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)

Orally administered phosphodiesterase type 5 (PDE5) inhibitors have become the first-line treatment option for erectile dysfunction (ED). Vardenafil is a potent and highly selective PDE5 inhibitor developed as an oral therapy for ED. Two pivotal, randomised, double-blind, multi-centre studies have evaluated the use of vardenafil in men with ED. Vardenafil improved the rate of achieving and maintaining an erection during sexual intercourse. Improvement was also noted in other aspects of sexual function, including confidence, orgasmic function and overall satisfaction. Vardenafil produces clinically and statistically significant improvements in erectile function regardless of age, baseline severity and aetiology and is efficacious for the treatment of ED in diabetic and postradical prostatectomy patients. Vardenafil has a rapid onset of action, in which erections sufficiently rigid for eventual intercourse completion can be achieved as early as 16 min after ingestion. Vardenafil 20 mg has sustained long-term efficacy by providing up to 92% of patients with improved erections during > 2 years of treatment. Vardenafil is well-tolerated, with an adverse event profile typical of this class of PDE5 inhibitors. The most common adverse events were headache, flushing, rhinitis and dyspepsia, which were mild-to-moderate in severity and they generally attenuated with continued use. Vardenafil may be associated with transient reductions in blood pressure and commensurate increases in heart rate, with the overall incidence of cardiovascular-related adverse events similar to that of placebo. Although claims can be made about potential features of benefit for each of the currently marketed PDE5 inhibitors, there are at present, no non-pharmaceutical company sponsored, peer-reviewed, head-to-head trials that have been published.
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PMID:Vardenafil: a novel type 5 phosphodiesterase inhibitor for the treatment of erectile dysfunction. 1510 74

The mechanism of action of the phosphodiesterase type 5 (PDE5) inhibitors (i.e., sildenafil, tadalafil, and vardenafil) involves inhibition of the PDE5 isoenzyme located in penile vascular smooth muscle cells. Sexual stimulation triggers the release of nitric oxide (NO), stimulating the release of guanylyl cyclase, leading to an increase in intracellular cyclic guanosine monophosphate (cGMP) concentrations, a decrease in intracellular calcium, and ultimately relaxation of the vascular smooth muscle in the corpus cavernosum and penile erection. The PDE5 inhibitors have no effect on the penis in the absence of sexual stimulation. Although the various PDE5 inhibitors differ with respect to selectivity and pharmacokinetic profiles, efficacy and safety of these agents are comparable in broad populations of men with erectile dysfunction (ED), including those with diabetes or those taking multiple antihypertensive agents. The most frequently reported adverse events of the PDE5 inhibitors are related to their mild vasodilatory effects and include headache, flushing, dyspepsia, and nasal congestion or rhinitis. Side effects are generally reversible and tend to diminish during continued treatment. Differences in pharmacokinetic properties among the PDE5 inhibitors include the fact that sildenafil and vardenafil have a shorter duration of action (approximately 4 h) compared with the longer period of responsiveness observed with tadalafil (up to 36 h). In addition, in the presence of high-fat food, absorption of sildenafil and vardenafil may be delayed; however, the rate and extent of tadalafil absorption are unaffected by high-fat food.
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PMID:Phosphodiesterase type 5 inhibitor differentiation based on selectivity, pharmacokinetic, and efficacy profiles. 1511 91

Trials of the efficacy and safety of vardenafil in the treatment of male erectile dysfunction (ED) were meta-analysed. All available databases were searched (January 1, 2001-November 30, 2003). Trials were eligible if they included men with ED, compared vardenafil with placebo, were randomized, were at least of 12 weeks duration, and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. Nine trials (6809 men) met the inclusion criteria. In results pooled from seven fixed-dose trials, vardenafil increases the Erectile Function domain of the International Index of Erectile Function questionnaire by 6.18 units (weighted mean difference (WMD)). Vardenafil also increases the percentage of erections firm enough to allow vaginal penetration (WMD: 26) and the percentage of sexual attempts that were successful per participant (WMD: 29.8). The percentage of men agreeing with the statement that 'the treatment they have been taking over the past 4 weeks improved their erections', is also in favour of vardenafil (relative risk (RR): 3). These efficacy variables appeared greater at higher doses, although there are no significant differences between 10 and 20 mg dose. The same results were extracted for the two flexible 'as needed' dosing trials. Discontinuations are greater at the vardenafil groups compared to placebo (RR: 2.25). Specific adverse events with vardenafil included flushing, dyspepsia, headache, and rhinitis. Vardenafil was not significantly associated with serious cardiovascular events or death. Vardenafil, in all treatment regimens, shows to possess superior efficacy to placebo in the treatment of patients with erectile dysfunction. More data is needed on patients' subgroups.
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PMID:Vardenafil (Levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports. 1522 25

Erectile dysfunction (ED) is a common medical disorder affecting elderly men. Sildenafil citrate has been shown to be an effective and well-tolerated oral agent for treating ED in the general population of adult men with ED of broad-spectrum etiology. Elderly men are more likely to have concomitant medical problems than the general population of men with ED. In this study, we examined the efficacy and safety of sildenafil administration in elderly patients with ED. Forty-four elderly men with ED (> or = 60 years old) of broad-spectrum etiology were treated with 25 mg or 50 mg doses of sildenafil citrate. Age ranged from 60 to 78 years (65 +/- 4.5; means +/- S.D.). Mean follow-up period was 12.3 +/- 6.5 months, with a range of 1 to 25 months. Primary efficacy assessments were performed using the International Index of Erectile Function 5 (IIEF5) before their first dose of sildenafil and after at least 4 weeks of therapy. Serum testosterone was measured before treatment. The mean IIEF5 among all patients increased from 8.5 +/- 3.9 to 20 +/- 4.2 after sildenafil use (P < 0.0001). In patients younger than 70 years, the IIEF5 score increased from 9.5 +/- 5.0 to 17 +/- 4.3 while in patients 70 years and older, the score increased from 8.2 +/- 3.6 to 21 +/- 3.9, a near normalization. The rate of improvement in younger men was higher than in older men. Serum testosterone before treatment was similar in the two groups. The most commonly experienced adverse events were flushing and dyspepsia, which occurred in 6.8% and 2.3%, respectively. No patients discontinued sildenafil treatment due to adverse events. In conclusion, oral sildenafil is efficacious and well tolerated by elderly men with ED, even among those older than 70 years.
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PMID:Clinical efficacy and safety of sildenafil in elderly patients with erectile dysfunction. 1527 3

Chronic heart failure (CHF) is an increasingly common cardiovascular disorder. Many patients who have CHF report moderate to marked decreases in the frequency of sexual activity, and up to 75% of patients report erectile dysfunction (ED). There are few controlled clinical data on the efficacy and safety of sildenafil citrate in men who have ED and CHF; thus, we evaluated these parameters in patients who had stable CHF. This was a double-blind, placebo-controlled, flexible-dose study. Men who had ED and stable CHF were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function. Secondary outcomes included the 5 functional domains of the International Index of Erectile Function, 2 global efficacy assessment questions, intercourse success rate, the Erectile Dysfunction Inventory of Treatment Satisfaction, and the Life Satisfaction Checklist. By week 12, patients who received sildenafil (n = 60) showed significant improvements on questions 3 and 4 compared with patients who received placebo (n = 72; p <0.002). Larger percentages of patients who received sildenafil reported improved erections (74%) and improved intercourse (68%) compared with patients who received placebo (18% and 16%, respectively). Intercourse success rates were 53% among patients who received sildenafil and 20% among those who received placebo. Patients who received sildenafil were highly satisfied with treatment and their sexual life compared with patients who received placebo. Sixty percent of patients who received sildenafil and 48% of patients who received placebo developed adverse events, including transient headache, facial flushing, respiratory tract infection, and asthenia. The incidence of events related to cardiovascular effects was low. Sildenafil is an effective and well-tolerated management of ED in men who have mild to moderate CHF.
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PMID:Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure. 1561 91

Inhibitors of phosphodiesterase type 5 (PDE-5) are well established as an oral treatment for the majority of patients with erectile dysfunction (ED). PDE-5 is found in high concentration in smooth muscle cells of the corpora cavernosa. However, enzymes of the PDE family are also expressed in various other tissues, including the brain. Little is known about its effects on the central nervous system (CNS), although it has been suggested that PDE-5 inhibitors might cross the blood-brain barrier. Side effects, such as headache, nasal congestion, flushing, nausea, are much more common. We describe a patient who had a transient global amnesia (TGA) after his first-ever use of tadalafil, a potent PDE-5 inhibitor. Despite the fact that the aetiology of TGA has not entirely been clarified at present, we consider the hypothesis of a causal relationship as tempting with respect to the current hypotheses of TGA pathophysiology. This case, together with others, suggests that PDE-5 inhibitors might be capable of exerting adverse effects in the CNS. Physicians should be aware of the possibility of neurological disturbances when prescribing PDE-5 inhibitors for ED.
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PMID:Transient global amnesia after intake of tadalafil, a PDE-5 inhibitor: a possible association? 1567 2

Erectile dysfunction (ED) affects up to 50% of men, between 40 and 70 years of age. In the first major trial of sildenafil in ED, at 24 weeks, improved erections were reported by 77 and 84% of men taking sildenafil 50 and 100mg, respectively. Subsequently, sildenafil has been reported to be effective in men with ED associated with diabetes and prostate cancer, and in psychogenic ED. Sildenafil is safe in men with coronary artery disease, provided it is not used with the nitrates (a contraindication). The most commonly reported adverse effects with sildenafil are headache, flushing and dyspepsia. Vardenafil is more potent and more selective than sildenafil at inhibiting phosphodiesterase-5. Vardenafil is similarly effective to sildenafil in the treatment of ED. The only advantage that vardenafil has over sildenafil is that it does not inhibit phosphodiesterase-6 to alter colour perception, a rare side effect which sometimes occurs with sildenafil. Tadalafil has a longer duration of action than sildenafil and vardenafil. Tadalafil is similarly effective as sildenafil in the treatment of ED. In comparison studies, tadalafil is preferred to sildenafil (50/100mg) by men with ED, possibly because of its longer duration of action. Of the phosphodiesterase inhibitors, tadalafil may displace sildenafil as the drug of choice among men with ED.
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PMID:Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. 1570 77

Phosphodiesterase 5 inhibitors are recommended as first-line treatment of erectile dysfunction in many guidelines, because of their convenience, higher efficacy, and less side-effects. Since its first launch in 1998, sildenafil has been currently the best investigated phosphodiesterase 5 inhibitor with respect to long-term trails and quantity. Clinical trials showed the efficacy of sildenafil compared with placebo in many of the groups of patients who have ED, including those with cardiovascular disease, diabetes mellitus, depression, radical prostatectomy and dialysis. Typically the adverse effects reported in patients from clinical trials of sildenafil have been mild to moderate, and commonly include flushing and dyspepsia and transient visual disturbances. This article summarized recent reports on efficacy and safety of phosphodiesters 5 inhibitors in the treatment of erectile dysfunction.
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PMID:[Efficacy and safety of phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction]. 1613 88

Erectile dysfunction (ED) profoundly affects the quality of life. The prevalence of ED in renal transplant recipients is reported by high as 50% to 60%. We evaluated the efficacy and safety of vardenafil in these patients with ED as well as its effects on graft function and on cylosporine or tacrolimus concentrations. Thirty-nine recipients with ED and serum creatinine values<2 mg/dL were treated with vardenafil. ED was assessed using the self-administered International Index of Erectile Function (IIEF). ED was diagnosed by using penile color-Doppler ultrasonography and intracavernosal injection. Vardenafil efficacy was assessed by readministering the IIEF questionnaire after 4 weeks of therapy. Serum creatinine levels, creatinine clearances, and cyclosporine/tacrolimus concentrations were measured before and after vardenafil therapy. Twenty-one recipients with ED served as placebo controls and 15 without ED as another control group. The IIEF scores improved from 12.80+/-3.5 to 26.46+/-2.4 in vardenafil-treated patients with ED (P<.001). Renal function and cyclosporine/tacrolimus concentrations did not change with vardenafil therapy. Side effects were observed in 7 (18%) patients: headache in three, palpitations in one, flushing in two, and dyspepsia in one. This study demonstrated that ED improved with vardenafil in renal transplant recipients with ED. For 4 weeks vardenafil therapy was free of side effects. Renal function tests did not change. Also, no dose change in immunosuppressive drugs was required during 4 weeks of verdanafil therapy.
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PMID:Efficacy and safety of vardenafil in renal transplant recipients with erectile dysfunction. 1679 9

The discovery that inhibition of phosphodiesterase-5 (PDE5) reduces the degradation of cGMP, allowing erectile function to occur by relaxation of penile smooth muscle, represents a revolutionary approach or the treatment of erectile dysfunction (ED). Three PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) are clinically available at this time, and extensive drug design efforts are registered for finding agents with a better activity, enhanced selectivity and reduced side effects. Many classes of such compounds have been reported, belonging to diverse chemical entities. The drug design has been very much facilitated after the report of the X-ray crystal structure of the PDE5 catalytic domain in complex with the three clinically used derivatives. PDE5 inhibitor therapy, has been found to be effective in special clinical populations, such as those with prostate cancer, diabetes, and cardiovascular disease. The duration of action of sildenafil and vardenafil is of about 4 hours, whereas that of tadalafil is of about 36 hours, and the overall safety of the treatments is good. There is a risk of hypotension if nitrates are given concurrently with the PDE5 inhibitors. Common side-effects include headache, facial flushing, nasal congestion, dyspepsia and transient visual impairment. There are pharmacological interactions between these drugs and other medications metabolized by the cytochrome P450 (P3A4 isoform), such as the azole antifungals, erythromycin and the HIV protease inhibitors.
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PMID:Phosphodiesterase 5 inhibitors--drug design and differentiation based on selectivity, pharmacokinetic and efficacy profiles. 1701 39


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