Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677481 (urinary frequency)
 1,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trospium chloride is a quaternary ammonium compound, which is a competitive antagonist at muscarinic cholinergic receptors. Preclinical studies using porcine and human detrusor muscle strips demonstrated that trospium chloride was many-fold more potent than oxybutynin and tolterodine in inhibiting contractile responses to carbachol and electrical stimulation. The drug is poorly bioavailable orally (< 10%) and food reduces absorption by 70%- 80%. It is predominantly eliminated renally as unchanged compound. Trospium chloride, dosed 20 mg twice daily, is significantly superior to placebo in improving cystometric parameters, reducing urinary frequency, reducing incontinence episodes, and increasing urine volume per micturition. In active-controlled trials, trospium chloride was at least equivalent to immediate-release formulations of oxybutynin and tolterodine in efficacy and tolerability. The most problematic adverse effects of trospium chloride are the anticholinergic effects of dry mouth and constipation. Comparative efficacy/tolerability data with long-acting formulations of oxybutynin and tolterodine as well as other anticholinergics such as solifenacin and darifenacin are not available. On the basis of available data, trospium chloride does not appear to be a substantial advance upon existing anticholinergics in the management of urge urinary incontinence.
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PMID:Trospium chloride: an update on a quaternary anticholinergic for treatment of urge urinary incontinence. 1836 May 55

*Oxybutynin inhibits contraction of the detrusor muscle in the overactive bladder by binding to muscarinic M(3) receptors and blocking acetylcholinergic activation. *The transdermal oxybutynin system, applied twice weekly, delivers continuous oxybutynin over a 96-hour patch wear period. The transdermal route of administration avoids the extensive first-pass metabolism of oxybutynin to its active metabolite, N-desethyloxybutynin. *In two well designed trials in patients with overactive bladder, transdermal oxybutynin 3.9 mg/day decreased the number of incontinence episodes and increased average voided volume to a significantly greater extent than placebo. Urinary frequency was improved to a significantly greater extent with transdermal oxybutynin than with placebo in one trial but not the other. *There was no significant difference between transdermal oxybutynin and extended-release oral tolterodine for any of these endpoints. *Health-related quality-of-life improvements with transdermal oxybutynin were shown in patients with overactive bladder in the open-label MATRIX trial, as demonstrated by significant improvements in all domains of the King's Health Questionnaire. *Transdermal oxybutynin is generally well tolerated in patients with overactive bladder. The majority of patients who discontinued transdermal oxybutynin treatment in two pivotal trials did so because of application-site reactions. However, none discontinued treatment because of dry mouth.
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PMID:Transdermal oxybutynin. 1927 76

Vasopressin antagonists increase the serum sodium concentration in patients who have euvolemia and hypervolemia with hyponatremia in the short term (</=30 days), but their safety and efficacy with longer term administration is unknown. SALTWATER was a multicenter, open-label extension of the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT-1 and SALT-2). In total, 111 patients with hyponatremia received oral tolvaptan for a mean follow-up of 701 days, providing 77,369 patient-days of exposure. All patients had hyponatremia at randomization in SALT-1 and SALT-2, and 85% continued to have hyponatremia at entry in SALTWATER. The most common adverse effects attributed to tolvaptan were pollakiuria, thirst, fatigue, dry mouth, polydipsia, and polyuria. Six drug-related adverse effects led to study discontinuation. The increase in serum sodium exceeded the desired 1 mmol/L per h at initiation in five patients. Hypernatremia (>145 mmol/L) led to discontinuation in one patient. Mean serum sodium increased from 130.8 mmol/L at baseline to >135 mmol/L throughout the observation period (P < 0.001 versus baseline at most points). Responses were comparable between patients with euvolemia and those with heart failure but more modest in patients with cirrhosis. In conclusion, prolonged administration of tolvaptan maintains an increased serum sodium with an acceptable margin of safety.
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PMID:Oral tolvaptan is safe and effective in chronic hyponatremia. 2050 68

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

An 80-year-old man had systemic malaise and pollakiuria, which developed about 40 days before admission. He underwent treatment at a urology department, but his symptoms did not improve. Since dry mouth additionally developed, he visited his family doctor. As his casual blood glucose level was 629 mg/dl and HbA1c was 12.4%, the patient was referred to our department and admitted on the same day. Continuous intravenous infusion of fast-acting insulin and saline were initiated after admission, and dietary therapy at 1,520 kcal/day was initiated on the following day. Anti-GAD antibody and anti-IA-2 antibody were positive, confirming that the disease was acute-onset autoimmune type 1 diabetes mellitus. A sliding scale of fast-acting insulin followed by intensified therapy using insulin glargine and insulin aspart was performed in the early phase, but the treatment was switched to twice-daily biphasic insulin aspart 30 injection because no diabetic complication was present, although the patient was already totally blind and required assistance from his family for self-injection and to improve his quality of life (QOL). Blood glucose control was favorable, and the patient was discharged on April 2.
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PMID:[A very elderly case of acute-onset autoimmune type 1 diabetes mellitus]. 2130 Nov 63

Interferon alpha is a molecule frequently used in the treatment of chronic hepatitis B, C, and D, with immunomodulatory and antiviral activity. It is also used in some cancer types. It has been widely claimed that interferon alpha triggers autoimmunity, with its broad adverse effect profile. Here we present the case of a 29-year-old male patient with chronic hepatitis B diagnosis who developed type 1 diabetes mellitus and autoimmune thyroiditis during treatment with interferon alfa-2b. Within four months of initiation of treatment with interferon alfa-2b, the patient presented to our clinic with dry mouth, urinary frequency (8 to 10 times per day), drinking plenty of water, night time urination, and tiredness. He was admitted to the clinic when his fasting blood glucose level was detected to be high. After examinations, the patient was diagnosed with type 1 diabetes and autoimmune thyroiditis and began to receive treatment with insulin and propranolol. Fasting blood glucose levels were controlled and thyroid hormones decreased to normal levels within one month after the treatments began. For patients who will receive treatment with interferon alpha, especially those individuals with chronic hepatitis, pancreatic autoantibodies should be checked and close monitoring should be performed as there may be glucose tolerance impairment in patients with high titers. In addition, follow-up with thyroid function tests should be performed prior to and during the treatment.
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PMID:Chronic hepatitis B with type I diabetes mellitus and autoimmune thyroiditis development during interferon alpha therapy. 2250 48

The aim of the randomised, double blind, placebo controlled study was to evaluate the efficacy, tolerability and safety of solifenacin, a once-daily M3 selective receptor antagonist, in patients with overactive bladder syndrome. Following a single blind 2-week placebo run in period, patients who complained from symptoms of OAB for at least 6 months, were randomized to 4 weeks of solifenacin in 5 mg once daily doses or placebo. 171 patients were enrolled in the study and 157 patients completed the study. Patients with solifenacin had significantly improved micturitions per 24 hours after first week of treatment (1.75 +/- 0.63 vs. 2.64 +/- 0.48, p < 0.001), and after four weeks (1.56 +/- 0.58 vs. 2.71 +/- 0.45, p < 0.001) compared to placebo group. The mean number of urgency episodes per 24 hours had significantly decreased in patients with solifenacin compared to placebo after first week (5.75 +/- 1.43 vs. 6.65 +/- 0.65, p < 0.001), and after four weeks of treatment (5.77 +/- 1.33 vs. 6.54 +/- 0.50, p < 0.001). Solifenacin was also significantly more effective than placebo in reducing the mean number of episodes of severe urgency from baseline to end point (5.83 +/- 1.16 vs. 6.48 +/- 0.50, p < 0.001). Compared with changes obtained with placebo, episodes of urinary frequency were significanlty reduced after first week (0.3 vs. -0.5, p < 0.001) and four weeks check up periods in patients treated with solifenacin (0.19 vs. -0.15, p < 0.001). Episodes of nocturia was significantly reduced in patients treated with solifenacin after first week (0.3 vs. -0.5, p < 0.001), and after four weeks treatment period (0.45 vs. -0.50, p < 0.001). The number of incontinence episodes was also significantly decreased in solifenacin group compared to placebo group after first week (1.06 +/- 0.57 vs. 2.74 +/- 0.47, p < 0.001) and four weeks check up (0.96 +/- 0.57 vs. 2.75 +/- 0.43, p < 0.001). The most common adverse effects with solifenacin were dry mouth and constipation. Adverse effects were mild or moderate severity. The discontinuation rate owing to adverse effects was 4.5%-6.7% with solifenacin and 3.8%-6.1% with placebo, respectively. According to subjective estimation, significant improvement was achieved in 71 (92.21%) of patients treated with solifenacin and in 68 (85%) patients treated with placebo there was no change in OAB symptoms compared to baseline values. UDI score was significantly improved after solifenacin (22.26 +/- 5.91 vs. 29.61 +/- 8.45, p < 0.001) compared to placebo. IIQ score was significantly decreased in patients with solifenacin (36.25 +/- 10.34 vs. 46.86 +/- 6.81, p < 0.001) compared to placebo. In conclusion, solifenacin is a safe and effective treatment alternative for patients with overactive bladder symptoms.
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PMID:The efficacy and safety of solifenacin in patients with overactive bladder syndrome. 2281 27

Pediatric gliosarcoma (GS) is a rare variant of glioblastoma multiforme. The authors describe the case of an unusual pontine location of GS in a 9-year-old boy who was initially diagnosed with low-grade astrocytoma (LGA) that was successfully controlled for 4 years. Subsequently, his brain tumor transformed into a GS. Prior treatment of his LGA included subtotal tumor resection 3 times, standard radiation therapy, and Gamma Knife procedure twice. His LGA was also treated with a standard chemotherapy regimen of carboplatin and vincristine, and his GS with subtotal resection, high-dose cyclophosphamide, and thiotepa with stem cell rescue and temozolomide. Unfortunately, he developed disseminated disease with multiple lesions and leptomeningeal involvement including a tumor occupying 80% of the pons. Upon presentation at our clinic, he had rapidly progressing disease. He received treatment with antineoplastons (ANP) A10 and AS2-1 for 6 years and 10 months under special exception to our phase II protocol BT-22. During his treatment with ANP his tumor stabilized, then decreased, and, ultimately, did not show any metabolic activity. The patient's response was evaluated by magnetic resonance imaging and positron emission tomography scans. His pathology diagnosis was confirmed by external neuropathologists, and his response to the treatment was determined by central radiology review. He experienced the following treatment-related, reversible toxicities with ANP: fatigue, xerostomia and urinary frequency (grade 1), diarrhea, incontinence and urine color change (grade 2), and grade 4 hypernatremia. His condition continued to improve after treatment with ANP and, currently, he complains only of residual neurological deficit from his previous surgery. He achieved a complete response, and his overall and progression-free survival is in excess of 13 years. This report indicates that it is possible to obtain long-term survival of a child with a highly aggressive recurrent GS with diffuse pontine involvement with a currently available investigational treatment.
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PMID:Long-term survival (>13 years) in a child with recurrent diffuse pontine gliosarcoma: a case report. 2413 26

Muscarinic receptors have long been the target receptors for treatment of patients with overactive bladder (OAB). These patients experience symptoms of urgency, urinary frequency and nocturia, with or without urge incontinence (the involuntary leakage of urine associated with urge). Fesoterodine, a pro-drug, structurally and functionally related to tolterodine, is the newest agent developed for the treatment of OAB. Fesoterodine is broken down to the active metabolite, 5-hydroxy-methyl-tolterodine (5-HMT) by non-specific esterases. This metabolism results in the complete breakdown of the parent compound and is responsible for dose related improvements in clinical efficacy and health related quality of life. Like other antimuscarinic agents including tolterodine, fesoterodine is associated with improvements in clinical variables related both to bladder filling (decreasing micturition frequency and increasing mean voided volume) and urgency (urgency and urge incontinence episodes). Improvements in health related quality of life following treatment with fesoterodine is indicated by improvements in 7 of the 9 variables measured by the King's Health Questionnaire. Also like other antimuscarinic agents, fesoterodine use is associated with adverse events including dry mouth. However the incidence of dry mouth is reduced with fesoterodine, compared to oxybutynin, due to the improved bladder selectivity of 5-HMT.
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PMID:Role of fesoterodine in the treatment of overactive bladder. 2419 8

To analyze the characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy (DN) and its compliance with traditional Chinese medicine (TCM)symptom, for the sake of providing a basis for clarifying the rules of TCM syndrome differentiation in DN. Adopting the traditional epidemiological retrospective method, thirty-eight TCM syndromes and urinary protein with medium or low molecular weight, as well as urinary enzyme, including 24 h urinary protein (Upro), urinary albumin( UAlb), urinary retinal binding protein( URBP), urinary cystatin C (UCysC), urinary N-acetyl-beta-D-glucosaminidase (UNAG), were collected from 108 patients with stage III DN, and a multiple factor regression analysis between them was conducted. As the results, the levels of Upro, UAlb, URBP, UCysC, and UNAG were increased in 108 patients with stage III DN. Qi-Yin deficiency type was the major type. The level of UAlb in patients with Qi-Yin deficiency type was significantly higher than those without Qi-Yin deficiency type (P < 0.05). The elevation of Upro with the factors as swift digestion with rapid hungering, lassitude and lack of strength, weakness of waist and knees was complied, the elevation of UA1b with the factors as dry mouth with desire to drink, the elevation of URBP with the factors as numbness of extremities, shortness of breath, the elevation of UCysC with the factors as clear urine in large amounts, and the elevation of UNAG with the factors as frequent micturition, were complied respectively. In conclusion, for 108 stage III DN patients. The increase in urinary protein spectrum including UAlb, URBP, UCysC, and UNAG is the major characteristic. Shen and Pi are the major organs related to the appearance of urinary protein; Pi-Shen deficiency is the basic pathogenesis. The level of UAlb is taken as one of the objective syndrome factors for Qi-Yin deficiency type. The levels of UNAG and UCysC are possibly the objective syndrome factors for Shen-Qi deficiency type.
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PMID:[Characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy and its regression analysis with traditional Chinese medicine symptom]. 2479 9


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