, even subtle, should not be overlooked, as well as the introduction of fludrocortisone in isolated hypoaldosteronism and discontinuation of iatrogenic drugs.
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PMID:Hyponatremia and antidiuresis syndrome. 2211 69

Hyponatremia, defined as a serum sodium concentration of <135 mmol/L, often develops as a consequence of elevated levels of arginine vasopressin (AVP) hormone. AVP elevation can occur in a number of common clinical conditions, including syndrome of inappropriate secretion of AVP, volume depletion, postoperative states, heart failure, cirrhosis, neuroendocrine disorders and trauma. A history of concurrent illness and medication use, assessment of extracellular fluid volume as well as measurement of serum and urine osmolality and urine sodium concentration will help to establish the primary underlying causes. Presence or absence of significant neurologic signs and symptoms must guide treatment. Symptomatic hyponatremia must be treated promptly with 3% hypertonic saline to increase the serum sodium by 1-2 mmol/L per hour until symptoms abate, or a total magnitude of correction of 12 mmol/L in 24 hours or 18 mmol/L in 48 hours is achieved. Initial infusion rate (ml/kg per hour) can be estimated by body weight (kg) x desired rate of increase in sodium (mmol/L per hour). An overly rapid increase in sodium (>12 mmol/L per 24 hours) may result in serious neurologic injury. Fluid restriction and loop diuretic are frequently employed to treat volume overload. Vasopressin receptor antagonists provide prompt and effective water diuresis and increase in serum sodium concentration in both euvolemic and hypervolemic hyponatremia. In this review article, the author introduces a problem-solving approach to dissect the different clinical cases with hyponatremia and presents simple algorithms for the evaluation and management of hyponatremia that are useful at the bedside to improve quality, safety and cost-effectiveness of the patient's care.
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PMID:Hyponatremia: a problem-solving approach to clinical cases. 2230 36

Hyponatremia is a common problem in patients with advanced cirrhosis. It develops slowly (paralleling the rate of progression of the liver disease) and usually produces no neurological symptoms, although it may exacerbate hepatic encephalopathy. For patients awaiting liver transplantation a low serum sodium level is a strong predictor of pretransplant mortality, independent of the Model for End-stage Liver Disease score (MELD). The pathogenesis of hyponatremia is related to the hemodynamic changes and secondary neurohormonal adaptations that occur in patients with cirrhosis and ascites. The nonosmotic release of arginine vasopressin is the principle cause of the hyponatremia and vasopressin-receptor antagonists are a new class of drugs recently approved for treatment of cirrhotic hyponatremia. In this article we review the safety and efficacy of V2-receptor antagonists in patients with cirrhosis, ascites and hyponatremia.
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PMID:Vasopressin V2-receptor antagonists in patients with cirrhosis, ascites and hyponatremia. 2257 Jun 79


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