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)

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

Although sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of pulmonary hypertension (PH), safety and effectiveness have not been studied during coadministration with beraprost, an oral prostacyclin analogue. To address this issue, we administered oral beraprost (40 microg) on day 1 and beraprost (40 microg) plus sildenafil (25 mg) on days 2 to 6 patients with moderate to severe PH. Although sildenafil plus beraprost produced transient flushing in 2 of 6 patients, systemic hemodynamics and arterial and venous gas analyses were similar in comparisons between the 2 treatment groups. In contrast, sildenafil plus beraprost therapy resulted in a 2.2-fold greater reduction in mean pulmonary arterial pressure and a 1.6-fold greater reduction in pulmonary vascular resistance compared with beraprost alone, and reductions in these parameters persisted longer with combination therapy than with beraprost alone. Addition of oral sildenafil to beraprost appears to represent a safe and effective therapeutic option, at least in the acute phase, for patients with pulmonary hypertension.
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PMID:Addition of oral sildenafil to beraprost is a safe and effective therapeutic option for patients with pulmonary hypertension. 1577 14

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

Inhibition of phosphodiesterase-5 (PDE5) reduces the degradation of cyclic guanosine monophosphate, which allows erectile function to occur by relaxation of penile smooth muscle. Three PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) in a range of doses are available. PDE5 therapy, compared with placebo, significantly improves scores on the International Index of Erectile Function and has been found to be effective in special clinical populations, such as those with prostate cancer, diabetes, and cardiovascular disease. Sildenafil and vardenafil show some interaction with food intake. Time to onset of action is usually 30-120 minutes, but there are reports of shorter times to onset of action. The duration of action of sildenafil and vardenafil is about 4 hours, whereas that of tadalafil is about 36 hours. The overall safety of the treatments is good, even in patients with a history of cardiovascular disease. However, there is a risk of hypotension if nitrates are given concurrently. Increased QTc intervals have been reported, the longest with vardenafil, shortest with tadalafil, and intermediate with sildenafil. Priapism and prolonged erection are rare adverse events. Common side-effects include headache, facial flushing, nasal congestion, and dyspepsia. There may be interactions with other medications metabolized in a similar way, such as erythromycin and HIV protease inhibitors.
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PMID:The efficacy and safety of PDE5 inhibitors. 1615 23

Within 6 months of approval by the U.S. Food and Drug Administration (FDA), 5.3 million prescriptions were written for sildenafil citrate. It represented the first clearly effective and FDA-approved oral therapy for the treatment of ED. The chemical structure of sildenafil is very similar to the cyclic guanosine monophosphate molecule with which it competes, in the enzyme phosphodiesterase type-5. Sildenafil binds to the phosphodiesterase-5 enzyme, preventing the breakdown of cyclic guanosine monophosphate through competitive inhibition. The onset of action for sildenafil can be as short as 20 minutes and the duration of action may be as long as three half-lives (18 hours). Anecdotal evidence suggests that many men describe an erectogenic effect for almost 24 hours. The safety of sildenafil has been established in many pre- and postapproval studies at doses as high as eight times the maximum recommended dose. It is likely that the rare instance of myocardial infarction after taking sildenafil as directed, is due more to the activity of sexual intercourse rather than the medication itself. Efficacy have been established in patients with diabetes, parkinsonism, spinal cord injury, and those on antihypertensive (single- and multiple-therapy) agents. It has also been shown to be effective in reversing selective serotonin reuptake inhibitor-induced sexual side effects. Initial concerns about sildenafil with respect to ocular safety were based on misinterpretation of the FDA submission data. The two most common side effects are headache and flushing, both of which are short-lived and easily treated.
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PMID:Four-year review of sildenafil citrate. 1698 12

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

First-dose success of phosphodiesterase type 5 (PDE5) inhibitors may be adversely affected in patients with comorbidities. This article reports first-dose success rates for vardenafil 10 mg in men with erectile dysfunction (ED) and associated comorbidities who participated in the challenge phase of the Reliability--Vardenafil for Erectile Dysfunction I study. This study involved an open-label, single-dose, 1-week challenge period where patients who achieved SEP-2 (penetration) success were randomised to vardenafil 10 mg or placebo for 12 weeks in a double-blind manner. The first-dose success rates for SEP-2 and SEP-3 (maintenance of erection to completion of intercourse) were stratified according to comorbidities. Safety was assessed using adverse events (AEs). Of 600 men who received a single 10 mg dose of vardenafil, 32% had hypertension, 16% had diabetes and 19% had dyslipidaemia. Vardenafil demonstrated overall effectiveness, including first-dose SEP-2 and SEP-3 success rates in patients with and without specific comorbidities. Initial overall success rates for SEP-2 and SEP-3 during the challenge phase were 87% and 74% respectively. First-dose SEP-2 and SEP-3 success rates were 84% and 66% in men with hypertension (n = 191); 84% and 72% in men with dyslipidaemia (n = 116); and 75% and 58% in men with diabetes (n = 95). Vardenafil was well tolerated and most AEs, including the most frequently reported flushing (3.5%), were mild to moderate in intensity. Vardenafil 10 mg is generally well tolerated and efficacious, providing first-dose success with a consistently high rate of reliability of penetration and maintenance of erection in men with ED and associated comorbidities.
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PMID:First-dose success with vardenafil in men with erectile dysfunction and associated comorbidities: RELY-I. 1707 35

Raynaud's phenomenon is a common disorder with vasospasm of the digital arteries causing pallor with cyanosis and/or rubor. It can be primary (idiopathic), where it is not associated with other diseases, or secondary to several diseases or conditions, including connective tissue diseases, such as scleroderma and systemic lupus erythematosus. Raynaud's is often mild enough to not require treatment; however, with secondary Raynaud's there is not only vasospasm but also fixed blood vessel defects so the ischaemia can be more severe. Complications can include digital ulcers and could, rarely, lead to amputation. Treatment is often non-pharmacological including avoiding cold and smoking cessation. Calcium channel antagonists, such as nifedipine, are often considered when treatment is needed; however, adverse effects of these drugs can include hypotension, vasodilatation, peripheral oedema and headaches. Other treatments have been studied in randomised, controlled trials including classes of drugs, such as angiotensin II inhibitors, selective serotonin reuptake inhibitors, phosphodiesterase-5 inhibitors (e.g. sildenafil), nitrates (topical or oral; the latter can be limited by adverse effects, such as flushing, headache and hypotension), and for more serious Raynaud's or its complications prostacyclin agonists may be used. There are two large studies that demonstrate that endothelin receptor blockade with bosentan can reduce the number of new digital ulcers in scleroderma patients. However, it does not affect the healing period. Thus, Raynaud's is common and often requires non-pharmacological treatment. When secondary Raynaud's is suspected, such as Raynaud's with an older age at onset or other features of connective tissue disease, then an appropriate history, physical examination and laboratory tests may be indicated to reach an appropriate diagnosis. There have been advances in pharmacological treatment, but some of the treatments are limited by adverse effects.
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PMID:The diagnosis and treatment of Raynaud's phenomenon: a practical approach. 1735 12

Vardenafil is a selective phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. It was found to be effective in a high percentage of patients and a broad spectrum of underlying conditions. It potentiates the increase in intracellular cGMP in the corpora cavernosa in response to sexual stimuli, resulting in enhanced and prolonged erections. The overall tolerability and safety profile is acceptable, with headache, flushing, rhinitis and dyspepsia being the major reported side effects. Importantly, tolerability and safety in cardiovascular patients seems to be good with no significant increase in cardiovascular events that could be directly attributed to the pharmacologic agent. Only mild blood-pressure lowering effects were observed in healthy individuals, as well as hypertensive patients on multiple antihypertensive agents. However, special caution is mandatory if vardenafil is administered in combination with alpha-blockers, as significant hypotension might occur. Importantly, any drug serving as a nitric oxide donor is contraindicated in combination with vardenafil.
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PMID:Vardenafil: a selective inhibitor of phosphodiesterase-5 for the treatment of erectile dysfunction. 1747 42


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