RESUMO
It is believed that indaziflam gives a longer period of weed control compared to clomazone, irrespective of the type or texture of the soil. Thus, the aim of this study was to evaluate pre-emergent control in five problematic weed species of family Poaceae to sugarcane, using the herbicides indaziflam and clomazone in two soils of different textures. Two experiments were carried out, one in a soil of a sandy-loam texture and the other in a clayey soil. For both experiments, a randomised block design of split plots was chosen, with four replications. The treatments consisted of the herbicides indaziflam (75 and 100 g ai ha-1), clomazone (1080 g ai ha-1) and a control with no herbicide. In the subplots, the treatments were Digitaria horizontalis, Panicum maximum, Rottboellia cochinchinensis, Urochloa decumbens and Urochloa plantaginea. Both herbicides were more effective in the clayey soil, but with indaziflam (100 g ai ha-1), more than 90% control of the weeds remained after 240 days after application (DAA), whereas for clomazone, control remained only up to 90 DAA. The herbicide clomazone did not satisfactorily control the weeds in the sandy-loam soil. The herbicide indaziflam did not control U. decumbens in the sandy-loam soil. D. horizontalis and R. cochinchinensis were the most sensitive species to the herbicide indaziflam, irrespective of soil texture.
Assuntos
Saccharum , Controle de Plantas Daninhas , Poaceae , HerbicidasRESUMO
In the present study, we investigated the cardioactive glycosides oleandrin and ouabain, and compared them to digoxin in a model of cardiotoxicity induced by doxorubicin. Adult rats were distributed into four experimental groups. Each group was challenged with a single intraperitoneal application of doxorubicin at a dose of 12 mg/kg. Then, they were treated with saline solution and the glycosides oleandrin, ouabain, and digoxin at a dose of 50 µg/kg, for 7 days. They underwent echocardiography, electrocardiography, hematologic, biochemical tests, and microscopic evaluation of the heart. All animals presented congestive heart failure, which was verified by a reduction in the ejection fraction. Oleandrin and digoxin were able to significantly reduce (p < 0.05) the eccentric remodeling caused by doxorubicin. Oleandrin and digoxin were significantly lower (p < 0.05) than the control group in maintaining systolic volume and left ventricular volume in diastole. Other parameters evaluated did not show significant statistical differences. All animals showed an increase in erythrocyte count, and an increase in the duration of the QRS complex on the ECG and myocardial necrosis at the histopathological analysis. It is concluded that the glycosides oleandrin, ouabain, and digoxin in the used dosage do not present therapeutic potential for the treatment of congestive heart failure caused by doxorubicin.
Assuntos
Cardenolídeos/farmacologia , Glicosídeos Cardíacos/farmacologia , Cardiotônicos/farmacologia , Digoxina/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Ouabaína/farmacologia , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Cardenolídeos/toxicidade , Glicosídeos Cardíacos/toxicidade , Cardiotônicos/toxicidade , Cardiotoxicidade , Digoxina/toxicidade , Modelos Animais de Doenças , Doxorrubicina , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Ouabaína/toxicidade , Ratos Wistar , Recuperação de Função FisiológicaRESUMO
Digoxin is a cardiotonic glycoside that is traditionally used for the treatment of heart failure and atrial fibrillation in humans and animals. However, the use of digoxin is still a challenge in clinical practice due to its narrow therapeutic range and its potential interaction with several drugs, which could facilitate the development of toxicity. A 12-year-old Labrador retriever was referred with a clinical diagnosis of heart failure and atrial fibrillation, anorexia, vomiting, and diarrhea. He had been medicated with digoxin, furosemide, lisinopril, and amiodarone. The patient also showed clinical signs of hip osteoarthritis and received firocoxib for four days. He additionally received drugs for gastrointeritis. The electrocardiogram demonstrated atrial fibrillation and signs of digitalis toxicity. Laboratory examination showed a high concentration of plasma digoxin, and 5 days after withdrawal of the drugs, the symptoms disappeared, as did the digitalis effects seen in the previous electrocardiogram.(AU)
A digoxina é um glicosídeo cardiotônico tradicionalmente utilizado no tratamento de insuficiência cardíaca e fibri-lação atrial em humanos e animais. Porém, o uso da digoxina continua sendo um desafio na prática clínica devido a sua estreita faixa terapêutica, bem como a sua potencial interação com diversos fármacos, facilitando o desenvolvimento de toxicidade. Um Labrador Retriever de 12 anos de idade foi encaminhado com diagnóstico clinico de insuficiência cardíaca, apresentando fibrilação atrial, anorexia, vômitos e diarreia. Ele vinha sendo medicado com digoxina, furosemida, lisinopril e amiodarona. Ele havia sido concomitantemente medicado com firocoxibe por quatro dias para tratamento de osteoartrite coxo-femoral, além de medicamentos para gastroenterite. O eletrocardiograma demonstrou fibrilação atrial e sinais de toxicidade digitalica. O exame laboratorial revelou alta concentração de digoxina plasmática sendo que, cinco dias após a suspensão dos medica-mentos, o paciente já apresentava melhora clinica acentuada, enquanto os efeitos digitálicos observados no eletrocardiograma anterior desapareceram.(AU)
Assuntos
Animais , Cães , Digoxina/efeitos adversos , Digoxina/uso terapêutico , Fibrilação Atrial/diagnóstico , Eletrocardiografia/veterinária , Insuficiência Cardíaca/diagnósticoRESUMO
Resumen La Digitalis purpúrea ha sido utilizada por sus propiedades terapéuticas desde la antigüedad hasta nuestros días. Su difundido uso, tanto como la diversidad de indicaciones que tuvo, permitió que también se conociese desde antaño los riesgos a la salud para quien recibiese una dosis excesiva. La toxicología actual conoce y maneja perfectamente la intoxicación digitálica, sin embargo, muchas historias relacionadas con su uso son poco conocidas. Se presentan algunas de estas historias, muchas de ellas relacionadas con el mundo del arte.
Abstract Digitalis purpurea has been used because of its therapeutic properties since ancient times up to our days. Its wide- spread use as well as the variety of indications that it covered allowed to know the risks for health in case of overdose. Present toxicology is aware and knows perfectly well how to treat digitalic poisoning. However, many stories about digitalis are little known. Here, we show you some of them, specially the ones related with arts.
Assuntos
Digitalis/efeitos adversos , Digitalis/toxicidade , Medicina nas Artes , Intoxicação por Plantas , Plantas Medicinais/efeitos adversos , Arte , Digitalis/efeitos dos fármacosRESUMO
Los digitálicos son fármacos con capacidad de aumentar la contractilidad miocárdica (inotrópico positivo), que han desempeñado un rol primordial en el tratamiento de pacientes con insuficiencia cardiaca; su uso inapropiado puede traer complicaciones serias a estos pacientes, incluso, hasta la muerte. La más importante de estas complicaciones es la intoxicación digitálica, originada por la sobredosis de dichos fármacos, a causa de la combinación del efecto inhibitorio en la conducción nodal y la estimulación sobre las fibras individuales auriculares y ventriculares. Debido al uso frecuente de estos medicamentos en todos los niveles de atención de salud y lo difícil que resulta diagnosticar dicha complicación por la complejidad de su cuadro clínico y de su expresión electrocardiográfica, se realizó una revisión bibliográfica exhaustiva sobre el tema para brindar amplia información, que permita una atención adecuada a los pacientes con este diagnóstico
Digitalis are drugs with the capacity of increasing myocardial contractility (inotropic positive agents) which have carried out an important role in the treatment of heart failure; their inappropriate use can bring severe complications to the patient, even, to death. The most important in these complications is the digitalis toxicity, originated by the overdose of these drugs, caused by the combination of the inhibitory effect in the nodal conduction and stimulation on the individual atrial and ventricular fibers. Due to the frequent use of these medications at all levels of medical care and to the difficulty in diagnosing this complication caused by the complexity of their clinical pattern and of their electrocardiographic expression, an exhaustive literature review was carried out on the topic to give a wide information that allows an appropriate care to the patients with this diagnosis
Assuntos
Humanos , Masculino , Feminino , Glicosídeos Digitálicos/intoxicação , Glicosídeos Digitálicos/farmacologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Contração Miocárdica/efeitos dos fármacos , Intoxicação , Overdose de Drogas/metabolismoRESUMO
Resumen: Las redes neuronales artificiales (RNA) son un método computacional extensamente utilizado para resolver problemas complejos y realizar predicciones en sistemas de relación no lineal. En este trabajo se utilizaron RNA para predecir la respuesta fisiológica obtenida al adicionar una concentración específica de digoxina a corazones de Tivela stultorum, un organismo modelo para probar fármacos cardíacos que se pretenden utilizar en humanos. Las entradas de la RNA fueron el peso, volumen, largo y ancho del corazón, la concentración de digoxina, el volumen utilizado para la dilución de digoxina, el máximo y mínimo de contracción, tiempo de llenado, y frecuencia cardíaca antes de adicionar la digoxina, las salidas fueron el máximo y mínimo de contracción, tiempo de llenado y frecuencia cardíaca esperados después de agregar digoxina al corazón. Las RNA se entrenaron, validaron y probaron con los resultados de experimentos in vivo. Para elegir la red óptima se utilizó el valor más pequeño del error medio cuadrado. Se obtuvo una correlación alta entre los valores predichos y calculados, excepto en el caso del tiempo de llenado. Se lograron obtener predicciones acertadas de la cardioactividad de la almeja T. stultorum cuando se les agrega una concentración específica de digoxina haciendo uso de RNA; esto con el fin de utilizarse como una herramienta para facilitar las pruebas en el laboratorio de los efectos de la digoxina.
Abstract: Artificial neural networks (ANN) are a computational method that has been widely used to solve complex problems and carry out predictions on nonlinear systems. Multilayer perceptron artificial neural networks were used to predict the physiological response that would be obtained by adding a specific concentration of digoxin to Tivela stultorum hearts, this organism is a model for testing cardiac drugs that pretends to be used in humans. The MLP-ANN inputs were weight, volume, length, and width of the heart, digoxin concentration and volume used for diluting digoxin, and maximum contraction, minimum contraction, filling time, and heart rate before adding digoxin, and the outputs were the maximum contraction, minimum contraction, filling time, and heart rate that would be obtained after adding digoxin to the heart. ANNs were trained, validated, and tested with the results obtained from the in vivo experiments. To choose the optimal network, the smallest square mean error value was used. Perceptrons obtained a high performance and correlation between predicted and calculated values, except in the case of the filling time output. Accurate predictions of the T. stultorum clams cardioactivity were obtained when a specific concentration of digoxin was added using ANNs with one hidden layer; this could be useful as a tool to facilitate laboratory experiments to test digoxin effects.
RESUMO
Si bien las hojas de digital purpúrea (Digitalis purpurea) se empleaban desde el año 500 D.C., fue el Dr. WilliamWhitering, de Inglaterra, quien investigó sus propiedades y en 1785 escribió un libro que ingresó entre los clásicos de la historia de la medicina: An account of the foxglove and some of its medical uses, with practical remarks on dropsy and other diseases. Esta revisión repasa la historia de la digital, su mecanismo de acción, y los trabajos más recientes que revaloran los efectos de esta medicación, recomendada actualmente a menores dosis de digoxina que las clásicamente aceptadas, capaz de reducir las hospitalizaciones y mejorar la sobrevida, en especial en pacientes con grados avanzados de insuficiencia cardíaca y medicados con inhibidores de la enzima convertidora de angiotensina, beta-bloqueantes, antagonistas de la aldosterona y diuréticos. Quizás aún falta precisar su valor definitivo, pero es indudable que la digital marcó una etapa definitiva en los dominios de la Cardiología y que, junto a la amapola, la quina y la belladona, constituye el grupo de las cuatro principales plantas que han llevado alivio a las enfermedades del hombre(AU)
Although the leaves of Digitalis purpurea had been used since 500 D.C., it was the English physician William Withering who studied its properties. In 1785 he wrote the book called ôAn account of the foxglove and some of its medical uses: with practical remarks on dropsy and other diseasesö which became one of the classics in the history of medicine. This article reviews the history of digitalis, its mechanism of action, and recent studies which underline the importance of this medication. Digitalis is presently prescribed at lower doses than tradionally indicated; it is effective in reducing hospital stays, and improving survival, especially in patients with advanced stages of heart failure and receiving inhibitors of the angiotensin converting enzyme, beta-blockers, aldosterone antagonists, and diuretics.Even though its definitive value is yet to be determined, it is certain that digitalis has a role to play in the domains ofCardiology and belongs to the group of the four principal plants that have brought relief to human diseases, along with the poppy, Peruvian bark, and belladona (AU)
Assuntos
Humanos , Digitalis/farmacologia , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/terapia , História da Medicina , Plantas Medicinais/efeitos dos fármacos , Farmacologia/história , Cardiologia/história , Literatura de Revisão como AssuntoRESUMO
Si bien las hojas de digital purpúrea (Digitalis purpurea) se empleaban desde el año 500 D.C., fue el Dr. WilliamWhitering, de Inglaterra, quien investigó sus propiedades y en 1785 escribió un libro que ingresó entre los clásicos de la historia de la medicina: An account of the foxglove and some of its medical uses, with practical remarks on dropsy and other diseases. Esta revisión repasa la historia de la digital, su mecanismo de acción, y los trabajos más recientes que revaloran los efectos de esta medicación, recomendada actualmente a menores dosis de digoxina que las clásicamente aceptadas, capaz de reducir las hospitalizaciones y mejorar la sobrevida, en especial en pacientes con grados avanzados de insuficiencia cardíaca y medicados con inhibidores de la enzima convertidora de angiotensina, beta-bloqueantes, antagonistas de la aldosterona y diuréticos. Quizás aún falta precisar su valor definitivo, pero es indudable que la digital marcó una etapa definitiva en los dominios de la Cardiología y que, junto a la amapola, la quina y la belladona, constituye el grupo de las cuatro principales plantas que han llevado alivio a las enfermedades del hombre
Although the leaves of Digitalis purpurea had been used since 500 D.C., it was the English physician William Withering who studied its properties. In 1785 he wrote the book called An account of the foxglove and some of its medical uses: with practical remarks on dropsy and other diseases which became one of the classics in the history of medicine. This article reviews the history of digitalis, its mechanism of action, and recent studies which underline the importance of this medication. Digitalis is presently prescribed at lower doses than tradionally indicated; it is effective in reducing hospital stays, and improving survival, especially in patients with advanced stages of heart failure and receiving inhibitors of the angiotensin converting enzyme, beta-blockers, aldosterone antagonists, and diuretics.Even though its definitive value is yet to be determined, it is certain that digitalis has a role to play in the domains ofCardiology and belongs to the group of the four principal plants that have brought relief to human diseases, along with the poppy, Peruvian bark, and belladona
Assuntos
Humanos , Digitalis/farmacologia , História da Medicina , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/terapia , Cardiologia/história , Farmacologia/história , Literatura de Revisão como Assunto , Plantas MedicinaisRESUMO
El dolor torácico es un motivo de consulta muy frecuente tanto en servicios de urgencias como en consulta externa, se estima que aproximadamente el 20% de las consultas de adultos no quirúrgicas en un servicio general de urgencias, corresponde a dolor torácico. La mayoría de ellos (85 a 90%) no se deben a síndrome coronario agudo (o infarto agudo de miocardio) o a otra potencialmente mortal. No encontramos informada en la literatura médica, una propuesta para el manejo de estos pacientes con homeopatía. Se revisó en medicinas internas y semiologías las diversas formas de presentación de dolor torácico, acorde con varios orígenes: Coronario, Gastroesofágico, Costocondral (Reumático) o Pleural. Seguidamente, se investigó en un repertorio digital (Radar 7) los medicamentos que mejor puntuaban según los síntomas más frecuentes, pretendiendo abarcar la totalidad sintomática del paciente. Se hizo una revisión y resumen de varias materias médicas de 20 medicamentos mejor puntuados y finalmente se elaboró un algoritmo con dos de los síntomas más característicos en las diversas modalidades de dolor torácico. Los medicamentos analizados fueron: Acónitum, Argentum Nitricum, Arsénicum Album, Árnica, Aurum Metálicum, Bryonia, Cactus Grandiflorus, Calcárea Carbónica, Carbo Vegetábilis, Causticum, Digitalis, Kali Carbónicum, Nux Vómica, Phosphorus, Spongia Tosta y Sulphur. A modo de ejemplo, en el dolor torácico de tipo opresivo o anginoso acompañado de angustia y temor a la muerte, los medicamentos más puntuados son: Acon, Dig, Arn y Cact.
Assuntos
Humanos , Dor no Peito , Medicamento Homeopático , Sintomas Repertoriais , Colômbia , Literatura de Revisão como AssuntoRESUMO
Aim: To evaluate the reliability of linear measurements in virtual models by comparing measurements performed on virtual models obtained from alginate impression scans, plaster model and measurements performed on conventional plaster model. Methods: The sample comprised 26 randomly selected patients to have impressions of their upper and lower jaws taken using alginate and their bite registration using a wax bite. The virtual models were obtained by scanning the alginate impression and the plaster model in a laser surface scanner (R700; 3Shape, Copenhagen, Denmark), and the measurements were performed using the Ortho Analyser (3Shape) proprietary software. The linear measurements of the size of the teeth mesial to distal, arch perimeter, intercanine distance and intermolar distance in the upper and lower arches were performed on plaster models, digital impressions and digital models, by three observers and repeated after 15 days on 8 models for intra-observer evaluations. Data were tabulated and analyzed statistically. Intra-class correlation to check the agreement of intra and inter-observers and ANOVA test were used to analyze the differences between measurements of digital models from impression and digital models from plaster. Results: The results showed a statistically significant difference (pd"0.05) for the posterior teeth, anterior teeth, upper arch perimeter and lower inter-canine distance, comparing the digital models with plaster models, but these differences are considered clinically non-significant. Conclusions: Digital models were proven be reliable and clinically acceptable for measuring tooth width, perimeter arches, intercanine and intermolar distances.
Assuntos
Ortodontia , Modelos Dentários , Diagnóstico , DigitalisRESUMO
OBJETIVO: o objetivo deste estudo é apresentar as etapas do processo de confecção da cápsula do aparelho de amplificação sonora individual intra-aural por meio da digitalização. MÉTODO: foram utilizadas otoplásticas e os equipamentos Legato para realizar o escaneamento e Envisiontec para sinterização, ambos disponibilizados pela empresa Phonak. RESULTADOS: os resultados sinalizam para cápsula de aparelho de amplificação sonora individual intra-aurais, plenamente satisfatórias, sendo constatada todas as vantagens documentadas pelo fabricante. CONCLUSÃO: a nova técnica de confecção de cápsula por meio de processo de digitalização demonstrou ser eficaz com alta qualidade e mantendo a impressão fiel da orelha, além de durabilidade significativa.
PURPOSE: the objective of this study is to present the steps involved in making the capsule of intra-aural hearing aids through scanning. METHOD: we used the Legato otoplasty equipment in order to perform scanning and Enisiontec for sintering, both provided by the company Phonak. RESULTS: the results point out to capsule-ear hearing aid, as being fully satisfying and with all the benefits documented by the manufacturer. CONCLUSION: a new technique in order to make the capsule through the scanning process has been proven effective and with high quality and keeping the faithful imprint of the ear, in addition to significant durability.
RESUMO
Infantile digital fibromatosis or Reye's tumor is a benign fibroproliferative tumor, the etiopathogenesis of which has yet to be fully clarified. It typically presents at birth or in the first year of life and is characterized by a firm, flesh colored or erythematous nodule or nodules located on the digits. These lesions tend to regress spontaneously.
A fibromatose digital infantil ou tumor de Reye é um tumor fibroso benigno de etiologia desconhecida, presente ao nascimento ou com aparecimento no primeiro ano de vida. Caracteriza-se por nódulos firmes, únicos ou múltiplos, normocrômicos ou eritematosos, localizados nas falanges, com tendência à regressão espontânea.
Assuntos
Humanos , Lactente , Masculino , Fibroma/patologia , Dedos do Pé/patologia , Imuno-HistoquímicaRESUMO
Introdução: O objetivo deste estudo é avaliar as propriedades do escoamento e radiopacidade de dois cimentos endodônticos, Endofill e EZ-Fill de acordo com a especificação número 57 da ADA. Método: Para análise do escoamento foram feitas 20 amostras divididas em GRUPO 1 (Endofill) e GRUPO 2 (EZ-Fill). Para tal 0,5 ml do cimento era depositado no centro de uma placa de vidro de 10 X 10 cm. Decorridos 3 minutos, outra placa de vidro e um peso de chumbo, totalizando 120 g, foram colocados sobre o material. Após 10 min o peso foi removido e a média do diâmetro maior e menor dos discos obtidos foi determinada por um paquímetro. Para a análise da radiopacidade 10 anéis metálicos foram utilizados: 5 do Grupo 3 (EZ-Fill) e 5 do Grupo 4 (Endofill) foram preenchidos com os cimentos. Os corpos de prova foram radiografados com uma escala de alumínio com 10 degraus uniformes. Para a obtenção das radiografias foi utilizado um aparelho de raio X Dabi Atlante a uma distância foco objeto de 400 mm e tempo de exposição 0,1 seg. As radiografias foram digitalizadas, armazenadas em um microcomputador e analisadas através de um software específico. Os dados foram submetidos ao teste t de Student a 5% apresentando diferença significante (p<0,0001). Resultados: Os resultados encontrados demonstraram escoamento superior a 25 mm em ambos os cimentos dos grupos 1 e 2 e radiopacidade superior a 3 mm de alumínio dos grupos 3 e 4, cumprindo-se a especificação número 57 da ADA. Conclusão: O cimento Endofill apresentou escoamento superior, enquanto o cimento EZ-Fill apresentou maior radiopacidade
Introduction: The purpose of this study is to evaluate the flow properties and radiopacity of two root canal sealers filling, the Endofill (Grossman of cement) and EZ-Fill according to ADA specification number 57 for filling materials). Methods: 20 samples were divided into two groups: Group 1 (Endofill), Group 2 (EZ-Fill).Each group was composed of 10 samples. For the analysis of flow 0.5 ml of material was loaded into a disposable syringe and deposited in the center of a placar glass 10 cm X 10 cm. 180 seconds after the start of operation, another plate of glass and a weight of lead were placed over the material, totaling 120 g. 10 minutes after the beginning of the mixture the weight was removed and the average diameter of the largest and smallest of the disc obtained was determined by a caliper. For the analysis of radiopacity, 10 metal rings, 5 of Group 3 (EZ-Fill) and 5 of Group 4 (Endofill) containing holes of 2 mm in height and 10 mm in diameter were filled with cement. The samples were radiographed together with a ranger of 99% aluminum (alloy 1100) with 10 uniform steps (1 mm to 10 mm thick). To obtain the radiographs an X-ray apparatus Dabi Atlante (70 kvp, 8 mA) was used to a focus object distance of 400 mm and exposure time 0.1 seconds. The radiographs were digitized using a Kodak scanner ? LS 85 Film Digitizer, USA, stored in a microcomputer and analyzed by a specific software for reading images (Image J). The data were submitted to the Student t test at 5% showing a significant difference (p < 0.0001). Results: The results obtained were: flow higher than 25 mm in both cements of Group 1 (Endofill 54.69 mm) and Group 2 (EZ-Fill 42.41 mm) and radiopacity of Group 3 (EZ-Fill) equivalent to 10 mm of aluminum and Group 4 (Endofill) equivalent to 7 mm aluminum. It was concluded that the cement Endofill showed a higher flow than the cement EZ-Fill and the EZ-Fill cement presented a higher radiopacity of the cement Endofill
Assuntos
Escoamento Superficial , Cimentos Dentários , Digitalis , Raios X , Intensificação de Imagem RadiográficaRESUMO
Digitalis, particularly digoxin, have played an important role in the treatment of heart failure (HF) for over 200 years. In the past three decades, with the greatest knowledge of the pathophysiology of the disease, neurohumoral blockers were more effective in reducing morbidity and mortality and gained greater prominence. In addition, studies have suggested that digoxin does not reduce the risk of death and, in some cases, may even increase it. Thus, its use has been questioned and discouraged. This review aims to look at the pharmacology of digoxin, studies on its benefits and risks in patients with moderate to severe systolic HF and diastolic HF also. This review looks forward to answering the following question: Is there still room for the use of digitalis in HF?.
Los digitálicos, y digoxina en particular, han jugado un papel importante en el tratamiento de la insuficiencia cardíaca (IC) por más de 200 años. En las últimas tres décadas, con un mayor conocimiento de la fisiopatología de la enfermedad, los bloqueadores neurohumorales se mostraron más eficaces en la reducción de la morbi-mortalidad y ganaron mayor prominencia. Además, los estudios han sugerido que digoxina no reduce el riesgo de muerte y, en algunos casos, puede incluso aumentarlo. De esta manera, su uso ha sido muy cuestionado y desalentado. Esta revisión trata de contemplar la farmacología de digoxina, los estudios sobre sus beneficios y los riesgos en pacientes con IC sistólica moderada a severa y también en la IC diastólica. Se busca con esta revisión, contestar la siguiente pregunta: ¿existe todavía espacio para el uso del digitálicos en la IC?.
Os digitais, e a digoxina em especial, têm desempenhado papel importante no tratamento da Insuficiência Cardíaca (IC) há mais de 200 anos. Nas últimas três décadas, com o maior conhecimento da fisiopatologia da doença, os bloqueadores neuro-humorais mostraram-se mais eficazes em reduzir a morbi-mortalidade e ganharam maior destaque. Além disso, estudos sugeriram que a digoxina não reduz o risco de morrer e, em algumas situações, pode, inclusive, aumentá-lo. Desta forma, seu uso chegou a ser bastante questionado e desestimulado. Esta revisão procura contemplar a farmacologia da digoxina, os estudos sobre seus benefícios e riscos em pacientes com IC sistólica moderada a grave e também na IC diastólica. Procuramos, com esta revisão, responder à seguinte questão: ainda existe espaço para o uso de digitais na IC?.
RESUMO
Pese a su reducido margen de seguridad, los digitálicos siguen utilizándose en el tratamiento de la insuficiencia cardiaca congestiva y la fibrilación auricular crónica. Con el descubrimiento de su estructura, se han realizado remodelaciones para disminuir su toxicidad. Investigaciones recientes reportan que la eficacia digitálica radica en la electronegatividad del anillo "D" esteroideo, generada por la lactona e hidroxilo que poseen estos compuestos. En el presente trabajo, damos cuenta de la importancia que tiene esta propiedad molecular, que aunada a la conformación estructural, dan lugar a cambios significativos en las propiedades farmacológicas como el inotropismo y el margen de seguridad. Así, evaluamos una serie de once compuestos derivados de digitoxigenina, con grupos que sustituyen sobre el anillo "D" al hidroxilo y/o la lactona, los cuales denominamos -OH, -Lac, D-01, D-02, D-03, D-07, D-14, D-15, D-20, D-21 y D-22. La electronegatividad y la energía conformacional de cada compuesto se determinaron por el método Duhamm. El estudio farmacológico se realizó en corazones aislados de cobayo con base en el modelo de Langendorff y, en corazón de perro conforme al modelo cardiopulmonar de Starling. Los resultados permiten observar que la modulación de la acción digitálica está centrada, estructuralmente, en los sustituyentes de la fracción "D". El efecto inotrópico positivo y el margen de seguridad, medido como el cociente de la dosis tóxica sobre la dosis inotrópica, están relacionados con el aumento de electronegatividad y con una disminución de las energías rotacional y translacional que definen la conformación molecular; en consecuencia, estas propiedades son imprescindibles en la eficacia digitálica.
In spite their reduced therapeutic index, digitalis-type drugs continue being used for treating diseases such as congestive heart failure and chronic atrial fibrillation. Thanks to the development of several methods, their structural determination has been feasible, so, structural modifications have been worked out to modulate their toxicity. Several reports realizes that efficacy for these digitalis-type drugs lies on the electronegativity centered on the steroidal moiety (D-ring) generated by either lactone and hydroxyl sub-stituents attached to the steroidal moiety. In this work, we report how electronegativity, and so structural conformation, does modify their pharmacological properties, e.g., inotropism and safety margin. Thus, we evaluated a series of eleven drugs derived from digitoxigenin, named -OH, -Lac, D-01, D-02, D-03, D-07, D-14, D-15, D-20, D-21 and D-22, with groups that substitute both lactone and hydroxyl groups on the steroidal D-ring. Electronegativity and conformational energy were determined by Duhamm's method. The pharmacological evaluation for these drugs was accomplished in guinea pigs isolated hearts (according to the model proposed by Langendorff) and dog's isolated heart (as established by Starling's in vivo model). The results may suggest that digitalis-like action lies on the substituents attached to the D-ring. Positive inotropic effect and therapeutic index are related with increases in electronegativity as well with decreases in rotational and traslational energies; therefore, these molecular properties have such importance for the digitalis efficacy. (Arch Cardiol Mex 2003; 73:11-17).
Assuntos
Animais , Cobaias , Masculino , Cardiotônicos/farmacologia , Glicosídeos Digitálicos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Estimulação QuímicaRESUMO
Objetivo - Estudar a funçäo ventricular esquerda pela ecocardiografia modo M de pacientes sintomáticos com prolapso da válvula mitral (PVM) primário, sem insuficiência mitral significante, durante a prova da fenilefrina, antes e após a digitalizaçäo. Métodos - Foram estudados 31 pacientes com PVM e 10 indivíduos normais como grupo de controle. Pela ecocardiografia modo M foram medidos: percentagem do encurtamento sistólico (DD), fraçäo de ejeçäo (FE) e velocidade média de encurtamento circunferencial e velocidade média de encurtamento circunferencial das fibras (Vcf). Os traçados ecocardiográficos foram realizados em repouso e durante a infusäo lenta de fenilefrina (40-60 ug/min) a fim de permitir aumentos da pressäo arterial sistólica de 20 a 30 mmHg. Resultados - Em repouso, o tamanho e a funçäo cardíaca foram normais em ambos os grupos, porém durante a infusäo de fenilefrina, 27 pacientes apresentaram diminuiçöes na DD (de 37.7 ñ 4,6 para 31, 0 ñ 4,0, p < 0,001, na FE (de 0,76 ñ 0,05 para 0,66 ñ 0,6, p 0,001 e no Vef (de 1,05 ñ 0,77 para 0,76 ñ 0,13 cir/s, p < 0,001). Desse grupo, 20 pacientes após a digitalizaçäo, durante o teste de fenilefrina, näo apresentaram alteraçöes na DD (de 38,3 ñ 5,0 para 39,2 ñ 3,8 NS); FE (de 0,77 ñ 0,06 para 0,77 ñ 0,004, NS) e no Vef (de 1,05 ñ 0,19 para 0,94 ñ 0,13, cir/s, NS). Esses pacientes, digitalizados, durante o teste ergométrico submáximo apresentaram aumentos significantes do trabalho total (de 617 ñ 248 para 982 ñ 244 watts, p < 0,001) e da eficiência cardíaca (de 25,0 ñ 11,5 para 37,2 ñ 10,4, p 0,001). Por outro lado, a infusäo de fenilefrina no grupo controle, näo provocou alteraçöes na DD, FE e VcF. Conclusäo - Pacientes sintomáticos com PVM primário, sem insuficiência mitral significativa, apresentam durante a prova de fenilefrina uma total recuperaçäo da disfunçäo ventricular esquerda, quando digitados, com melhora significativa do trabalho total e da eficiência cardíaca no teste de esforço
Purpose - To study the left ventricular function by M-mode echocardiography in symptomatic patients with primary mitral valve prolapse (MVP), without significant mitral regurgitation, during the phenylephrine test, before and after digitalization. Methods - Thirty one patients with MVP and 10 normal subjects as a control group were studied by M mode echocardiography: Percentage of systolic shortening ( DD), ejection fraction (EF) and mean velocity of circunferential fibers shortening (Vcf) were measured. The echocardiographic recordings were obtained at rest and during the continuous infusion of phenylephrine (40-60 ug/min) in order to allow an increase of 20-30 mmHg in systalic pressure. Results - At rest, cardiac size and function were normal in both groups. During phenylephrine infusion in 27 patients a decrease in DD (from 37.7 ±4.6 to 31.0 ± 4.0, p<0.001); in EF (from 0.76 ± 0.05 to 0.66 ± 0.6, p<0.001); in Vcf (from 1.05 ± 0.77 to 0.76 ± 0.13, p<0.001) were observed. From this group 20 patients received digoxin. After the digitalization the phenylephrine test did not cause changes in DD (from 38.3 ± 5.0 to 39.2 ± 3.8, NS); in EF (from 0.77 ± 0.06 to 0.77 ± 0.04, NS); in Vcf (from 1.05 ± 0.19 to 0.94 ± 0.13,NS). These patients during the submaximal exercise test, showed significant increases at the total work load (from 617 ± 248 to 982 ± 244 watts, p<0.001) and cardic efficiency (from 25.0 ± 11.5 to 37.2 ± 10.4, p<0.001). On the other hand the phenylephrine infusion in the control group did not result in changes in DD, EF and Vcf. Conclusion - Symptomatic patients with primary MVP showed total recovering of left ventricular dysfunction with digitalization during the phenylephrine test, with improvement of cardiac efficiency