Effects of PDE type 5 inhibitors on Left Ventricular Diastolic Dysfunction in Resistant Hypertension / Efeitos dos Inibidores da PDE do Tipo 5 sobre a Disfunção Diastólica Ventricular Esquerda na Hipertensão Arterial Resistente

Resistant hypertension (RHTN) is a multifactorial disease characterized by blood pressure (BP) levels above goal (140/90 mmHg) in spite of the concurrent use of three or more antihypertensive drugs of different classes. Moreover, it is well known that RHTN subjects have high prevalence of left ventricular diastolic dysfunction (LVDD), which leads to increased risk of heart failure progression. This review gathers data from studies evaluating the effects of phosphodiesterase-5 (PDE-5) inhibitors (administration of acute sildenafil and short-term tadalafil) on diastolic function, biochemical and hemodynamic parameters in patients with RHTN. Acute study with sildenafil treatment found that inhibition of PDE-5 improved hemodynamic parameters and diastolic relaxation. In addition, short-term study with the use of tadalafil demonstrated improvement of LVDD, cGMP and BNP-32 levels, regardless of BP reduction. No endothelial function changes were observed in the studies. The findings of acute and short-term studies revealed potential therapeutic effects of IPDE-5 drugs on LVDD in RHTN patients.

A Hipertensão arterial resistente (HAR) é uma doença multifatorial caracterizada por níveis pressóricos acima das metas (140/90 mmHg), a despeito de tratamento farmacológico otimizado de 3 ou mais fármacos anti-hipertensivos de diferentes classes. Pacientes diagnosticados como hipertensos resistentes apresentam alta prevalência de disfunção diastólica do ventrículo esquerdo (DDVE) que proporciona risco aumentado para insuficiência cardíaca. Esta revisão reúne dados de estudos prévios avaliando os efeitos dos inibidores de fosfodiesterase-5 (PDE-5) (administração aguda de sildenafil e de curto prazo de tadalafil) na função diastólica e nos parâmetros bioquímicos e hemodinâmicos em pacientes com HAR. O estudo agudo com sildenafil demonstrou que a inibição da PDE-5 melhorou os parâmetros hemodinâmicos e de relaxamento diastólico. Além disso, o estudo curto prazo com o uso de tadalafil revelou melhora da DDVE e dos níveis de GMPc e BNP-32, independente de redução de pressão arterial. A função endotelial não apresentou alteração com ambos os tratamentos. Os resultados dos estudos agudo e de curto prazo sugerem efeitos terapêuticos potenciais dos fármacos inibidores da PDE-5 na disfunção diastólica em pacientes com HAR.

PDE5 Inhibitor Treatment Persistence and Adherence in Brazilian Men: Post-hoc Analyses from a 6-Month, Prospective, Observational Study

Purpose Characterize persistence and adherence to phosphodiesterase type - 5 inhibitor (PDE5I) on-demand therapy over 6 months among Brazilian men in an observational, non-interventional study of Latin American men naïve to PDE5Is with erectile dysfunction (ED). Materials and Methods Men were prescribed PDE5Is per routine clinical practice. Persistence was defined as using ≥ 1 dose during the previous 4 - weeks, and adherence as following dosing instructions for the most recent dose, assessed using the Persistence and Adherence Questionnaire. Other measures included the Self - Esteem and Relationship (SEAR) Questionnaire, and International Index of Erectile Function (IIEF). Multivariate logistic regression was used to identify factors associated with persistence/adherence. Results 104 Brazilian men were enrolled; mean age by treatment was 53 to 59 years, and most presented with moderate ED (61.7%). The prescribed PDE5I was sildenafil citrate for 50 (48.1%), tadalafil for 36 (34.6%), vardenafil for 15 (14.4%), and lodenafil for 3 patients (2.9%). Overall treatment persistence was 69.2% and adherence was 70.2%; both were numerically higher with tadalafil (75.0%) versus sildenafil or vardenafil (range 60.0% to 68.0%). Potential associations of persistence and/or adherence were observed with education level, ED etiology, employment status, and coronary artery disease. Improvements in all IIEF domain scores, and both SEAR domain scores were observed for all treatments. Study limitations included the observational design, brief duration, dependence on patient self - reporting, and limited sample size. Conclusion Approximately two-thirds of PDE5I-naive, Brazilian men with ED were treatment persistent and adherent after 6 months. Further study is warranted to improve long-term outcomes of ED treatment. .

Inibidores da fosfodiesterase do tipo 5 e perda auditiva neurossensorial subita / Phosphodiesterase Type 5 Inhibitors and sudden sensorineural hearing loss

O uso de inibidores da fosfodiesterase do tipo 5 como sildenafil, vardenafil e tadalafil tem aumentado atualmente e alguns destes pacientes vêm apresentando perda auditiva neurossensorial súbita. OBJETIVO: Apresentar dois casos de pacientes que apresentaram surdez súbita em uso eventual do medicamento e revisar estudos sobre o uso de inibidores da fosfodiesterase do tipo 5 e surdez súbita. MÉTODO: Estudo analítico de dois casos e revisão sobre o tema no banco de dados da Pubmed/ MedLine e Bireme utilizando as palavras-chave inibidores da fosfodiesterase e surdez súbita e seus correlatos na língua inglesa. RESULTADOS: Os pacientes analisados são jovens, sem comorbidades, em uso de inibidores da fosfodiesterase do tipo 5 e após terapia combinada para o tratamento da surdez súbita, apenas um deles obteve melhora auditiva. Nove estudos científicos foram encontrados. Estudos pré-clínicos e clínicos, transversais e prospectivos foram revisados. CONCLUSÃO: O aumento da ocorrência na prática clínica e relatos científicos na literatura sugerem que o uso de inibidores da fosfodiesterase do tipo 5 seja encarado como fator de risco para surdez súbita. Novos estudos com amostras maiores e grupo controle são necessários para investigar esta associação. .

Phosphodiesterase type 5 Inhibitors, such as sildenafil, vardenafil and tadalafil have been increasingly used today and some of the users have developed sudden sensorineural hearing loss. OBJECTIVE: To present two patients with sudden deafness developed after an occasional use of the drug and review studies on the use of phosphodiesterase type 5 inhibitors and sudden hearing loss. METHOD: Analytical study of two cases and review of the subject matter in the Pubmed/Medline and Bireme databases using the keywords: phosphodiesterase type 5 inhibitors and sudden deafness and its correlates in the English language. RESULTS: The patients analyzed are young without additional disorders, using phosphodiesterase type 5 inhibitors, and after combination treatment for sudden hearing loss only one had hearing improvement. We found nine scientific studies and reviewed preclinical studies, clinical trials, prospective and cross-sectional investigations. CONCLUSION: Increased occurrence in clinical practice and scientific reports in the literature suggest that the phosphodiesterase type 5 inhibitors are considered a risk factor for sudden deafness. Further studies with larger samples and control groups are needed for better assessing this association. .

Tratamiento médico de la fisura anal con tadafilo tópico como principio activo / Medical treatment of chronic anal fissure with topical tadalafil

Introducción: La fisura anal es una úlcera lineal dolorosa que generalmente, aparece en la línea media posterior del canal anal, extendiéndose desde la línea dentada hasta el margen del ano. Su persistencia se debe al espasmo anómalo del músculo del esfínter interno. Hasta hace poco, la curación definitiva de las fisuras solo se logró mediante procedimientos quirúrgicos dirigidos a la ablación del espasmo esfinteriano. Diseño: Estudio prospectivo, controlado y aleatorio para comprobar la hipótesis de que la aplicación tópica de una preparación de Tadalafilo es un método efectivo y seguro para relajar el músculo liso y promover la cicatrización de la fisura anal. Población y métodos: Se seleccionaron los pacientes que acudieron a la consulta de coloproctología del HCC con diagnóstico de fisura anal (726). Todos fueron sometidos a una historia clínica y examen físico, antes del comienzo del tratamiento y seguimiento por 1 año. Los pacientes fueron divididos en tres grupos: Grupo A: tratados de forma médica con AINES por via oral, sediluvios y pomadas tópicas de esteroides 3 veces al dia. Grupo B: tratados con nitroglicerina 0,25% locales crema 3 veces al día. Grupo C: tratados con toxina botulínica inyectada 1 sola dosis en el espesor del esfínter interno del ano. Grupo D: tratados con formula magistral crema tópica de Tadalafilo aplicada 3 veces al día. Grupo E: pacientes a quienes se les realiza la Esfinterotomía Lateral Interna una vez que se considera ha fracasado el manejo médico y tratamiento farmacológico. Resultados: Se encontró predominio del sexo femenino con 370 pacientes (50.97%). Las edades en las cual se agrupó mayor cantidad de individuos fue entre los 26 a 35 años con 218 pacientes (30,02%). Predominó el diagnóstico de fisura crónica con 382 casos (52,61 %). El tratamiento inicial que se utilizó más frecuentemente fue el quirúrgico con 270 pacientes (37,19%), seguido de Tadalafilo tópico con 196 pacientes (26,99%)...

Introduction: Anal fissure is a painful linear ulcer usually appears in the posterior midline of the anal canal, extending from the dentate line to the margin of the anus. Its persistence is due to spasm abnormal internal sphincter muscle. Until recently, a definitive cure was achieved only cracks by surgical procedures aimed at ablation of the sphincter spasm. Design: Prospective. controlled trial to test the hypothesis that topical application of a preparation of Tadalafil is a safe and effective method to relax the smooth muscle and promote healing of anal fissure. Population and methods: We selected patients who attended the consultation of Coloproctology of HCC diagnosed with anal fissure (726). AIl underwent a medical history and physical examination before starting treatment and followed for 1 year. The patients were divided into three groups: Group A: treated medical oral NSAlDs, topical ointments sediluvios and steroids 3 times a day. Group B: treated with local nitroglycerin cream 0.25% 3 times a day. Group C: treated with botulinum toxin injection 1 dose in the thickness of the internal anal sphincter. Group D: treated with topical cream formulation TadalafiI masterfully applied 3 times a day. Group E: patients who underwent lateral internal sphincterotomy is considered after failed medical management and pharmacological treatment. Results: There was a predominance of females with 370 patientes (50.97%). The ages at which more individuals grouped was between 26 to 35 years with 218 patients (30.02%). The predominant diagnosis of chronic fissure with 382 cases (52.61%). The initial treatment was most frequently used surgical treatment of 270 patients (37.19%), followed by topical Tadalafil 196 patients (26.99%). The initial treatment had less failure was the use of topical Tadalafil 10 cases (1.37%), which required surgery...

Evaluation of Tadalafil effect on lower urinary tract symptoms of benign prostatic hyperplasia in patients treated with standard medication

OBJECTIVES: To evaluate safety and efficacy of tadalafil on lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in patients treated with standard medication. MATERIALS AND METHODS: In this case-controlled randomized clinical trial, from November 2008 to August 2009, 132 patients with obstructive and irritative urinary tract symptoms due to BPH, IPSS > 8, no indication for surgical intervention and that reached plateau levels of response to treatment were selected. These patients were randomly allocated in two groups (each containing 66 patients). The treatment group received standard treatment of BPH and tadalafil (10 mg nightly); the placebo group received only standard treatment of BPH. IPSS, maximum urinary flow rate (Qmax) and quality of life were assessed before and after a 3-month period of study. RESULTS: Before treatment, mean IPSS, Qmax and quality of life values in the treatment and placebo groups were 13.06 ± 4.37 and 13.66 ± 4.25, 8.92 ± 2.96 mL/s and 9.09 ± 2.91 mL/s, 2.93 ± 0.86 and 2.66 ± 0.78, respectively. After treatment, mean IPSS, Qmax, and quality of life values in treatment group were 7.66 ± 3.99, 9.99 ± 4.76 mL/s and 1.80 ± 0.98, respectively. These findings were compared to corresponding values of the placebo group (11.37 ± 3.64, 8.73 ± 2.22 mL/s and 2.19 ± 0.53, respectively): IPSS and quality of life were significantly different but Qmax didn't show a significant change. CONCLUSIONS: Tadalafil improves quality of life and urinary symptoms in patients with LUTS suggestive of BPH, but doesn't have any significant effect on Qmax. Therefore, this drug may be effectively used in combination with standard medical therapies for BPH.

Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy

OBJECTIVE: To evaluate the change in penile size r bilateral nerve sparing retropubic radical prostatectomy (BNSRRP) and possible effect of Tadalafil. MATERIALS AND METHODS: A total of 65 patients underwent BNSRRP and they were evaluated prospectively for a whole year of follow-up . The patients were randomized to control without rehabilitation (Group 1) or Tadalafil rehabilitation group (Group 2). The patients were evaluated at months 3, 6 and 12 postoperatively for erectile function, penile measurements (flaccid penile length, penile length at maximum erection, penile circumference at flaccid status, and penile circumference at maximum erection), penile abnormalities and general health status. Statistical analysis was performed by Chi-Square test and significance was defined as p value < 0.05. RESULTS: In Group 1 there was significant decrease in penile measurements at month 3 compared to preoperative measurements. There was decrease in all parameters at month 6 compared to month 3 but only the decrease in penile length at maximum erection was significant. There were no significant differences between postoperative months 6 and 12 for all measurements. In Group 2 there was a tendency to decrease in all measurements at month 3 compared to baseline. There was no significant difference for penile measurements between postoperative 3rd and 6th months and between 6th month and the first year. CONCLUSION: Although further large sampled trials are needed to describe the possible positive effect of tadalafil or other PDE5-I's on penile size after BNSRRP, tadalafil rehabilitation is effective in preserving penile size especially in the early postoperative period after BNSRRP.

Efficacy and safety of PDE-5 inhibitor tadalafil in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life threatening disease for which phosphodiesterase-5 inhibitor sildenafil is recently approved. We aimed to evaluate the efficacy and safety of tadalafil, a long acting congener of sildenafil, in treatment of PAH related to previous left to right shunt lesions. METHODS: In this blinded, cross over study, 11 patients with severe PAH related to congenital left to right shunt lesions (Eisenmenger syndrome) were randomly assigned to tadalafil (20 mg daily) or placebo for 4 weeks period, separated by a wash out period of at least 2 weeks. They were symptomatic with a six minute walk distance (6MWD)>or=50 m. The change in 6MWD, echo-Doppler determined pulmonary artery systolic pressure (PASP), WHO Class and modified Borg Dyspnea Index (BDI) were assessed after each therapy. RESULTS: Eight patients who completed the study protocol were analyzed. Tadalafil was associated with a significant increase in 6MWD (mean 409.25 SD 40.25 m vs 319.37 SD 42.39 m, p<0.0001), reduction in PASP (88.75 SD 23.26 mmHg vs 109.5 SD 23.78 mmHg, p<0.0001), improvement in BDI (4.62 SD 2.56 vs 6.37 SD 2.61, p=0.021) and WHO Class (6 patients vs 2 patients), compared to placebo. Tadalafil was well tolerated with no significant untoward effects. CONCLUSIONS: Tadalafil, in patients with PAH related to previous congenital left to right shunt lesions, lead to a significant improvement in exercise capacity (6MWD), PASP and WHO Class with reduced perceived exertion and was well tolerated.

Use of Tadalafil for Treating Pulmonary Arterial Hypertension Secondary to Chronic Obstructive Pulmonary Disease

Pulmonary arterial hypertension (PAH) secondary to chronic obstructive pulmonary disease (COPD) is incurable and it has an unpredictable survival rate. Two men who suffered from COPD presented with progressive dyspnea and edema, respectively. PAH, as estimated by the peak velocity of tricuspidal regurgitation, and the depressed myocardial performance index (MPI) of the right ventricle (RV) were noted on echocardiography. In addition to the baseline therapy for their depressed ventilatory function, we prescribed tadalafil 10 mg orally every other day for 2 weeks and then we doubled the dosage. They well tolerated the medication without any notable side effects. After 4 weeks of tadalafil treatment, the patients' pulmonary arterial pressure was decreased and the MPI of the RV was improved in both. The exercise capacity, as measured by the respiratory oxygen uptake, also improved from 10.9 mL/kg/min to 13.8 mL/kg/min in one patient. We report here on 2 patients with PAH secondary to COPD, and they showed notable improvement of their pulmonary hemodynamics and exercise capacity with the administration of tadalafil.

Tadalafil para o tratamento da hipertensão arterial pulmonar idiopática / Tadalafil as treatment for idiopathic pulmonary arterial hypertension

O uso de inibidores de fosfodiesterase, mais especificamente o sildenafil, no tratamento da hipertensão arterial pulmonar mostrou bons resultados, indicados por melhora dos parâmetros hemodinâmicos e da capacidade funcional. Poucos estudos existem a respeito dos efeitos de seus análogos como o tadalafil. O presente caso refere-se a uma paciente com hipertensão arterial pulmonar idiopática em classe funcional IV (NYHA) com resposta significativa ao uso de tadalafil.

Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.