Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lower urinary tract disorders include disorders affecting continence (stress urinary incontinence, urge urinary incontinence, and benign prostatic hyperplasia) and male erectile dysfunction. Although none of these conditions are fatal, they affect overall quality of life. Throughout modern medicine the treatment of these conditions was limited to psychological counseling or surgical intervention. In recent years, research defining the physiological mechanisms of continence and male sexual function has aided in the pharmacologic design of approaches to these conditions. These agents can act both centrally or on the peripheral genitourinary smooth muscle to alleviate disease symptoms. Incontinence is primarily treated with agents that act directly on the bladder smooth muscle such as muscarinic antagonists. However, afferent blockade to attenuate the spinalbulbospinal reflex pathway including mixed norepinephrine/serotonin reuptake inhibitors may provide a key breakthrough. Erectile dysfunction treatment has been revolutionized via the discovery of the nitric oxide pathway and phosphodiesterase 5 inhibitors. New peripheral targets as well as centrally acting agents represent potential emerging therapies. In this review, the pharmacologic basis of treatment of these disorders is discussed with special emphasis on emerging new therapeutics.
 ...
PMID:Emerging pharmacologic approaches for the treatment of lower urinary tract disorders. 1471 92

In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic, pre-neoplastic, and non-neoplastic), and improvement in lower urinary tract symptoms. Despite the regulatory approval of compounds to treat erectile dysfunction (ED), benign prostatic hyperplasia, a number of treatments for overactive bladder, and stress urinary incontinence, there remains a deficiency in addressing a number of conditions that arise out of pathophysiological dysfunction resulting in lower urogenital tract sexual conditions. In terms of late-stage clinical development, significant progress has most recently been made in MSD development, especially in understanding further a common and complex sexual dysfunction--that of premature ejaculation. The search also continues for compounds that improve ED in terms of better efficacy and superior safety profile compared to the currently marketed phosphodiesterase-5-inhibitors. Whilst there are no approved medications to treat the subtypes of FSD, there has been significant progress in attempting to better understand how to appropriately assess treatment benefit in clinical trial settings for this difficult to diagnose and treat condition. This review will focus on late-stage human clinical development pertaining to MSD and FSD.
 ...
PMID:Late-stage clinical development in lower urogenital targets: sexual dysfunction. 1646 80

There are several conditions associated with dysfunction of the lower urinary tract or which result in a reduction in the ability to engage in satisfactory sexual function and result in significant bother to sufferers, partners and/or carers. This review describes some of the animal models that may be used to discover safe and effective medicines with which to treat them. While alpha adrenoceptor antagonists and 5-alpha-reductase inhibitors deliver improvement in symptom relief in benign prostatic hyperplasia sufferers, the availability of efficacious and well-tolerated medicines to treat incontinence is less well served. Stress urinary incontinence (SUI) has no approved medical therapy in the United States and overactive bladder (OAB) therapy is limited to treatment with muscarinic antagonists (anti-muscarinics). SUI and OAB are characterised by high prevalence, a growing ageing population and a strong desire from sufferers and physicians for more effective treatment options. High patient numbers with low presentation rates characterizes sexual dysfunction in men and women. The introduction of Viagra in 1998 for treating male erectile dysfunction and the success of the phosphodiesterase type 5 inhibitor class (PDE5 inhibitor) have indicated the willingness of sufferers to seek treatment when an effective alternative to injections and devices is available. The main value of preclinical models in discovering new medicines is to predict clinical outcomes. This translation can be established relatively easily in areas of medicine where there are a large number of drugs with different underlying pharmacological mechanisms in clinical usage. However, apart from, for example, the use of PDE5 inhibitors to treat male erectile dysfunction and the use of anti-muscarinics to treat OAB, this clinical information is limited. Therefore, current confidence in existing preclinical models is based on our understanding of the biochemical, physiological, pathophysiological and psychological mechanisms underlying the conditions in humans and how they are reflected in preclinical models. Confidence in both the models used and the pharmacological data generated is reinforced if different models of related aspects of the same disorder generate confirmatory data. However, these models will only be fully validated in retrospect once the pharmacological agents they have helped identify are tested in humans.
 ...
PMID:Animal models in urological disease and sexual dysfunction. 1646 85

Management of adverse events related to cancer therapies are seen as tertiary prevention. Concerning prostate cancer, dealing with secondary effects of treatments is crucial. Indeed, if recent advances in cancer therapy have lead to an acceptable overall prognosis, these results face increasing cases of adverse events that can dramatically impact quality of life. Localized prostate cancer management (by radical prostatectomy, brachytherapy, external radiation therapy, hormonal treatment) leads to two main secondary effects: bladder and urinary sphincter dysfunction on one hand and sexual disorders on the other hand. Urinary disorders are stress urinary incontinence (mainly after radical prostatectomy), storage symptoms and overactive bladder, and outflow obstruction (mainly after radiation therapy). Stress urinary incontinence can be managed by pelvic floor muscle training and behavioural treatment. In case of failure, and after one year of evolution, surgical options are indicated (periurethral injections, artificial urinary sphincter, tapes and balloons). Storage symptoms respond to medical management (anticholinergics), and obstructive symptoms are treated by alpha-blockers, self-catheterization or surgery if necessary. Sexual disorders are erectile dysfunction, pelvic floor discomfort, orgasm disorder, and penile retraction and fibrosis. Available options gather medical treatment by phosphodiesterase-5 inhibitors, Vacuum, and penile prosthesis. Recent advances in this field point out the role of early penile rehabilitation and prevention of sexual disorders. Although often associated in the same patients, sexual and urinary disorders following prostate cancer management are often considered separately. Their combined treatment should be an objective for both clinical practice and research. New treatments for stress urinary incontinence management (latero-urethral balloons, new male slings) and for erectile dysfunction (penile rehabilitation, treatment penile retraction and optimal use of phosphodiesterase-5 inhibitors) will extend the therapeutic options in the next future, and improve the level of care for patients with prostate cancer.
 ...
PMID:[Urinary and sexual disorders following localised prostate cancer management]. 2122 Feb 29