Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344232 (blurred vision)
 2,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extended-release oxybutynin (Ditropan XL) uses an osmotic system (OROS) to deliver a controlled amount of oxybutynin chloride into the gastrointestinal tract over a 24-hour period when taken once daily. Oxybutynin binds to M3 muscarinic receptors on the detrusor muscle of the bladder, preventing acetylcholinergic activation and relaxing the muscle. Mean peak plasma concentrations are lower with extended-release oxybutynin 15mg once daily than with conventional immediate-release oxybutynin 5mg taken 3 times daily. Relative bioavailabilities of parent drug and metabolite N-desethoxybutynin are 153 and 69%, respectively, for extended-release oxybutynin when compared with immediate-release oxybutynin. In short (< or =6 weeks) randomised, double-blind clinical trials of patients with detrusor instability, extended-release oxybutynin 5 to 30mg once daily significantly reduced the mean weekly number of urge incontinence episodes by 84 to 90%. Extended-release oxybutynin had similar efficacy to immediate-release oxybutynin. Adverse events reported by patients taking extended-release oxybutynin were dose-related anticholinergic effects, most frequently dry mouth, somnolence, constipation, blurred vision and dizziness. A large noncomparative study demonstrated that approximately two thirds of the patients prescribed extended-release oxybutynin for detrusor instability were still taking the medication 6 months later.
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PMID:Extended-release oxybutynin. 1075 30

A wealth of clinical evidence supports the view that muscarinic receptor antagonists are effective in the treatment of overactive bladder. However, treatment-limiting adverse effects such as dry mouth, constipation, and blurred vision have restricted the usefulness of previously available agents, such as oxybutynin. A real need therefore existed for effective and well-tolerated agents for the long-term management of the troublesome symptoms of overactive bladder. This review outlines the various approaches that have been used in attempts to overcome the tolerability problems of oxybutynin. It also describes how advances in our understanding of muscarinic receptors and bladder function has led to the potential development of either tissue- or subtype-selective antimuscarinic agents with improved tolerability. Drugs that have been developed in this way include tolterodine and darifenacin, each of which shows some bladder selectivity in animal models. Unlike darifenacin, however, the bladder selectivity of tolterodine has been confirmed by numerous clinical studies. Tolterodine's improved tolerability compared with oxybutynin, along with its equivalent therapeutic efficacy at recommended dosages, permits patients to experience the beneficial effects of long-term treatment. Tolterodine therefore represents a real alternative for the long-term management of overactive bladder. The results of ongoing clinical studies with darifenacin are awaited before it can be concluded that selective antagonism of M(3) receptors leads to improved tolerability over existing agents in the treatment of overactive bladder. Similarly, the potential improvements in tolerability associated with different dosage formulations of oxybutynin, and the clinical utility of S-oxybutynin, are yet to be conclusively demonstrated.
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PMID:Muscarinic receptor antagonists in the treatment of overactive bladder. 1076 51

This study was undertaken to analyse the clinical and immunological features in a large group of Lambert-Eaton Myasthenic Syndrome (LEMS) patients (n = 110). In the Japanese LEMS patients studied, there was a male predominance with a male to female ratio of 3:1. The age at onset of neurological symptoms ranged between 17 and 80 years with a mean of 62 years. Malignancy was detected in 69% of the patients, of whom 61% had small cell lung carcinoma (SCLC). Neurological symptoms preceded a diagnosis of malignancy in 84% of cases. The neurological findings were similar in all patients and consisted of lower limb weakness in 97%, upper limb weakness in 80%, hyporeflexia in 85%, autonomic dysfunction in 37% (dry mouth in 31%, constipation in 11%, impaired sweating, urinary disturbance, impotence, and blurred vision in less than 10%), blepharoptosis in 28% and ophthalmoplegia in 5%. Signs of cerebellar involvement are noted in 9% and all of these patients had SCLC. Of 110 patients with LEMS, 85% had detectable antibodies against P/Q-type voltage-gated calcium channel (P/Q-type VGCC). Seronegative patients (15%) had similar neurological findings, but a lower incidence of SCLC than seropositive patients. The clinical features of our patients were very similar to those observed in British LEMS patients (n = 50), but autonomic features in our study were less prevalent than reported in British patients.
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PMID:[The Lambert-Eaton myasthenic syndrome: a study of 110 Japanese cases]. 1079 Oct 87

We report the case of a 72-year-old female with pure autonomic failure, a rare entity, whose diagnosis of autonomic dysfunction was determined with a series of complementary tests. For approximately 2 years, the patient has been experiencing dizziness and a tendency to fall, a significant weight loss, generalized weakness, dysphagia, intestinal constipation, blurred vision, dry mouth, and changes in her voice. She underwent clinical assessment and laboratory tests (biochemical tests, chest X-ray, digestive endoscopy, colonoscopy, chest computed tomography, abdomen and pelvis computed tomography, abdominal ultrasound, and ambulatory blood pressure monitoring). Measurements of catecholamine and plasmatic renin activity were performed at rest and after physical exercise. Finally the patient underwent physiological and pharmacological autonomic tests that better diagnosed dysautonomia.
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PMID:Hormonal and cardiovascular reflex assessment in a female patient with pure autonomic failure. 1101 9

Although the exact aetiology of overactive bladder is unknown to date, pharmacological therapy has been targeted to both the central and peripheral nervous systems. Potential CNS targets include GABA, opioid, serotonin (5-HT), dopamine and glutaminergic receptors as well as the alpha-adrenoceptors. Potential PNS targets include muscarinic receptors, calcium and potassium channels and alpha- and beta-adrenergic receptors. Since acetylcholine is the primary excitatory neurotransmitter involved in bladder (detrusor) contraction and emptying, anticholinergic agents are the primary compounds used clinically to decrease involuntary detrusor contractions. Anticholinergic therapy has a stabilising effect on the bladder (detrusor muscle); increases bladder capacity; decreases frequency of involuntary detrusor contractions; and delays the initial urge to void, but does not affect warning time. However, the clinical utility of antimuscarinic therapy is limited by the lack of receptor selectivity, resulting in the classic anticholinergic side effects of dry mouth, blurred vision, constipation and potentially, CNS effects such as somnolence and impaired cognitive function. These unwanted side effects often result in premature discontinuation of therapy and poor compliance. Previous attempts to develop uroselective alpha-adrenergic receptor antagonists have not been successful and although research continues, the hope that this class of agents would be viable alternatives to the anticholinergics remains to be proven in the clinical setting. The recent demise of several potassium channel openers does not augur well for the future of this class of agent. The reasons for the discontinuation of trials with these agents have not been fully elucidated, but one must assume that they were not uroselective and the cardiovascular side effects rendered them less than useful clinically. The serotonin re-uptake inhibitors appear to be promising novel therapeutic agents aimed at controlling bladder over-activity through specific CNS pathways. The sensory side of the micturition reflex is a potential therapeutic target. Agents to desensitise afferent nerve endings involved in C-fibre afferent reflexes include capsaicin and resiniferatoxin. Their clinical applicability is currently being evaluated. Finally, the recent findings related to the role of the P2X3 receptor in the sensory aspects of bladder filling have created new interest in the future development of agents that will improve the management of this prevalent and debilitating condition.
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PMID:Pharmacological agents for the treatment of urinary incontinence due to overactive bladder. 1111 81

We reviewed the side effects of antidepressants. Tricyclic antidepressants(TCAs) are associated with a higher frequency of adverse events than those of SSRIs and SNRIs, particularly with respect to anticholinergic-like effects(dry mouth, constipation, and blurred vision), delirium, and cardiovascular adverse events. On the other hand, SSRIs have some special side effects that include nausea, sexual dysfunction, and extrapyramidal symptoms. With regard to milnacipran, a member of the SNRI family, dysuria occurs at a higher frequency than with TCAs or SSRIs. When side effects occur, clinicians give patients symptomatic treatment or substitute the drugs that cause the adverse effects with other antidepressants that have different pharmacological effects.
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PMID:[Side effects and its countermeasures of antidepressant]. 1151 54

Overactive bladder (OAB) is a chronic, distressing condition characterised by symptoms of urgency (sudden overwhelming urge to urinate) and frequency (urinating more than eight times daily), with or without urge urinary incontinence (sudden involuntary loss of urine). It affects millions of people of all ages and both sexes world wide, with greater prevalence in women and the elderly. The treatment of OAB is aimed at reducing debilitating symptoms, which have a significant effect on all aspects of an individual's quality of life, including social, domestic, psychological, occupational, physical and sexual functioning. Anticholinergic agents are currently recommended as first-line therapy for OAB. Their use results in significant clinical improvement in patients, although a lack of selectivity for receptors in the bladder may lead to troublesome side effects, including dry mouth, blurred vision, somnolence, dizziness and constipation. Recent research efforts have focused on developing drugs with a reduced propensity for causing these problems. Of the available anticholinergic agents, oxybutynin and tolterodine are the most widely used to treat OAB. Studies directly comparing tolterodine immediate-release (IR) with oxybutynin IR have shown that the two agents have similar efficacy. However, tolterodine IR is significantly better tolerated, particularly with respect to the incidence and severity of dry mouth. An extended-release formulation of tolterodine (4 mg capsules) has recently been developed to allow for once-daily dosing. In addition to greater convenience, tolterodine extended-release has shown enhanced efficacy and tolerability compared with tolterodine IR.
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PMID:Current pharmacotherapeutic strategies for overactive bladder. 1208 83

The mainstay of pharmacologic treatment of overactive bladder is anticholinergic therapy. Cholinergic blockade is efficacious in decreasing the symptoms of urgency, frequency, and urge incontinence, but also is associated with undesirable side effects such as dry mouth, blurred vision, constipation, and central nervous system side effects. The property of anticholinergic agents that has been associated with increased efficacy and tolerability is receptor specificity. The safety of anticholinergic agents has been associated with the pharmacokinetics, metabolism, protein binding, and ability to penetrate the blood brain barrier. Trospium chloride, available in Europe for more than 20 years and under review by the US Food and Drug Administration for the treatment of overactive bladder, is a quaternary amine that is minimally metabolized, not highly protein-bound, and theoretically should not cross the blood brain barrier. Some of the characteristics of this unique anticholinergic agent are reviewed in this article and the relative contributions of these factors are discussed.
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PMID:Trospium chloride: a quaternary amine with unique pharmacologic properties. 1462 95

Overactive bladder syndrome (OAB) is a symptomatic diagnosis based on the presence of urgency, with or without urge incontinence, and usually accompanied by frequency and nocturia, in the absence of obvious pathologic or metabolic disease. Initial management of OAB requires an integrated approach using behavioral and pharmacologic methods. Patients should be educated about the functioning of the lower urinary tract system, fluid and dietary management, timed or prophylactic voiding and bladder training regimens, the keeping of micturition charts or bladder diaries, and pelvic floor exercises. Although the effectiveness of muscarinic receptor antagonists for the treatment of OAB has been shown, adverse effects, such as dry mouth, constipation, and blurred vision have somewhat limited their usefulness. Newer agents that are more bladder selective have been and continue to be developed. The concept of clinical effectiveness-a combination of efficacy, tolerability, and compliance-can be used to evaluate not only how well a drug works, but also the side-effect profile and bothersomeness and how likely patients are to continue treatment. Patients who do not respond to antimuscarinic treatment of OAB may do so because of a variety of nonpharmacologic and pharmacologic reasons. Most cases of OAB are not cured, but rather the symptoms are reduced, with an associated improvement in the patients' quality of life. Patients who have failed behavioral and pharmacologic intervention may respond to neuromodulation and augmentation cystoplasty. Future approaches may include (1) other types of systemic pharmacologic therapy; (2) intravesical administration of drugs, including blockers of afferent input; (3) intradetrusor injection of botulinum toxin; (4) the use of tissue engineering to simplify augmentation cystoplasty; (5) genetic interventions to reverse neuroplasticity changes; and (6) combinations of these approaches.
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PMID:Diagnosis and treatment of the overactive bladder. 1466 3

Overactive bladder (OAB) syndrome has been recognised by the International Continence Society as an important symptom syndrome that affects millions of people worldwide. Quality of life is affected in most people with OAB; however, the aetiology is unknown. Some researchers suggest that it is because of a damage to central inhibitory pathways or sensitisation of peripheral afferent terminals in the bladder, others suggest that it is a bladder muscle problem; the reality is probably a spectrum encompassing these two main explanations. Therefore, treatment is difficult and is aimed at alleviating symptoms (being those of urgency, with or without urge incontinence, usually with frequency and nocturia) rather than treating the cause. A thorough patient history and physical examination are required to establish a possible diagnosis. Frequency/volume charts form an important aid to the diagnosis. Once a presumptive diagnosis is made, conservative management forms the first line of treatment and includes lifestyle modifications, bladder training and pelvic floor exercises. If this fails, pharmacotherapy, in the form of anticholinergic drugs, is initiated. There are many antimuscarinic drugs, for example oxybutynin, tolterodine and trospium chloride. Each has a different specificity to bladder muscarinic receptors, thus producing different adverse effect profiles (e.g. dry mouth, blurred vision and constipation). Different individuals experience these adverse effects to different extents. New anticholinergic drugs, that have undergone phase III trials and are more specific to the muscarinic M3 human bladder receptor, are being introduced to the market in 2004 (e.g. solifenacin succinate and darifenacin). In addition to adverse effect profile, cost and improvement in quality of life are important factors in choosing treatment. Further research is being conducted on other types of drugs and different administration modalities, for example intravesical botulinum toxin A. Sacral nerve neuromodulation is emerging as a potential treatment, but if all treatments fail then surgery is the last resort.
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PMID:Drug treatment of overactive bladder: efficacy, cost and quality-of-life considerations. 1525 26


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