Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyponatremia is the most common electrolyte disorder in hospitalized patients and is associated with the risk of intractable seizures and death. The effectiveness of conventional therapies for hyponatremia is inconsistent, and the rapid correction of plasma sodium levels is thought to result in the occurrence of neurological complications. Arginine vasopressin (AVP) is the primary regulator of renal electrolyte-free water reabsorption via AVP-receptor type 2 (V2-R), and inappropriate or excessive AVP secretion independent of serum osmolality frequently causes excessive water retention, which is the etiological basis of hyponatremia. Therefore, the use of V2-R antagonists as anti-hyponatremic drugs in the clinical setting is anticipated to be reliable and safe. Conivaptan hydrochloride (YM087) is a novel dual AVP-R antagonist for AVP-R types 1a (V1a) and V2-R. In vitro studies have shown that it possesses high affinity for V1a-R and V2-R without any species differences. It also potently inhibited AVP-induced intracellular signaling through human V2 and V1a receptors with no agonistic activity. Conivaptan hydrochloride improved the plasma sodium concentration and plasma osmolality in hyponatremic rats, and its effectiveness was demonstrated in hyponatremic patients. This drug has been approved for use in the United States, which will bring relief to patients with hyponatremia.
 ...
PMID:New topics in vasopressin receptors and approach to novel drugs: research and development of conivaptan hydrochloride (YM087), a drug for the treatment of hyponatremia. 1915 43

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.
 ...
PMID:Novel agents for the treatment of hyponatremia: a review of conivaptan and tolvaptan. 2092 41