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Annual Review of Pharmacology and... Jan 2023Cyclic guanosine monophosphate (cGMP), an important intracellular second messenger, mediates cellular functional responses in all vital organs. Phosphodiesterase 5... (Review)
Review
Cyclic guanosine monophosphate (cGMP), an important intracellular second messenger, mediates cellular functional responses in all vital organs. Phosphodiesterase 5 (PDE5) is one of the 11 members of the cyclic nucleotide phosphodiesterase (PDE) family that specifically targets cGMP generated by nitric oxide-driven activation of the soluble guanylyl cyclase. PDE5 inhibitors, including sildenafil and tadalafil, are widely used for the treatment of erectile dysfunction, pulmonary arterial hypertension, and certain urological disorders. Preclinical studies have shown promising effects of PDE5 inhibitors in the treatment of myocardial infarction, cardiac hypertrophy, heart failure, cancer and anticancer-drug-associated cardiotoxicity, diabetes, Duchenne muscular dystrophy, Alzheimer's disease, and other aging-related conditions. Many clinical trials with PDE5 inhibitors have focused on the potential cardiovascular, anticancer, and neurological benefits. In this review, we provide an overview of the current state of knowledge on PDE5 inhibitors and their potential therapeutic indications for various clinical disorders beyond erectile dysfunction.
Topics: Male; Humans; Phosphodiesterase 5 Inhibitors; Erectile Dysfunction; Sildenafil Citrate; Cyclic GMP; Neoplasms
PubMed: 36206989
DOI: 10.1146/annurev-pharmtox-040122-034745 -
International Urology and Nephrology Oct 2017Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat ED. This... (Comparative Study)
Comparative Study Meta-Analysis Review
AIMS
Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat ED. This systematic review and meta-analysis were conducted to directly compare tadalafil with sildenafil for the treatment of ED.
METHODS
We designed a strategy for searching the PubMed, Embase, EBSCO, Web of Science and Cochrane library databases; the reference lists of the retrieved studies were also investigated. A literature review was performed to identify all published randomized or non-randomized controlled trials that compared tadalafil with sildenafil for the treatment of ED and to assess the quality of the studies. Two investigators independently and blindly screened the studies for inclusion. The meta-analysis was performed using RevMan 5.0.
RESULTS
A total of 16 trials that compared tadalafil with sildenafil for the treatment of ED were included in the meta-analysis. In the meta-analysis, tadalafil and sildenafil appeared to have similar efficacies and overall adverse event rates. However, compared with sildenafil, tadalafil significantly improved psychological outcomes. Furthermore, the patients and their partners preferred tadalafil over sildenafil, and no significant difference was found in the adherence and persistence rates between tadalafil and sildenafil. Additionally, the myalgia and back pain rates were higher and the flushing rate was lower with tadalafil than with sildenafil.
CONCLUSION
Tadalafil shares a similar efficacy and safety with sildenafil and significantly improves patients' sexual confidence. Furthermore, patients and their partners prefer tadalafil to sildenafil. Hence, tadalafil may be a better choice for ED treatment.
Topics: Back Pain; Controlled Clinical Trials as Topic; Erectile Dysfunction; Flushing; Humans; Male; Myalgia; Patient Preference; Phosphodiesterase 5 Inhibitors; Self Efficacy; Sildenafil Citrate; Tadalafil
PubMed: 28741090
DOI: 10.1007/s11255-017-1644-5 -
Neonatology 2016In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating...
In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.
Topics: Clinical Protocols; Consensus; Europe; Expert Testimony; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Monitoring, Physiologic; Postnatal Care; Practice Guidelines as Topic; Respiration, Artificial; Sildenafil Citrate
PubMed: 27077664
DOI: 10.1159/000444210 -
European Heart Journal Apr 2018We aimed to determine whether treatment with sildenafil improves outcomes of patients with persistent pulmonary hypertension (PH) after correction of valvular heart... (Comparative Study)
Comparative Study Randomized Controlled Trial
Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial.
AIMS
We aimed to determine whether treatment with sildenafil improves outcomes of patients with persistent pulmonary hypertension (PH) after correction of valvular heart disease (VHD).
METHODS AND RESULTS
The sildenafil for improving outcomes after valvular correction (SIOVAC) study was a multricentric, randomized, parallel, and placebo-controlled trial that enrolled stable adults with mean pulmonary artery pressure ≥ 30 mmHg who had undergone a successful valve replacement or repair procedure at least 1 year before inclusion. We assigned 200 patients to receive sildenafil (40 mg three times daily, n = 104) or placebo (n = 96) for 6 months. The primary endpoint was the composite clinical score combining death, hospital admission for heart failure (HF), change in functional class, and patient global self-assessment. Only 27 patients receiving sildenafil improved their composite clinical score, as compared with 44 patients receiving placebo; in contrast 33 patients in the sildenafil group worsened their composite score, as compared with 14 in the placebo group [odds ratio 0.39; 95% confidence interval (CI) 0.22-0.67; P < 0.001]. The Kaplan-Meier estimates for survival without admission due to HF were 0.76 and 0.86 in the sildenafil and placebo groups, respectively (hazard ratio 2.0, 95% CI = 1.0-4.0; log-rank P = 0.044). Changes in 6-min walk test distance, natriuretic peptides, and Doppler-derived systolic pulmonary pressure were similar in both groups.
CONCLUSION
Treatment with sildenafil in patients with persistent PH after successfully corrected VHD is associated to worse clinical outcomes than placebo. Off-label usage of sildenafil for treating this source of left heart disease PH should be avoided. The trial is registered with ClinicalTrials.gov, number NCT00862043.
Topics: Aged; Double-Blind Method; Female; Heart Failure; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Male; Placebos; Pulmonary Wedge Pressure; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents
PubMed: 29281101
DOI: 10.1093/eurheartj/ehx700 -
Nature Aging Dec 2021We developed an endophenotype disease module-based methodology for Alzheimer's disease (AD) drug repurposing and identified sildenafil as a potential disease risk... (Randomized Controlled Trial)
Randomized Controlled Trial
We developed an endophenotype disease module-based methodology for Alzheimer's disease (AD) drug repurposing and identified sildenafil as a potential disease risk modifier. Based on retrospective case-control pharmacoepidemiologic analyses of insurance claims data for 7.23 million individuals, we found that sildenafil usage was significantly associated with a 69% reduced risk of AD (hazard ratio = 0.31, 95% confidence interval 0.25-0.39, P<1.0×10). Propensity score stratified analyses confirmed that sildenafil is significantly associated with a decreased risk of AD across all four drug cohorts we tested (diltiazem, glimepiride, losartan and metformin) after adjusting age, sex, race, and disease comorbidities. We also found that sildenafil increases neurite growth and decreases phospho-tau expression in AD patient-induced pluripotent stem cells-derived neuron models, supporting mechanistically its potential beneficial effect in Alzheimer's disease. The association between sildenafil use and decreased incidence of AD does not establish causality or its direction, which requires a randomized clinical trial approach.
Topics: Humans; Alzheimer Disease; Sildenafil Citrate; Endophenotypes; Retrospective Studies; Data Mining
PubMed: 35572351
DOI: 10.1038/s43587-021-00138-z -
Ultrasound in Obstetrics & Gynecology :... Feb 2019
Topics: Fetal Growth Retardation; Humans; Sildenafil Citrate
PubMed: 30741451
DOI: 10.1002/uog.20202 -
Ugeskrift For Laeger Dec 2023Introduction Acetylsalicylic acid (ASA) has commonly been touted for its potential to extend the aesthetic lifespan (EL) of Christmas trees when added to the water in... (Comparative Study)
Comparative Study
Introduction Acetylsalicylic acid (ASA) has commonly been touted for its potential to extend the aesthetic lifespan (EL) of Christmas trees when added to the water in the tree stand. This study examined the efficacy of ASA in prolonging the aesthetic longevity of spruce branches, in comparison to placebo and sildenafil. Intervention We conducted a triple-blinded, randomised clinical trial, wherein 60 spruce branches were allocated to one of three treatment arms in a 1:1:1 ratio. The primary intervention was ASA, compared against both placebo and sildenafil treatments. The study's primary endpoint was the EL of the spruce branches. Results All participating branches completed the study. No statistically significant differences were observed in the survival times across the three groups: ASA 17 days (standard deviation (SD): 6), placebo 20 days (SD: 8), and sildenafil 21 days (SD: 7); p = 0.30. Both the log-rank test and adjusted Cox proportional-hazards analyses failed to show any significant variations in aesthetic survival time among the treatment arms (p > 0.05). Conclusion Given our findings, there is no empirical support for the widely held recommendation of adding ASA to the water at the base of a Christmas tree to extend its aesthetic lifespan. Funding none. Trial registration none.
Topics: Humans; Aspirin; Sildenafil Citrate; Water; Picea
PubMed: 38084621
DOI: No ID Found -
BMC Pulmonary Medicine Apr 2022Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number...
BACKGROUND
Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number of mechanisms have been proposed to explain the beneficial effects of SGLT2 inhibitors. The purpose of this study was to determine whether dapagliflozin can improve pulmonary vascular remodelling and the efficacy of dapagliflozin as an add-on therapy to sildenafil in rats with pulmonary arterial hypertension (PAH).
METHODS
A monocrotaline (MCT)-induced PAH rat model was used in our study. MCT-injected rats were randomly divided into four groups and treated for 3 weeks with daily per os treatment with vehicle, dapagliflozin (1 mg/kg/day), sildenafil (25 mg/kg/day), or a combination of dapagliflozin (1 mg/kg/day) and sildenafil (25 mg/kg/day). Haemodynamic measurements, histological analysis, enzyme-linked immunosorbent assay and western blotting analysis were employed to detect the changes in PAH rats after treatments.
RESULTS
Dapagliflozin significantly attenuated MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in PAH rats. Dapagliflozin effectively decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats. Moreover, dapagliflozin attenuated nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in lung tissues and the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in plasma. However, dapagliflozin as an add-on therapy to sildenafil in rats with PAH did not show a more pronounced beneficial effect on right ventricular systolic pressure and pulmonary vascular remodelling in MCT rats than sildenafil alone.
CONCLUSIONS
Dapagliflozin reduces right ventricular systolic pressure and pulmonary vascular remodelling in a rat model of PAH. However, combination therapy with dapagliflozin and sildenafil was not more effective than monotherapy with sildenafil in PAH rats.
Topics: Animals; Benzhydryl Compounds; Disease Models, Animal; Familial Primary Pulmonary Hypertension; Glucosides; Humans; Hypertension, Pulmonary; Monocrotaline; Pulmonary Arterial Hypertension; Pulmonary Artery; Rats; Sildenafil Citrate; Vascular Remodeling
PubMed: 35413880
DOI: 10.1186/s12890-022-01939-7 -
International Journal of Environmental... Sep 2022Sildenafil, a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect, has been investigated concerning various conditions during pregnancy. Per... (Review)
Review
Sildenafil, a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect, has been investigated concerning various conditions during pregnancy. Per indication, we herein review the rationale and the most relevant experimental and clinical studies, including systematic reviews and meta-analyses, when available. Indications for using sildenafil during the second and third trimester of pregnancy include maternal pulmonary hypertension, preeclampsia, preterm labor, fetal growth restriction, oligohydramnios, fetal distress, and congenital diaphragmatic hernia. For most indications, the rationale for administering prenatal sildenafil is based on limited, equivocal data from in vitro studies and rodent disease models. Clinical studies report mild maternal side effects and suggest good fetal tolerance and safety depending on the underlying pathology.
Topics: Female; Fetal Growth Retardation; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Phosphodiesterase 5 Inhibitors; Pre-Eclampsia; Pregnancy; Sildenafil Citrate
PubMed: 36141480
DOI: 10.3390/ijerph191811207 -
Tidsskrift For Den Norske Laegeforening... Sep 2019
Topics: Behind-the-Counter Drugs; Erectile Dysfunction; Humans; Male; Norway; Physician-Patient Relations; Sildenafil Citrate; Taboo; Urological Agents
PubMed: 31556514
DOI: 10.4045/tidsskr.19.0578