Phosphodiesterase 5 Inhibitors for Erectile Dysfunction

2005 ◽  
Vol 39 (7-8) ◽  
pp. 1286-1295 ◽  
Author(s):  
Stephen M Setter ◽  
Jason L Iltz ◽  
Jack E Fincham ◽  
R Keith Campbell ◽  
Danial E Baker
Keyword(s):  
Clinical Trial ◽  
Erectile Dysfunction ◽  
Data Extraction ◽  
Pde5 Inhibitor ◽  
Clinical Trial Data ◽  
Research Review ◽  
Pde5 Inhibitors ◽  
Search Terms ◽  
Review Articles ◽  
Phosphodiesterase 5

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.

scholarly journals Phenanthrenes from Eulophia macrobulbon as Novel Phosphodiesterase-5 Inhibitors

2017 ◽  
Vol 12 (1) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Prapapan Temkitthawon ◽  
Kanokwan Changwichit ◽  
Nantaka Khorana ◽  
Jarupa Viyoch ◽  
Khanit Suwanborirux ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Erectile Dysfunction ◽  
Chemical Constituents ◽  
Pde5 Inhibitor ◽  
Pde5 Inhibitors ◽  
New Class ◽  
Phosphodiesterase 5 Inhibitors ◽  
Phosphodiesterase 5

Phosphodiesterase 5 (PDE5) inhibitors can be used for the treatment of erectile dysfunction and pulmonary hypertension. In order to search for new leads of PDE5 inhibitors, we investigated the chemical constituents of the tubers of Eulophia macrobulbon (E.C. Parish & Rchb. f) Hook. f A new phenanthrene, 9,10-dihydro-4-(4′-hydroxybenzyl)-2,5-dimethoxyphenanthrene-1,7-diol (1) and three known phenanthrenes i.e., 1-(4′-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (2), (9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol (3) and 1,5,7-trimethoxyphenanthrene-2,6-diol) (4) were isolated. Among these, 2 was the most potent PDE5 inhibitor (IC50 =1.67±0.54 μM) evaluated by the [3H]cGMP radioassay method, whereas 1 showed mild activity (IC50 = 62.3±3.3 μM). Their inhibitory selectivities against PDE5 over PDE6 were also studied. This study suggests phenanthrenes as a new class of PDE5 inhibitors.

Cutaneous Reaction to Drugs Used for Erectile Dysfunction: Case Report and Review of the Literature

2006 ◽  
Vol 10 (3) ◽  
pp. 128-130 ◽  
Author(s):  
Renee A. Beach ◽  
Frank Murphy ◽  
Ronald B. Vender
Keyword(s):  
Erectile Dysfunction ◽  
Drug Eruption ◽  
Pde5 Inhibitor ◽  
Sexual Performance ◽  
Pde5 Inhibitors ◽  
Fixed Drug Eruption ◽  
The Past ◽  
Fixed Drug ◽  
Performance Satisfaction ◽  
Phosphodiesterase 5

Background: In the past 9 years, drugs for erectile dysfunction (ED) have been increasingly prescribed for men with erectile difficulty. These drugs, phosphodiesterase 5 (PDE5) inhibitors, help men with ED obtain and sustain an erection, improving both sexual function and sexual performance satisfaction. However, these drugs contain side effects. Objectives: A 56-year-old man developed an erythematous, circle-shaped lesion on his penis. The lesion was recurrent, with evidence of desquamation. The aim was to determine the source of the recurrent lesion based on its morphology and the patient's verbal history. Results: A clinical diagnosis of fixed drug eruption owing to use of the PDE5 inhibitor tadalafil (Cialis) was made. He was not rechallenged with the drug. However, he experienced a subsequent recurrence of the eruption on inadvertent rechallenge. Conclusions: We believe this case to be the first report of this type of reaction owing to tadalafil. Therefore, fixed drug eruption is a newly observable side effect of this drug.

Regulatory frameworks for clinical trial data sharing during the Pandemic and beyond: A scoping review (Preprint)

2021 ◽  
Author(s):  
Nachiket Gudi ◽  
Prashanthi Kamath ◽  
Trishnika Chakraborty ◽  
Anil G. Jacob ◽  
Shradha Parsekar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Data Sharing ◽  
Scoping Review ◽  
Data Extraction ◽  
Grey Literature ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Policy Documents ◽  
Regulatory Documents ◽  
Share Data

BACKGROUND Data sharing from clinical trials is well recognized and has widely gained recognition amid the COVID-19 pandemic. The competing interests of powerful stakeholders expressed through data exclusivity practices make clinical trial data sharing a complex phenomenon. The wider acceptance of data sharing practices in the absence of mandated policy creates uncertainty among trial investigators to count for risks vs benefit from sharing trial data. Data sharing becomes further complex as the trial data sharing is governed by the regional policies. This drew our attention to explore policies for informed data sharing. OBJECTIVE This scoping review aimed to map the existing literature around the regulatory documents that guide trial investigators to share clinical trial data. METHODS We followed a Joanna Briggs Institute scoping review approach and have reported the article according to the PRISMA extension for Scoping reviews (PRISMA-ScR). In addition to the use of the electronic databases, a targeted website search was performed to access relevant grey literature. The articles were screened at the title-abstract and the full text stages based on the selection criteria. All the included articles for data extraction were in English language. Data extraction was done independently using a pre-tested data extraction sheet. Included literature focused on clinical trial data sharing policies, guidelines, or SOPs. A narrative synthesis approach was used to summarize the findings. RESULTS This scoping review identified four articles and 13 policy documents from the grey literature. A majority of the clinical trial agencies require an agreement for data sharing between the data requestor/organization and trial agency. None of the policy documents mandates informed consent for data sharing. The time interval to share data underlying results, varies from six to 18 months from the time of trial publication. Depending upon trial data, policies follow both controlled and open access models. Regulatory documents identified in both scientific and grey literature emphasized on good research principles of protection of privacy of participant data and data anonymization through data sharing agreement between the data requester and trial agency. Need for an informed consent and cost of data sharing, timeline to share data, incentives, or reward to promote data sharing and capacity building for data sharing have remained grey areas in these policy documents. CONCLUSIONS This paper acknowledges the vital role of clinical data sharing from a public health perspective. We found that given the challenges around clinical trial data sharing, developing a feasible mechanism for data sharing is important. We suggest that standardizing data sharing processes by framing a concise policy with key elements of data sharing mechanisms could be easier to practice rather than a rigid and comprehensive data sharing policy. CLINICALTRIAL This scoping review protocol has not been registered and published.

scholarly journals Audiometry Results and TEOAE and DPOAE Amplitudes in Men Taking a Phosphodiesterase Type 5 Inhibitor for Erectile Dysfunction

2017 ◽  
Vol 96 (7) ◽  
pp. E34-E39 ◽  
Author(s):  
Sertan Öntepeli ◽  
Nuray Bayar Muluk ◽  
Devrim Tuğlu ◽  
Timuçin Şipal
Keyword(s):  
Erectile Dysfunction ◽  
Otoacoustic Emissions ◽  
Pde5 Inhibitor ◽  
Post Treatment ◽  
Guanosine Monophosphate ◽  
Pde5 Inhibitors ◽  
Cochlear Blood Flow ◽  
Distortion Product ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type

We conducted a prospective study of transient evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) in men who were taking an oral phosphodiesterase type 5 (PDE5) inhibitor for erectile dysfunction. Our study group was made up of 30 men (60 ears), aged 34 to 60 years (mean: 50.9). They were randomly divided into three groups; 10 men were given sildenafil (Viagra) at 50 mg twice a week, 10 were given tadalafil (Cialis) at 20 mg twice a week, and 10 were given vardenafil (Levitra) at 20 mg twice a week. All patients took their drug for 3 weeks, for a total of 6 tablets for each patient. Audiometric tests and TEOAE and DPOAE measurements were performed before and after treatment. Post-treatment audiometry demonstrated improvement in hearing in all three groups. However, post-treatment TEOAE amplitudes and DPOAE amplitudes differed among the three groups; they were significantly higher in the sildenafil group at 1.0 kHz and the same in the tadalafil group; in the vardenafil group, the DPOAE amplitude was significantly lower at 3.0 kHz while there was no change in the TEOAE amplitude. We speculate that the possible mechanism for these findings is that PDE5 inhibitors block degradation of cyclic guanosine monophosphate (cGMP) and induce dilation of the cochlear microcirculation, resulting in an increase in cochlear blood flow. We also believe that the decrease in DPOAE amplitudes at 3.0 kHz seen in the vardenafil group may be related to an accumulation of nitric oxide/cGMP complex, which is toxic to the cochlea; however, since there was no change in TEOAE amplitude in the vardenafil group, this influence may be minimal. Further studies are needed to obtain a more comprehensive assessment of the effects of PDE5 inhibitors on hearing with the use of higher doses and longer durations of therapy.

scholarly journals Relaxant mechanism of Eulophia macrobulbon ethanolic extract and 1-(4΄-hydroxybenzyl)-4, 8-dimethoxyphenanthrene-2,7-diol on human corpus cavernosum

2019 ◽  
Vol 9 (5) ◽  
pp. 328
Author(s):  
Chaweewan Jansakul ◽  
Somreudee Yorsin ◽  
Jomkarn Naphatthalung ◽  
Kuldej Tachanaparugse ◽  
Kanokwan Changwichai ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Pde5 Inhibitor ◽  
Corpus Cavernosum ◽  
Ethanolic Extract ◽  
Good Choice ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Relaxant Effect ◽  
Phosphodiesterase 5 ◽  
Ca2 Channels

Background: Eulophia macrobulbon (E.C.Parish & Rchb.f.) Hook.F. has been shown to be a promising phosphodiesterase-5 (PDE5) inhibitor that relaxes rat isolated pulmonary artery.Objective: To test this plant’s possible application in human erectile dysfunction (ED) using an ethanolic extract of E. macrobulbon tubers (EM extract), and an isolated constituent, 1-(4΄-hydroxybenzyl)-4, 8-dimethoxyphenanthrene-2,7-diol (HDP).Methods: Dried tubers of EM were extracted with 95% ethanol and the HDP was isolated by several chromatographic methods. The relaxant mechanism of the EM extract and the HDP was studied on isolated human cavernosal strips (HC strip).Results: EM extract (0.1-3 mg/ml) relaxed HC strips precontracted with phenylephrine. The relaxant effect was not modified by N-nitro-L-arginine (L-NNA), ODQ, tetraethylammonium, nor glybenclamide. HDP (0.1-3 mM) relaxed HC strips precontracted with phenylephrine to the same extent as that of sildenafil. EM extract and HDP potentiated relaxation of the HC strips to glyceryl trinitrate in a similar manner to that of sildenafil. EM extract and sildenafil, but not HDP, increased cGMP content of the HC strips in a concentration-dependent manner. In the thapsigargin-pretreated HC strips, nifedipine or EM extract, but not HDP, suppressed the contractile response of the HC strips to phenylephrine. When nifedipine and/or SKF 96365 (stored-operated Ca2+ channel blocker) was added, followed by EM extract or HDP, further suppression was found in the case of HDP but not with EM extract. Ca2+ free Krebs solution suppressed the phenylephrine contraction on HC strips and further suppression was found when adding EM extract or HDP.Conclusion: These results indicate that EM extract causes a relaxation of HC strips by serving as an inhibitor of PDE5, of voltage- and stored-operated Ca2+ channels, and of intracellular Ca2+ mobilization. Thus EM extract might be a good choice for development as a functional food for erectile dysfunction in men. However, further studies are needed to identify other PDE5 and the Ca2+channel inhibiting components of the extract.

scholarly journals Liposomal Delivery of a Phosphodiesterase 5 Inhibitor Enhances Prostacyclin-Mediated Adenosine Triphosphate Release from Human Red Blood Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4803-4803
Author(s):  
Elizabeth Bowles ◽  
Randy Sprague ◽  
Nuran Ercal
Keyword(s):  
Side Effects ◽  
Red Blood Cells ◽  
Adenosine Triphosphate ◽  
Blood Cells ◽  
Conflicts Of Interest ◽  
Pde5 Inhibitor ◽  
Atp Release ◽  
Pde5 Inhibitors ◽  
Phosphodiesterase 5 ◽  
Human Rbcs

Abstract Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance (PVR) and right heart failure. Red blood cells (RBCs) of PAH patients fail to release the vasodilator, adenosine triphosphate (ATP), when deformed as would occur when traversing the lung. Such a defect could contribute to increased PVR. However, RBCs of PAH patients do release ATP in response to prostacyclin (PGI2) analogs and this is augmented by phosphodiesterase 5 (PDE5) inhibitors. Current PAH treatment includes PGI2 analogs and PDE5 inhibitors alone or in combination. Unfortunately, these drugs can have untoward side effects. Encapsulation of drugs within liposomes (small lipid-membraned vesicles) that can be targeted to RBCs has been shown to increase effectiveness and tolerability of some medications. The objective of this study was to determine if encapsulation of the PDE5 inhibitor zaprinast (ZAP) within liposomes is an effective means to deliver this class of drugs to human RBCs and if this approach would augment ATP release stimulated by the PGI2 analog UT-15c. Human RBCs were isolated and incubated with either blank liposomes (n=10), liposomes containing ZAP (n=9) or liposomes containing the PDE3 inhibitor, cilosatzol (CILO, n=10). RBCs (20% hematocrit) were then treated with UT-15c (1 µM). ATP release was measured before and 5, 10, and 15 min after the addition of UT-15c. In the presence of empty liposomes, the dose of UT-15c used did not stimulate ATP release. However, UT-15c did stimulate ATP release from RBCs pretreated with ZAP encapsulated by liposomes (P<0.01). The average time for maximal release was 9 ± 1 min. In contrast, when exposed to liposomes containing CILO, there was no ATP release following UT-15c administration. These studies demonstrate that the selective delivery of a PDE5 inhibitor to human RBCs potentiates UT-15c induced ATP release. Moreover the findings are consistent with the hypothesis that directed delivery of this class of drugs to PAH RBCs could be a new and important method to augment PGI2 analog-induced ATP release from these cells. Such an approach could significantly limit side effects of both drugs without compromise of their therapeutic effectiveness in PAH. Disclosures No relevant conflicts of interest to declare.

Dalteparin: A Low-Molecular-Weight Heparin

1997 ◽  
Vol 31 (2) ◽  
pp. 192-203 ◽  
Author(s):  
Patricia A Howard
Keyword(s):  
Clinical Trial ◽  
Molecular Weight ◽  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Low Molecular Weight Heparin ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Fixed Dose ◽  
Low Molecular Weight ◽  
Review Articles

Objective To discuss the chemistry, pharmacology, and pharmacokinetics of dalteparin, a low-molecular-weight heparin (LMWH), and to review the comparative clinical trial data evaluating the efficacy and safety of dalteparin and unfractionated heparin (UH) for the prophylaxis and treatment of venous thromboembolism. Data Sources A MEDLINE search identified pertinent English-language publications on dalteparin and venous thromboembolism. Key search terms were dalteparin, Fragmin, LMWH, and venous thromboembolism. The search was supplemented by review articles, articles obtained from the bibliographies of the review articles, and the dalteparin approval database. Study Selection The most pertinent studies describing the pharmacology and pharmacokinetics of dalteparin in humans were selected; all abstracts and clinical trials evaluating the use of dalteparin for antithrombotic therapy were reviewed. Review articles by authors of international reputation were selected. Data Extraction Pertinent information from the review articles on the pharmacology of LMWHs and UH was summarized. Clinical trial data were extracted for study design, patient demographics, therapeutic regimens, methods of evaluation, and outcomes. Data Synthesis Dalteparin is an LMWH indicated for patients undergoing abdominal surgery who are considered to be at risk for deep-vein thrombosis (DVT), which may lead to pulmonary embolism (PE). In this population, numerous clinical trials have demonstrated comparable efficacy between dalteparin and fixed-dose UH for DVT prophylaxis. Dalteparin has a predictable dose response and can be administered as a standard single daily subcutaneous dose for all patients. In therapeutic doses, dalteparin does not alter coagulation tests and therefore does not require routine laboratory monitoring, in contrast with adjusted-dose UH. Bleeding risks with dalteparin are comparable with and possibly less than those associated with UH. Preliminary studies suggest that dalteparin may be effective for other indications, including DVT prophylaxis for hip replacement surgery and the treatment of DVT and PE. Comparative cost-effectiveness data are not yet available. Conclusions Dalteparin is the second LMWH to receive approval by the Food and Drug Administration. Dalteparin is indicated for prophylaxis against DVT in patients undergoing abdominal surgery. Clinical studies have shown that single daily doses of dalteparin provide a safe and effective alternative to fixed-dose UH therapy. Additional studies are needed to determine the cost-effectiveness of dalteparin compared with UH and other LMWHs.

scholarly journals Phosphodiesterase-5 inhibitors and the heart: compound cardioprotection?

Heart ◽  
2018 ◽  
Vol 104 (15) ◽  
pp. 1244-1250 ◽  
Author(s):  
David Charles Hutchings ◽  
Simon George Anderson ◽  
Jessica L Caldwell ◽  
Andrew W Trafford
Keyword(s):  
Clinical Trials ◽  
Contractile Function ◽  
Myocardial Infarct ◽  
Pde5 Inhibitor ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Protective Effects ◽  
Pde5 Inhibitors ◽  
Treatment Benefit ◽  
Phosphodiesterase 5

Novel cardioprotective agents are needed in both heart failure (HF) and myocardial infarction. Increasing evidence from cellular studies and animal models indicate protective effects of phosphodiesterase-5 (PDE5) inhibitors, drugs usually reserved as treatments of erectile dysfunction and pulmonary arterial hypertension. PDE5 inhibitors have been shown to improve contractile function in systolic HF, regress left ventricular hypertrophy, reduce myocardial infarct size and suppress ischaemia-induced ventricular arrhythmias. Underpinning these actions are complex but increasingly understood cellular mechanisms involving the cyclic GMP activation of protein kinase-G in both cardiac myocytes and the vasculature. In clinical trials, PDE5 inhibitors improve symptoms and ventricular function in systolic HF, and accumulating epidemiological data indicate a reduction in cardiovascular events and mortality in PDE5 inhibitor users at high cardiovascular risk. Here, we focus on the translation of underpinning basic science to clinical studies and report that PDE5 inhibitors act through a number of cardioprotective mechanisms, including a direct myocardial action independent of the vasculature. We conclude that future clinical trials should be designed with these mechanisms in mind to identify patient subsets that derive greatest treatment benefit from these novel cardioprotective agents.

Tadalafil versus sildenafil citrate in the treatment of ED: Italian patients’ preferences and explanatory notes

2008 ◽  
Vol 75 (1) ◽  
pp. 24-31 ◽  
Author(s):  
F. Fusco ◽  
A. Lembo ◽  
G.M. Ludovico ◽  
F. Pirozzi Farina ◽  
F. Montorsi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Erectile Dysfunction ◽  
Crossover Study ◽  
Sexual Intercourse ◽  
Alternative Treatment ◽  
Sildenafil Citrate ◽  
Treatment Preference ◽  
Efficacy And Safety ◽  
Pde5 Inhibitors ◽  
Randomized Crossover Study

This is an open, multicentre, randomized, crossover study having the aim to evaluate the preference for sildenafil citrate or tadalafil in a population of Italian patients affected by ED, and to compare the efficacy and safety of these two drugs. Material and Methods. From October 2003 to November 2004, thirteen Italian centers enrolled ED patients (age >18) being in steady and naïve relation to ED treatment, both through PDE5 inhibitors and any other treatment option. These patients were randomized to sildenafil or tadalafil for 12 weeks, after which they were switched to the alternative treatment for a further 12 weeks. The preference was evaluated through the Treatment Preference Question (TPQ): “During this clinical trial you have taken tadalafil and sildenafil for the treatment of erectile dysfunction. Which medication do you prefer to take for the next 8 weeks of treatment?”. Moreover, patients were asked to express their preference as “strong” or “moderate” and to answer some questions to clarify the reasons behind their preference. SEP and IIEF-EF questionnaires were used for a comparison of efficacy. Results. 167 patients were enrolled, 144 of whom completed both treatment periods. On being asked the TPQ, 75% of patients (n=108) decided to continue treatment with tadalafil, in particular because it made it possible to have an erection many hours after taking the medication (first or second preference reason for 64.8% of patients), while 25% (n=36) preferred sildenafil (p=0.001). Both drugs improved the IIEF-EF and SEP scores compared to baseline, with a slightly but significantly greater improvement with tadalafil for both parameters. Conclusions. Tadalafil and sildenafil are both effective and well tolerated. Most of the patients prefer tadalafil thanks to the possibility of having sexual intercourse many hours after taking the medication.

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