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)

Sildenafil (Viagra) is a selective phosphodiesterase type 5 inhibitor (PDE5-I) approved for treatment of erectile dysfunction. Although relatively well-tolerated, sildenafil is associated with undesired effects including headache, flushing, dyspepsia, nasal congestion, and visual disturbances. In the present study we explored the impact of sildenafil on nasal airway parameters in young potent men. Eleven men (age 26.0 +/- 1.8 years) with normal BMI (25.7 +/- 0.5) and without nasal respiratory disorders were enrolled in a double-blind, crossover study. All men underwent evaluation of systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), SpO2%, acoustic rhinometry, and nasal endoscopy before and after placebo or sildenafil (50 mg) plus visual sexual stimulation (VSS). Nasal examination was performed using 0 degrees rigid telescopes, 4 mm in diameter. A Student's t test was used for direct comparisons, while the Kruskal-Wallis test (K-W) was utilized for multiple comparisons. After administration of sildenafil plus VSS, the minimum cross sectional area (MCA) was significantly lower that observed with either placebo (P = 0.03) or sildenafil alone (P = 0.003). However, the post-stimulation values did not demonstrate any significant differences among the different treatment arms (P = 0.48; DF = 2; K-W test). In contrast, endonasal volume (VOL) was significantly lower after sildenafil + VSS (P = 0.01), but not after placebo + VSS (P = 0.18). None of the other parameters monitored showed any significant variations. Rhinoscopy showed a characteristic increase of the volume of the inferior turbinates, with subjective differences between placebo and sildenafil. These preliminary results suggest that sildenafil reduces nasal volume, and that sexual stimulation may decrease nasal airflow by itself.
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PMID:Nasal congestion after visual sexual stimulation with and without sildenafil (Viagra): a randomized placebo-controlled study. 1790 71

Erectile dysfunction is a common multifactorial complication of diabetes mellitus. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. A recent Cochrane systematic review assessed the effects ofPDE-5 inhibitors in patients with diabetes mellitus and erectile dysfunction from 8 randomized placebo-controlled trials (a total of 1759 participants). The duration of therapy was mainly 12 weeks. The weighted mean difference (WMD) for the International Index of Erectile Function (erectile dysfunction domain) at the end of the study period was 6.6 in favour of the PDE-5 inhibitors arm. The relative risk for answering 'yes' to a global efficacy question ('did the treatment improve your erections?') was 3.8 in the PDE-5 inhibitors arm compared with the control arm. Headache and flushing were the most common adverse events, followed by flu-like symptoms, dyspepsia, myalgia, vision disorders and lower back pain. The overall risk ratio for developing any adverse reaction was 4.8 in the PDE-5 inhibitors arm as compared to the control arm. It was concluded that sufficient evidence exists that treatment with PDE-5 inhibitors can improve erectile dysfunction in diabetic men.
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PMID:[From the Cochrane Library: Phosphodiesterase inhibitors are effective in treating erectile dysfunction in diabetic men]. 1794 26

Prevalence and severity of erectile dysfunction (ED) increase with aging and are often associated with illnesses, like diabetes mellitus, heart disease, and hypertension, pathologically characterized by endothelial dysfunction and whose prevalence increases with age. The assumption that ED is mainly a neurovascular disease is supported by the evidence that specific phosphodiesterase type 5 (PDE5) inhibition produces an efficient erection in a wide range of ages and conditions. The availability of specific PDE5 inhibitors has enabled the development of effective treatment strategies, in this contest, tadalafil may be considered as the least "typical" PDE5 inhibitor. In clinical trials, tadalafil significantly enhanced, in patients of different ages, all efficacy outcomes across disease etiologies and severities. With an effectiveness lasting up to 36h, tadalafil allows patients to choose when to have sexual activities without the need to time it, showing positive feedback in terms of quality of life related to the treatment. Headache and dyspepsia were the most frequent side-effects of tadalafil, followed by back pain, nasal congestion, myalgia, and flushing, but the impact that long time action could have on effectiveness and safety is not yet entirely defined. The aim of this article is to critically review the available evidence from the tadalafil clinical research program and give the physician a rational approach for intervention in the treatment of ED and related diseases.
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PMID:Tadalafil in the treatment of erectile dysfunction; an overview of the clinical evidence. 1804 21

The objective of this study was to identify the use of phosphodiesterase type 5 inhibitors among university students from the city of Sao Paulo (SP) in Brazil. Male students (n=350) replied to a questionnaire about diagnosis of erectile dysfunction, the frequency and reason for the use of phosphodiesterase type 5 inhibitors, the specific medication used, whether their use was accompanied by a medical prescription and any reported side-effects. The results shows that a total of 53 (14.7%) students had already used this kind of medication without a prescription or medical diagnosis for erectile dysfunction, of which 53% reported using sildenafil, 37% tadalafil and 10% vardenafil. The main adverse side-effects reported were headache (23%) and flushing (10%) and the main reasons for using the inhibitor were curiosity (70%) and erectile improvement (12%).
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PMID:Use of phosphodiesterase-5 inhibitors by college students. 1879 70

Flushing is one of the most common vasodilation-related adverse effects associated with both nitrates and phosphodiesterase type 5 (PDE5) inhibitors. The present study aimed to investigate the effects of orchidectomy and ovariectomy on isosorbide dinitrate-, sildenafil-, vardenafil- and tadalafil-induced flushing of tail-skin in mice. Both orchidectomy and ovariectomy markedly increased the tail-skin temperature, a good parameter of flushing, induced by isosorbide dinitrate (500 microg/kg, i.p.). These observations suggest that both testosterone withdrawal and estrogen withdrawal are risk factors for isosorbide dinitrate-induced flushing. In contrast, sildenafil (100 mg/kg, p.o.)-, vardenafil (10 mg/kg, p.o.)- and tadalafil (40 mg/kg, p.o.)-induced flushing of tail-skin in mice was aggravated by ovariectomy but not by orchidectomy. Orchidectomized male mice, but not ovariectomized female mice, showed significantly lower levels of PDE5 mRNA expression in tail artery compared with those of sham-operated mice. The present findings suggest that estrogen withdrawal, but not testosterone withdrawal, is a risk factor for PDE5 inhibitor-induced flushing. These gender differences in the vascular adverse reactions of PDE5 inhibitors may be interpreted as occurring due to differences in the levels of PDE5 mRNA expression in peripheral arteries.
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PMID:Gender differences in tail-skin flushing induced by nitrates and phosphodiesterase type 5 inhibitors in a climacteric mouse model. 1981 43

The phosphodiesterase type 5 (PDE-5) inhibitors-sildenafil, vardenafil, and tadalafil-are used primarily in erectile dysfunction, but sildenafil is also indicated for pulmonary hypertension. Common adverse effects of vardenafil include headache, flushing, nasal congestion, dyspepsia, and nausea. Recently, PDE-5 inhibitors have been associated with adverse vision effects, and emerging evidence now indicates that they may also be responsible for hearing changes and hearing loss. We describe a patient who developed unilateral sudden sensorineural hearing loss possibly related to the use of vardenafil for erectile dysfunction. To our knowledge, only one other case of hearing loss related to this drug class has been published. Our patient was a 57-year-old man who came to the emergency department with right-sided mild-to-moderate hearing loss in the 500-3000-Hz range, confirmed by audiogram, that occurred after ingestion of vardenafil. The patient was hospitalized 2 days later for administration of intravenous dexamethasone, followed by oral prednisone. He reported that his hearing had improved on the fourth hospital day and was discharged 3 days later, continuing to taper the prednisone on an outpatient basis. A repeat audiogram after 10 days of corticosteroid therapy confirmed that his hearing in the 500-3000-Hz range was within normal limits. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score of 3) adverse reaction of sudden sensorineural hearing loss associated with vardenafil consumption. We also performed an analysis of hearing loss cases related to PDE-5 inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System database to compare the characteristics of our patient with those of other reported adverse event cases. Based on the temporal relation of the sudden sensorineural hearing loss to this patient's drug consumption, we propose that the vardenafil is a likely cause of the hearing loss. This case provides further evidence that PDE-5 inhibitor consumption should be considered as a possible cause in patients presenting with sudden sensorineural hearing loss.
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PMID:Sudden sensorineural hearing loss associated with vardenafil. 2003 Apr 81

Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH). The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings.
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PMID:Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension. 2053 62

Erectile dysfunction (ED) commonly affects the quality of life of men after treatment of prostate cancer. We conducted a placebo-controlled, crossover randomised trial to assess the efficacy and tolerability of sildenafil citrate in the treatment of ED developing after external beam radiation treatment (EBRT) of localized prostate cancer. Sixty-six patients who had developed ED following radiation treatment agreed to participate and were allocated to sildenafil or placebo to be taken prior to four sexual attempts. In the crossover period, subjects received the alternative tablet for a further four attempts. Allocation was centrally randomized, and researchers and patients were both blinded to the trial arm. Efficacy was assessed using the International Index of Erectile Function (IIEF) questionnaire and with a separate global efficacy question. Forty-three subjects completed the study. There was a significant increase in mean scores from baseline for all domains of the IIEF with sildenafil compared with placebo (P < 0.001). Affirmative response to the global efficacy question was more common after taking sildenafil compared with placebo. In approximately half of the patients, the improvement in the erectile function domain score corresponded to a moderate improvement in ED (e.g. success 'sometimes' to 'most times'). Sildenafil was associated with mild flushing, nasal stuffiness or indigestion in 8-10% patients and moderate flushing in 10%. The current study adds to the evidence that phosphodiesterase inhibitors are an effective and well-tolerated treatment for ED after EBRT for prostate cancer.
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PMID:Randomised, placebo-controlled, crossover trial of sildenafil citrate in the treatment of erectile dysfunction following external beam radiation treatment of prostate cancer. 2059 10

The pathology of pulmonary arterial hypertension (PAH) is characterized by vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. Experimental studies have shown the beneficial effect of phosphodiesterase type 5 (PDE-5) inhibitors on pulmonary vascular remodeling and vasodilatation. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil which significantly improve clinical status, exercise capacity and hemodynamics of PAH patients. Combination therapy of PDE-5 inhibitors with prostacyclin analogs and endothelin receptor antagonists may be helpful in management of PAH. The third PDE-5 inhibitor, vardenafil, is currently being investigated in PAH. Side effects are usually mild and transient and include headache, flushing, nasal congestion, digestive disorders, and myalgia.
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PMID:[Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension]. 2081 51

Udenafil is a potent phosphodiesterase type-5 inhibitor (PDE5) previously shown in studies conducted in populations of Eastern-Asian ethnicity, to significantly improve sexual function, in addition to a favourable safety profile. The purpose of this study was to evaluate the efficacy and safety of udenafil for the treatment of erectile dysfunction (ED), for the first time in a non-Eastern-Asian population. In this multicentre, randomized, double-blind, parallel, placebo-controlled study conducted in five centres in Turkey, 118 eligible subjects were randomized to receive udenafil 100 mg taken as on-demand or matching placebo for an 8-week treatment period. The primary efficacy variable was the change from baseline of the International Index of Erectile Function Questionnaire-Erectile Function Domain (IIEF-EFD) score, secondary efficacy variables were changes from baseline in IIEF Questionnaire Domains' 2-5 scores (Intercourse Satisfaction, Orgasmic Function, Sexual Desire, Overall Sexual Satisfaction) and IIEF Questionnaire Grand Total score, changes from baseline in penetration success rates (SEP2) and intercourse completion rates (SEP3) and evaluation of responses to the global assessment question (GAQ). Patients treated with udenafil demonstrated significantly higher increase in the IIEF-EFD scores compared with placebo-treated subjects [4.0 (95% CI: 1.3-6.6; p = 0.003)]. Similarly, greater improvements were observed in the scores for SEP2 [0.65 (95% CI: 0.02-1.3, p = 0.043)], SEP3 [0.9 (95% CI: 0.3-1.5, p = 0.003)] and two other IIEF Questionnaire Domains (Domain 4: Sexual Desire, Domain 5: Overall Sexual Satisfaction). The proportion of positive responses to the GAQ was greater in the udenafil compared to the placebo group (72.2% vs. 49.1%, p = 0.014). The most frequent treatment-emergent adverse events were headache, flushing and rhinorrhea, all of mild or moderate severity. This is the first study to demonstrate in a non-Eastern-Asian population that udenafil 100 mg taken as on-demand can effectively improve erectile function and is well tolerated.
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PMID:Efficacy and tolerability of udenafil in Turkish men with erectile dysfunction of psychogenic and organic aetiology: a randomized, double-blind, placebo-controlled study. 2378 19


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