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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurohypophysial hormone arginine vasopressin (AVP) is a cyclic nonpeptide whose actions are mediated by the stimulation of specific G protein--coupled membrane receptors pharmacologically classified into V1-vascular (V1R), V2-renal (V2R) and V3-pituitary (V3R) AVP receptor subtypes. The random screening of chemical compounds and optimization of lead compounds recently resulted in the development of orally active nonpeptide AVP receptor antagonists. Potential therapeutic uses of AVP receptor antagonists include (a) the blockade of V1-vascular AVP receptors in arterial hypertension, congestive heart failure, and peripheral vascular disease; (b) the blockade of V2-renal AVP receptors in the syndrome of inappropriate vasopressin secretion, congestive heart failure, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent dilutional hyponatremia; (c) the blockade of V3-pituitary AVP receptors in adrenocorticotropin-secreting tumors. The pharmacological and clinical profile of orally active nonpeptide vasopressin receptor antagonists is reviewed here.
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PMID:The basic and clinical pharmacology of nonpeptide vasopressin receptor antagonists. 1126 55

Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and disorders of water retention such as congestive heart failure and cirrhosis is a common problem encountered in the care of the medical patient. Thus far, available treatment modalities for disorders of excess arginine vasopressin (AVP) secretion or action have been suboptimal. The development of nonpeptide AVP V2 receptor antagonists represents a promising treatment option to directly antagonize the effects of elevated plasma AVP concentrations by increasing the water permeability of renal collecting tubules, thereby promoting excretion of retained water and normalizing hypoosmolar hyponatremia. In this review, SIADH and other water retaining disorders are briefly discussed, after which the published preclinical and clinical studies in the development of several nonpeptide AVP V2 receptor antagonists are summarized. The likely therapeutic indications and potential complications of these compounds, as well as their vascular effects, are also described.
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PMID:Vasopressin V2 receptor antagonists. 1147 29

Hyponatremia, whether due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or disorders of water retention such as congestive heart failure and cirrhosis, is a very common problem encountered in the care of medical patients. To date, available treatment modalities for disorders of excess arginine vasopressin (AVP) secretion or action have been limited and suboptimal. The recent discovery and development of nonpeptide AVP V(2) receptor antagonists represents a promising new treatment option to directly antagonize the effects of elevated plasma AVP concentrations at the level of the renal collecting ducts. By decreasing the water permeability of renal collecting tubules, excretion of retained water is promoted, thereby normalizing or improving hypo-osmolar hyponatremia. In this review, SIADH and other water retaining disorders are briefly discussed, after which the published preclinical and clinical studies of several nonpeptide AVP V(2) receptor antagonists are summarized. The likely therapeutic indications and potential complications of these compounds are also described.
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PMID:Vasopressin V2 receptor antagonists. 1220 Feb 24

Clinical and laboratory experiments have demonstrated that arginine vasopressin (AVP), renin-aldosterone system and catecholamines play a crucial role in water and sodium retention in edematous diseases, including congestive heart failure, nephrotic syndrome and liver cirrhosis. These hormonal secretions are all increased mediated through baroreceptor mediated afferent pathway, in which the tonic inhibition of hormonal release is attenuated by decreased effective circulatory blood volume. Increased plasma hormones augment their action in renal tubules. AVP increases abundance of aquaporin-2 protein in renal collecting duct cells, and enhances renal water reabsorption. Aldosterone enhances sodium reabsorption in distal nephron. Also, norepinephrine increases sodium reabsorption in proximal tubules, and in part augments renin-aldosterone system that increases sodium reabsorption in distal nephron.
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PMID:[Hormones and hemodynamics in edematous diseases]. 1567 18

Hyponatremia, the most common electrolyte disorder, occurs frequently in older people and in hospitalized patients. Physiological changes of aging that interact with diseases and drugs commonly present in older people put this population at greater risk for hyponatremia. It can accompany central nervous system disorders, pulmonary and renal disease, cancer, congestive heart failure, and liver cirrhosis, as well as many commonly used drugs. Delayed recognition can lead to symptomatic hyponatremia with consequent cerebral edema and possibly irreversible neurological damage. Symptoms and signs of hyponatremia may be subtle or not attributed to hyponatremia. Most cases are of the euvolemic type, in which extracellular fluid volume is normal and is often due to the syndrome of inappropriate secretion of antidiuretic hormone. Hyponatremia can also occur in association with hypervolemia or hypovolemia. Common to all of these circumstances is increased secretion of arginine vasopressin (AVP). Understanding of the pathophysiological basis of hyponatremia and of brain compensatory mechanisms is critical to safe treatment. Fluid restriction or infusion of hypertonic saline can improve symptoms and normalize serum sodium levels but does not address excess AVP, which in most cases is the underlying cause of the disorder. A major new approach to treatment of hyponatremia is the development of aquaretics: AVP-receptor antagonists that provide a targeted therapeutic approach to correcting the many kinds of hyponatremia caused by excess AVP levels.
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PMID:Hyponatremia and arginine vasopressin dysregulation: mechanisms, clinical consequences, and management. 1697 Jun 67

The neurohormone arginine vasopressin plays a significant role in the regulation of volume homeostasis, which is mediated via vasopressin type 2 (V2) receptors in the collecting tubules of the kidney. Diseases that are accompanied by abnormal volume homeostasis, including congestive heart failure and cirrhosis, are a frequent cause of hospital admissions and increasing healthcare costs. Recently, several nonpeptide V2 receptor antagonists have emerged as promising agents in the management of these conditions with the advantage of having no electrolyte abnormalities, neurohormonal activation or worsening renal insufficiency. Tolvaptan, a highly selective nonpeptide V2 receptor antagonist, has demonstrated an improvement in the volume status, osmotic balance and haemodynamic profile in preclinical and Phase II trials in patients with congestive heart failure and is currently undergoing testing in Phase III trials. This review discusses the evidence for the potential uses of tolvaptan, and its pharmacology and pharmacokinetics, particularly in congestive heart failure.
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PMID:Tolvaptan: a selective vasopressin type 2 receptor antagonist in congestive heart failure. 1663 91

Hyponatremia is a common electrolyte disorder associated with potentially serious or life-threatening consequences. Serum osmolality and sodium concentration [Na+] are regulated by thirst, the hormone arginine vasopressin (AVP), and renal water and sodium handling. Hyponatremia is frequently caused by dysregulation of AVP, which accompanies disorders of water retention, such as congestive heart failure (CHF) and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Clinical trials with AVP receptor antagonists have confirmed the important role of AVP in the pathophysiology of hyponatremia and suggest these agents are efficacious in treating hyponatremia associated with SIADH, cirrhosis, and CHF. Acting directly at AVP receptors in the renal tubules, these agents promote aquaresis - the electrolyte-sparing excretion of free water - in patients with hyponatremia. In clinical trials, AVP receptor antagonists have been shown to increase the serum [Na+] and urine output while decreasing urine osmolality.
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PMID:Vasopressin antagonists: role in the management of hyponatremia. 1683 88

This article discusses the pathophysiology of sodium and water retention in edematous disorders with a particular focus on cardiac failure, cirrhosis, and pregnancy. The body fluid volume hypothesis, which emphasizes the dominant role of arterial baroreceptors in renal sodium and water excretion, is reviewed. With arterial underfilling, either due to a decrease in cardiac output or peripheral arterial vasodilation, the normal central inhibition of the sympathetic nervous system activity and baroreceptor-mediated, nonosmotic arginine vasopressin (AVP) release is attenuated. The resultant increase in renal adrenergic activity stimulates the renin-angiotensin-aldosterone system. Although the resultant increase in systemic vascular resistance compensates for the primary arterial underfilling, this activation of the neurohumoral axis results in diminished sodium and water delivery to the renal collecting duct sites of aldosterone, AVP, and natriuretic peptide action. This diminished distal sodium and water delivery will be discussed as an important factor in the failure to escape from the sodium-retaining effects of aldosterone, the resistance to the natriuretic and diuretic effects of natriuretic peptides, and the diminished maximal solute-free water excretion in patients with edema. The role of the nonosmotic AVP release in water retention and hypo-osmolality/hyponatremia has been demonstrated in patients and experimental animals by administering nonpeptide, orally active vasopressin V2 receptor antagonists. These agents have been found to increase solute-free water excretion in patients with water-retaining, hyponatremic edema as well as in experimental animals.
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PMID:Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. 1684 85

Hyponatremia is the most frequent electrolyte disorder encountered in hospitalized patients. It is a state of relative water excess due to stimulated arginine vasopressin (AVP) and fluid intake greater than obligatory losses. This kind of hyponatremia occurs in the syndrome of inappropriate antidiuretic hormone secretion, congestive heart failure, and liver cirrhosis. Fluid restriction is the presently recommended treatment for hyponatremia. However, fluid restriction may be very difficult for patients to achieve, is slow to work, and does not allow a graded therapeutic approach. More efficient and specific treatments of hyponatremia are needed. In this respect, pharmacologic research has yielded a number of compounds exhibiting antagonistic qualities at the vasopressin V2 receptor. Among these agents, peptidic derivatives of AVP turned out to have intrinsic antidiuretic properties in vivo when given over days or weeks. The development of such agents for use in patients has not been pursued. However, several promising nonpeptide, vasopressin receptor antagonists have been described; these agents are VPA-985 (lixivaptan), YM-087 (conivaptan), OPC-41061 (tolvaptan), and SR-121463. Prospective, randomized, placebo-controlled trials performed with these agents found that they corrected hyponatremia efficiently and safely. Most of the studies were conducted over a 4- to 28-day period. Long-term studies will be needed in the future to address such issues as the eventual benefit to patients and the effects of vasopressin antagonists on morbidity and mortality of patients with hyponatremia.
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PMID:Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. 1684 91

The antidiuretic hormone arginine vasopressin (AVP) is primarily responsible for regulating osmotic and volume homeostasis of body fluids, largely through binding to vasopressin type 1A (V(1A)) and type 2 (V2) receptors. Increased AVP secretion leads to decreased free water excretion with resulting water retention, and can cause dilutional hyponatremia. A new class of medications known as AVP receptor antagonists induces free water diuresis without natriuresis or kaliuresis, an effect termed aquaresis. Numerous clinical trials show AVP antagonists to be effective at increasing free water excretion and serum sodium in patients with hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion or edema-forming states such as congestive heart failure and cirrhosis. This article reviews clinical trial data on the AVP antagonists in late development (lixivaptan, satavaptan, and tolvaptan) and recently approved for marketing (conivaptan).
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PMID:AVP receptor antagonists as aquaretics: review and assessment of clinical data. 1697 Jan 50


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