Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 32-year-old pregnant female was admitted to our hospital at 32 week gestation and was scheduled for emergent cesarean section because of fetal distress. She had been suffering hydrodipsia and dry mouth, and had lost 4 kg in 2 weeks. Hypernatremia, hyperchloremia, and lower urinary specific gravity were preoperatively noted. Her electrolyte imbalance was partially corrected by the infusion of 1400 ml of 5% glucose solution and 500 ml of acetated Ringer's solution, but unexpected hyperglycemia; 440 mg.dl-1, appeared before surgery. Cesarean section was successfully performed with spinal anesthesia. A 1566 g male infant was delivered with 1 and 5 min Apgar scores of 2 and 1. Hyperglycemia and secondary hypoglycemia occurred in the infant in the neonatal ICU. The mother's fluid loss, including blood and amniotic fluid, was estimated at 784 ml. Five hundred milliliters of acetated Ringer's solution and 1000 ml of half saline solution with 2.5% glucose were infused before delivery, followed by the glucose solution containing a low concentration of sodium after delivery. After surgery, high serum osmotic pressure and paradoxically low urinary osmotic pressure were found. The plasma antidiuretic hormone level was normal against the high serum osmotic pressure. The electrolyte imbalance and urinary osmotic pressure were improved by using I-deamino-8-d-arginine vasopressin, and DI was finally diagnosed. Hormonal therapy was discontinued on day 20, and the patient was discharged on day 21. Some pregnancies are complicated by transient DI. Anesthesiologists have to consider DI when a pregnant female has symptoms of dehydration and a significant electrolyte imbalance.
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PMID:[Anesthesia for cesarean section in a patient with transient diabetes insipidus]. 1264 72

Two single-center, double-blind, randomized, placebo-controlled, sequentially enrolled studies were conducted. In study 1, 8 subjects (6 active/2 placebo) received 60-, 90-, 120-, 180-, or 240-mg tolvaptan/matching placebo. In study 2, 9 subjects (6 active/3 placebo) received 180-, 240-, 300-, 360-, 420-, or 480-mg tolvaptan/matching placebo. Increases in tolvaptan C(max) were less than dose-proportional and plateaued at doses greater than 240 mg; AUC(infinity) increased proportionally with dose. Changes in serum K(+), creatinine clearance, and Na(+), K(+), and osmolality urinary excretion were similar to the placebo group for the 0- to 24-hour interval following dosing. Changes were observed in plasma arginine vasopressin, serum aldosterone, and plasma renin activity but were not clinically significant. Increases were seen in mean serum Na(+) concentrations (4-6 mEq/L), plasma osmolality ( approximately 8 mOsm/kg), and free water clearance ( approximately 6 mL/min) throughout 0 to 24 hours; none of these increases was dose dependent. Only total urine volume excretion (0-72 hours postdose) increased linearly with dose. As plasma tolvaptan concentrations increased, the duration that the urine excretion rate remained above baseline rates also increased. The most frequent adverse events--excess thirst, frequent urination, and dry mouth--appeared to be related to the pharmacological action of tolvaptan. No dose-limiting toxicities were observed.
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PMID:Pharmacokinetics, pharmacodynamics, and safety of tolvaptan, a nonpeptide AVP antagonist, during ascending single-dose studies in healthy subjects. 1792 89

Tolvaptan is an oral, once-daily nonpeptide arginine vasopressin V(2)-receptor antagonist under development for the treatment of hyponatremia and congestive heart failure. In Phase II clinical trials, tolvaptan, in addition to standard therapy, increased fluid loss, resulting in decreased body weight and improved edema and serum sodium without affecting blood pressure, heart rate or renal function in patients with heart failure. The compound appeared to be well tolerated and dose-dependent adverse events were generally realated to its pharmacological activity, such as thirst and dry mouth. In patients with hyponatremia, tolvaptan appears to be more effective than fluid restriction at improving sodium levels without an increase in adverse events. An international Phase III outcome study; Efficacy of Vasopressin antagonism in hEaRt failurE outcome Study with Tolvaptan (EVEREST), evaluating the long-term efficacy and safety of tolvaptan in patients hospitalized with worsening heart failure, is currently ongoing.
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PMID:Tolvaptan for the treatment of hyponatremia and congestive heart failure. 1980 53

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 cornerstone of treatment for syndrome of inappropriate antidiuretic hormone secretion (SIADH) is fluid restriction. Demeclocycline is sometimes used but its efficacy is based solely on laboratory endpoints. This drug also has the adverse effects shared by all tetracyclines. Tolvaptan antagonises receptors for arginine vasopressin, a hormone that regulates blood sodium levels by stimulating renal water resabsorption. Tolvaptan is now authorised in the European Union for the treatment of hyponatraemia due to SIADH. Clinical evaluation of tolvaptan in this setting is based on two comparative double-blind placebo-controlled trials including a total of 448 patients with SIADH or hyponatraemia from various other causes. The two trials were combined for analysis. However, because of major methodological flaws, no firm conclusions can be drawn concerning the efficacy in SIADH patients. It remains to be shown that tolvaptan improves symptoms of hyponatraemia (especially neuropsychiatric disorders) or even that it corrects hyponatraemia in these patients. The adverse effects observed in clinical trials were predictable, given the mechanism of action, and included thirst and dry mouth (respectively 16% and 8.4% of patients), hypernatraemia (1.7%), pollakiuria and polyuria. Tolvaptan is metabolised by the cytochrome P450 isoenzyme CYP 3A4, hence a high risk of pharmacokinetic interactions. In summary, there is no reason to use tolvaptan to treat the syndrome of inappropriate antidiuretic hormone secretion: its efficacy on symptoms or even on sodium levels has not been demonstrated, and its adverse effect profile is poorly documented. It is better to concentrate on non-drug management.
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PMID:Tolvaptan: any evidence of efficacy in SIADH? 2118 Mar 68