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1.
Int Heart J ; 61(2): 413-418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224603

RESUMO

Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.


Assuntos
Anticorpos Antinucleares/imunologia , Centríolos/imunologia , Antagonistas dos Receptores de Endotelina/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Escleroderma Sistêmico/imunologia , Vasodilatadores/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Bosentana/uso terapêutico , Cateterismo Cardíaco , Quimioterapia Combinada , Epoprostenol/análogos & derivados , Epoprostenol/uso terapêutico , Feminino , Volume Expiratório Forçado , Humanos , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Capacidade de Difusão Pulmonar , Pirimidinas/uso terapêutico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Sulfonamidas/uso terapêutico , Tadalafila/uso terapêutico , Tomografia Computadorizada por Raios X
2.
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 , Metanálise 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
3.
Trans Am Clin Climatol Assoc ; 130: 51-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516164

RESUMO

The field of sexual medicine, in reference to the science of the sexual response and the clinical management of sexual dysfunctions, has evolved remarkably in the last 25 years. Erection biology has been central in driving this progress and is measured considerably by the discovery, study, and clinical translation of a simple gaseous molecule, nitric oxide, which is operative in the penis. Nitric oxide functions extraordinarily as a neurotransmitter and molecular signal transducer. It is now well understood to be the principal molecular mediator of penile erection and to be a critical element involved in dysregulatory mechanisms of erection disorders ranging from erectile dysfunction to priapism. It is most familiarly associated with the scientific development of oral medications for treating erectile dysfunction, which has modernized the clinical management of this condition.


Assuntos
Disfunção Erétil/tratamento farmacológico , Óxido Nítrico/fisiologia , Ereção Peniana/fisiologia , Disfunção Erétil/metabolismo , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/uso terapêutico
4.
BMC Health Serv Res ; 19(1): 573, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412857

RESUMO

BACKGROUND: This study aims to assess the cost-effectiveness and budget impact of adopting sildenafil to the benefits package for the indication of pulmonary arterial hypertension (PAH), compared to beraprost. METHODS: Based on a societal perspective, a model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs). RESULTS: The economic model calculated the incremental cost-effectiveness ratio (ICER) per QALY gained for using sildenafil as first-line therapy compared to beraprost for the patient in functional class (FC) II and III, i.e. USD 3098 and USD 2827, respectively. The results indicated that in spite of sildenafil being more expensive than beraprost, generic sildenafil could potentially be a good value for money since ICER per QALY is below one times gross domestic product (GDP) per capita in Indonesia. Furthermore, budget impact analysis estimated that the incremental budget needed within 5 years for including sildenafil compared to beraprost for PAH patients starting in FC II and FC III was USD 436,775 and USD 3.6 million, respectively. CONCLUSIONS: Compared to beraprost, sildenafil would be preferable for the treatment of PAH patients in FC II and FC III in Indonesia. The additional budget for adopting sildenafil compared to beraprost as the treatment of PAH in the benefits package was estimated at around USD 4.0 million.


Assuntos
Epoprostenol/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Citrato de Sildenafila/economia , Vasodilatadores/economia , Orçamentos , Análise Custo-Benefício , Epoprostenol/economia , Epoprostenol/uso terapêutico , Humanos , Hipertensão Pulmonar/economia , Indonésia , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico
5.
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
6.
Free Radic Res ; 53(9-10): 993-1004, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31455116

RESUMO

Sildenafil is a phosphodiesterase type 5 inhibitor which confers cardioprotection against myocardial ischaemia/reperfusion (I/R) injury. The aim of this study was to determine if Trx1 participates in cardioprotection exerted by sildenafil in an acute model of I/R, and to evaluate mitochondrial bioenergetics and cellular redox status. Langendorff-perfused hearts from wild type (WT) mice and a dominant negative (DN-Trx1) mutant of Trx1 were assigned to placebo or sildenafil (0.7 mg/kg i.p.) and subjected to 30 min of ischaemia followed by 120 min of reperfusion. WT + S showed a significant reduction of infarct size (51.2 ± 3.0% vs. 30 ± 3.0%, p < .001), an effect not observed in DN-Trx. After I/R, sildenafil preserved state 3 oxygen consumption from WT, but had a milder effect in DN-Trx1 only partially protecting state 3 values. Treatment restored respiratory control (RC) after I/R, which resulted 8% (WT) and 24% (DN-Trx1) lower than in basal conditions. After I/R, a significant increase in H2O2 production was observed both for WT and DN-Trx (WT: 1.17 ± 0.13 nmol/mg protein and DN-Trx: 1.38 ± 0.12 nmol/min mg protein). With sildenafil, values were 21% lower only in WT I/R. Treatment decreased GSSG levels both in WT and DN-Trx1. In addition, GSSG/GSH2 ratio was partially restored by sildenafil. Also, an increase in p-eNOS/eNOS even before the myocardial ischaemia was observed with sildenafil, both in WT (14%, p > .05) and in DN-Trx (35%, p < .05). Active Trx1 is required for the onset of the cardioprotective effects of sildenafil on I/R injury, together with the preservation of cellular redox balance and mitochondrial function.


Assuntos
Mitocôndrias/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Animais , Masculino , Camundongos , Camundongos Transgênicos , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia
7.
Andrologia ; 51(9): e13364, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31304987

RESUMO

A cross-sectional survey was conducted in Egypt from November 2015 to June 2016. Sexually active adult men were interviewed by a questionnaire designed by the authors. All the participants were evaluated by the abridged 5-item version of the International Index of Erectile Function (IIEF). A total of 3,000 sexually active Egyptian males participated in this study, 946 (31.53%) reported using PDE5Is at least once, and 2054 (68.47%) have never used them. The majority of those who used PDE5Is obtained them for recreational purposes mainly for pleasure (58.35%) and to increase duration/frequency of the intercourse (15.6%). Only 26.05% used PDE5Is to treat ED. The main source of obtaining PDE5Is was friends, relatives and colleagues (62.79%); 25.16% of users obtained the drug by themselves, and 6.66% were prescribed the drug by a pharmacist. Only 5.39% of users obtained the drug after a specialist physician consultation. Sildenafil was the most commonly used PDE5I (90.6%), and most of the users (88.05%) used them in an occasional manner even in the presence of erectile dysfunction, while 11.95% used the drug in a regular manner for every intercourse. PDE5Is are frequently used by the Egyptian male population, and most of them seemed to take them as recreational medications.


Assuntos
Coito/psicologia , Disfunção Erétil/epidemiologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Prazer , Adulto , Estudos Transversais , Egito/epidemiologia , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/psicologia , Inibidores da Fosfodiesterase 5/farmacologia , Prevalência , Citrato de Sildenafila/farmacologia , Citrato de Sildenafila/uso terapêutico , Inquéritos e Questionários/estatística & dados numéricos
8.
J Vet Cardiol ; 23: 96-103, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31174734

RESUMO

Four dogs, referred for management of heartworm (HW) disease, were found to have HWs entangled in their tricuspid valve apparatus. None of the dogs were actively hemolyzing or showed signs of acute cardiovascular collapse that would have necessitated emergency transvenous HW extraction, and surgery was not performed at time of presentation. The dogs received pimobendan and sildenafil within 24 h of identifying HW in the tricuspid valve apparatus, and the HW moved to the pulmonary arteries within 2 days in most cases (median 2 days, range 1-14 days). All dogs survived to discharge from the original hospital admission and were subsequently treated with adulticide (melarsomine) without complication. All dogs were HW antigen negative 6 months after their last melarsomine injection. Four dogs appeared to respond positively to medical management aimed at decreasing pulmonary arterial pressure and improving the right ventricular function, but movement of HW out of the heart for other reasons cannot be excluded. This therapeutic option is not advised when dogs with HW disease are presented for acute collapse, ongoing hemolysis, and hypotension as surgical extraction is still considered the best option in these cases. It remains unknown if medical management is a safe option for all dogs with intracardiac HW without clinical signs of caval syndrome. Controlled prospective studies are required to determine the efficacy and safety of this treatment regimen in comparison with surgical extraction.


Assuntos
Dirofilariose/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Piridazinas/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Animais , Antígenos de Helmintos/sangue , Arsenicais/uso terapêutico , Dirofilaria/imunologia , Cães , Feminino , Filaricidas/uso terapêutico , Masculino , Triazinas/uso terapêutico , Valva Tricúspide/parasitologia , Vasodilatadores/uso terapêutico
9.
Artigo em Alemão | MEDLINE | ID: mdl-31083758

RESUMO

The perioperative management of patients with pulmonary hypertension requires an in-depth knowledge of the underlying disease, its related pathophysiology, effects of anaesthesia and surgery, as well as the appropriate pharmacotherapy. With respect to preoperative assessment, it is essential to review all available diagnostic findings, evaluate the patient's physical state, and to plan the anaesthetic procedure. Intraoperatively, the prevention of increases in pulmonary resistance and right ventricular decompensation appears essential. For this purpose, stress, hypothermia, decreased systemic perfusion, hypercapnia, hypoxemia, acidosis, and invasive mechanical ventilation should be avoided. If the pulmonary artery pressure exacerbates, application of inhaled nitric oxide or prostacyclins (iloprost), phosphodiesterase-III-inhibitors (milrinone) and phosphodiesterase-V-inhibitors (sildenafil), reflect first-line treatment options. In order to support the right ventricle, inotropes (adrenalin, dobutamine, levosimendan) or inodilators (milrinone) increase its contractility. Dependent on severity of disease and the magnitude of surgical intervention, patients with pulmonary hypertension require a specific continuous monitoring as well as trained staff in the postoperative period.


Assuntos
Anestesia Geral , Anestésicos , Hipertensão Pulmonar , Anestésicos/uso terapêutico , Humanos , Milrinona/uso terapêutico , Óxido Nítrico/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Vasodilatadores
10.
J Headache Pain ; 20(1): 48, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060491

RESUMO

BACKGROUND: Sildenafil and calcitonin gene-related peptide both dilate the intradural segments of the middle meningeal artery measured with 3.0 tesla (T) MR angiography. Here we hypothesized that an increase in field strength to 7.0 T and concomitant enhanced voxel resolution would lower variance in measurements of dilation in the intradural middle meningeal artery. METHODS: Five subjects completed two sessions at respectively 3.0 T and 7.0 T. Each session comprised MR angiography scans once before and twice after administration of sildenafil, calcitonin gene-related peptide or placebo in a three-way, crossover, double-blind, placebo-controlled design. RESULTS: Standard deviations of arterial circumference revealed no difference between 3.0 T and 7.0 T measurements (p = 0.379). We found a decrease in standard deviation from our original angiography analysis software (QMra) to a newer (LAVA) software package (p < 0.001). Furthermore, we found that the dilation after sildenafil and calcitonin gene-related peptide were comparable between 3.0 T and 7.0 T. CONCLUSIONS: Our findings suggest no gain from the increase in voxel resolution but cemented dilatory findings from earlier. The implemented software update improved variance in circumference measurements in the intradural middle meningeal artery, which should be exploited in future studies. TRIAL REGISTRATION: The study is part of a parent study, which is registered at ClinicalTrials.gov ( NCT03143465 ).


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Angiografia Cerebral/métodos , Angiografia por Ressonância Magnética/métodos , Artérias Meníngeas/diagnóstico por imagem , Transtornos de Enxaqueca/diagnóstico por imagem , Citrato de Sildenafila/farmacologia , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Artérias Meníngeas/efeitos dos fármacos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/fisiopatologia , Citrato de Sildenafila/uso terapêutico , Adulto Jovem
11.
Transplant Proc ; 51(5): 1435-1438, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079941

RESUMO

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Patients with severe PPHTN are contraindicated for liver transplant because of the associated risk of intraoperative acute right heart failure during reperfusion phase or massive volume infusion. Therefore, it has been recommended that patients with moderate to severe PPHTN undergo medical treatment to lower the pulmonary artery pressure before undergoing transplant. Herein, we report 3 patients with severe PPHTN who underwent sildenafil monotherapy before living donor liver transplant. None of the patients experienced associated adverse effects during sildenafil treatment, and the pulmonary artery pressure was effectively reduced before transplant. The first patient was diagnosed during anesthesia prior to transplant, and the mean pulmonary artery pressure was reduced by 34% after treatment. The second and third patients were followed-up with echography, and the estimated pulmonary artery systolic pressure were reduced by 34% and 47%, respectively. Pretransplant right heart catheterization also confirmed the reduction of the mean pulmonary artery pressure. Intraoperative hemodynamic parameters were stable, and the 3 patients were discharged uneventfully. After transplant, sildenafil was discontinued, and all patients remained in a stable clinical and functional status during follow-up.


Assuntos
Hipertensão Portal/tratamento farmacológico , Hipertensão Pulmonar/tratamento farmacológico , Transplante de Fígado/métodos , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Pulmonar/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade
12.
J Coll Physicians Surg Pak ; 29(6): S43-S44, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142418

RESUMO

Methylmalonic acidemia or aciduria (MMA) is an inborn error of metabolism that results in the accumulation of methylmalonic acid in blood with an increased excretion in urine. MMA usually presents in early infancy and its effects vary from mild to life-threatening. The clinical symptoms mainly include vomiting, dehydration, hypotonia, developmental delay, and failure to thrive. An association between pulmonary arterial hypertension (PAH) and MMA has been rarely reported. In the present work, the authors report a 16-month boy, who was admitted to the Pediatric Department for cyanosis and fever. He had a family history of primary pulmonary hypertension in a sister. The echocardiography showed a mild pericardial effusion and PAH. The metabolic screening led to the diagnosis of MMA. The condition of the baby worsened rapidly- and he died a few days later. Physicians should be aware about this atypical presentation of the disease, which can be fatal if not diagnosed and managed promptly.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Cianose/etiologia , Hipertensão Pulmonar Primária Familiar/diagnóstico , Ácido Metilmalônico/metabolismo , Insuficiência Renal/etiologia , Taquicardia/etiologia , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Evolução Fatal , Febre/etiologia , Humanos , Lactente , Masculino , Ácido Metilmalônico/sangue , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico
13.
Am J Ther ; 26(4): e520-e526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30946047

RESUMO

Pulmonary hypertension is a life-threatening illness with debilitating physical and emotional consequences. The progression of this devastating disease is characterized by a continuous increase in pulmonary vascular resistance, which results in elevated pulmonary artery pressure and leads to right heart failure. Treatment is focused on targeting the underlying complex etiology via the endothelin, prostacyclin, and nitric oxide (NO) pathways. Emergence of new treatments over the past 2 decades has led to improvement in the functional status and time to clinical worsening. Even with recent advances, outcomes remain suboptimal. Phosphodiesterase-5 (PDE-5) inhibitors, such as sildenafil, were approved for treatment of pulmonary arterial hypertension (PAH) by the Food and Drug Administration (FDA) in 2005, which holds promise in improving quality of life and therefore making this class of medications effective palliative therapy agents. In this review, we summarize the emergence of sildenafil as a treatment for PAH and its role as palliative therapy.


Assuntos
Cuidados Paliativos/métodos , Inibidores da Fosfodiesterase 5/uso terapêutico , Qualidade de Vida , Citrato de Sildenafila/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
BMC Pulm Med ; 19(1): 80, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30991994

RESUMO

BACKGROUND: Systemic artery to pulmonary artery fistulas (SA-PAFs), are extremely rare in people without congenital heart disease. In this group of patients pulmonary arterial hypertension was reported in the single case. Then, we describe a case of multiple SA-PAFs, which were the cause of severe nonreversible arterial pulmonary hypertension in a patient who had a right-sided pneumothorax 35 years earlier. CASE PRESENTATION: 52-year-old male Caucasian patient with echocardiographically confirmed pulmonary hypertension (PH) was admitted to cardiology department due to exertional dyspnea and signs of right ventricle failure. Routine screening for causes of secondary PH was negative. Right heart catheterization (RHC) confirmed a high degree arterial PH [mean pulmonary artery pressure (mPAP); 50,6 mmHg, pulmonary wedge pressure (PWP); 11,3 mmHg, pulmonary vascular resistance (PVR); 11,9 Wood's units (WU)] irreversible in the test with inhaled nitric oxide. Oxygen saturation (SaO2) of blood samples obtained during the first RHC ranged from 69.3 to 73.2%. Idiopathic pulmonary arterial hypertension was diagnosed. Treatment with inhaled iloprost and sildenafil was initiated. Control RHC, performed 5 months later showed values of mPAP (59,7 mmHg) and PVR (13,4 WU) higher in comparison to the initial measurement, SaO2 of blood obtained during RHC from upper lobe artery of the right lung was elevated and amounted 89.7%. Then, pulmonary arteriography was performed. Lack of contrast in the right upper lobe artery with the evidence of retrograde blood flow visible as a negative contrast in the right pulmonary artery was found. Afterwards, right subclavian artery arteriography detected a huge vascular malformation communicating with right upper lobe artery. Following computed tomography angiogram (angio-CT) additionally revealed the enlargement of bronchial arteries originated fistulas to pulmonary artery of right upper lobe. In spite of intensive pharmacological treatment, including the therapy of pulmonary hypertension and percutaneous embolisation of the fistulas, the patient's condition continued to deteriorate further. He died three months after embolisation due to severe heart failure complicated by pneumonia. CONCLUSION: Non-congenital SA-PAFs are extremely rare, however, they should be excluded in patients with pulmonary arterial hypertension and history of inflammatory or infectious disease of the lung and pleura, pneumothorax, cancer or Takayashu's disease and after chest trauma.


Assuntos
Fístula Artério-Arterial/complicações , Cateterismo Cardíaco , Hipertensão Pulmonar Primária Familiar/diagnóstico , Pneumotórax/complicações , Angiografia por Tomografia Computadorizada , Hipertensão Pulmonar Primária Familiar/tratamento farmacológico , Evolução Fatal , Insuficiência Cardíaca/fisiopatologia , Humanos , Iloprosta/uso terapêutico , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/patologia , Pressão Propulsora Pulmonar , Citrato de Sildenafila/uso terapêutico , Resistência Vascular
16.
Clin Perinatol ; 46(2): 291-310, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010561

RESUMO

Rates of bronchopulmonary dysplasia (BPD) are increasing. After preterm birth, there are important developmental periods in which neonates are more vulnerable to stressful events. These periods are opportunities for pharmacologic interventions. Many drugs remain inadequately tested and no new drugs have been approved in more than 25 years for BPD prevention or therapy. More progress is needed in defining appropriate end points based on the pathophysiology of BPD and postdischarge chronic pulmonary insufficiency of prematurity and to develop effective new drugs. In addition, much work is needed to better define perinatal factors, early postnatal findings, and physiologic phenotypes or endotypes.


Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/prevenção & controle , Administração por Inalação , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Cafeína/uso terapêutico , Diuréticos/uso terapêutico , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Fator de Crescimento Insulin-Like I/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Óxido Nítrico/uso terapêutico , Oxigenoterapia , Inibidores da Fosfodiesterase 5/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Gravidez , Cuidado Pré-Natal , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Surfactantes Pulmonares/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Vitamina A/uso terapêutico , Vitaminas/uso terapêutico
17.
BMJ Case Rep ; 12(4)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015245

RESUMO

General lymphatic anomaly (GLA) is a very rare disorder, characterised by multifocal lymphatic malformations into various tissues that is due to congenital abnormalities of lymphatic development. No treatment has ever proved its efficiency.We report a 22-year-old man with recurrent bronchial casts due to thoracic involvement of GLA. After a 6-month treatment with sildenafil (20 mg three times a day), a phosphodiesterase 5 inhibitor, chest CT scan showed a complete regression of ground-glass opacities and lung function test results improved substantially and remained stable for 1 year. The treatment was well tolerated.This observation suggests that sildenafil may be a therapeutic approach to be tested in thoracic involvement of GLA.


Assuntos
Pneumopatias/congênito , Pneumopatias/tratamento farmacológico , Linfangiectasia/congênito , Linfangioleiomiomatose/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Linfangiectasia/diagnóstico por imagem , Linfangiectasia/tratamento farmacológico , Linfangiectasia/patologia , Linfangioleiomiomatose/congênito , Linfangioleiomiomatose/diagnóstico por imagem , Anormalidades Linfáticas/diagnóstico por imagem , Masculino , Inibidores da Fosfodiesterase 5/uso terapêutico , Doenças Raras , Testes de Função Respiratória/métodos , Citrato de Sildenafila/administração & dosagem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Adulto Jovem
18.
Curr Pharm Des ; 25(5): 601-608, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30894101

RESUMO

BACKGROUND: Persistent pulmonary hypertension (PPH) is one of the main causes of mortality and morbidity in infants affected by congenital diaphragmatic hernia (CDH). Since the structural changes that lead to PPH take place already in utero, a treatment starting in the prenatal phase may prevent the occurrence of this complication. OBJECTIVE: To summarize the development process of antenatal sildenafil for CDH. METHODS: The pharmacokinetics and efficacy of sildenafil have been assessed in the rat and the rabbit model. The transfer of the drug through the human placenta has been measured with the ex-vivo placenta perfusion model. Results from this experiment are being incorporated in a pregnancy-physiologically based pharmacokinetic (p- PBPK) model. A phase I-IIb placental transfer and safety study is ongoing. RESULTS: Sildenafil administration to pregnant rats and rabbits led to therapeutic foetal drug levels without maternal and foetal toxicity, although it was associated with impaired vascular development in foetuses with nonhypoplastic lungs. Peak concentrations and 24-hour exposure were higher in pregnant rabbits compared to nonpregnant ones. In rat and rabbit foetuses with CDH, sildenafil rescued the lung vascular anomalies and partially improved parenchymal development. Sildenafil crossed the human placenta at a high rate ex-vivo, independently from the initial maternal concentration. CONCLUSION: There is preclinical evidence that maternally administered sildenafil prevents the vascular changes that lead to PPH in CDH newborns. The phase I/IIb clinical study together with the p-PBPK model will define the maternal dose needed for a therapeutic effect in the foetus. Foetal safety will be investigated both in the clinical study and in the sheep. The final step will be a multicentre, randomized, placebo-controlled trial.


Assuntos
Hérnias Diafragmáticas Congênitas/tratamento farmacológico , Pulmão/efeitos dos fármacos , Citrato de Sildenafila/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Feminino , Humanos , Recém-Nascido , Placenta/metabolismo , Gravidez , Coelhos , Ratos , Ovinos , Citrato de Sildenafila/farmacocinética
19.
Int J Impot Res ; 31(2): 65-70, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30837718

RESUMO

The arrival of Pfizer's blue pill Sildenafil in 1998 brought a great relief both to patient and physician signalling the start of a great era of medical therapy in sexual medicine. Since then the sexual medicine experts have been prescribing sildenafil in erectile dysfunction with acceptable minor adverse events. But the use of sildenafil in premature ejaculation (PE) is still debated. 2018 being the 20th anniversary of sildenafil, we have compiled interesting facts about the role of sildenafil in PE from various original articles, systematic reviews, meta-analyses, economic brochures and sexual medicine committee guidelines. The major issues in most of these studies were the heterogeneity in the definition of PE and estimating the exact ejaculatory latency time. This perspective article highlights the positive role of sildenafil in the management of PE (even without ED) with acceptable adverse events. Now that we have a standardised definition of PE from International Society of Sexual Medicine (ISSM) and a psychogenic component in PE definition, more randomised placebo-controlled studies are required to further establish its role.


Assuntos
Ejaculação , Ejaculação Precoce/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , História do Século XX , História do Século XXI , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Citrato de Sildenafila/história
20.
Int J Impot Res ; 31(2): 61-64, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30837719

RESUMO

Erectile dysfunction (ED) is a common side effect to radical prostatectomies, even with nerve-sparing procedures. To ameliorate the problem so-called "penile rehabilitation" programs have been developed. The most widely used method of this is subscribing sildenafil or other PDE5-inhibitors to patients following surgery. This is based on a theory that these drugs may increase penile oxygenation and provide antiapoptotic factors (primarily NO and cGMP), thus protecting the penile tissue in a period with reduced nerve function following the surgery. Preclinical studies have confirmed the potential of sildenafil in this context and early human trials have suggested that a steady ingestion of sildenafil might protect the structural integrity of the penis. However, subsequent well-designed trials have not been able to confirm the initial findings. This fits well with sildenafil's mechanism of action because it does not actually induce erections or the production of either nitric oxide or cGMP. Rather, the drug enhances effects of an erectile response induced by neurotransmitters from the cavernous nerves. Therefore, sildenafil should no longer be offered as a sole means of penile rehabilitation. Rather, more research is needed, and clinicians need to apply a broader concept of sexual rehabilitation in postprostatectomy ED.


Assuntos
Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostatectomia/efeitos adversos , Citrato de Sildenafila/uso terapêutico , Disfunção Erétil/etiologia , Humanos , Masculino , Ereção Peniana/efeitos dos fármacos , Pênis/efeitos dos fármacos , Pênis/fisiopatologia , Próstata/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica
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