RESUMO
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.
Assuntos
Inibidores da Fosfodiesterase 5/administração & dosagem , Priapismo/prevenção & controle , Tadalafila/administração & dosagem , Adulto , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Seguimentos , Humanos , Masculino , Priapismo/enzimologia , Estudos Prospectivos , Recidiva , Prevenção Secundária , Adulto JovemRESUMO
El priapismo es una complicación de la anemia drepanocítica y se define como una erección prolongada, dolorosa y persistente del pene de más de 4 horas de duración sin estimulación sexual asociada. El 95 por ciento de las crisis de priapismo en estos pacientes es de tipo isquémico o de bajo flujo y constituyen una emergencia médica que, de no diagnosticarse y tratarse adecuadamente, provoca necrosis del tejido y disfunción eréctil. En este trabajo se revisan el diagnóstico y las opciones terapéuticas actuales y futuras de esta grave complicación(AU)
Priapism is a common complication of sickle cell disease and it is characterized by a prolonged, painful and persistent erection of the penis lasting more than 4 hours without associated sexual stimulation. The 95 percent of priapism crisis in these patients is ischemic type and represents a medical emergency that can provoke erectile tissue necrosis and erectile dysfunction if not treated properly. In this paper we reviewed the diagnosisand the current and perspectives therapeutic options of this severe complication(AU)
Assuntos
Humanos , Masculino , Priapismo/cirurgia , Priapismo/complicações , Priapismo/diagnóstico , Priapismo/prevenção & controle , Priapismo/tratamento farmacológico , Hidroxiureia/uso terapêutico , Traço Falciforme/complicaçõesRESUMO
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.
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.
Assuntos
Humanos , Masculino , Adulto , Adulto Jovem , Priapismo/prevenção & controle , Inibidores da Fosfodiesterase 5/administração & dosagem , Tadalafila/administração & dosagem , Priapismo/enzimologia , Recidiva , Estudos Prospectivos , Seguimentos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Prevenção SecundáriaRESUMO
PURPOSE: To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. RESULTS: Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. CONCLUSIONS: The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.
Assuntos
Dipiridamol/farmacologia , Isquemia/prevenção & controle , Pênis/irrigação sanguínea , Priapismo/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Vasodilatadores/farmacologia , Animais , Antioxidantes/análise , Biomarcadores/sangue , Modelos Animais de Doenças , Precondicionamento Isquêmico/métodos , Masculino , Malondialdeído/sangue , Oxidantes/sangue , Estresse Oxidativo , Ereção Peniana/efeitos dos fármacos , Pênis/patologia , Priapismo/patologia , Distribuição Aleatória , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Albumina Sérica , Albumina Sérica Humana , Fatores de Tempo , Resultado do TratamentoRESUMO
ABSTRACT Purpose To investigate the protective effects against ischemia reperfusion injury of dipyridamole in a model of induced priapism in rats. Materials and Methods Twenty-four male Sprague-Dawley rats were divided into four groups, control, P/R, P/R+DMSO and P/R+D. 3ml blood specimens were collected from vena cava inferior in order to determine serum MDA, IMA, TAS, TOS and OSI values, and penile tissue was taken for histopathological examination in control group. Priapism was induced in P/R group. After 1h, priapism was concluded and 30 min reperfusion was performed. In P/R+DMSO group 1ml/kg DMSO was administered intraperitoneally 30 min before reperfusion, while in P/R+D group 10mg/kg dipyridamole was administered intraperitoneally 30 min before reperfusion. Blood and penis specimens were collected after the end of 30 min reperfusion period. Sinusoidal area (µm2), tears in tunica albuginea and injury parameters in sinusoidal endothelium of penis were investigated. Results Histopathological examination revealed no significant changes in term of sinusoidal area. A decrease in tears was observed in P/R+D group compared to P/R group (p<0.05). Endothelial injury decreased in P/R+D group compared to P/R group (p>0.05). There were no significant differences in MDA and IMA values between groups. A significant increase in TOS and OSI values was observed in P/R+D group compared to P/R group. A significant decrease in TAS levels was observed in P/R+D group compared to the P/R group. Conclusions The administration of dipyridamole before reperfusion in ischemic priapism model has a potential protective effect against histopathological injury of the penis.
Assuntos
Animais , Masculino , Pênis/irrigação sanguínea , Priapismo/prevenção & controle , Vasodilatadores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Dipiridamol/farmacologia , Isquemia/prevenção & controle , Pênis/patologia , Priapismo/patologia , Fatores de Tempo , Ereção Peniana/efeitos dos fármacos , Albumina Sérica , Biomarcadores/sangue , Distribuição Aleatória , Reprodutibilidade dos Testes , Resultado do Tratamento , Oxidantes/sangue , Ratos Sprague-Dawley , Estresse Oxidativo , Precondicionamento Isquêmico/métodos , Modelos Animais de Doenças , Albumina Sérica Humana , Malondialdeído/sangue , Antioxidantes/análiseRESUMO
Hydroxyurea is one of the most successfully used therapies for sickle cell disease. Results of many clinical trials point to hydroxyurea administration for patients with frequent painful crises and acute chest syndrome. Priapism is one of the complications that could be prevented by hydroxyurea, but there are few reports demonstrating the results. Since November 1993, hydroxyurea has been used in our clinic for preventing priapism in patients with stuttering or major attacks who are still capable of achieving intercourse on demand. Five patients were enrolled in the study, and 4 cases benefited by this treatment. After the initial treatment for the acute attack, all five patients developed stuttering priapism. Hydroxyurea was then introduced at the initial dose of 10 mg/kg, and as the hydroxyurea dosage increased, the number or length of priapism episodes decreased. One to two months after the maximal dose (20-35 mg/kg) was introduced, the episodes disappeared. In two patients, we were forced to administer over 30 mg hydroxyurea/kg to abort the episodes, and, in another patient, 25 mg/kg was necessary. All patients present normal sexual activity. Hydroxyurea was discontinued in two patients, but stuttering priapism reappeared. Hydroxyurea was then re-introduced, and priapism disappeared. One patient, using 20 mg hydroxyurea/kg, had a 6-year remission of priapism after hydroxyurea administration; however, he experienced stuttering priapism, 1 month before a major attack, that progressed to impotence. During that month, he did not seek medical attention. In conclusion, the data here presented suggests that hydroxyurea may prevent priapism attacks in sickle cell disease, probably at higher doses than usually prescribed for painful crisis prevention.
Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Hidroxiureia/administração & dosagem , Priapismo/tratamento farmacológico , Adolescente , Adulto , Relação Dose-Resposta a Droga , Seguimentos , Humanos , Hidroxiureia/toxicidade , Masculino , Priapismo/etiologia , Priapismo/prevenção & controle , Comportamento Sexual/efeitos dos fármacos , Resultado do TratamentoRESUMO
A double-blind, placebo-controlled crossover study was conducted in 11 patients with stuttering atacks of priapism and homozygous sickle-cell (SS) disease. Stilboestrol 5 mg daily was better than the placebo in preventing attacks (AU)