Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertensionA randomized prospective study
Hossein A. GhofraniRobert VoswinckelFrank ReichenbergerHorst OlschewskiP HAREDZAB KARADASRalph T. SchermulyNorbert WeißmannWerner SeegerFriedrich Grimminger
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Since the introduction of the phosphodiesterase type 5 (PDE-5) inhibitor sildenafil in 1998, there has been a fundamental change in the treatment of erectile dysfunction (ED). Sildenafil has already been used by over 20 million men in over 100 countries, with a death rate similar to that of general population. The success rate of sildenafil amounts to an average of over 80%, and sildenafil has become the first choice for patients with ED. The development of two new PDE-5 inhibitors, vardenafil and tadalafil, has added to the options for the treatment of ED. In this review, a comparison is made of the pharmcodynamics, pharmacokinetics and adverse reactions between the three PDE-5 inhibitors to assess their efficacy and safety.
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The PDE-5 inhibitors, i.e., phosphodiesterase-5 inhibitors like sildenafil, vardenafil, and tadalafil, are the most used in premature erectile dysfunction. Many literature reviews suggest that these classes of drugs are commonly used in erectile dysfunction. Many of these reviews suggest that these inhibitors (PDE-5) are used in many other diseases apart from erectile dysfunction. So, in this review, we find the main mechanism of action of PDE-5 inhibitors in different disease conditions. These inhibitors have a major role in different diseases like erectile dysfunction, memory enhancement, cancer (cell proliferation), lower urinary tract symptoms, and pulmonary arterial hypertension. This class of drug also acts through the cGMP pathway. We found that cGMP plays an important role in different diseases like erectile dysfunction, cancer, and memory enhancement. So, in this review, we show the mechanism of PDE-5 inhibitor in different disease conditions. Keywords: PDE-5, Erectile dysfunction, Memory enhancement, cGMP, Pulmonary arterial hypertension.
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The causes of male erectile dysfunction (ED) are quite variable and are now commonly divided into etiologies such as ischemia, smooth muscle damage, or altered blood flow.Although varying rates of ED have been reported in literature, the number of men with ED is projected to increase worldwide by 2025 to approximately 322 million.Since the introduction of phosphodiesterase 5 (PDE5) inhibitors, there has been a paradigm shift in the treatment of ED because PDE5 inhibitors address a broad spectrum of etiologies for ED.Today, the American Urological Association recommends the use of three PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) as a first-line therapy for the treatment of ED.This review evaluates the pharmacological mechanism of PDE5 inhibitors along with the impact and use of sildenafil, vardenafil, tadalafil, and avanafil.By increasing intracellular cGMP levels, PDE5 inhibitors have been shown to be effective in the treatment of ED.Through their effects on other cellular signaling pathways, PDE5 inhibitors have the potential for treating other urologic conditions as well.The use of PDE5 inhibitors can also be combined to produce a synergistic effect in conditions such as male hypogonadism and benign prostatic hyperplasia in addition to ED.
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Purpose of review Phosphodiesterase 5 inhibitors are preferred by most men for the oral treatment of erectile dysfunction. In many guidelines, this therapy is recommended as first-line therapy because of convenience, high efficacy, and low rates of side-effects. Sildenafil was the first drug for the treatment of erectile dysfunction, introduced in 1998. There are now two new phosphodiesterase 5 inhibitors, vardenafil and tadalafil, for which approval was recently given in the European Union and is expected this year in the United States. Recent findings Sildenafil has proved to be a very effective medicinal product. According to initial studies, vardenafil and tadalafil have demonstrated efficacy comparable to that of sildenafil. However, fewer data are available evaluating the adverse effects of vardenafil and tadalafil, particularly on their long-term use and their use in high-risk groups. Interestingly, vardenafil and tadalafil have a higher potency than sildenafil. Moreover, the long life of tadalafil has been associated with an erectogenic potential of the drug lasting for more than 24 h. The advantage of this is the possibility of a patient engaging in sexual activity more than once after a single administration of the drug. Summary In the future, in addition to sildenafil, the new phosphodiesterase 5 inhibitors vardenafil and tadalafil will play an important role in the management of erectile dysfunction, depending on the patient's health profile.
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OBJECTIVE To review the pharmacologic and clinical trial data of the Food and Drug Administration–approved phosphodiesterase 5 (PDE5) inhibitors for the treatment of erectile dysfunction (ED). DATA SOURCES Primary research and review articles were identified through a search of ScienceDirect, PubMed/MEDLINE, and International Pharmaceutical Abstracts (1990–August 2004). The following search terms were used in the Medicine Dentistry and Pharmacology, Toxicology, and Pharmaceutical Sciences subcategories: phosphodiesterase 5 inhibitor, PDE5 inhibitor, erectile dysfunction, sildenafil, vardenafil, tadalafil, prostatectomy, and diabetes. Web of Science (1990–August 2004) was used to search for additional abstracts using the same search terms as above. The package inserts for sildenafil, vardenafil, and tadalafil were also consulted. STUDY SELECTION AND DATA EXTRACTION All identified research, review articles, and abstracts were assessed for relevance, and all relevant information was included. Priority was given to the primary medical literature and clinical trial reports. DATA SYNTHESIS ED is a common disorder in males with increased prevalence associated with age and presence of cardiovascular disease, prostatectomy, or diabetes mellitus. Sildenafil, vardenafil, and tadalafil are selective PDE5 inhibitors currently available for treatment of ED. Their pharmacology and pharmacokinetics vary slightly, but with potentially important clinical differences in duration of activity; all have similar clinical efficacy and adverse effect profiles in patients with ED of various causes. CONCLUSIONS Sildenafil, vardenafil, and tadalafil are safe and effective PDE5 inhibitors for the treatment of ED.
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Reason for posting: Phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra), are drugs used to treat erectile dysfunction that have long been recognized to cause temporary, minor visual changes in less than 10% of users.[1][1] However
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Erectile dysfunction (ED) is a common complication of diabetes mellitus. In four independent, 12-week, randomised, placebo-controlled clinical trials that evaluated the pro-erectile properties of the selective phosphodiesterase type 5 (PDE-5) inhibitors, sildenafil (Viagra) (25—100 mg), tadalafil (10 and 20 mg) and vardenafil (10 and 20 mg) in men with ED secondary to diabetes mellitus, all the active drugs were significantly superior to placebo. In this difficult-to-treat population, the greatest difference from placebo for the overall responder rate of diabetic men reporting improved erections occurred with vardenafil 20 mg (72% vs. 13% for placebo). All the PDE-5 inhibitors were generally well tolerated. There were fewer reports of visual disturbance with vardenafil or tadalafil than with sildenafil, which may be due to their greater selectivity for PDE-5 inhibition and less cross-reactivity with retinal PDE-6 inhibition. The studies suggest there may be significant differences between the three drugs. However, only head-to-head studies will determine true differences in both efficacy and side effect profile.
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