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1.
Medicine (Baltimore) ; 99(3): e18712, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011446

RESUMO

BACKGROUND: Drug therapy for lower urinary tract symptoms (LUTS) secondary to benign prostate hyperplasia (BPH) is a major and popular method. However, the therapeutic strategy is still not clear enough up to now. The purpose of this study was to compare the relative safety and efficacy of different types of phosphodiesterase type 5 inhibitors (PDE5-Is) with tamsulosin for the treatment of LUTS secondary to BPH. METHODS: Databases including PubMed, OpenGrey, Embase, Cochrane Library, and Web of Science will be searched to identify qualified studies. We will use the Stata version 13.0 to conduct the network meta-analysis (NMA) with a random or fixed effects model of Bayesian framework. International prostate symptom score (IPSS), maximum urinary flow fate (Qmax) and their credible intervals (CI) will be used to compare every medical intervention with the efficacy and safety, including sildenafil plus tamsulosin, tadalafil plus tamsulosin, vardenafil plus tamsulosin. And the ranking of probability of different interventions will be estimated by comparing the surface under the cumulative ranking curve (SUCRA). RESULTS: A high quality-synthesis of the current evidence for comparing with different doses or types of PDE5-Is combined with tamsulosin to the treatment of LUTS secondary to BPH will be provided. CONCLUSIONS: This NMA and systematic review will generate evidence to help choose the best combination for treatment of LUTS secondary to BPH.PROSPERO registration number: PROSPERO CRD 42019139062.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Tansulosina/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Teorema de Bayes , Quimioterapia Combinada , Humanos , Masculino , Meta-Análise em Rede , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Citrato de Sildenafila/uso terapêutico , Tadalafila/uso terapêutico , Tansulosina/administração & dosagem , Tansulosina/efeitos adversos , Dicloridrato de Vardenafila/uso terapêutico
2.
Urology ; 135: 66-70, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31541647

RESUMO

OBJECTIVE: To define age-specific normal Color Doppler Duplex Ultrasound (CDDU) parameters based on a large institutional database of men referred for vascular erectile testing, but found to have normal and sustained rigidity following penile injection of alprostadil. METHODS: A retrospective review of patients who underwent CDDU from January 1, 2005 to December 31, 2014 was conducted. The indications for CDDU assessments included complaint of erectile dysfunction refractory to PDE-5 inhibitors, new-onset penile curvature, or secondary consultation for erectile dysfunction. Pearson correlation test was used to evaluate the association between ordinal age groups with peak systolic velocity (PSV) and resistive index (RI) measurements to determine the effect of age on erectile response. RESULTS: A total of 2043 patients underwent CDDU from January 1, 2005 to December 31, 2014. 259 patients (12.7%) with a mean age 53.7 and a mean BMI of 27.2 were noted to have normal erectile rigidity and normal Doppler parameters (PSV >35 cm/s, RI >0.90). Prolonged erection, defined by need to inject phenylephrine reversal agent at 1-2 hours, occurred in 93% of patients. When age was categorized by decade, a negative correlation coefficient was obtained for previsual sexual stimulation PSV (-0.09, P = .164) and postvisual sexual stimulation PSV (-0.23, P = .005). CONCLUSION: In men with normal vascular erections there appears to be a significant, age-related decline in postvisual sexual stimulation PSV without compromise to cavernous venous occlusion as measured by RI. We have used Doppler parameters in patients without vascular ED to define age-specific normalcy.


Assuntos
Envelhecimento/fisiologia , Disfunção Erétil/diagnóstico , Ereção Peniana/fisiologia , Pênis/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/efeitos dos fármacos , Pênis/irrigação sanguínea , Pênis/fisiologia , Fenilefrina/administração & dosagem , Fenilefrina/antagonistas & inibidores , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Retrospectivos , Falha de Tratamento , Agentes Urológicos/uso terapêutico , Adulto Jovem
3.
Medicine (Baltimore) ; 98(50): e18317, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852117

RESUMO

BACKGROUND: Male infertility is a worldwide problem with limitations in the treatment. Phosphodiesterase-5 inhibitors (PDE5is) is the first choice for the treatment of erectile dysfunction (ED), but more and more studies show that it has a certain effect on male infertility in recent years. The literatures of PDE5is related to male infertility have shown inconsistent results, and there is currently no high quality of systematic review to evaluate the effects of PDE5is on semen quality in male infertility patients. METHODS: The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Clinicaltrials.org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry and Cochrane Library were retrieved. Grey literature will be searched in Open Grey. Related Randomized controlled trials (RCTs) were collected and selected before October 20, 2019. We will search English literature and Chinese literature with search terms "male infertility", "phosphodiesterase-5 inhibitors", "PDE5i", "Tadalafil", "Sildenafil", "Vardenafil", "Udenafil", "Avanafil", "semen" and "sperm". Sperm concentration, motility and morphology, sperm DNA fragmentation index, number of per ejaculate, sperm viability and adverse events will be evaluated. RevMan 5.3 and Stata 14.0 will be used for Systematic review and Meta-analysis. This protocol reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement, and we will report the systematic review by following the PRISMA statement. CONCLUSION AND DISSEMINATION: Efficacy and safety of PDE5is on male sperm quality in infertile men will be assessed. The results will be published in a public issue journal to provide evidence-based medical evidence for urologists and andrologists to make clinical decisions. REGISTRATION INFORMATION: PROSPERO CRD42019142980.


Assuntos
Infertilidade Masculina/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Inibidores da Fosfodiesterase 5/uso terapêutico , Contagem de Espermatozoides , Resultado do Tratamento
4.
Medicine (Baltimore) ; 98(51): e18361, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860994

RESUMO

BACKGROUND: Diabetic mellitus erectile dysfunction (DMED) refers to erectile dysfunction (ED) secondary to diabetes. As people's lifestyle changes and the population ages, the incidence of DMED continues to increase. Many clinical trials have proven that PDE5-inhibitors-vardenafil has a significant effect in the treatment of Diabetic mellitus erectile dysfunction. In this systematic review, we aim to evaluate the effectiveness and safety of PDE5-inhibitors-vardenafil for Diabetic mellitus erectile dysfunction. METHODS: We will search PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to February 2019.We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of Diabetic mellitus erectile dysfunction. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of PDE5-inhibitors-vardenafil for treating Diabetic mellitus erectile dysfunction. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018095185.


Assuntos
Complicações do Diabetes , Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Dicloridrato de Vardenafila/uso terapêutico , Humanos , Masculino , Metanálise como Assunto , Revisão Sistemática como Assunto
5.
Nihon Yakurigaku Zasshi ; 154(5): 259-264, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735755

RESUMO

Chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is commonly diagnosed in men younger than 50 years old. It is characterized by pelvic pain, voiding symptoms and sexual dysfunction. The considerable discomfort or pain experienced has a negative impact on the quality of life of patients and is a huge economic burden because of the high recurrence rate and the low cure rate. Appropriate animal models are essential for the development of new drugs for the treatment of CP/CPPS, and several rodent models induced by different methods and over different time frames have been established. This article reviews studies of three in vivo rodent models of prostatitis, namely, chemical-induced, autoimmune-induced and hormone-associated models reported by us and other investigators. Recent clinical investigation has suggested that tadalafil improves the International Prostatic Symptom Score and the total National Institutes of Health Chronic Prostatitis Symptom Index score of patients with benign prostatic hyperplasia with CP/CPPS, which enables us to investigate the effect of tadalafil on the pelvic-pain-related behavior and prostatic inflammation in two of these prostatitis model types, experimental autoimmune prostatitis (EAP) and hormone/castration-induced prostatitis (HCP). Both models showed the pelvic-pain-related behavior and prostatic inflammation that are characteristic of chronic prostatitis. In EAP, tadalafil suppressed both the pelvic-pain-related behavior and the prostatic inflammation. In HCP, tadalafil suppressed the pelvic-pain-related behavior. These results mimic the clinical findings. Therefore EAP and HCP are suitable for the evaluation of the potency of drugs for the treatment of CP/CPPS.


Assuntos
Dor Crônica/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostatite/complicações , Tadalafila/uso terapêutico , Animais , Modelos Animais de Doenças , Humanos , Masculino , Roedores
7.
Urologiia ; (4): 130-134, 2019 Sep.
Artigo em Russo | MEDLINE | ID: mdl-31535819

RESUMO

Lower urinary tract symptoms (LUTS) in combination with benign prostatic hyperplasia and erectile dysfunction are more common than commonly thought. Unfortunately, urologists often dont ask about concomitant erectile dysfunction in patients with irritative or obstructive symptoms, which leads to the progression of underline disease, a deterioration in the quality of sexual life, and, as a result, overall quality of life. The relevant studies of recent years dedicated to feasibility of using tadalafil 5 mg a day are analyzed in the article. In addition, the results of scientific work conducted on the Department of Urology and Andrology of Faculty of Fundamental Medicine of Lomonosov Moscow State University, whose aim was to study the efficiency of phosphodiesterase-5 inhibitors in patients with LUTS of varying severity in combination with other types of drugs, are presented. Tadalafil in a dose 5 mg leads to a decrease in the severity of LUTS, as confirmed by a decrease in the mean I-PSS score by 2.19 points in the presented studies. No significant changes were found in Qmax (>0,05). We also proved in our work that phosphodiesterase-5 inhibitor can supplement any combined therapy for benign prostatic hyperplasia in the case of concomitant erectile dysfunction. Tadalafil in a dose 5 mg once a day can be recommended as monotherapy for patients with moderate LUTS caused by benign prostatic hyperplasia with concurrent erectile dysfunction, as an alternative to conventional treatment schemes.


Assuntos
Disfunção Erétil , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Hiperplasia Prostática , Carbolinas , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Humanos , Masculino , Moscou , Qualidade de Vida , Tadalafila , Resultado do Tratamento
8.
Arch Esp Urol ; 72(7): 670-676, 2019 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31475678

RESUMO

OBJECTIVES: To investigate the efficacy of tadalafil 5mg in patients with lower urinary tract symptoms who failed alpha blocker treatment. PATIENTS AND METHODS: Twenty-three patients were included. Patient consent was obtained after explaining the efficacy of tadalafil 5mg in lower urinary tract symptoms. Before initiating tadalafil 5mg treatment, prostate cancer and urinary tract infection in the patients were eliminated. IPSS, IIEF-5 and Qmax values were assessed before and one month after tadalafil 5mg treatment. Difference between two assessments was evaluated by the Wilcoxon method. RESULTS: After 1 month of Tadalafil 5mg treatment, IPSS decreased and IIEF-5 and Qmax increased. The difference between two assessments were statistically significant. CONCLUSION: Tadalafil 5mg once daily in the treatment of BPH/LUTS is found to be successful in patients who failed previous alpha blocker treatment.


Assuntos
Sintomas do Trato Urinário Inferior/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Tadalafila/uso terapêutico , Disfunção Erétil , Humanos , Masculino , Hiperplasia Prostática , Resultado do Tratamento
9.
Vet J ; 251: 105347, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492386

RESUMO

Pulmonary hypertension (PH) is associated with substantial morbidity and if untreated, mortality. The human classification of PH is based on pathological, hemodynamic characteristics, and therapeutic approaches. Despite being a leading cause of PH, little is known about dogs with respiratory disease and/or hypoxia (RD/H)-associated PH. Therefore, our objectives were to retrospectively describe clinical features, diagnostic evaluations, final diagnoses and identify prognostic variables in dogs with RD/H and PH. In 47 dogs identified with RD/H and PH, chronic airway obstructive disorders, bronchiectasis, bronchiolar disease, emphysema, pulmonary fibrosis, neoplasia and other parenchymal disorders were identified using thoracic radiography, computed tomography, fluoroscopy, tracheobronchoscopy, bronchoalveolar lavage, and histopathology. PH was diagnosed using transthoracic echocardiography. Overall median survival was 276.0 days (SE, 95% CI; 216, 0-699 days). Dogs with an estimated systolic pulmonary arterial pressure (sPAP) ≥47mmHg (n=21; 9 days; 95% CI, 0-85 days) had significantly shorter survival times than those <47mmHg (n=16; P=0.001). Estimated sPAP at a cutoff of ≥47mmHg was a fair predictor of non-survival with sensitivity of 0.78 (95% CI, 0.52-0.94) and specificity of 0.63 (95% CI, 0.38-0.84). Phosphodiesterase-5 (PDE5) inhibitor administration was the sole independent predictor of survival in a multivariable analysis (hazard ratio: 4.0, P=0.02). Canine PH is present in a diverse spectrum of respiratory diseases, most commonly obstructive disorders. Similar to people, severity of PH is prognostic in dogs with RD/H and PDE5 inhibition could be a viable therapy to improve outcome.


Assuntos
Doenças do Cão/diagnóstico , Hipertensão Pulmonar/veterinária , Hipóxia/veterinária , Transtornos Respiratórios/veterinária , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/etiologia , Cães , Ecocardiografia/veterinária , Feminino , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipóxia/fisiopatologia , Masculino , Inibidores da Fosfodiesterase 5/uso terapêutico , Transtornos Respiratórios/fisiopatologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
10.
J Vet Cardiol ; 24: 7-19, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31405557

RESUMO

INTRODUCTION: Canine pulmonary hypertension (PH) is associated with high morbidity and mortality. Tadalafil, a phosphodiesterase-5 inhibitor used commonly in humans with PH, has not been evaluated in a clinical trial in dogs with naturally occurring PH. Our objectives were to compare the efficacy of tadalafil and sildenafil on PH assessed by peak tricuspid regurgitant flow velocity, estimated systolic pulmonary arterial pressure gradient, voluntary activity, quality of life, and safety profiles in dogs with moderate to severe PH. ANIMALS: Twenty-three dogs with echocardiographic evidence of moderate to severe PH were enrolled. METHODS: A prospective short-term, randomized, double-blinded pilot study was carried out. Dogs with PH were randomly allocated to receive sildenafil or tadalafil for 2 weeks and assessed via echocardiography, activity monitors, and owner-reported outcomes. RESULTS: Collectively, phosphodiesterase-5 inhibition significantly decreased (improved) quality of life scores (p = 0.003) and visual analog score (p = 0.024) without significant between-treatment difference of these variables. Phosphodiesterase-5 inhibition did not significantly affect peak tricuspid regurgitant flow velocity (p = 0.056) or voluntary activity (p = 0.27). A total of 33% (7/21) of dogs experienced at least one adverse event during the study (tadalafil, n = 5; sildenafil, n = 2) with no significant difference between treatment type and incidence of adverse events (p = 0.36). DISCUSSION: In this pilot study, phosphodiesterase-5 inhibition led to apparent improvement in quality of life scores without documenting superiority of tadalafil over sildenafil. CONCLUSION: Tadalafil at a dose of 2 mg/kg once daily appears to be a viable alternative to sildenafil in dogs with moderate to severe PH.


Assuntos
Doenças do Cão/tratamento farmacológico , Hipertensão Pulmonar/veterinária , Inibidores da Fosfodiesterase 5/uso terapêutico , Animais , Doenças do Cão/fisiopatologia , Cães , Método Duplo-Cego , Eletrocardiografia/veterinária , Feminino , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Inibidores da Fosfodiesterase 5/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Distribuição Aleatória , Índice de Gravidade de Doença , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/uso terapêutico , Inquéritos e Questionários , Tadalafila/administração & dosagem , Tadalafila/uso terapêutico , Resultado do Tratamento
11.
Curr Urol Rep ; 20(10): 58, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468204

RESUMO

PURPOSE OF REVIEW: Lower urinary tract symptoms (LUTS) and sexual health have common links. Medical and surgical treatments for LUTS can significantly affect various domains of sexual health including erectile function, ejaculatory function, and libido. This review summarizes recent findings. RECENT FINDINGS: Current literature demonstrates a strong association between LUTS, sexual health, and metabolic syndrome. The role of miRNA is also being investigated. Combination medical therapy with phosphodiesterase 5 inhibitors (PDE5-I) shows promise but needs further investigation. Newer surgical therapies for benign prostatic hyperplasia (BPH) aim to preserve sexual function without sacrificing efficacy and durability. Although we are beginning to acknowledge the link between LUTS and sexual health, a better understanding of the underlying biochemistry is needed. Only then can more effective therapies be developed. Further prospective studies should focus on the long-term durability and safety of treatments for both conditions.


Assuntos
Sintomas do Trato Urinário Inferior/complicações , Sintomas do Trato Urinário Inferior/terapia , Síndrome Metabólica/complicações , Saúde Sexual , Ejaculação , Humanos , Libido , Masculino , Síndrome Metabólica/cirurgia , Ereção Peniana , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Prospectivos , Hiperplasia Prostática/complicações
12.
Am J Case Rep ; 20: 1144-1147, 2019 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-31377751

RESUMO

BACKGROUND Sildenafil is a pulmonary vasodilator and its efficacy has been well established in patients with group 1 pulmonary hypertension. There are no established guidelines regarding its use in acute right ventricle failure. In our experience, it can be used as an adjunctive therapy in acute right ventricle failure due to pulmonary embolism, to reduce right ventricle afterload and hence improve size and function of the right ventricle. CASE REPORT This is a case report where sildenafil was used as a rescue agent to achieve improvement in the right ventricle size and function in a case of acute onset massive pulmonary embolism with acute right ventricle failure in the scenario where systemic thrombolytic therapy was contraindicated. CONCLUSIONS Improvement of right ventricle size and function was achieved using phosphodiesterase-5 Inhibitors in a case of acute right ventricle failure due to acute massive pulmonary embolism. There are no established guidelines regarding this clinical approach, however, given its efficacy in this case as adjunctive therapy in treatment of acute right ventricle, larger studies are needed to further establish its utility.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Embolia Pulmonar/complicações , Vasodilatadores/uso terapêutico , Disfunção Ventricular Direita/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Direita/etiologia
13.
Curr Urol Rep ; 20(7): 40, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31168725

RESUMO

PURPOSE OF REVIEW: In this article, we review why patients may fail medical therapy for benign prostatic hyperplasia (BPH) and by doing so, gain a better understanding of the disease process and how to optimize the care of these patients. RECENT FINDINGS: A growing body of literature has attempted to better characterize the various mechanisms by which patients develop BPH as well as identify predictors of disease progression and treatment failure. BPH is a heterogenous disease process. A more personalized approach to treatment, including patient selection for medical or surgical management, would allow us to optimize patient care.


Assuntos
Resistência a Medicamentos , Hiperplasia Prostática/tratamento farmacológico , Falha de Tratamento , Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas Adrenérgicos alfa/uso terapêutico , Fatores Etários , Ensaios Clínicos como Assunto , Progressão da Doença , Quimioterapia Combinada , Humanos , Masculino , Obesidade/complicações , Inibidores da Fosfodiesterase 5/uso terapêutico , Antígeno Prostático Específico/análise , Prostatite/complicações
14.
Eur J Med Chem ; 177: 269-290, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158744

RESUMO

Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50 = 3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole) were evaluated in comparison to MY 5445 (4b) in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment.


Assuntos
Analgésicos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Ftalazinas/uso terapêutico , Analgésicos/síntese química , Analgésicos/química , Animais , Masculino , Camundongos Endogâmicos C57BL , Estrutura Molecular , Inibidores da Fosfodiesterase 5/síntese química , Inibidores da Fosfodiesterase 5/química , Ftalazinas/síntese química , Ftalazinas/química , Solubilidade , Relação Estrutura-Atividade
15.
Prog Urol ; 29(6): 326-331, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31151915

RESUMO

INTRODUCTION: Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment of erectile dyfunction (ED). Cost of PDE5i is not covered by health insurance company in France. Few studies have examined the potential impact of the introduction of generic products of PDE5i on price non-compliance. The aim of the study was to compare the non-compliance rate because of price among patients treated for DE with generics of PDE5i and those treated with brand-name medications. METHOD: A multi-centre, cross-sectional, study that analyzed the answers to a questionnaire distributed to consultations in four hospitals for a period of twenty-eight months. Patients were included if they had DE treated for at least 3 months. The proportions between the two groups were compared with a non-inferiority test Wilcoxon-Mann-Whitney. RESULTS: One hundred and seventy-seven questionnaires were analyzed. Patients treated with generic PDE5i were significantly (α<0.05) as non-compliant because of price as patients treated with treated with brand-name PDE5i, respectively 34% (28/82) and 38% (36/95). The main causes of non-compliance were: high treatment costs, a lower than expected effect, lack of opportunity or sexual desire. The proportion of patients splitting the PDE5i tablet to achieve savings was 19% (33/177). To find the lowest price, 57% (101/177) of patients had consulted several pharmacies. These patients consulted 2.4±1.5 pharmacies. In the study population, 44% (78/177) of patients compared prices on commercial websites on the Internet. CONCLUSION: Patients treated with generic PDE5i are as unobservant as those treated with brand-name PDE5i. LEVEL OF EVIDENCE: 3.


Assuntos
Comércio , Medicamentos Genéricos/economia , Medicamentos Genéricos/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Inibidores da Fosfodiesterase 5/economia , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade
16.
Urologiia ; (1): 119-124, 2019 Apr.
Artigo em Russo | MEDLINE | ID: mdl-31184029

RESUMO

Tadalafil is a drug from the phosphodiesterase-5 inhibitors (PDE-5) group, which is used to treat erectile dysfunction (ED), lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) and ED with LUTS in patients with BPH. The efficacy and safety of tadalafil were reviewed. The focus was on cardiovascular safety of tadalafil due to frequent cardiovascular comorbidities in patients with ED. We concluded that tadalafil is well tolerated and safe in patients with cardiovascular comorbidities and, in addition, has a beneficial effect on the cardiovascular system.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Disfunção Erétil , Sintomas do Trato Urinário Inferior , Tadalafila , Doenças Cardiovasculares/complicações , Sistema Cardiovascular/efeitos dos fármacos , Disfunção Erétil/complicações , Disfunção Erétil/tratamento farmacológico , Humanos , Sintomas do Trato Urinário Inferior/complicações , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Masculino , Inibidores da Fosfodiesterase 5/efeitos adversos , Inibidores da Fosfodiesterase 5/uso terapêutico , Hiperplasia Prostática/complicações , Tadalafila/efeitos adversos , Tadalafila/uso terapêutico , Resultado do Tratamento
17.
Health Qual Life Outcomes ; 17(1): 103, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200710

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) remains a life-threatening condition, despite modern therapies. We prospectively investigated the therapeutic health-related quality of life (HRQOL) effects of goal-oriented sequential combination therapy based on exercise capacity in patients newly diagnosed with PAH. METHODS: To examine the changes in HRQOL in PAH patients, we treated 30 patients newly diagnosed with PAH with goal-oriented sequential combination therapy based on exercise capacity. We monitored exercise capacity by cardiopulmonary exercise testing and observed the benefit of using a peak VO2 cut-off of 15 mL/kg/min to guide combination therapy. First-line treatment was an endothelin receptor antagonist (ERA); second-line treatment was the addition of a phosphodiesterase-5 inhibitor (PDE-5I). At baseline and at 3, 6, and 12 months, HRQOL was evaluated by using the eight-item Medical Outcomes Survey Short Form Health Survey. RESULTS: At 12 months, 100% of PAH patients were receiving an ERA, and 82% an ERA + PDE-5I. The mean physical component summary (PCS) score was 33.5 at baseline, 41.2 at 3 months, 40.8 at 6 months, and 42.0 at 12 months, and the mean mental component summary (MCS) scores were 45.6, 47.0, 50.0, and 50.1, respectively. PCS score was significantly greater at 3 months than at baseline (P = 0.035). MCS score was comparable at 3 months and at baseline, but was significantly greater at 6 and 12 months than at baseline (P = 0.033, P = 0.028, respectively). Thus, PCS score improved soon after initiation of therapy, and MCS score improved later. CONCLUSIONS: Together, these results suggest that goal-oriented sequential combination therapy based on exercise capacity improves HRQOL in patients with PAH.


Assuntos
Antagonistas dos Receptores de Endotelina/uso terapêutico , Exercício , Hipertensão Pulmonar , Inibidores da Fosfodiesterase 5/uso terapêutico , Qualidade de Vida , Adulto , Terapia Combinada , Tolerância ao Exercício , Feminino , Humanos , Hipertensão Pulmonar/psicologia , Hipertensão Pulmonar/terapia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
18.
Urol J ; 16(3): 255-259, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31204438

RESUMO

PURPOSE: Recently, controversy exists regarding the oncologic outcomes associated with the use of phosphodi-esterase 5 inhibitor (PDE5i). Therefore, we attempted to verify the effect of PDE5i on biochemical recurrence (BCR) following radical prostatectomy (RP) in patients with prostate cancer (PCa). MATERIALS AND METHODS: From January 2011 to May 2016, 351 patients who had undergone bilateral neurovas-cular bundle saving and who were confirmed as having pT2N0M0 disease were included in the present study. We divided these patients into three groups: no PDE5i use, PDE5i use on demand , and PDE5i use for rehabilitation. We retrospectively analyzed the effect of PDE5i on BCR of PCa. Mean follow-up period was 34.4 months and mesurement of outcome was whether the patients developed BCR during regular follow-up. RESULTS: 25 (7.1%) patients showed BCR and univariate analysis found no significant differences in BCR between the three groups (5 (6.9%) in no PDE5i use, 8 (9.5%) in PDE5i use on demand, 12 (6.2%) in PDE5i use for rehabili-tation). Multivariable analyses showed that treatment type was not a significant factor for BCR between the groups with no PDE5i use and PDE5i use (HR = 1.34 [0.49-3.70]; P = .573) and between the groups with on demand and rehabilitation use (HR = 1.37 [0.35-5.37]; P = .646). Kaplan-Meier survival curves show that there were no significant differences in PSA recurrence-free survival in three groups (P > .05). CONCLUSION: Use of PDE5is was not associated with any adverse effects on BCR after RP in patients with PCa.


Assuntos
Recidiva Local de Neoplasia/epidemiologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostatectomia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Inibidores da Fosfodiesterase 5/efeitos adversos , Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Estudos Retrospectivos
19.
Medicine (Baltimore) ; 98(20): e15632, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096477

RESUMO

BACKGROUND: It is commonly reported a limitation of therapeutic strategy in Eisenmenger syndrome (ES) historically. This qualitative systematic review is conducted to evaluate the safety and efficacy of pulmonary arterial hypertension-specific drug therapy (PAH-SDT) for ES patients for a clinical therapeutic strategy based on evidence. METHODS: PubMed, EMBASE, and the Cochrane Library databases have been systematically reviewed up to January 2019. Two reviewers independently conducted a literature search, quality evaluation, and data extraction. The occurrence of death, deterioration, and adverse events (AEs) has respectively been described as a count or percentage. Meta-analysis was conducted by Stata 15.1, and weighted mean differences (WMD) with 95% confidence intervals (CI) were recorded for continuous data. Randomized-effect model or fixed-effect model was applied according to the heterogeneity test. RESULTS: Fifteen citations recruiting 456 patients associated with ES were eventually pooled, which involved 4 RCTs, 6 prospective studies, and 5 retrospective studies. Within the first year, it indicated PAH-SDT significantly ameliorated exercise capacity in 6-minute walk distance (6MWD) (I = 60.5%; WMD: 53.86 m, 95% CI [36.59, 71.13], P < .001), functional class (FC) (WMD = -0.71, 95% CI [-0.98, -0.44], P < .001) and Borg dyspnea index (WMD = -1.28, 95% CI [-1.86, -0.70], P < .001), in addition to hemodynamics, especially mean pulmonary arterial pressure by 5.70 mmHg (WMD = -5.70 mmHg, 95% CI [-8.19, -3.22], P < .001) and pulmonary vascular resistance by 4.20 wood U (WMD: -4.20, 95% CI [-7.32, -1.09], P = .008), but unsatisfactory effects in oxygen saturation at exercise (P = .747). In a prolonged medication, bosentan, a dual ERA, has been proved acting an important role in improving exercise tolerance of patients with ES (6MWD: I = 47.5%; WMD: 88.68 m, 95% CI [54.05, 123.3], P < .001; FC: I = 0.0%; WMD = -0.65, 95% CI [-1.10, -0.19], P = .006). While a nonsignificant change of 6MWD was noted in a long-term therapy of ambrisentan (P = .385). There existed rare evidence about the efficacy and safety of macitentan, phosphodiesterase-5 inhibitors (PDE5i), and prostanoids in a prolonged medication. Most AEs were recorded as mild to moderate with PAH-SDT, but about 4.3% individuals treated with endothelin receptor antagonists (ERAs) suffered from serious ones, and 3.9% suffered from death. CONCLUSIONS: This systematic review and meta-analysis proved PAH-SDT as a safe and effective role in ES in an early stage. However, in a long-term treatment, bosentan has been supported for a lasting effect on exercise tolerance. A further multicenter research with a large sample about pharmacotherapy of ES is necessary.


Assuntos
Anti-Hipertensivos/uso terapêutico , Complexo de Eisenmenger/tratamento farmacológico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostaglandinas/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Bosentana/uso terapêutico , Antagonistas dos Receptores de Endotelina/administração & dosagem , Antagonistas dos Receptores de Endotelina/efeitos adversos , Tolerância ao Exercício/efeitos dos fármacos , Hemodinâmica , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Oxigênio/sangue , Fenilpropionatos/uso terapêutico , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/efeitos adversos , Prostaglandinas/administração & dosagem , Prostaglandinas/efeitos adversos , Piridazinas/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico
20.
Gastroenterology ; 157(3): 672-681.e4, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31103628

RESUMO

BACKGROUND & AIMS: Phosphodiesterase 5 (PDE5) inhibitors have been proposed to have chemopreventative effects on colorectal cancer (CRC), although data are needed from population-based studies. We performed a nationwide cohort study to investigate the association between the use of PDE5 inhibitors and the risk of CRC in men with benign colorectal neoplasms. METHODS: We identified men who received a diagnosis of benign colorectal neoplasm from July 2005 through March 2015 who were listed in the Swedish Hospital Discharge Register. We linked data with those from other national Swedish registers to obtain information about the prescription of PDE5 inhibitors and CRC diagnoses. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 4823 patients were prescribed PDE5 inhibitors during the study period; the incidence rate of CRC was 2.64 per 1000 person-years for men prescribed PDE5 inhibitors compared with 4.46 per 1000 person-years for men without a prescription. We found a significant negative association between PDE5 inhibitor use and risk of CRC (adjusted HR, 0.65; 95% CI, 0.49-0.85); the decreased risk of CRC was associated with an increased cumulative dose of PDE5 inhibitors (P = .003). PDE5 prescription was associated with greater reduction in risk of advanced-stage CRC (adjusted HR, 0.61; 95% CI, 0.37-1.00) than early-stage CRC (adjusted HR, 0.70; 95% CI, 0.50-0.98), but the difference was not significant. CONCLUSIONS: In a nationwide population-based study of men with a diagnosis of benign colorectal neoplasm in Sweden, we found evidence that use of PDE5 inhibitors is associated with a reduced risk of CRC. Further studies are needed to confirm the observed association.


Assuntos
Anticarcinógenos/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Inibidores da Fosfodiesterase 5/uso terapêutico , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Suécia/epidemiologia , Fatores de Tempo
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