sildenafil-citrate and Nervous-System-Diseases

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.

Topics: Anemia, Sickle Cell; Blood Transfusion; Clinical Trials as Topic; Disease Management; Gastrointestinal Diseases; Humans; Hydroxyurea; Hypertension, Pulmonary; Muscular Diseases; Nervous System Diseases; Pain; Phenotype; Piperazines; Purines; Retinal Diseases; Sildenafil Citrate; Sulfones; Treatment Outcome

Sildenafil citrate (Viagra) is a potent orally active cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor that is effective as a peripheral conditioner in the treatment of male erectile dysfunction (ED) of organic, psychogenic or mixed aetiology. Sildenafil is the first effective oral agent in the management of ED that has had a revolutionary impact on management of ED. The present review has been subdivided into five major sections. Based on the most recent peer-reviewed publications, the first section is aimed at critically evaluating PDE5 selectivity as well as the pharmacokinetics and pharmacodynamics of the drug, mainly to assess the best doses for each group of patients (i.e. adult and elderly men). Effectiveness in a broad spectrum ED population is the subject of the second section of the review, principally reporting post-marketing company-independent results. Safety and tolerability are the key concerns of the third section, with a broad consideration of the most commonly reported adverse events. Special attention has been paid to the cardiovascular safety of the drug, chiefly outlining the positive and potentially protective cardiac effects of sildenafil. Moreover, the impact of sildenafil in special patient populations is considered, namely in men complaining of diabetes mellitus, depression, neurological disorders, renal failure and those who have undergone a radical prostatectomy. Sildenafil and the ageing male has been especially underlined. Finally, the review covers a few new potential applications of sildenafil in ED patients with regard to high-dose treatment and combination therapy. The review ends with several considerations regarding the direct and/or indirect impact of sildenafil over quality of life and quality of partnership.

Topics: Adult; Aged; Contraindications; Diabetes Complications; Drug Administration Schedule; Drug Therapy, Combination; Erectile Dysfunction; Hemodynamics; Humans; Impotence, Vasculogenic; Male; Nervous System Diseases; Phosphodiesterase Inhibitors; Piperazines; Product Surveillance, Postmarketing; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Topics: Age Factors; Aging; Cardiovascular Diseases; Databases, Factual; Diabetes Complications; Endocrine System Diseases; Erectile Dysfunction; Humans; Internet; Male; Morbidity; Nervous System Diseases; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Following the notification of forty cases of varying degrees of vision loss in patients using phosphodiesterase-5 (PDE-5) inhibitors, the FDA (Food and Drug Administration) examined the possible link between these treatments of erectile dysfunction and NOIAN (nonarteritic anterior ischemic optic neuropathy). Following this investigation, the FDA requested modification of the summary of product characteristics (SPC) for this therapeutic category. The authors review this problem, especially in France.. The authors performed a search of the Pubmed database and the French Pharmacovigilance database.. Since September 2006, 11 publications concerning 19 cases (14 with sildenafil and 2 with tadalafil) have been published. The mean age of these patients was 59.5 years (range: 42 to 69). Doses varied from 50 to 100 mg for sildenafil and 20 mg for tadalafil. Adverse effects (loss of visual acuity and decreased visual field) occurred between 30 min and 36 h after oral dosing. In 5 cases, treatment had been taken for more than one year. Ocular fundus examination showed papilloedema associated with several haemorrhages. Three patients presented a positive challenge. Several patients had a known risk factor for the development of NOIAN. One case was also reported to French Pharmacovigilance.. The population with erectile dysfunction also often presents generalized endothelial disease, which also constitutes a risk factor for NOIAN. Although no cases of NOIAN were reported during the initial clinical trials, the rapid onset of NOIAN after the dose of PDE-5 inhibitor and several cases of positive challenge suggest a possible causal relationship with these drugs. The ocular action of PDE-5 inhibitors could be explained by a modification of retinal blood flow related to their pharmacological effects.. The link between PDE-5 inhibitors and NOIAN has not been formally established. Before new studies are conducted to clarify this situation, practitioners must be aware of the potential ocular adverse effects related to the dose of PDE-5 inhibitors so that they can inform patients and notify any new cases. The SPCs of PDE-5 inhibitors were modified at the request of the FDA on 8 July 2005.

Topics: Biopsy; Carbolines; Erectile Dysfunction; Humans; Male; Nervous System Diseases; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; United States; United States Food and Drug Administration