Efeito da associação da tadalafila com a tansulosina no trato urinário inferior de ratos e de humanos

• Ano de defesa: 2012
• Autor(a) principal: Regadas, Rommel Prata
• Orientador(a): Silva, Lúcio Flávio Gonzaga
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Inibidores de Fosfodiesterase; Antagonistas Adrenérgicos alfa; Hiperplasia Prostática
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/19268

Recently, it has been observed an association between BPH and ED. It was reported that patients with ED treated with inhibitory phosphodiesterase type 5 (IPDE5) improves erection and LUTS. The pathophysiology of lower urinary tract symptoms (LUTS) is not completely known, so it is necessary that clinical and experimental studies are made to clarify the mechanisms involved in its origin. However, despite the knowledge that there is improvement in LUTS, it is not known whether IPDE5 works during storage, emptying, or both. It is not yet known if the association IPDE5 with alpha blocker is better than its use alone or whether this association is safe. The aim of this study was to evaluate the safety of the combination of tamsulosin with daily tadalafil as well as its effect on lower urinary tract in human and rats by urodynamic study. Methods: it was an experimental study using rats with chronic bladder outlet obstruction induced by L-NAME and a randomized clinical trial, double-blind, placebo-controlled study. In the experimental study, the animals were divided into 05 groups. Group 1: six rats were treated without medication; Group 2: six rats were treated with L- NAME (60 mg/Kg/dia); Group 3: six rats were treated with L- NAME and tansulosin (1mg/kg); Group 4: seven rats were treated with L- NAME and tadalafil (5mg/kg); grupo 5: six rats were treated with L- NAME, tadalafil and Tansulosina. After thirty days of oral treatment, the animals underwent urodynamic study. The urodynamic variables were evaluated. In the filling phase: non-void contractions (NVC), volume threshold (VT), pressure threshold (TP) and in the voiding phase: peak pressure (PP), micturition frequency (FM), basal pressure (PB) and residual volume. In the clinical study, it was performed a randomized clinical trial, double-blind, placebo-controlled study during the period October 2010 to September 2011. All patients had LUTS associated with BPH and were evaluated with International Prostate Symptom Score (I-PSS) and urodynamic study at baseline and 30 days after treatment. Patients were separated into two groups: Group 1 (20 patients) - daily tadalafil 5mg and placebo and Group 2 (20 patients) tamsulosin 0.4 mg and tamsulosin 0.4 mg. Results: it was found that the animals in group 2 showed a significant increase in the frequency of detrusor contraction (p <0.05), frequency micturition cycles (p <0.05) and residual volume (p <0.01) when compared to group 1. Animals in group 3 showed a significant reduction of non-voiding contractions, when compared to group 2. The group 4 animals showed significant reduction in frequency of micturition cycles (p <0.05) and residual volume (p <0.05) compared to group 2. Animals in group 5 showed a significant reduction in non-voiding contractions (p <0.05), frequency of micturition cycles (p <0.05) and residual volume (p <0.01) compared to group 2. In the clinical study, the age of patients (p=0.19) and the average volume of the prostate (P=0.28) were similar. The association of tamsulosin with tadalafil 5mg was more effective in improving the total score of the I-PSS and voiding sub-score. But comparing the groups there is no difference between the storage sub-score, Quality of Life, maximum flow and detrusor pressure at maximum flow. There were no major side effect Conclusion: The combination of tamsulosin and tadalafil daily is safe and better than the isolated use of tamsulosin to treat patients with lower urinary tract symptoms associated with benign prostatic hyperplasia and rats with chronic bladder outlet obstruction.