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)

Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with increased morbidity and mortality. The recognition of the central role that arginin vasopressin plays in the pathogenesis of hyponatremia and the discovery that its actions are mediated by stimulation of V(1A) and V(2) receptors have led to the development of a new class of drugs, the arginin vasopressin antagonists. Conivaptan is a nonselective V(1A) and V(2) receptors antagonist that was the first of this class to be approved by the FDA for the management of euvolemic and hypervolemic hyponatremia. Its short-term safety and efficacy for the correction of hyponatremia have been established by multiple double-blind, randomized, controlled studies. Blocking the effects of arginin vasopressin on V(2) receptors produces aquaresis--the electrolyte-sparing excretion of water--an ideal approach to correct hypervolemic hyponatremia. The nonselectivity of conivaptan offers a theoretical advantage for its use in heart failure that may merit further exploration.
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PMID:Conivaptan and its role in the treatment of hyponatremia. 2005 44

Hyponatremia is the most commonly encountered electrolyte abnormality. If uncorrected, it can lead to seizure, coma, or death due to brain stem herniation. Once the serum osmolality and volume status of the patient is determined, treatment should be initiated to correct the serum sodium by 8 to 12 mEq/L within the first 24 hours. Arginine vasopressin (AVP) antagonists represent a new class of drugs indicated to treat hypervolemic and euvolemic hyponatremia. Conivaptan is a nonselective AVP antagonist that is available intravenously, and tolvaptan is a V2 selective AVP antagonist that is available as an oral tablet. Both agents produce highly effective and safe aquaresis to increase serum Na levels. Both agents have limited data in heart failure patients, but have been shown to produce significant decreases in pulmonary capillary wedge pressure, body weight, and signs and symptoms of heart failure. Neither drug has been approved for the treatment of heart failure, to date. There were no cases of osmotic demyelination syndrome with these agents, and the most common adverse events during studies were dry mouth and thirst. Overall, both conivaptan and tolvaptan are promising agents that can be used in hospitalized patients. Further studies are needed to assess the appropriateness of their use in symptomatic hyponatremic patients, and to determine their benefits in terms of disease outcome and length of stay to justify the high acquisition costs.
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PMID:Novel agents for the treatment of hyponatremia: a review of conivaptan and tolvaptan. 2092 41

Arginine vasopressin (AVP) is increased in patients with heart failure (HF). Its actions are linked to free water reabsorption (V2-) and arteriolar vasoconstriction (V1a receptor). AVP can exacerbate the cardiorenal syndrome with excess fluid retention and afterload increase. Tolvaptan (TOL; selective V2 antagonist) and Conivaptan (CON; dual V1a/V2 antagonist) are two AVP antagonists that counteract the action of AVP with distinct profiles. We investigated the therapeutic effects of CON and TOL in an acute HF model. Mongrel dogs were paced continuously at 220 beats/min. After 14 days, the animals underwent acute testing. Dogs were instrumented to measure cardiac output, blood pressure, pulmonary artery pressure, and left ventricular dP/dtmax. Additionally, during the acute experiments, vasopressin was infused intravenously (4 mU/kg/min) to achieve constant and controlled pathophysiological levels of AVP. Subsequently, animals received either CON or TOL (n = 6; 0.1-mg/kg bolus). There were no significant differences in effect on mean arterial pressure, dP/dtmax, central venous pressure, and urine output between CON and TOL. In contrast, cardiac output increased by 0.15 l/min after CON and decreased by 0.6 l/min after TOL (P < 0.01). Accordingly, the total peripheral resistance increased after TOL by 250 dyn*s/cm and decreased after CON by 125 dyn*s/cm (P < 0.01). In conclusion, it was demonstrated that in an acute HF model, CON lowered, whereas TOL increased afterload. The results suggest that dual V1a/V2 blockade in the acute HF setting could be beneficial compared with selective V2 blockade. Chronic experiments are needed to determine whether this finding can translate into a sustained clinical advantage.
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PMID:Differentiation of arginine vasopressin antagonistic effects by selective V2 versus dual V2/V1a receptor blockade in a preclinical heart failure model. 2119 48

Conivaptan is a nonspecific arginine vasopressin receptor antagonist that has been used as therapy in adults who have hypervolemic hyponatremia due to congestive heart failure. Its use in children with congestive heart failure has not been reported. We describe the use of conivaptan in a 4-month-old infant girl with severe hypervolemic hyponatremia and heart failure. A therapeutic weight-based dose was extrapolated from the adult dose. Conivaptan therapy was administered for 48 hours, after which the patient recovered from her hyponatremia without untoward effects. Arginine vasopressin receptor antagonists such as conivaptan may be useful as therapy for hyponatremia associated with heart failure. Further studies are required before conivaptan can be recommended for routine use in children.
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PMID:Conivaptan therapy in an infant with severe hyponatremia and congestive heart failure. 2310 79

Hyponatremia is a very common electrolyte abnormality, associated with poor short- and long-term outcomes in patients with heart failure (HF). Two opposite processes can result in hyponatremia in this setting: Volume overload with dilutional hypervolemic hyponatremia from congestion, and hypovolemic hyponatremia from excessive use of natriuretics. These two conditions require different therapeutic approaches. While sodium in the form of normal saline can be lifesaving in the second case, the same treatment would exacerbate hyponatremia in the first case. Hypervolemic hyponatremia in HF patients is multifactorial and occurs mainly due to the persistent release of arginine vasopressin (AVP) in the setting of ineffective renal perfusion secondary to low cardiac output. Fluid restriction and loop diuretics remain mainstay treatments for hypervolemic/ dilutional hyponatremia in patients with HF. In recent years, a few strategies, such as AVP antagonists (Tolvaptan, Conivaptan, and Lixivaptan), and hypertonic saline in addition to loop diuretics, have been proposed as potentially promising treatment options for this condition. This review aimed to summarize the current literature on pathogenesis and management of hyponatremia in patients with HF.
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PMID:Hyponatremia in Heart Failure: Pathogenesis and Management. 3084 91


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