Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxybutynin (Ditropan) is widely utilized in treatment of incontinence due to neurogenic bladder dysfunction. We prepared its R and S enantiomers and evaluated their antimuscarinic, Ca++-channel antagonistic and spasmolytic effects in guinea pig detrusor strips and ileal longitudinal muscle. Ussing chambers were used to assess inhibition of carbachol-induced mucosal Cl-secretion in vitro. The enantiomers and the racemate were also tested in in vivo preparations for local anesthetic activity and for antimuscarinic activity in the slow filling cystometrogram. Stereoselective antimuscarinic effects [R)OXY:(R/S)OXY:(S)OXY) were evident for isolated ileal longitudinal (0.12:1.0:4.5) and bladder detrusor muscle (0.5:1.0:13) isolated ileal mucosa (0.2:1:8.9) and acetylcholine stimulated phosphoinositide turn-over in vitro (0.24:1.0:39). Stereoselectivity was also evident for the volume-induced contractions of the cystometrogram in vivo (0.7:1:15). In contrast, no stereoselectivity was observed for Ca++-channel antagonism, spasmolytic and local anesthetic properties of (R/S)OXY and its enantiomers.
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PMID:R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine. 284 72

Overactive bladder (OAB) syndrome affects millions of people worldwide. In addition to adversely affecting quality of life, the direct and indirect costs in managing patients with OAB incur a substantial financial burden on health services. Among the approved anticholinergics for treating OAB, oxybutynin is the most extensively studied drug in clinical trials. The principle metabolite of oxybutynin has a higher affinity for muscarinic receptors in salivary glands which lead to significantly high dry mouth rates. This prompted the development of alternative formulations of oxybutynin aiming to achieve better tolerability whilst sustaining efficacy. This editorial examines the efficacy and tolerability of transdermal oxybutynin (OXY-TD) in treating OAB. Articles were retrieved from PubMed between 2000 to the present day relating to OXY-TD. Data is presented from phase I-IV trials. The results from placebo-controlled trials indicate that OXY-TD is efficacious in treating patients with OAB associated with urge urinary or mixed incontinence. Systemic side effects most notably dry mouth, appear to be less with this formulation compared with oral anticholinergics. However, further study is required in different OAB populations. The main limitation appears to be related to application site adverse events such as pruritus and erythema. OXY-TD is likely to find its place as first-line pharmacotherapy in the clinicians' armamentarium in treating OAB.
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PMID:Evolution of transdermal oxybutynin in the treatment of overactive bladder. 1817 9

The increasing proportion of elderly persons in the global population, and the implications of this trend in terms of increasing rates of chronic diseases such as type 2 diabetes mellitus, continue to be a cause for concern for clinicians and healthcare policy makers. The diagnosis and treatment of type 2 diabetes in the elderly is challenging, as age-related changes alter the clinical presentation of diabetic symptoms. Once type 2 diabetes is diagnosed, the principles of its management are similar to those in younger patients, but with special considerations linked to the increased prevalence of co-morbidities and relative inability to tolerate the adverse effects of medication and hypoglycaemia. In addition, there are many underappreciated factors complicating diabetes care in the elderly, including cognitive disorders, physical disability and geriatric syndromes, such as frailty, urinary incontinence and pain. Available oral antihyperglycaemic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors and thiazolidinediones. Unfortunately, as type 2 diabetes progresses in older persons, polypharmacy intensification is required to achieve adequate glycaemic control with the attendant increased risk of adverse effects as a result of age-related changes in drug metabolism. The recent introduction of the incretins, a group of intestinal peptides that enhance insulin secretion after ingestion of food, as novel oral antihyperglycaemic treatments may prove significant in older persons. The two main categories of incretin therapy currently available are: glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). The present review discusses the effect of aging on metabolic control in elderly patients with type 2 diabetes, the current treatments used to treat this population and some of the more recent advances in the field of geriatric type 2 diabetes. In particular, we highlight the efficacy and safety of GLP-1 and DPP-4 inhibitors, administered as monotherapy or in combination with other oral antihyperglycaemic agents, especially when the relevant clinical trials included older persons. There is strong evidence that use of incretin therapy, in particular, the DPP-4 inhibitors, could offer significant advantages in older persons. Clinical evidence suggests that the DPP-4 inhibitors vildagliptin and sitagliptin are particularly suitable for frail and debilitated elderly patients because of their excellent tolerability profiles. Importantly, these agents lack the gastrointestinal effects seen with metformin and alpha-glucosidase inhibitors taken alone, and have a low risk of the hypoglycaemic events commonly seen with agents that directly lower blood glucose levels.
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PMID:New approaches to treating type 2 diabetes mellitus in the elderly: role of incretin therapies. 1894 59

This article provides an overview of the results of the MATRIX study. Subsequent articles will provide more detailed results of other findings in this study. Overall, this study found that OXY-TDS administration resulted in improvement in HRQoL, with the medication having its greatest effect on the impact of incontinence, severity of symptoms, and role limitations. OXY-TDS was well tolerated, with a low prevalence of anticholinergic adverse events noted. The next article will focus on results in populations older than 65 years and in those older than 80 years.
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PMID:The MATRIX study: assessment of health-related quality of life in adults with the use of transdermal oxybutynin. 1934 80

The MATRIX study consisted of a large population of older adults. In addition to those over the age of 65, this study included 131 patients > or =85 years old. Even though these adults were community-based, many of them had similar medical histories, comorbidities, use of multiple medications and urinary incontinence histories as those residing in long-term care settings. This study found OXY-TDS to be effective in improving quality of life in these older adults. In addition, there was a low incidence of adverse events, particularly anticholinergic events. Overall, this study supports the use of OXY-TDS in older adults-those residing in community and nursing facility settings. The next article in this series will present other results of the MATRIX study, including the changes in nocturia and pad use, as well as the effect of OXY-TDS in participants with prostate problems.
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PMID:The MATRIX study: evaluating the data in older adults. 1934 87

Overactive bladder (OAB), clinically defined as urinary urgency, with or without incontinence, generally accompanied by an increase in urinary frequency and nocturia, after any local disease or metabolic disorder that would explain these symptoms have been ruled out, is a highly prevalent condition that affects millions of men and women worldwide. Not only can the symptoms of OAB be very bothersome, but OAB can have significant detrimental effects on many aspects of individuals' lives, representing a particularly impactful health burden to quality of life and productivity. Besides a wide range of conservative treatments, the clinical efficacy of which remains an open issue, antimuscarinics are the mainstay of pharmacotherapy for this condition but anticholinergic troublesome side effects like dry mouth, and the patient's perception of lack of efficacy and poor adherence, are common reasons of abandonment of treatment. An alternative to oral administration treatment, with a lower incidence of dry mouth and other anticholinergic adverse effects, might be attractive to patients and a real treatment option for physicians. Delivery of oxybutynin directly through the skin with oxybutynin transdermal (OXY-TDS) avoids the first-pass hepatic metabolism that occurs with orally administered oxybutynin and prevents the appearance of anticholinergic adverse events. OXY-TDS being equally effective than oral treatment improves adherence, persistence, and patient satisfaction. The aim of this review is to focus on evidence available of the use of OXY-TDS in the management of patients with OAB, and to help clinicians in the challenges involved in the treatment options for patients with this condition.
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PMID:Insights into the Management of Overactive Bladder with Transdermal Oxybutynin: A Practical Review. 3288 26