Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sildenafil is the first orally administered available treatment for erectile dysfunction. It produces a selective vasodilatation of corpus carvernosum, mediated by the inhibition of phosphodiesterase 5, an enzyme that degrades GMPc. Its therapeutic efficacy has been demonstrated in organic as well as psychogenic or mixed erectile dysfunction. Most of its adverse effects, such as headache, flushing, gastroesophageal reflux and color vision disturbances, are related to the mechanism of action. Its interactions with other medications, can have severe adverse consequences. The concomitant use of sildenafil with drugs that release nitric oxide in their molecule, can produce severe hypotension. In patients with coronary heart disease or cardiac failure, this interaction can cause death. Sildenafil is metabolized in the liver through cytochrome P-450. This enzymatic system can be inhibited by cimetidine, ketoconazole or erythromycin. These drugs can increase plasma concentrations of sildenafil. We must identify the groups of patients that will have a better response to the drug and those in whom the drug will be useless. We must also know more about the security profile of the drug. With time, we will know the real role of sildenafil in the treatment of erectile dysfunction.
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PMID:[Sildenafil (viagra) at the time of warnings]. 1034 69

BACKGROUND: The introduction of the drug sildenafil (Viagra; Pfizer, New York, NY) into the armamentarium for treatment of erectile dysfunction is a major advance. Many of the patients who will benefit from its use have cardiovascular disease. Erectile dysfunction and cardiovascular disease share common risk factors. Although the metabolic demands of sexual activity are modest and the associated risk for coronary events is low, the clinician caring for cardiac patients needs to be aware of the pharmacology and hemodynamic profile of sildenafil in those with heart disease who use cardioactive drugs. METHODS AND RESULTS: We reviewed the current literature relating to the pharmacology, hemodynamic profile, efficacy, safety, and clinical application of sildenafil in patients with cardiovascular disease. Sildenafil is highly effective in the treatment of erectile dysfunction. The overall incidence of cardiovascular adverse events is low and similar to placebo. Current postmarketing data do not suggest an increase in cardiovascular death in sildenafil users. The drug is contraindicated in those taking organic nitrates. It should be used with caution and on an individual basis in patients who have active coronary ischemia and heart failure with tenous blood pressure and volume status. CONCLUSIONS: When used with discretion, sildenafil is safe, effective, and has the potential to greatly enhance quality of life in the relatively large proportion of the population with heart disease.
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PMID:Viagra and Cardiovascular Disease. 1068 47

Erectile dysfunction (ED) in men is amenable to correction with Viagra in a majority of patients. The accumulated experience of prescribing Viagra across the broad continuum of men suffering from ED is sufficient for a meaningful assessment of the safety of Viagra in clinical practice. The use of Viagra necessitates caution in cardiac failure and when used within six months of acute myocardial infarction and stroke. It is inadvisable in patients with unstable angina pectoris. The co-administration of Viagra with organic nitrates, for example, glyceryl trinitrate or isosorbide dinitrate, is unsafe. The relative contraindications to Viagra in cardiovascular disease are uncontrolled hypertension and impaired cardiac reserve. With respect to interactions with other drugs, the potential influence on the metabolism of Viagra by medications that affect the cytochrome-P-450 system does not translate into clinical effects. The vasodilatory properties of sildenafil citrate are largely responsible for unwanted effects. The most common side effects are headache, flushing (due to vasodilation), and dyspepsia (due to relaxation of the smooth muscle of the gastroesophageal sphincter with reflux). In the recommended single-dose range (25-100 mg), the use of Viagra for erectile dysfunction, in the absence of contraindications, is extremely safe provided the drug is taken under proper conditions.
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PMID:The clinical safety of viagra. 1207 89

Sildenafil citrate is the first oral phosphodiesterase type 5 inhibitor approved for the treatment of erectile dysfunction. The wide use of sildenafil by patients with erectile dysfunction and cardiovascular disease has resulted in a considerable number of independent studies investigating the cardiovascular safety and functional role of the phosphodiesterase type 5-cyclic guanosine monophosphate-nitric oxide pathway in the cardiovascular system. Endothelial dysfunction, defined as a reduction in the bioavailability of nitric oxide, is associated with many of the common risk factors for cardiovascular disease and erectile dysfunction. Sildenafil has been demonstrated to improve the vasomotor aspect of endothelial dysfunction in patients with heart failure and diabetes. Hemodynamic studies suggest that sildenafil is a modest vasodilator with the potential to increase coronary blood flow and coronary flow reserve. In patients with ischemic heart disease, sildenafil is associated with reductions in mean arterial and pulmonary pressure with little effect on heart rate, cardiac output, and systemic or pulmonary vascular resistance. The absence of an effect on cardiac output supports the lack of an inotropic effect of sildenafil. This is consistent with the finding that sildenafil has no effect on cyclic adenosine monophosphate levels in the vasculature. Finally, exciting reports have emerged from clinical experience with the use of phosphodiesterase type 5 inhibitors in patients with pulmonary hypertension.
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PMID:Coronary and systemic hemodynamic effects of sildenafil citrate: from basic science to clinical studies in patients with cardiovascular disease. 1241 49

Endothelial dysfunction is associated with impairment of aerobic capacity in patients with heart failure and may play a role in the progression of disease. Impaired endothelium-dependent vasodilation in patients with heart failure can be attributed to decreased bioavailability of nitric oxide and attenuated responses to nitric oxide in vascular smooth muscle. Impaired vasodilation in response to nitric oxide derived from vascular endothelium or organic nitrates in vascular smooth muscle may be related in part to increased degradation of the second messenger cyclic guanosine monophosphate by type 5 phosphodiesterase. Sildenafil, a specific type 5 phosphodiesterase inhibitor currently approved for the treatment of erectile dysfunction, has been shown to acutely enhance endothelium-dependent vasodilation in patients with heart failure. Further studies are warranted to characterize the safety and efficacy of type 5 phosphodiesterase inhibition in the treatment of chronic heart failure.
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PMID:Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure. 1255 72

Sildenafil has proven effective in the therapy of male erectile dysfunction. However, little is known about other potential beneficial effects of sildenafil. Meanwhile, first observations have been made in numerous medical disciplines and disorders. Small doses of sildenafil may be a useful adjunct to inhaled iloprost in the management of pulmonary hypertension. In female sexual dysfunction and infertility, genital blood flow and endometrial thickening are enhanced after application of the compound. In gastrointestinal disorders, sildenafil also exerts several effects which might be of clinical relevance. In patients with heart failure, endothelial dysfunction is influenced by the phosphodiesterase-5 (PDE 5) inhibitor and exercise capacity might be improved. Moreover, in the treatment of Raynaud's phenomenon, a disease without highly effective medical treatment option yet, first observations with sildenafil seem to be promising.
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PMID:Non erectile dysfunction application of sildenafil. 1282 48

Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
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PMID:Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. 1295 49

Erectile dysfunction (ED) often is caused by endothelial dysfunction and may be a sign that a patient has vascular disease elsewhere in the body. Risk factors for coronary artery disease such as lipid abnormalities, smoking, diabetes, and hypertension also are risk factors for ED. Oral therapy for ED, such as sildenafil, inhibits phosphodiesterase-5 (PDE-5) and the breakdown of cyclic guanosine monophosphate. PDE-5 inhibitors have been shown to be safe and effective for the therapy for ED, but remain contraindicated in patients receiving organic nitrates. These agents are mild vasodilators and are being investigated for their treatment potential for patients with pulmonary hypertension, heart failure, and endothelial dysfunction.
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PMID:Erectile dysfunction in the cardiac patient. 1462

beta-Adrenoceptor blocking agents (beta-blockers) have been established as therapeutics for treatment of patients with hypertension, ischemic heart diseases, chronic heart failure, arrhythmias, and glaucoma. However, their clinical use is limited because some patients are adversely affected by their side effects. The discovery of cardioselective (beta(1)-selective) blockers has overcome some of the problems. Current retrospective studies have revealed that vasodilating beta-blockers (so-called beta-blockers of the third generation) have advantages over the conventional type of beta-blockers in terms of minimizing the adverse effects and improving the disease-derived dysfunction, thus enhancing the quality of life variables. Some of the possible advantages include improvement of insulin resistance, decrease in low-density lipoprotein cholesterol in association with increase in high-density lipoprotein cholesterol, attenuation of bronchial asthma attack and respiratory dysfunction, alleviation of coronary vasospasm provocation, peripheral circulatory disturbances, and erectile dysfunction, and better patient compliance. Release of nitric oxide, antioxidant action, beta(2)-adrenoceptor activation, Ca(2+) entry blockade, and other mechanisms underlying the vasodilating action may be responsible for the beneficial therapeutic effects of these agents.
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PMID:Vasodilating beta-adrenoceptor blockers as cardiovascular therapeutics. 1465 11

In the past 12 months, the FDA has approved important new pharmaceutical drugs and devices of particular interest to primary health care providers. The drugs include: Oxytrol (for urinary incontinence), Valtrex (for reducing the risk of heterosexual transmission of genital herpes), Femring (for vaginal delivery of hormone therapy), Uroxatral (for benign prostatic hypertrophy), Levitra (for erectile dysfunction), Flumist (for preventing influenza), Xolair (for asthma), Raptiva (for psoriasis), Cubicin (for skin infections), Crestor (for hypercholesterolemia), and Coreg (for severe heart failure).
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PMID:Drug approval highlights for 2003. 1487 68


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