Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphodiesterases are enzymes that catalyze the degradation of the cyclic nucleotides, cyclic AMP and cyclic GMP, to the corresponding 5' nucleotide monophosphates. Ten different phosphodiesterase families have been described to date. These enzymes exist as homodimers and there is structural similarity between the different families. However, they differ in several respects like selectivity for cyclic nucleotides, sensitivity for inhibitors and activators, physiological roles and tissue distribution. Interest in these enzymes has increased tremendously, both within the medical community and in the general public as a consequence of sildenafil (Viagra), the medication recently introduced for the treatment of erectile dysfunction. Sildenafil mediates its effects by inhibiting phosphodiesterase 5. Some biochemical and molecular biological aspects of this enzyme are presented here. To achieve satisfactory erection, normal penile innervation is required. Nitrogen monoxide, the transmitter substance in these nerves, activates guanylyl cyclase, thereby increasing cyclic GMP production. The increased levels of cyclic GMP cause relaxation of smooth muscles in penile vessels and this leads to an erection. Erection is dependent on elevated levels of cyclic GMP and sildenafil mediates its effects by inhibiting the degradation of cyclic GMP. Other functions that are mediated by the phosphodiesterases explain visual disturbances, flushing and decreased blood pressure that are some of the side effects seen with sildenafil treatment. Furthermore, the potentially fatal consequence of combining sildenafil and nitrovasodilators is discussed.
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PMID:[Phosphodiesterase 5--the enzyme inhibited by sildenafil (Viagra)]. 1021 Sep 55

This prospective open-label extension study was carried out to evaluate the effectiveness of sildenafil (Viagra) in the treatment of male erectile dysfunction in Nairobi, Kenya. A total of 219 adult male patients with erectile dysfunction were instructed to take 50 mg, 25 mg, or 100 mg of sildenafil orally 1 hour prior to planned sexual activity, but not more than once every 24 hours. Patients were reviewed at 4-week intervals for 16 weeks to assess the efficacy and adverse effects of the drug. The age range was 33-80 years with a mean of 62.5 years and a peak incidence in the 60-69 year age group. The causes of erectile dysfunction were organic (n = 119, 54.34%), psychogenic (n = 85, 38.81%), and mixed (n = 15). 200 patients (91.32%) had improved sexual function after treatment with Viagra. This improvement included improved erectile and orgasmic functions and overall sexual satisfaction. 157 patients responded to the 50-mg treatment regimen; 40, to the 25-mg regimen; and 3, to the 100-mg regimen. No improvement in sexual function was reported in 19 patients (8.68%) after Viagra administration. In addition, 7 patients reported mild and transient adverse effects of the drug, including mild headache, dyspepsia, facial flushing, nausea, and vomiting. In conclusion, oral sildenafil (Viagra) is an effective well-tolerated and simple treatment for male erectile dysfunction in the majority of cases. However, the cost of treatment may prohibit and limit its wide use by many deserving patients in this area.
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PMID:Sildenafil (Viagra) in the treatment of male erectile dysfunction in Nairobi. 1077 79

Impotence, a common problem especially among older men, can now be treated with Viagra, This oral pill, unlike previous approved treatments mostly involving local injections, does not directly cause penile erection, but increases response to sexual stimulation. It acts by enhancing the relaxant effects of nitric acid on smooth muscle, and thus increases blood flow to certain areas of the penis, leading to erection. It has been evaluated in many randomized trials and in all was more successful in inducing erection than placebos. The most common side-effects include headache, flushing and indigestion, but there have also been reports of fatalities. We describe a 75-year-old man who had an acute myocardial infraction in the past and who had maturity-onset diabetes and hypertension. In the week prior to admission he had a cardiac scan following a few weeks of exacerbation of anginal pain for which he had been taking nitrites. He took a Viagra pill without prescription or medical advice and 2 hours later, during intercourse with his wife, developed audible respiratory distress and lost consciousness. His wife started cardiac massage but not mouth-to-mouth breathing. The emergency team found ventricular fibrillation and gave 5 electrical shocks and amines and atropine. He remained unconscious, but his pulse returned and he was hospitalized. He then had several generalized convulsions treated with i.v. valium. 20 minutes after admission there was asystole and all attempts at resuscitation failed. Cardiovascular status must be considered prior to prescribing Viagra, and the associated risk evaluated.
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PMID:[Viagra--the first oral treatment for impotence that is not lacking in fatal effects]. 1090 27

The long-term efficacy and safety of oral Viagra (sildenafil citrate), a selective phosphodiesterase 5 inhibitor, and the effect of withdrawing treatment were evaluated in men with erectile dysfunction (ED). In 233 men with ED of psychogenic or mixed organic/psychogenic aetiology, 16 weeks of open-label, flexible-dose sildenafil treatment (10-100 mg) was followed by eight weeks of double-blind, fixed-dose, randomised withdrawal to placebo or continued treatment with sildenafil. Sildenafil was taken as needed (not more than once daily) approximately 1 h prior to sexual activity. The main outcome measures were a global efficacy question, a sexual function questionnaire, an event log of erections, and adverse event recording. In the open-label phase, 200 of 216 patients (93%) reported improved erections with sildenafil; 28 patients (12%) discontinued treatment. In the double-blind phase, the significant improvements in the frequency and duration of erections were maintained in the sildenafil group but returned to pre-treatment values in patients on placebo (P values < 0.0001 versus placebo). The most frequent adverse events in the sildenafil group during the double-blind phase were flushing (7%), headache (6%), and dyspepsia (5%). Of the 192 patients enrolled in the 1-y extension, 90% completed the study; only two patients (1%) were withdrawn due to lack of efficacy. In men with ED of psychogenic or mixed aetiology, oral sildenafil is effective and well-tolerated both at the initiation of therapy and during long-term treatment. For most patients, sildenafil treatment must be continued for improvements in erectile function to be maintained.
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PMID:Long-term efficacy and safety of oral Viagra (sildenafil citrate) in men with erectile dysfunction and the effect of randomised treatment withdrawal. 1104 12

Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction (ED) of organic aetiology. This study assessed the efficacy and tolerability of sildenafil for treating ED of psychogenic and mixed psychogenic/organic aetiology. Men with ED of psychogenic and mixed aetiology were randomised in a double-blind, fixed-dose study to placebo (n = 95) or sildenafil 10 mg (n = 90), 25 mg (n = 85), or 50 mg (n = 81) once daily for 28 days. Efficacy was evaluated with two global efficacy questions, a patient log of erectile activity, a sexual function questionnaire and a partner questionnaire. Patients receiving sildenafil had significantly more grade 3 (hard enough for penetration) or grade 4 (fully hard) erections per week than patients receiving placebo, and a greater proportion of patients receiving sildenafil reported that treatment had improved their erections (p < 0.001). Results of the sexual function questionnaire demonstrated significant improvement for patients with ED receiving sildenafil compared with patients receiving placebo for frequency, hardness and duration of erections (p < 0.01), and for enjoyment of sexual intercourse and satisfaction with sex life (p < 0.05). The results of the partner questionnaire were consistent with the results reported by patients and showed that treatment with sildenafil was associated with significant improvement in the partners' own sex lives (p < 0.001). Adverse events were mostly mild to moderate in nature. The commonest adverse events were headache, dyspepsia, flushing, myalgia, arthralgia and flu syndrome. Discontinuations due to treatment-related adverse events were few, ranging from 1.1% to 6.2% for patients receiving different doses of sildenafil and 4.2% for patients receiving placebo. Sildenafil is an effective and well-tolerated treatment for ED of psychogenic or mixed aetiology with once-daily dosing.
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PMID:Sildenafil citrate (Viagra) is effective and well tolerated for treating erectile dysfunction of psychogenic or mixed aetiology. 1122 Sep 82

Sildenafil (Viagra, Pfizer, Inc.) is a new orally effective therapy for the treatment of men with erectile dysfunction (ED). It is a specific and selective inhibitor of phosphodiesterase Type 5 (PDE5), an enzyme which is an important modulator of smooth muscle relaxation in the corpus cavernosum. In the presence of a sexual stimulus, inhibition of PDE5 results in improved smooth muscle relaxation within the sinusoids of the corpus cavernosum and the penile arteries. This results in improved erections in men with ED. In clinical trials, sildenafil has been found to be effective in improving the erections of large numbers of men with ED secondary to a range of causes. The presence of PDE5 in other tissues such as vascular smooth muscle results in side effects such as headache, flushing, indigestion and nasal congestion. These side effects are dose-dependent and well-tolerated. The introduction of sildenafil in many countries around the world has revolutionised the assessment and treatment of men with ED.
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PMID:Sildenafil. 1124 56

Hypertension is an important risk factor for erectile dysfunction (ED). Consequently, there is a high coincidence between hypertension and ED. Oral sildenafil (Viagra) is an effective treatment for ED in patients with treated or untreated hypertension. The most common adverse events of sildenafil (headache, flushing, hypotension) result from its moderate vasodilating properties. The concomitant use of sildenafil and organic nitrates is contraindicated because it may lead to a potentiation of the decreases in blood pressure and thus cause life-threatening hypotension. In contrast, the concomitant use of sildenafil and different classes of antihypertensive agents (beta-blockers, alpha-blockers, diuretics, ACE inhibitors, calcium antagonists) may lead to additive but not to potentiating blood pressure decreases. Thus, this combination is unlikely to cause clinically significant hypotension or an increased incidence of adverse events. Sildenafil is an effective and well-tolerated treatment for ED in patients taking concomitant antihypertensive medication, including those on multidrug regimens.
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PMID:[Interaction between sildenafil and antihypertensive drugs: what is evidence-based?]. 1159 59

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

A 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of flexible-dose sildenafil citrate (Viagra) treatment (25, 50 or 100 mg) in Brazilian and Mexican men with erectile dysfunction (ED) of broad-spectrum etiology. Efficacy was assessed on the basis of responses to the 15-item International Index of Erectile Function (IIEF) questionnaire, completed at baseline and after 12 weeks of treatment. At end point, mean scores for all IIEF domains of sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction) were significantly (P<0.0001) higher in the sildenafil group (n=109) than in the placebo group (n=105). These findings confirm the significant increases in frequency of penetration and frequency of maintained erections reported previously. Sildenafil treatment was well tolerated. The most common adverse events were headache and flushing. In conclusion, sildenafil is a well-tolerated and effective treatment for ED of broad-spectrum etiology in Latin American men.
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PMID:Efficacy and safety of flexible-dose oral sildenafil citrate (Viagra) in the treatment of erectile dysfunction in Brazilian and Mexican men. 1216 65

Our objectives were: (1) to determine the efficacy, safety, and tolerability of sildenafil citrate (Viagra) administered to men with broad-spectrum erectile dysfunction (ED) in southern Latin America; and (2) to correlate Rigiscan measurements assessing ED etiology with the investigator's assessment. A total of 141 men with broad-spectrum ED (mean age 57) were enrolled in a randomized, 12-week, double-blind, placebo-controlled, flexible-dose escalation study of sildenafil. After the 12-week treatment period, the mean score for the primary efficacy variables had risen significantly: for the sildenafil group, 66.2% from baseline for question 3 of the International Index of Erectile Function and 77.6% for question 4, vs 15.1% and 21.2% for the placebo group, respectively (P<0.0001). Rigiscan data confirmed investigator assessments of etiology. Headache and flushing, usually mild and transient, were the most common adverse events. Sildenafil was an effective, well-tolerated treatment for men in southern Latin America with broad-spectrum ED.
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PMID:Sildenafil citrate (Viagra) in the treatment of men with erectile dysfunction in southern Latin America: a double-blind, randomized, placebo-controlled, parallel-group, multicenter, flexible-dose escalation study. 1216 66


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