ABSTRACT
Purpose: We aimed to investigate the antioxidant activity of nebivolol against possible damage to the ovarian tissue due to the application of deltamethrin as a toxic agent, by evaluating histopathological proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNF-α) signal molecules immunohistochemically. Methods: The animals were divided into three groups as control, deltamethrin and deltamethrin + nebivolol groups. Vaginal smears were taken after the animals were mated and detected on the first day of pregnancy. After the sixth day, deltamethrin (0.5 mL of 30 mg/kg BW undiluted ULV), and 2 mL of sterile nebivolol solution were administered intraperitoneally every day for 6-21 periods. After routine histopathological follow-up, the ovarian tissue was stained with hematoxylin and eosin stain. Results: Control group showed normal histology of ovarium. In deltamethrin group, hyperplasic cells, degenerative follicles, pyknotic nuclei, inflammation and hemorrhagic areas were observed. Nebivolol treatment restored these pathologies. Deltamethrin treatment increased TNF-α and PCNA reaction. However, nebivolol decreased the expression. Conclusions: It was thought that deltamethrin toxicity adversely affected follicle development by inducing degeneration and apoptotic process in preantral and antra follicle cells, and nebivolol administration might reduce inflammation and slow down the apoptotic signal in the nuclear phase and regulate reorganization.
Subject(s)
Animals , Rats , Ovary/drug effects , Toxicity , Nebivolol/administration & dosage , AntioxidantsSubject(s)
Humans , Male , Middle Aged , Coronary Artery Disease/pathology , Cardiomegaly/complications , Coronary Vessel Anomalies/drug therapy , Coronary Vessel Anomalies/diagnostic imaging , Coronary Vessels/pathology , Spironolactone/administration & dosage , Time Factors , Echocardiography , Risk Factors , Electrocardiography , Nebivolol/administration & dosage , Olmesartan Medoxomil/administration & dosage , Computed Tomography Angiography/methods , Treatment Adherence and Compliance , Heart Atria/physiopathologyABSTRACT
Introdução: O remodelamento ósseo é um processo complexo que depende do balanço entre formação e reabsorção óssea, mecanismo regulado pelas células ósseas e fatores sistêmicos, como o Sistema Nervoso Simpático (SNS). Os mediadores deste sistema são capazes de regular o metabolismo ósseo através dos receptores adrenérgicos expressos na superfície dos osteoblastos. Entretanto, o papel dos receptores ß-adrenérgicos ainda não está totalmente elucidado no processo de diferenciação osteogênica. Objetivos: avaliar o papel dos receptores ß-adrenérgicos na diferenciação osteoblástica de células tronco mesenquimais da medula óssea de ratos normotensos e espontaneamente hipertensos (SHR). Métodos: Ratos machos Wistar e SHR (10 semanas) foram utilizados para a coleta da medula óssea a partir do fêmur, as quais foram plaqueadas em garrafas de cultivo celular e depois em placas de 24 poços, onde receberam o meio osteogênico (MO: MEM, mais 50 µg/mL de ácido ascórbico, 10 mM de ß-glicerofosfato e 10-8 M de dexametasona), e o tratamento com Isoprenalina (0,01 µM), Carvedilol (1 µM), antagonista adrenérgico não seletivo, ou Nebivolol (0,1 µM), antagonista ß1-adrenérgico. O ensaio de proliferação celular (MTT) e a atividade de fosfatase alcalina (Fal) foram realizados nos dias 7, 10 e 14. A mineralização foi avaliada no dia 14 através do vermelho de Alizarina. A expressão gênica dos marcadores osteogênicos e dos receptores ß1 e ß2 adrenérgicos foi avaliada no dia 7 por RT-PCR em tempo real. A atividade proteolítica da metaloproteinase de matriz (MMP-2) foi avaliada no mesmo período utilizando zimografia. As vias da MAPK também foram avaliadas ao final de 7 dias. Resultados: A Isoprenalina reduz a fosfatase alcalina na linhagem de células Wistar nos dois primeiros períodos, e ao final de 14 dias apresenta um aumento significativo. A adição dos -bloqueadores reverte tal resposta. Em SHR a Isoprenalina proporciona aumento da atividade de fosfatase alcalina no período intermediário. O Nebivolol inibe essa resposta no mesmo período e, em 7 dias, é capaz de reverter a redução causada pelo agonista. A Isoprenalina aumentou a expressão de todos os fatores de transcrição e o bloqueio dos receptores reverteu essa condição A Isoprenalina aumenta a expressão de Opn, Ocn e BSP nas células de animais Wistar, e em SHR aumenta apenas Ocn e o tratamento com Carvedilol corrige. A atividade de MMP-2 também foi reduzida pelo Nebivolol apenas no grupo Wistar. Além disso, o Nebivolol reduziu a expressão gênica do receptor ß1-adrenérgico. O ensaio de mineralização mostrou menor deposição mineral em Wistar. O Nebivolol também mediou a redução da fosforilação das vias da MAPK neste mesmo grupo de células. Conclusão: Nossos dados sugerem que o receptor ß1-adrenérgico pode estar envolvido na diferenciação osteogênica de células de ratos Wistar mas não em células de ratos SHR(AU)
Introduction: Bone remodeling is a complex process that depends on the balance between formation and resorption bone, a process which is regulated by bone cells and systemic factors, like the Sympathetic Nervous system (SNS). The mediators of these system are able to regulate bone metabolism through adrenergic receptors on the surface os the osteoblastos. However, the role of ß-adrenergic receptors is not clear in he osteogenic differentiation process. Thus, in this study we aimed to evaluate the role of B-adrenergic receptor on osteoblastic differentiation of bone marrow mesenchymal stem cells from normotensive and Spontaneously Hypertensive Rats (SHR). Methods: 70-days-old male Wistar and SHR rats were used for bone marrow collection from femurs, which was placed in cell culture flasks and after in to 24-well plates, where they received osteogenic medium (OM: MEN, plus 50 µg/mL ascorbic acid, 10 mM ß glycerophosphate, and 10-8 M dexamethasone) and the treatment with Isoprenaline (0.01 µM), Carvedilol (1µM), non-selective adrenergic receptor antagonist, or Nebivolol (0,1 µM), ß1-adrenergic receptor antagonist. Cell proliferation (MTT assay) and alkaline phosphatase specific activity (Alp) were analyzed at day 7, 10 and 14. Mineralization was evaluated at day 14, by Alizarin Red S. Gene expression of osteogenic markers and B1 and B2-adrenergic receptor were evaluated at day 7, by real time-RT-PCR. The proteolytic activity of matrix metalloproteinase 2 (MMP-2) were evaluated at day 7 using gelatin zymography. The MAPK pathway was evaluated at the same period. Results: Isoprenaline provides increased alkaline phosphatase activity in the intermediate period. The addition of Nebivolol includes this response over this same period and, within 7 days, was able to reverse the reduced agonist reduction. Isoprenaline increased expression of all transcription factors and receptor blockade reversed this condition Isoprenaline increases expression of Opn, Ocn and BSP in Wistar animal cells, and in SHR only increases Ocn and Carvedilol-corrected treatment. MMP-2 was reduced by Nebivolol treatment just at Wistar cells. Besides that, Nebivolol reduced Adrb1 gene expression at day 7 in Wistar group. Mineralization showed that Nebivolol reduced mineral deposition in Wistar. Nebivolol reduced MAPK proteins phosphorylation. Conclusion: Our results suggest that ß1 adrenergic receptor seems to be involved in the osteogenic differentiation of cells from Wistar rats but not in SHR cells(AU)
Subject(s)
Animals , Rats , Receptors, Adrenergic, beta , Mesenchymal Stem Cells , Hypertension , Osteoblasts , Rats, Inbred SHR , Sympathetic Nervous System , Bone and Bones , Bone Marrow , Bone Resorption , Receptors, Adrenergic , Rats, Wistar , Nebivolol , IsoproterenolABSTRACT
Abstract Purpose: To investigate the biochemical, histopathologic, and spermatogenetic changes in the detorsionated testicle after experimental torsion and to study the antioxidant effects of pheniramine maleate and nebivolol. Methods: Twenty-four Sprague-Dawley male rats were divided into 4 groups: Group 1: Sham; Group 2: Torsion/Detorsion (T/D); Group 3: T/D + Pheniramine maleate (PM); Group 4: T/D + Nebivolol (NB) group. Paroxanase (PON), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stres index (OSI) were measured, and spermatogenetic and histopathologic evaluation was performed in tissue and blood samples. Results: The evaluation of tissue TAS indicated no statistically significant difference in Group 3 compared to Group 2. A statistically significant increase was detected in Group 4 compared to Group 2. Serum PON levels revealed a statistically significant increase in Groups 3 and 4 compared to Groups 1 and 2. The Johnsen testicular biopsy score decreased in Groups 3 and 4, but the decrease was not statistically significant. Conclusions: Pheniramine maleate and nebivolol have antioxidant effects against ischemia-reperfusion damage. They also support tissue recovery, which is more significantly observed by nebivolol.
Subject(s)
Animals , Male , Rats , Pheniramine/pharmacology , Spermatic Cord Torsion/drug therapy , Testis/drug effects , Oxidative Stress/drug effects , Nebivolol/pharmacology , Antioxidants/pharmacology , Spermatic Cord Torsion/pathology , Spermatogenesis/drug effects , Testis/blood supply , Testis/pathology , Time Factors , Reperfusion Injury/drug therapy , Rats, Sprague-Dawley , Adrenergic beta-Antagonists/pharmacology , Aryldialkylphosphatase/blood , Histamine H1 Antagonists/pharmacologyABSTRACT
Abstract Background: More than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties. Objectives: To evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF. Methods: Twenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO2). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months. Results: After treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO2 and 123I-MIBG scintigraphic parameters. Conclusion: Despite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.
Resumo Fundamento: Mais de 50% dos pacientes com insuficiência cardíaca têm fração de ejeção preservada (ICFEN). A cintilografia marcada com iodo 123 com metaiodobenzilguanidina (123I-MIBG) e o teste cardiopulmonar do exercício (TCPE) são marcadores de prognóstico da ICFEN. O nebivolol é um betabloqueador com propriedade vasodilatadora. Objetivos: Avaliar o impacto da terapia com nebivolol sobre as variáveis da cintilografia com 123I-MIBG e do TCPE em pacientes com ICFEN. Métodos: Vinte e cinco pacientes realizaram cintilografia com 123I-MIBG para avaliar a taxa de washout e a relação coração/mediastino precoce e tardia. Durante o TCPE, foi analisado o comportamento da pressão arterial sistólica (PAS), frequência cardíaca (FC) durante o esforço e a recuperação (FCR) e o consumo de oxigênio (VO2). Após avaliação inicial, separamos nossa amostra em grupos controle versus intervenção, iniciamos o nebivolol e repetimos os exames após 3 meses. Resultados: Após o tratamento, o grupo intervenção apresentou melhora na PAS (149 mmHg [143,5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0,016]), FC em repouso (78 bpm [65,5-84 bpm] versus 64,5 bpm [57,5-75,5 bpm, p = 0,028]), PAS no pico do esforço (235 mmHg [216,5-249 mmHg] versus 198 mmHg [191-220,5 mmHg], p = 0,001), FC no pico do esforço (124,5 bpm [115-142 bpm] versus 115 bpm [103,7-124 bpm], p = 0,043) e FCR no 1º minuto (6,5 bpm [4,75-12,75 bpm] versus 14,5 bpm [6,7-22 bpm], p = 0,025) e no 2º minuto (15,5 bpm [13-21,75 bpm] versus 23,5 bpm [16-31,7 bpm], p = 0,005), porém não apresentou mudança no VO2 de pico e nos parâmetros da cintilografia com 123I-MIBG. Conclusão: Apesar de um melhor controle da PAS e na FC em repouso e durante o esforço e uma melhora na FCR, o nebivolol não ocasionou efeito positivo sobre o VO2 de pico e nos parâmetros da cintilografia com 123I-MIBG. A ausência de efeito sobre a atividade adrenérgica pode ser a causa da falta de efeito sobre a capacidade funcional.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Vasodilator Agents/therapeutic use , Radiopharmaceuticals , 3-Iodobenzylguanidine , Nebivolol/therapeutic use , Heart Failure/physiopathology , Oxygen Consumption/drug effects , Stroke Volume/physiology , Blood Pressure/physiology , Radionuclide Imaging , Prospective Studies , Exercise Test/methods , Adrenergic beta-1 Receptor Agonists/therapeutic use , Heart Failure/drug therapy , Heart Failure/diagnostic imaging , Iodine RadioisotopesABSTRACT
β Blockers such as propranolol and labetalol are known to induce toxic myopathy because of their partial β₂ adrenoceptor agonistic effect. Nebivolol has the highest β1 receptor affinity among β blockers, and it has never been reported to induce rhabdomyolysis until now. We report a patient who developed rhabdomyolysis after changing medication to nebivolol. A 75-year-old woman was admitted to our hospital because of generalized weakness originating 2 weeks before visiting. Approximately 1 month before her admission, her medication was changed from carvedilol 12.5 mg to nebivolol 5 mg. Over this time span, she had no other lifestyle changes causing rhabdomyolysis. Her blood chemistry and whole body bone scan indicated rhabdomyolysis. We considered newly prescribed nebivolol as a causal agent. She was prescribed carvedilol 12.5 mg, which she was previously taking, instead of nebivolol. She was treated by hydration and urine alkalization. She had fully recovered and was discharged.
Subject(s)
Aged , Female , Humans , Chemistry , Labetalol , Life Style , Muscular Diseases , Nebivolol , Propranolol , RhabdomyolysisABSTRACT
ABSTRACT The objective of this investigation was to develop a novel oral edible gel dosage form for nebivolol hydrochloride, with suitable rheological characteristics that can provide a means of administering the drug to dysphagic and geriatric patients. Edible gels were prepared using low acetylated gellan gum and sodium citrate in different concentrations. The effect of concentration of the solution on gelation time, viscosity, and drug release was studied. Optimized formulation had "spoon thick" consistency that is considered suitable for dysphagic patients as suggested by National Dysphagia Diet Task Force. The optimized formulation containing gellan gum (0.4 % w/v) and sodium citrate (0.3 % w/v) showed more than 95% drug release in 20 minutes. This formulation also showed significantly better pharmacokinetic profile when compared to marketed conventional tablets in New Zealand white rabbits (n = 3). Optimized formulation was found stable for 6 months when stored at 25 °C ± 0.2 °C/60 ± 5% RH. From this study, it can be concluded that the novel edible gel dosage form containing nebivolol hydrochloride may prove to be more efficacious in the treatment of hypertension in dysphagic patients.
RESUMO O objetivo deste trabalho foi desenvolver um gel comestível para veiculação de cloridrato de nebivolol, com características reológicas adequadas, que podem fornecer meio de administrar o fármaco em casos de disfagia orofaríngea e pacientes geriátricos. Géis comestíveis foram preparados utilizando goma gelana de baixa acetilação e citrato de sódio, em diferentes concentrações. Estudou-se o efeito da concentração da solução no tempo de gelificação, a viscosidade e a liberação do fármaco. A formulação otimizada apresentava consistência de pudim, o que é considerado adequado para pacientes disfágicos como sugerido pela National Dysphagia Diet Task Force. A formulação otimizada contendo 0,4% (m/v) de goma gelana e 0,3% (m/v) de citrato de sódio mostrou que mais de 95% de fármaco foi liberado em 20 minutos. Esta formulação também mostrou, significativamente, melhor perfil farmacocinético, quando comparado com os comprimidos convencionais comercializados administrados a coelhos brancos neozelandeses (n = 3). A formulação otimizada manteve-se estável durante 6 meses, armazenada a 25 oC ± 0,2 °C/60 ± 5% de UR. A partir deste estudo, conclui-se que a nova forma de gel comestível contendo cloridrato de nebivolol pode ser mais eficaz no tratamento de hipertensão em pacientes portadores de disfagia.
Subject(s)
Rabbits , Chemistry, Pharmaceutical , Dosage Forms , Nebivolol/analysis , Deglutition Disorders/prevention & controlABSTRACT
Objective: Postoperative atrial fibrillation is a common complication after cardiac surgery, with an incidence as high as 20-50%. Increased age is associated with a significant increase in postoperative atrial fibrillation risk. This common complication is associated with higher morbidity and mortality rates. The aim of this study was to assess the efficacy of nebivolol in preventing atrial fibrillation following coronary artery bypass surgery in patients over 60 years of age. Methods: In this prospective randomized study, 200 patients who were candidates for elective coronary artery bypass surgery were divided into two groups. The first group was administered with nebivolol and the second group was administered with metoprolol. Treatment was initiated four days prior to surgery, and patients were monitored for atrial fibrillation until discharge. Forty-one patients recieved 50 mg metoprolol succinate daily, which was initiated minimum 4 days before surgery. Results: Demographic data were similar in both groups. The incidence of postoperative atrial fibrillation in both groups was similar, with no significant difference being identified [n=20 (20%); n=18 (18%), P=0.718; respectively]. There were not any mortality at both groups during study. Inotropic agent requirement at ICU was similar for both groups [n=12 (12%), n=18 (18%), P=0.32]. Conclusion: We compared the effectiveness of nebivolol and metoprolol in decreasing the incidence of postoperative atrial fibrillation, and determined that nebivolol was as effective as metoprolol in preventing postoperative atrial fibrillation at patients. Nebivolol may be the drug of choice due to its effects, especially after elective coronary artery bypass surgery. .
Objetivo: Pós-operatório fibrilação atrial é uma complicação comum após a cirurgia cardíaca, com uma incidência tão elevada quanto 20-50%. O aumento da idade está associado com elevação significativa no risco de pós-operatório da fibrilação atrial. Esta complicação comum é associada com taxas de morbidade e mortalidade. O objetivo deste estudo foi avaliar a eficácia do nebivolol na prevenção da fibrilação atrial após cirurgia de revascularização do miocárdio de pacientes acima de 60 anos de idade. Métodos: Neste estudo prospectivo e randomizado, duzentos pacientes candidatos à cirurgia de revascularização do miocárdio foram divididos em dois grupos. O primeiro grupo foi administrado com nebivolol e o segundo grupo, com metoprolol. O tratamento foi iniciado quatro dias antes da cirurgia, e os pacientes foram monitorados para fibrilação atrial até a alta. Quarenta e um pacientes receberam 50 mg de sucinato de metoprolol diário, que foi iniciado, no mínimo, 4 dias antes da cirurgia. Resultados: Os dados demográficos foram semelhantes nos dois grupos. A incidência de fibrilação atrial pós-operatória em ambos os grupos foi semelhante, com nenhuma diferença significativa sendo identificado [n=20 (20%); n=18 (18%), P=0,718; respectivamente]. Não houve mortalidade em ambos os grupos durante o estudo. A necessidade de agente inotrópico em UTI foi semelhante nos dois grupos [n=12 pessoas (12%), n=18 (18%), P=0,32]. Conclusão: Nós comparamos a eficácia do nebivolol e metoprolol na diminuição da incidência de fibrilação atrial no pós-operatório, e verificamos que nebivolol foi tão eficaz como metoprolol na prevenção de fibrilação atrial no pós-operatório em pacientes. Nebivolol pode ser a droga de escolha devido aos seus efeitos, especialmente depois da cirurgia revascularização do miocárdio. .
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adrenergic beta-1 Receptor Antagonists/therapeutic use , Atrial Fibrillation/prevention & control , Benzopyrans/therapeutic use , Coronary Artery Bypass/adverse effects , Ethanolamines/therapeutic use , Metoprolol/therapeutic use , Postoperative Complications/prevention & control , Age Factors , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Nebivolol , Postoperative Period , Prospective Studies , Postoperative Complications/drug therapy , Reproducibility of Results , Risk Factors , Statistics, Nonparametric , Treatment OutcomeABSTRACT
Formulation of FDT (fast dispersing tablets) of nebivolol was optimized and evaluated using simplex lattice design (SLD). The influence of type and concentration of three disintegrants viz., Ac-Di-Sol, Primojel and Polyplasdone XL on hardness, friability and disintegration time of tablet was studied. Response surface plot and the polynomial equations were used to evaluate influence of polymer on the tablet properties. Results were statistically analyzed using ANOVA, and a p < 0.05 was considered statistically significant. Results reveal that fibrous integrity and optimal degree of substitution in Primojel and Ac-Di-Sol are mainly responsible for the hardness of the tablet. Use of Polyplasdone in higher percentage in tablet formulation may result in high friability. Increase in concentration of Ac-Di-Sol increases the disintegration time but increased concentration of Primojel in the tablet formulation decreases the disintegration time. This is also evident from model terms for disintegration time with a high 'F' value of 14.69 and 'p' value of 0.0031 (<0.05). The reason could be that Primojel has higher swelling properties and an optimum hydration capacity, which favors fast disintegration of a tablet. In conclusion, careful selection of disintegrant for FDT could improve their properties. Use of Simplex Lattice Design for formulation development could simplify the formulation process and reduce the production cost.
Otimizou-se e avaliou-se formulação de comprimidos de dispersão rápida (CDR) de nebivolol, usando planejamento de grade simplex (PGS). Estudou-se a influência do tipo e da concentração de três desintegrantes viz, Ac-Di-Sol, Primojel e Poliplasdona XL, na dureza, friabilidade e tempo de desintegração do comprimido. O gráfico de superfície de resposta e as equações polinomiais foram utilizados para avaliar a influência do polímero nas propriedades do comprimido. Os resultados foram analisados estatisticamente por ANOVA, considerando-se p < 0,05 como estatisticamente significativo. Os resultados revelam que a integridade das fibras e o grau de substituição ótimo no Primojel e Ac-Di-Sol são os principais responsáveis pela dureza do comprimido. O uso de Poliplasdona em maior porcentagem na formulação pode produzir friabilidade elevada. O aumento de Ac-Di-Sol aumenta o tempo de desintegração, mas o aumento da concentração de Primojel na formulação diminui o tempo de desintegração. Isto é, também, evidente no modelo de tempo de desintegração com alto valor de "F" de 14,69 e "p" de 0,0031 (< 0,05). A razão poderia ser que o Primojel tem maiores propriedades de intumescimento e ótima capacidade de hidratação, favorecendo a desintegração rápida do comprimido. Em conclusão, a cuidadosa seleção de um desintegrante para CDR poderia aprimorar suas propriedades. O uso do PGS para o desenvolvimento da formulação poderia simplificar o processo de formulação e reduzir o custo de produção.
Subject(s)
Tablets/analysis , Nebivolol/analysis , Tablets/chemical synthesis , Hepatocyte Growth FactorABSTRACT
Antecedentes: Descripción de la condición de salud de interés (indicación): La isquemia miocárdica es un problema causado por el estrechamiento de las arterias que irrigan el corazón. Cuando hay obstrucciones en las arterias, se disminuye el flujo de sangre y oxígeno que irriga el músculo cardiaco. En el momento en que \r\naumentan los requerimientos de oxígeno, como con el ejercicio, el corazón no puede satisfacer la demanda del mismo, por lo cual se generan los síntomas. La cardiopatía isquémica es un síndrome que abarca una serie de patologías que incluyen: la angina estable e inestable, síndrome coronario agudo, y la cardiopatía isquémica crónica. Descripción de la tecnología: El nebivolol es un beta bloqueador selectivo ß-1 de los receptores cardíacos, posee acción vasodilatadora, su acción es prolongada. Es empleado en el tratamient o de la hipertensión arterial, angina de pecho, insuficiencia cardíaca congestiva. Evaluación de efectividad y seguridad: Pregunta de evaluación: En adultos mayores de 18 años con isquemia miocárdica, no complicada¿ Cuál es la efectividad y seguridad de nebivolol comparado con metoprolol como tratamiento ambulatorio de primer a línea? La pregunta de investigación fue refinada y validada con base en: autorización de mercadeo de la tecnología para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de las tecnologías en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (código ATC: Anatomical, Therapeutic, \r\nChemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad (reportes de evaluación de tecnologías, revisiones sistemáticas de la literatura), uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, etc), consulta con expertos temáticos (especialistas clínicos), y otros actores clave. No se identificaron otros comparadores relevantes para la evaluación. Población: Adultos mayores de 18 años con \r\nisquemia miocárdica, no complicada. Tecnología de interés: Nebivolol. Metodología: Búsqueda de literatura, Búsqueda en bases de datos electrónicas. Conclusiones: Efectividad: no se identificó evidencia de efectividad que describa el uso de nebivolol comparado con metoprolol para el tratamiento de la isquemia miocárdica. \r\nSeguridad: no se identificó evidencia de seguridad que describa el uso de nebivolol comparado con metoprolol para el tratamiento de la isquemia miocárdica. Costo-efectividad: no se identificaron estudios de costo-efectividad para Colombia.
Subject(s)
Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Outpatients , Myocardial Ischemia/drug therapy , Nebivolol/administration & dosage , Technology Assessment, Biomedical , Treatment Outcome , Myocardial Ischemia , Colombia , Acute Coronary Syndrome , Angina, Stable , Angina, UnstableABSTRACT
The majority of hypertensive patients do not achieve target blood pressure for a variety of reasons, including insufficient medication, drug resistance, and noncompliance. There remains a significant need to develop new agents to better control hypertension. Nebivolol is a third-generation beta-adrenergic receptor blocker which is very highly cardioselective and has direct vasodilator properties via stimulation of endothelial nitric oxide synthase activity. Aliskiren is the first orally active inhibitor of renin as an antihypertensive agent. It is associated with dose-related falls in blood pressure comparable to other major classes of antihypertensive drugs with a placebo level of side effects. Endothelin is a powerful vasoconstrictor peptide. An endothelin-receptor antagonist such as bosentan significantly lowered blood pressure in patients with essential hypertension. Vasopeptidase inhibitors inhibit neutral endopeptidase and angiotensin converting enzymes, but side-effects such as angio-oedema and cough remain to be overcome. AngQb vaccine in hypertensive patients showed a marked reduction in early morning blood pressure without serious adverse events.
Subject(s)
Humans , Amides , Angiotensins , Antihypertensive Agents , Benzopyrans , Blood Pressure , Cough , Drug Resistance , Endothelins , Ethanolamines , Fumarates , Hypertension , Nebivolol , Neprilysin , Nitric Oxide Synthase Type III , Renin , SulfonamidesABSTRACT
<p><b>AIM</b>To investigate the effect of substituting beta-blockers with nebivolol on the erectile function of patients suffering from essential hypertension.</p><p><b>METHODS</b>Forty-four young and middle-aged men (31-65 years) with essential hypertension visited our outpatient clinic and took beta-blocker treatment (atenolol, metoprolol or bisoprolol) for more than 6 months. All the patients completed a questionnaire regarding erectile function (International Index for Erectile Function). Patients were then switched to an equipotent dose of nebivolol for 3 months and, at the end of this time period, filled out the same questionnaire.</p><p><b>RESULTS</b>Twenty-nine out of the 44 (65.9%) patients who took beta-blockers (atenolol, metoprolol or bisoprolol) had exhibited erectile dysfunction (ED). Their systolic and diastolic blood pressure did not change significantly with the treatment switch. In 20 out of these 29 (69%) patients, a significant improvement in the erectile function score was exhibited after 3 months of nebivolol administration, and in 11 of these 20 patients, erectile function was normalized.</p><p><b>CONCLUSION</b>Nebivolol seems to have a beneficial effect on ED (possibly due to increased nitric oxide availability); however, further prospective, randomized, placebo-controlled studies are needed to confirm the beneficial effects of nebivolol.</p>