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      Daily use of phosphodiesterase type 5 inhibitors as prevention for recurrent priapism Translated title: Prevenção do priapismo recorrente com a utilização diária de inibidores da fosfodiesterase tipo 5

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          Abstract

          Summary Objective: The pathogenesis of recurrent priapism is currently being investigated based on the regulation of the phosphodiesterase 5 (PDE5) enzyme. We explored the daily use of PDE5 inhibitors to treat and prevent priapism recurrences. Method: We administered PDE5 inhibitors using a long-term therapeutic regimen in seven men with recurrent priapism, with a mean age of 29.2 years (range 21 to 35 years). Six men (85.7%) had idiopathic priapism recurrences and one man (24.3%) had sickle cell disease-associated priapism recurrences. Tadalafil 5 mg was administered daily. The mean follow-up was 6.6 months (range 3 to 12 months). Results: Daily long-term oral PDE5 inhibitor therapy alleviated priapism recurrences in all patients. Five (71.4%) had no episodes of priapism and two (28.6%) referred decrease in their episodes of priapism. All patients referred improvement in erectile function. Conclusion: These findings suggest the hypothesis that PDE5 dysregulation exerts a pathogenic role for both sickle cell disease-associated priapism and for idiopathic priapism, and that it offers a molecular target for the therapeutic management of priapism. These preliminary observations suggest that continuous long-term oral PDE5 inhibitor therapy may treat and prevent recurrent priapism.

          Translated abstract

          Resumo Objetivo: Uma das teorias propostas para explicar a etiologia do priapismo recorrente está baseada no mecanismo de regulação da fosfodiesterase tipo 5. Estudamos o uso diário dos inibidores de fosfodiesterase tipo 5 no tratamento e na prevenção do priapismo recorrente. Método: Sete homens com diagnóstico de priapismo recorrente, com idade média de 29,5 anos (21 a 35 anos), utilizaram inibidor de fosfodiesterase tipo 5 em dose diária (tadalafila 5 mg/dia) por período prolongado. Seis homens (85,7%) apresentavam priapismo recorrente de etiologia idiopática, e um homem (24,3%), de etiologia associada à anemia falciforme. O seguimento médio foi de 6,6 meses (3 a 12 meses). Resultados: Todos os pacientes se beneficiaram com a utilização de inibidores de fosfodiesterase tipo 5. Cinco (71,4%) não apresentaram nenhum episódio de priapismo e dois (28,6%) relataram diminuição dos episódios. Todos os pacientes relataram melhora da função erétil. Conclusão: Estes achados sugerem que a hipótese do mecanismo de regulação da fosfodiesterase tipo 5 exerce papel importante na patogenia do priapismo recorrente. O uso contínuo e diário de inibidores da fosfodiesterase tipo 5 pode ser uma opção no tratamento do priapismo recorrente.

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          American Urological Association guideline on the management of priapism.

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            Phosphodiesterase-5A dysregulation in penile erectile tissue is a mechanism of priapism.

            The molecular mechanism for priapism is not well characterized. Although the nitric oxide (NO) pathway is known to mediate penile erection under normal conditions, we hypothesized that the mechanism of priapism rests in aberrant downstream signaling of this pathway based on our previous findings that mice lacking the gene for endothelial nitric oxide synthase (eNOS-/-) and mice lacking both neuronal NOS (nNOS) and eNOS (nNOS-/-, eNOS-/-) have a tendency for priapic activity. We investigated the role of downstream guanylate cyclase and phosphodiesterase type 5 (PDE5A) expression and function in mediating these responses in eNOS-/- and nNOS-/-, eNOS-/- mice. Erectile responses to both cavernous nerve stimulation and intracavernosal injection of the NO donor diethylamine-NONOate were augmented in eNOS-/- and nNOS-/-, eNOS-/- mice but not in WT or nNOS-/- mice. PDE5A protein expression and activity and cGMP levels were significantly lower in eNOS-/- and nNOS-/-, eNOS-/- mice, and this effect was reproduced in WT corpus cavernosum exposed to NOS inhibitors. Moreover, cavernous nerve stimulation was associated with a marked augmentation of cavernosal cGMP levels, suggesting that, although lower at baseline, the production of cGMP is unchecked in eNOS-/- and nNOS-/-, eNOS-/- mice upon neurostimulation. Transfection of eNOS-/- mice with an adenovirus encoding eNOS resulted in a normalization of PDE5A protein and activity as well as a correction of priapic activity. Coupled with the observation that sickle cell disease mice (which show a priapism phenotype) evince dysregulated PDE5A expression/activity, these data suggest that PDE5A dysregulation is a fundamental mechanism for priapism.
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              Priapism: current principles and practice.

              Priapism, a pathologic condition of persistent penile erection in the absence of sexual excitation, is a true erectile disorder. Although it may seem to affect only a small population of male individuals, it carries major significance. Possible complications of the disorder include penile fibrosis and permanent erectile dysfunction. All health care professionals should appreciate the importance of the disorder and be prepared to follow current principles of diagnosis and treatment to reduce or avert its complications.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                ramb
                Revista da Associação Médica Brasileira
                Rev. Assoc. Med. Bras.
                Associação Médica Brasileira (São Paulo, SP, Brazil )
                0104-4230
                1806-9282
                August 2017
                : 63
                : 8
                : 689-692
                Affiliations
                [2] São Paulo orgnameUniversidade Federal de São Paulo orgdiv1Escola Paulista de Medicina Brazil
                [1] São Paulo orgnameUniversidade Federal de São Paulo orgdiv1Escola Paulista de Medicina Brazil
                Article
                S0104-42302017000800689
                10.1590/1806-9282.63.08.689
                b8fd5575-1247-443c-b382-322bdb1851f9

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 03 July 2017
                : 21 July 2017
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 9, Pages: 4
                Product

                SciELO Brazil


                priapism,cyclic nucleotide phosphodiesterases type 5,erectile dysfunction,priapismo,fosfodiesterases nucleotídicas cíclicas tipo 5,disfunção erétil

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