RESUMO
Este trabalho teve como objetivo avaliar os efeitos da aplicação tópica de fármacos bloqueadores adrenérgicos (AR) sobre o processo de reparo periodontal de dentes reimplantados em ratos. Inicialmente, cultura de fibroblastos do ligamento periodontal humano foi utilizada para avaliar qualitativamente a citotoxicidade de soluções etanólicas de fentolamina (bloqueador α-AR) e propranolol (bloqueador ßAR) em diferentes doses (0,75 µg/mL, 2,5 µg/mL, 10 µg/mL e 100 µg/mL), após 24 horas de exposição. Posteriormente, modelo animal de avulsão e reimplante dentário foi utilizado para avaliar o potencial antirreabsortivo do bloqueio adrenérgico local com géis de fentolamina (F) ou propranolol (P), em excipiente de carboximetilcelulose (CMC). Incisivos superiores direitos foram extraídos de 48 ratos Wistar machos, armazenados em guardanapo de papel por 30 minutos, e distribuídos aleatoriamente em oito grupos (n=6) de acordo com a medicação intracanal: F0.75, F10 e F100 receberam gel de fentolamina nas concentrações 0,75 µg/mL, 10 µg/mL e 100 µg/mL, respectivamente; P2.5, P10 e P100 receberam gel de propranolol nas concentrações 2,5 µg/mL, 10 µg/mL e 100 µg/mL, respectivamente; HC e CMC receberam pasta de hidróxido de cálcio e gel de carboximetilcelulose, respectivamente. Os animais foram eutanasiados 30 dias após o reimplante e as seguintes análises foram realizadas: microtomografia (volume, superfície, proporção e densidade de tecido mineralizado), histomorfometria (áreas de reabsorção radicular inflamatória, reabsorção por substituição, anquilose e reparo periodontal) e histoquímica (atividade osteoclástica). Os dados foram analisados estatisticamente por meio de ANOVA e teste de Tukey ou Kruskal Wallis e teste de Dunn, de acordo com sua normalidade (α=5%). A análise qualitativa da viabilidade celular demonstrou que a dose de 100 µg/mL dos fármacos apresentou alta citotoxicidade, com 100% das células inviáveis, e as demais doses propiciaram viabilidade celular semelhante. As análises microtomográfica e histomorfométrica das amostras in vivo não revelaram qualquer diferença estatística significante entre os fármacos testados e suas diferentes doses (p>0,05). No entanto, P10 e F10 apresentaram qualitativamente um melhor resultado, pois foram os únicos grupos classificados com áreas de intenso reparo periodontal (P10) e de discreta reabsorção radicular inflamatória (F10 e P10). O tratamento com F10 e P10 diminuiu significativamente o número de osteoclastos em comparação com as outras medicações tópicas (p<0,05). Concluiu-se que a aplicação tópica de géis de fentolamina e propranolol na dose de 10 µg/mL diminuiu significativamente a atividade osteoclástica sem causar efeitos citotóxicos.(AU)
This study aimed to evaluate the effects of topical application of adrenergic (AR) blocking drugs on the periodontal repair process of replanted teeth in rats. First, culture of human periodontal ligament fibroblasts was used to qualitatively assess the cytotoxicity of ethanolic solutions of phentolamine (α-AR blocker) and propranolol (ßAR blocker) at different doses (0.75 µg/mL, 2.5 µg/mL, 10 µg/mL and 100 µg/mL) after 24 hours of exposure. Then, animal model of tooth avulsion and replantation was used to evaluate the anti-resorptive potential of local adrenergic blockade with phentolamine (Ph) or propranolol (Pr) gels, in carboxymethylcellulose excipient (CMC). Maxillary right incisors were extracted from 48 male Wistar rats, stored in paper napkins for 30 minutes, and randomly distributed into eight groups (n = 6) according to intracanal medication: Ph0.75, Ph10 and Ph100 received phentolamine gel at concentrations of 0.75 µg/mL, 10 µg/mL and 100 µg/mL, respectively; Pr2.5, Pr10 and Pr100 received propranolol gel at concentrations of 2.5 µg/mL, 10 µg/mL and 100 µg/mL, respectively; CH and CMC received calcium hydroxide paste and carboxymethylcellulose gel, respectively. The animals were euthanized 30 days after replantation and the following analyzes were performed: microtomography (volume, surface, proportion and density of mineralized tissue), histomorphometry (areas of inflammatory root resorption, replacement root resorption, ankylosis and periodontal repair) and histochemistry (osteoclastic activity). Data were analyzed statistically by means of ANOVA and Tukey's test or Kruskal Wallis and Dunn's test, according to their normality (α = 5%). The qualitative analysis of cell viability demonstrated that the dose of 100 µg/mL of the drugs presented high cytotoxicity, with 100% of the cells non-viable, and the other doses provided similar cell viability. Microtomographic and histomorphometric analyzes of in vivo samples did not reveal any significant statistical difference between the tested drugs and their different doses (p>0.05). However, Pr10 and Ph10 presented qualitatively a better result, as they were the only groups classified with areas of intense periodontal repair (Pr10) and discrete inflammatory root resorption (Ph10 and Pr10). Treatment with Ph10 and Pr10 significantly decreased the number of osteoclasts compared to the other topical medications (p<0.05). It was concluded that topical application of phentolamine and propranolol gels at a dose of 10 µg/mL significantly decreased osteoclastic activity without causing cytotoxic effects(AU)
Assuntos
Humanos , Avulsão Dentária/complicações , Fentolamina/efeitos adversos , Reimplante Dentário/classificação , Reabsorção de Dente/prevenção & controle , Antagonistas Adrenérgicos/efeitos adversosRESUMO
This open-label, multi-center study from Mexico compared the efficacy and safety of oral sildenafil and phentolamine in men with erectile dysfunction. Patients received sildenafil (25-100 mg; n=123) or phentolamine (40 mg; n=119) for 8 weeks, and efficacy was assessed using the International Index of Erectile Function (IIEF) as well as two global efficacy questions. Mean scores for the erectile function domain of the IIEF were significantly higher for sildenafil (27.23 +/- 0.62; P=0.0001) than for phentolamine (19.35 +/- 0.66). Approximately twice as many men receiving sildenafil had successful attempts at sexual intercourse (88% vs 42%), improved erections (95% vs 51.1%), and improved ability to have sexual intercourse (94.4% vs 46.4%) compared with phentolamine. The most common adverse events included rhinitis, headache, tachycardia, and nausea, with a higher frequency reported in patients receiving phentolamine than sildenafil (41% vs 33%), with the exception of headache, which was reported more frequently in sildenafil users. Overall, sildenafil was more effective and appeared to be better tolerated than phentolamine for the treatment of erectile dysfunction.
Assuntos
Antagonistas Adrenérgicos alfa/administração & dosagem , Disfunção Erétil/tratamento farmacológico , Fentolamina/administração & dosagem , Piperazinas/uso terapêutico , Vasodilatadores/uso terapêutico , Administração Oral , Adolescente , Antagonistas Adrenérgicos alfa/efeitos adversos , Antagonistas Adrenérgicos alfa/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Coito , Disfunção Erétil/fisiopatologia , Humanos , Masculino , México , Pessoa de Meia-Idade , Fentolamina/efeitos adversos , Fentolamina/uso terapêutico , Piperazinas/efeitos adversos , Purinas , Citrato de Sildenafila , Sulfonas , Resultado do Tratamento , Vasodilatadores/efeitos adversosRESUMO
The usefulness, complications and reasons for discontinuing the self-injection program with a combination of papaverine, phentolamine and prostaglandin E1 were evaluated in 189 patients (mean age 57.2 y), who were included from April 1993 to September 1995 (mean follow-up 10.25 months). Patients were split into two groups: Active, those who continued with the program (48%); and Inactive, those who discontinued treatment or failed to attend consultation after five months from the last visit (52%). Only 30% of the inactive group reported failure to achieve response with the self-injected doses. Fibrosis in 5.3% and prolonged erection in 3.7% were the most severe complications. Patients lacking organic pathology showed a clear tendency to reduce the drug dose during treatment, recover spontaneous erections and discontinue the program for reasons unrelated to drug efficacy. The triple drug mixture provides an effective alternative in the treatment of impotence, with a low rate of complications.
Assuntos
Alprostadil/administração & dosagem , Disfunção Erétil/tratamento farmacológico , Papaverina/administração & dosagem , Ereção Peniana , Fentolamina/administração & dosagem , Vasodilatadores , Adulto , Idoso , Alprostadil/efeitos adversos , Alprostadil/uso terapêutico , Fibrose/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Papaverina/efeitos adversos , Papaverina/uso terapêutico , Pênis/patologia , Fentolamina/efeitos adversos , Fentolamina/uso terapêutico , Autoadministração , Resultado do TratamentoRESUMO
PURPOSE: We compared the efficacy and short-term adverse effects of 1 ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine versus 1 ml. 30 micrograms./ml. prostaglandin E1 in patients undergoing pharmacological erection testing. MATERIALS AND METHODS: A total of 60 patients (mean age 58 years) with a history of sexual erectile dysfunction longer than 6 months was randomly classified into 6 groups to be tested 1 week apart with the 2 solutions and with placebo to evaluate erection response and short-term adverse effects. RESULTS: Of the patients tested with papaverine plus phentolamine 54% responded with erections adequate for penetration, compared to 50% of those tested with prostaglandin E1 (p > 0.05). Prolonged erection occurred in 18% of patients tested with papaverine plus phentolamine and 15% of those tested with prostaglandin E1 (p > 0.05). Pain was reported by 15 and 35% of patients, respectively (p < 0.05). CONCLUSIONS: One ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine has the same efficacy and equal prolonged erection rate as 1 ml. 30 micrograms./ml. prostaglandin E1 but the latter agent induces significantly more pain.
Assuntos
Alprostadil/administração & dosagem , Impotência Vasculogênica/tratamento farmacológico , Papaverina/administração & dosagem , Fentolamina/administração & dosagem , Vasodilatadores/administração & dosagem , Adulto , Idoso , Alprostadil/efeitos adversos , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Papaverina/efeitos adversos , Satisfação do Paciente , Fentolamina/efeitos adversos , Vasodilatadores/efeitos adversosAssuntos
Humanos , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Diazepam/efeitos adversos , Diazepam/farmacologia , Etomidato/efeitos adversos , Etomidato/farmacologia , Hemodinâmica , Midazolam/efeitos adversos , Midazolam/farmacologia , Morfina/efeitos adversos , Morfina/farmacologia , Fentolamina/efeitos adversos , Fentolamina/farmacologia , Propofol/efeitos adversos , Propofol/farmacologia , Tiopental/efeitos adversos , Tiopental/farmacologiaRESUMO
We report 16 cases of priapism in 13 of 404 patients who received intracavernous injection of vasoactive drugs to induce erection. In 10 patients the complication presented following injection of papaverine and phentolamine in combination. Despite reducing the dose of both agents, one patient had another episode of priapism. One patient who had been receiving papaverine alone in increasing doses with no results, developed priapism after the first injection of the combined treatment modality and again after the dose of both drugs had been reduced. Three cases presented priapism after injection with papaverine alone. One presented the complication again after injection of a reduced dose. The patients were seen after a sustained erection of 20 hours maximum on 15 occasions and one patient was seen after a sustained erection of 36 hours.