Gene/Protein Disease Symptom Drug Enzyme Compound
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 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erectile dysfunction (ED) has serious negative consequences on both sexual experience and emotional well being and affects a broad range of age groups. The prevalence of ED is associated with increasing age and has been reported to be as high as 70%. Although the disorder is common and underdiagnosed, its treatment can significantly improve patients' quality of life. Systemic treatment with oral phosphodiesterase type-5 (PDE-5) inhibitors is the current standard of care for patients with ED. Some patients, however, have absolute contraindications for PDE-5 inhibitors. In addition, these agents can be associated with adverse effects. Furthermore, because PDE-5 inhibitors are not as effective in patients who have undergone radical prostatectomy or who have severe vascular disease, a substantial unmet medical need exists among patients who have ED as a result of these conditions. Consequently, PDE-5 inhibitor therapy is associated with a high rate of discontinuation, as are intracavernosal or transurethral therapies, which are inconvenient and invasive. Several studies, including four double-blind, placebo-controlled, Phase II trials, show that alprostadil topical cream is efficacious and well-tolerated in ED in patients with mild-to-severe symptoms, in those undergoing treatment for cardiovascular diseases and diabetes and in otherwise healthy ED patients. Thus, alprostadil topical cream is a potential first-choice alternative for ED in patients who do not respond or who cannot tolerate or do not accept PDE-5 inhibitor therapy.
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PMID:Topical alprostadil cream for the treatment of erectile dysfunction. 1501 30

Erectile Dysfunction (ED) is common in men with diabetes. Diabetic men are three times as likely to develop ED as non-diabetic men. The cause is multifactorial, but most commonly reflects endothelial dysfunction and autonomic neuropathy. Diabetes and vascular disease often coexist and ED may be a marker for silent occlusive arterial disease, for which the patient should be screened. Many men still do not volunteer their problem, hence, routine questioning by health care professionals is an important part of the overall management because of the deleterious effect of ED on relationships, self-esteem and quality of life. Treatment is effective in the majority and all options should be considered, beginning with the much preferred oral phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil). Female Sexual Dysfunction or Disorder (FSD) is more difficult to define and specific studies in diabetics are limited. Problems with arousal, lubrication and orgasmic dysfunction occur, but the fatigue of diabetes may be influencing these complaints, and in general, psychological issues appear to predominate.
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PMID:Sexual dysfunction and diabetes. 1516 Nov 20

Erectile dysfunction (ED) is common in cardiac patients and shares the same risk factors--smoking, hypertension, hyperlipidaemia and diabetes mellitus. Sexual activity is not unduly stressful to the heart and, providing patients are properly assessed using established guidelines, sexual intercourse can be enjoyed without increased risk. The treatment of ED in patients with cardiovascular disease has been transformed by the introduction of the oral phosphodiesterase type 5 inhibitors, the first of which was sildenafil. Success in restoring erectile function is possible in up to 80% of patients (depending on the aetiology) with minimal adverse effects. A synergistic hypotensive effect with nitrates, and almost certainly nicorandil, is the only major contraindication. ED in asymptomatic patients may be a marker of silent vascular disease or increased vascular risk factors and should alert the physician to the need for cardiac risk screening. ED is common in patients with cardiovascular disease and should be routinely enquired about. ED is a distressing condition for the man and his partner, and severely impairs quality of life. Patients with cardiovascular disease and patients with diabetes represent the largest group of patients with ED, the majority of whom benefit from the drug therapies currently available. Addressing ED in patients with cardiovascular disease can lead to a substantial improvement in quality of life and success is not difficult to achieve.
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PMID:Treatment of erectile dysfunction in patients with cardiovascular disease : guide to drug selection. 1523 91

Since the etiology of erectile dysfunction is frequently related to endothelial dysfunction, a problem in common with much vascular disease, erectile dysfunction disproportionately affects patients with cardiovascular disease. With the development of phosphodiesterase 5 inhibitors, the first of which was sildenafil (Viagra), an effective oral medication became available. The question of safety of these drugs, especially in patients with latent or overt coronary artery disease, is of concern. Sildenafil relaxes smooth muscle and therefore lowers systolic and diastolic blood pressure slightly. With organic nitrates, the drop in blood pressure is potentiated, at times dangerously, thereby making it contraindicated to take nitrates within 24 hours of using sildenafil. In double-blind, placebo-controlled trials, there was no difference between sildenafil subjects and control patients in the incidence of myocardial infarction, cardiovascular, and total deaths. Coronary disease patients with stable angina, controlled on medications, were included in the trials. Therefore, sildenafil, as a drug, is safe in such patients. With a patient with coronary artery disease suddenly engaging in the physical exercise associated with sexual intercourse, there is the danger of increased risk of precipitating myocardial infarction or death. The cardiovascular metabolic cost of sexual activity is reviewed and appears to be approximately at the level of 3-5 metabolic equivalents of exercise. Sexual activity occurs within 2 hours of the onset of an acute myocardial infarction in <1.0% of patients. Although sexual intercourse is estimated to increase the risk of myocardial infarction by a factor of 2x, there is still only a very small increase in risk, a risk acceptable to patients who feel their quality of life will be markedly improved by their ability to engage in sexual activity.
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PMID:Should the patient with coronary artery disease use sildenafil? 1531 86

Pulmonary arterial hypertension is a severe pulmonary vascular disease characterized by elevated pulmonary vascular resistance and low cardiac output. Prior to prostacyclin therapy, it was a fatal disease with a median survival of 3 years. In recent years, the understanding and treatment of the disease have significantly improved patient outcome. The new therapeutic guidelines are based on the finding that vasoconstriction and vascular remodeling correlated with endothelial dysfunction, endothelin overexpression and diminished prostacyclin and nitric oxide synthesis. This article outlines the new classification and the current therapeutic guidelines accepted in the world presenting the role of prostacyclins, endothelin antagonist, phosphodiesterase V inhibitor, and the potential value of combination therapies.
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PMID:[Pulmonary hypertension--classification and treatment: new guidelines]. 1584 62

More than 30 million men are estimated to have erectile dysfunction (ED) in the United States. Worldwide, ED is estimated to affect more than 150 million men, and that number is expected to exceed 300 million men by the year 2025. The prevalence of ED ranges from 7% in men aged 18-29 years to 85% in men aged 76-85 years. In addition, a recent report showed that 68% of patients with ED aged 18 years and older have at least one comorbid diagnosis of hypertension, hyperlipidaemia, diabetes or depression, and research suggests that ED may be an early indicator of systemic vascular disease. Viagra (sildenafil citrate), the first-in-class phosphodiesterase type 5 (PDE5) inhibitor, was introduced in 1998 for the treatment of ED. In the 7 years since its market launch, more than 750,000 physicians have prescribed sildenafil to more than 23 million men, helping establish an excellent safety and efficacy record. Clinical studies have demonstrated that sildenafil successfully treats ED of varied organic, psychogenic or mixed aetiology, and is effective in men with ED and comorbidities such as hypertension, hyperlipidaemia, diabetes or depression. Sildenafil was a breakthrough medication that addressed a previously unfulfilled medical need. The impact of sildenafil has stimulated academic, clinical and industrial research to better understand the nature of sexual function and develop better treatment and management for sexual dysfunctions such as ED. With the advent of other erectogenic therapies for the treatment of ED, this 7-year update will focus on the unique history and development of sildenafil, its current use and applications and its future directions and indications. Special emphasis is placed on the impact of sildenafil on our understanding of sexual health and on the extensive safety and efficacy data that have been amassed from numerous clinical trials.
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PMID:Past, present, and future: a 7-year update of Viagra (sildenafil citrate). 1592 97

Because most men with erectile dysfunction have underlying vascular disease, it is important to update the cardiovascular safety profile of medications used in the treatment of erectile dysfunction. This retrospective analysis evaluated serious cardiovascular treatment-emergent adverse events (CVTEAEs) reported in 36 clinical trials of tadalafil, a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction. A serious CVTEAE was defined as myocardial infarction, cardiovascular death, or cerebrovascular death. In the 36 trials, 12,487 men (mean age 55 years) with erectile dysfunction received tadalafil, with 5,771 patient-years (PYs) of exposure, and 2,047 men (mean age 56 years) received placebo, with 460 PYs of exposure. Tadalafil 2 to 50 mg was taken as needed, 3 times/week, or once a day. Co-morbidities at baseline included hypertension (31%), diabetes (21%), hyperlipidemia (17%), and coronary artery disease (5%). Across all trials, the incidence rate of serious CVTEAEs was 0.40/100 PYs in tadalafil-treated patients and 0.43/100 PYs in placebo-treated patients. In patients taking tadalafil as needed, 3 times/week, or once a day, the incidence rates of serious CVTEAEs ranged from 0.17 to 0.54/100 PYs across placebo-controlled and open-label trials. In conclusion, the incidence rates of serious CVTEAEs were comparable among men with erectile dysfunction taking tadalafil as needed, 3 times/week, or once a day, and these rates were also comparable with those in placebo-treated patients. In this clinical trial population of men with erectile dysfunction, tadalafil was not associated with an increased risk for serious cardiovascular adverse events.
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PMID:Cardiovascular safety update of Tadalafil: retrospective analysis of data from placebo-controlled and open-label clinical trials of Tadalafil with as needed, three times-per-week or once-a-day dosing. 1676 34

Erectile dysfunction affects over half of all men between 50 and 70 years of age, and by the age of 40, about 40% of men may suffer from some form of erectile dysfunction. Many disease states, such as diabetes, hypertension, depression, and vascular disease, are associated with the condition, which may occur many years prior to the onset of these disorders. The phenomenal success of sildenafil in improving erections in men with erectile dysfunction is due to the fact that the drug, as a phosphodiesterase inhibitor, improves the relaxation of smooth muscle cells, which become dysfunctional with the aging process. However, not everyone responds to this medication, mainly because the efficacy of the drug is directly dependent on the release of nitric oxide from the nerve terminals of the cavernosal nerve, and this may become defective with aging/certain disease states. The goal of gene therapy for organic impotence is to allow the patient to sustain physiologically elicited erections without resorting to pharmacological treatment immediately prior to the sexual act. Experimental efforts in gene therapy for erectile dysfunction are likely to continue intensively in a series of directions, some specific to the nature of the selected gene to be manipulated or the physiology of the corpora cavernosa itself, and others extrapolatable from the advancement of gene therapy in general.
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PMID:Future strategies for treating erectile dysfunction. 1698 14

Erectile dysfunction (ED) has multifactor pathogenesis, with neurological, vascular, endocrinological and psychogenic components described. However, about 50-85% of ED population report the presence of one or more comorbidities i.e. hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair endothelial function and, erection is a basically vascular event that necessitates an intact endothelium to occur. Hence, ED may be mostly considered as the clinical manifestation of a disease affecting penile circulation as a part of a generalized vascular disorder due to atherosclerosis. Orally active drugs, i.e. phosphodiesterase type-5 inhibitors (PDE5-i), are a group of on-demand drugs licensed for ED treatment and appear to offer advantages over past therapies in terms of ease of administration and cost, and they are now widely advocated as first-line therapy. The recent discovery that chronic not on-demand administration of these drugs may improve erectile and endothelial response in men previously unresponding to on-demand regimes, opens a new scenario in the treatment of men with ED and comorbidities. Finally, the recent approval of PDE5-i sildenafil for the treatment of pulmonary arterial hypertension represents the new challenge for these class of drugs. Aim of this article will be to provide an update on the pathophysiology of ED and how to use of different available PDE5-i in approaching sexual dysfunctional men, pointing out on their characteristic of efficacy and safety and different indications in special sub-populations.
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PMID:Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. 1701 40

In addition to combination treatment of pulmonary artery hypertension (PHT) with currently available drug options (endothelin-receptor inhibitors, phosphodiesterase-5 inhibitors, prostanoids). Numerous new drugs of other substance groups are being tested in preclinical and clinical studies. Most of the newly tried drugs use previously identified mechanisms of action that are involved in the development and progression of the underlying vascular disease. This has led to a certain paradigm shift which, in addition to vasodilatation and anti-platelet aggregation treatment, increasingly focuses on antiproliferative effects with the aim of preventing or regressing vascular remodelling. Of particular interest in this connection are tyrosine kinase inhibitors, which inhibit the action of such peptide growth factors as platelet-derived growth factor. Imatinib, one of this class of action, has given promising results in experimental studies and several case reports. Another greatly promising approach in the treatment of PHT are activators and simulators of soluble guanylyl cyclase, which are also currently being investigated in clinical trials.
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PMID:[Future aspects of the treatment of pulmonary arterial hypertension]. 1713 2


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