Flutter atrial fetal ? relato de caso e discussão terapêutica / Fetal atrial flutter ? case report and therapeutic discussion

A taquicardia fetal ocorre em 0,4-0,6% de todas as gestações. Das taquiarritmias fetais sustentadas, o flutter atrial é a segunda mais comum. Quando não tratada corretamente, causa insuficiência cardíaca fetal e pode ser necessária a interrupção precoce da gestação. O diagnóstico das taquiarritmias é feito, principalmente, pela ecocardiografiaintraútero. O tratamento de primeira escolha é a administração oral materna de digoxina. Caso não haja resposta adequada ou o feto evolua com hidropisia, é necessário associar outro antiarrítmico como sotalol ou amiodarona. Neste relato, iniciou-se com digoxina; e, em função da ausência de resposta, foi associada propafenona. Sotalol ou amiodarona não foram usados devido à bradicardia e à hipotensão materna.

Fetal tachycardia occurs in 0.4 - 0.6% of all pregnancies. Out of the sustained fetal tachyarrhythmias, the atrial flutter is the second most common. It causes fetal heart failure when not properly treated, and early pregnancy interruption may be required. The diagnosis of tachyarrhythmias is mainly achieved by intra-uterus echocardiography. The first choice treatment is the maternal oral administration of digoxin. The association with other antiarrhythmics such as sotalol or amiodarone is needed if there is no response to digoxin or if the fetus evolves with dropsy. In this case report, the treatment began with digoxin and because there was no response, it was associated with propafenone. Sotalol or amiodarone were not used due to maternal bradycardia and hypotension.

Determinación del margen terapéutico y estudio de la equivalencia biofarmacéutica de las tabletas multifuentes de digoxina de 0.25 mg / Determination of therapeutic range and study of biopharmaceutical equivalence of two multisource Digoxin tablets of 0.25 mg

Determinar teóricamente el margen terapéutico y experimentalmente, los parámetros de la equivalencia biofarmacéutica de dos lotes de tabletas de multifuentes de digoxina de 0,25 mg. Material y Métodos: Se estudiaron dos lotes, cada una de 200 tabletas de multifuentes de digoxina de 0,25 mg, asignándoles el código de multifuente TDH025lote 105031 y TDF025 lote 10940431. El margen terapéutico teórico se determinó mediante la fórmula farmacocinética VT = Fracción α/ Fracción α predicha x concentración usual; luego, por diferencia de la CmE y CME se obtuvo el margen terapéutico. El Método analítico utilizado para la cuantificación del principio activo, fue el descrito en la Farmacopea Internacional de la Organización Mundial de la Salud (OMS); la prueba de desgaste por rozamiento y el grado de dureza, se determinó de acuerdo a la USP. Resultados: el margen terapéutico fue 1,2 ng/ml; los parámetros de la equivalencia biofarmacéutica: porcentajes de principio activo de los dos lotes de medicamentos multifuentes se encontraron dentro del rango de aceptación (90-110%) propuestos por la USP y la OMS: El desgaste por rozamiento del TDH025 presentó un 0,55% y el TDF025 tuvo un 0,56%, ambos valores estuvieron por debajo del 1% (valor aceptable) y la dureza indicó un soporte de choque mecánico aceptable. Las 06 tabletas se desintegraron completamente, al pasar por un tamiz Nº 10 (1700 μM), en un medio de disolución simulado de pH gástrico e intestinal en un tiempo menor de 5 minutos. Conclusión: Se demostró la equivalencia biofarmacéutica de los medicamentos multifuentes de digoxina de 0,25 mg TDH025 lote 105031 y del TDF025 lote 10940431, de acuerdo al criterio de aceptación de la USP y OMS, el principio activo (digoxina) cuantificado en cada lote estuvo dentro del rango de 90-110%; los parámetros de desgaste por rozamiento y la dureza, indicaron una adecuada estabilidad en su tiempo de vida útil...

To determine the therapeutic safety theoretically and experimentally, the biopharmaceutical equivalence parameters of two batches of multisource Digoxin tablets of 0.25mg. Material and Methods: Two batches, each of 200 tablets multisource digoxin 0.25 mg were studied, assigning code multisource TDH025 Lot 105031 and TDF025 Lot 10940431. The therapeutic range was determined by theoretical formula VT = αFraction pharmacokinetics / αpredicted fraction by usual concentration x, then by the difference CmE and CME, the therapeutic range was obtained. The analytical method used for quantification of the active ingredient, was described in The International Pharmacopoeia of the World Health Organization (WHO); while the fretting test and the hardness was determined according to the USP. Results: The therapeutic index is 1.2 ng/ml; and evaluation of the parameters of the biopharmaceutical equivalence percentages of active ingredient of the two lots of multisource drugs are within the acceptance range (90-110%) given in the USP and WHO. The fretting of TDH025 fretting batch 105031 was 0.55% and TDF025 was 0.56%, both values are below 1% which is acceptable value; and hardness indicates an acceptable mechanical shock endurance. The 06 tablets were completely disintegrated, passing through a No. 10 (1700 uM) sieve, in a dissolution medium simulating gastric and intestinal pH in less than 5 min. Conclusion: Biopharmaceutical equivalence of multisource drugs digoxin 0.25 mg TDH025 TDF025 batch batch 105031 and 10940431 was demonstrated according to the acceptance criteria of the WHO and USP, the active ingredient (digoxin) quantified in each batch were within the range of 90-110%; attrition and hardness parameters indicate adequate stability in their lifetime...

Estimulación de cardenólidos en brotes de Digitalis purpurea L. cultivados in vitro mediante elicitores / Stimulation of cardenolides production in Digitalis purpurea L. shoot cultures by elicitors addition

Digitalis purpurea L. es una de las principales fuentes de cardenólidos tales como digoxina y digitoxina. Estos fármacos son ampliamente usados en la disfunción cardíaca y para regular las arritmias del corazón. El presente trabajo se realizó con el objetivo de estudiar el efecto de tres elicitores en el cultivo de brotes de Digitalis purpurea var. Roter Berggold para incrementar la producción in vitro de cardenólidos. La elicitación es una estrategia para incrementar la producción de biomasa y metabolitos secundarios en el cultivo in vitro. Los elicitores evaluados fueron ChitoPlant (0,001; 0,01; 0,1 g.L-1); SilioPlant (0,01; 0,1; 1,0 g.L-1) y Jasmonato de metilo (60, 80 y 100 µM), descritos por primera vez para el incremento de cardenólidos. Se demostró que la elicitación es una estrategia viable para el incremento de cardenólidos en brotes de D. purpurea. El ChitoPlant®, redujo la altura sin afectación en el resto de las variables morfológicas evaluadas. Además indujo un incremento significativo en el contenido de cardenólidos. El SilioPlant® (0,01 g.L-1) no provocó afectaciones en la biomasa e incrementó significativamente la síntesis de cardenólidos en los brotes en 3,6 y 6,9 veces el contenido de digoxina y digitoxina respectivamente. La elicitación con el jasmonato de metilo provocó una reducción de la biomasa. Los contenidos de digoxina y digitoxina se incrementaron ligera y significativamente con 80 y 100 µM de jasmonato de metilo respectivamente. El mejor resultado integral se obtuvo con 0,01 g.L-1 de SilioPlant, el cual indujo la mayor producción neta de cardenólidos por frasco de cultivo (4,72 µg digoxina y 88,27 µg digitoxina).

Digitalis purpurea L. is one of the main sources of cardenolides such as digitoxin and digoxin. These drugs are widely used to strengthen cardiac diffusion and to regulate heart rhythm. The aim of this study was to evaluate the influence of three elicitors on shoots of Digitalis purpurea var. Roter Berggold in semisolid media in order to increase cardenolides biosynthesis. Elicitation is a strategy to increase biomass and secondary metabolites production on in vitro cultures. The elicitors evaluated were ChitoPlant (0,001; 0,01; 0,1 g.L-1); SilioPlant (0,01; 0,1; 1,0 g.L-1) and Methyl jasmonate (60, 80, 100 µM), which are reported here to induce cardenolide production for first time. Elicitation resulted an effective strategy to increase cardenolide production on D. purpurea shoot cultures. ChitoPlant induced a decrease in shoots length, but had no effect on the rest of morphological parameters evaluated. As well, ChitoPlant increased cardenolide content. SilioPlant (0,01 g.L-1) did not affect biomass production and at the same time, increased in 3,6-fold and 6,9-fold digoxin and digitoxin content respectively. Elicitation with Methyl jasmonate resulted in decreased biomass production. Digoxin and digitoxin content was slight and significantly increased by Methyl jasmonate 80 and 100 µM respectively. The best integral result was reached with 0,01 g.L-1 of SilioPlant, which induced the highest net yields per culture flask (4,72 µg of digoxin and 88,27 µg of digitoxin).

Manejo terapeútico de algunas arritmias fetales / Therapeutic management of some fetal arrhythmias

Introducción: la electrocardiografía fetal constituye la prueba de oro para el diagnóstico de las arritmias en la vida posnatal, algo difícil de lograr en la vida prenatal incluso con la ecografía prenatal de alta resolución. Las taquiarritmias supraventriculares son las que se manifiestan con frecuencias cardíacas superiores a 180 latidos por min y pueden asociarse a mortalidad fetal en un tercio de los casos, sobre todo cuando se asocia a hidropesía fetal o cuando se establece por más de 15 días. El tratamiento permite la reversión de la arritmia o el control ventricular en el menor tiempo posible. Objetivos: comprobar la respuesta intraútero de la taquiarritmia al tratamiento farmacológico. Métodos: se realizó un estudio descriptivo prospectivo observacional de un universo de 24 fetos con el diagnóstico de taquiarritmia fetal que se diagnosticaron y atendieron en el Departamento Provincial de Genética de La Habana y en el Hospital Ginecobstétrico "Ramón González Coro" entre los años 2003 y 2012. Resultados: las taquiarritmias se observaron en 24 fetos (40,6 %). Las madres menores 30 años fueron las más representadas en el grupo de mujeres del estudio, unido al índice de masa corporal sobrepeso y específicamente las pacientes nulíparas. Casi la mitad de la muestra no requirió tratamiento farmacológico (45,8 %) todas con el diagnóstico ecocardiográfico de extrasístoles y sola una con compromiso orgánico del corazón. Conclusiones: la flecainida se utilizó, en la cuarta parte de la muestra y mostró una resolutividad de 83,3 % en los fetos intraútero. La sobrevida de los fetos tratados farmacológicamente por vía oral fue 100 %.

Introduction: fetal electrocardiography is the gold standard for diagnosis of arrhythmias in postnatal life. This is difficult to achieve in prenatal life even with high-resolution prenatal ultrasound. Supraventricular tachyarrhythmias are manifested with heart rates above 180 beats per min and may be associated with fetal death in one third of cases, especially when associated with fetal hydrops or when it is set for over 15 days. Treatment allows the reversal of ventricular arrhythmia or control in the shortest possible time. Objective: to test tachyarrhythmia in uterus response to drug treatment. Methods: an observational prospective descriptive study was conducted in a universe of 24 fetuses with the diagnosis of fetal tachyarrhythmia that were diagnosed and treated at the Provincial Department of Genetics, Havana and at the Ramón González Coro Maternal Hospital from 2003 to 2012. Results: tachyarrhythmias were observed in 24 fetuses (40.6 %). Mothers younger than 30 were the most represented in this study group, together with BMI overweight and nulliparous patients specifically. Almost half of the sample did not require drug (45.8 %) treatment, all with extrasystoles echocardiographic diagnosis and only one with organic heart involvement. Conclusions: flecainide was used in a quarter of the sample and showed 83.3 % resoluteness of fetuses in uterus. Survival of fetuses pharmacologically orally treated was 100 %.

Problemas asociados al uso de digoxina en pacientes geriátricos / Problems associated to the use of digoxin in the elderly patients

OBJETIVO: identificar los problemas asociados al uso de digoxina en pacientes ancianos. MÉTODOS: se seleccionaron los pacientes a partir de los certificados médicos, por digoxina, archivados en las farmacias, y luego de dar su consentimiento de participación se realizaron sucesivas entrevistas. Se tuvo en cuenta enfermedad para la que fue indicado el medicamento, individualización de la prescripción, dosis empleada e intervalo de dosificación prescrito. Se valoró además las prescripciones potencialmente inapropiadas, según criterios de Beers. RESULTADOS: en el 100 % de los pacientes se detectó algún problema asociado al empleo de la digoxina. Entre los problemas detectados estuvieron: interacciones medicamentosas (100 %), probable uso para tratar enfermedades no indicadas (82 %), empleo de dosis superiores a las indicadas (62 %) y uso de intervalo de dosificación irregular (47 %). Entre los fármacos interactuante se detectaron 58 prescripciones potencialmente inapropiadas para el paciente anciano, las cuales representaron el 26,6 % del total de prescripciones. CONCLUSIONES: se detectó alta incidencia de problemas asociados al uso de digoxina en el paciente anciano, por lo que se hace necesario realizar un trabajo conjunto "médico-farmacéutico-paciente" en aras de ganar en calidad de la prescripción y uso de la digoxina en el adulto mayor.

OBJECTIVE: to identify the problems related to the use of digoxin in elderly patients. METHODS: the selection of patients was based on the medical certificates for the use of digoxin, which were filed in the drugstores, and on the patient's consent to be involved in interviews. The research took into account the disease for which digoxin was prescribed as treatment, the individualization of prescription, the prescribed dosage and dosing intervals, in addition to the assessment of potentially inappropriate prescriptions according to Beers criteria. RESULTS: all the participating patients presented with some problems related to the use of digoxin. The most common were drug interactions (100 %), likely use to treat nonprescribed diseases (82 %), use of a dose higher than the recommended one (62 %) and irregular dosing interval (47 %). Among drug interactions were 58 potentially inappropriate prescriptions for elderly patients, which accounted for 26.6 % of total prescriptions. CONCLUSIONS: there was a high incidence rate of problems associated with the use of digoxin in the elderly, so it is necessary to work together, meaning the physician, the pharmacist and the patient, in order to increase prescribing quality for the use of digoxin in the elderly.

Tratamento otimizado e redução da frequência cardíaca na insuficiência cardíaca crônica / Optimized treatment and heart rate reduction in chronic heart failure

FUNDAMENTO: A Insuficiência Cardíaca (IC) é uma síndrome que cursa com má evolução nas formas avançadas. O bloqueio neuro-hormonal modifica essa história natural; no entanto, ele com frequência é subotimizado. OBJETIVO: Neste estudo procuramos verificar em qual percentual médicos cardiologistas habituados no tratamento da IC conseguem prescrever as doses-alvo dos medicamentos de comprovada eficácia. MÉTODOS: Foram selecionados consecutivamente 104 pacientes ambulatoriais com disfunção sistólica, todos sob tratamento estabilizado. Avaliaram-se dados demográficos e o tratamento verificando-se as doses atingidas. Os achados são apresentados em percentual e fizeram-se correlações entre as diferentes variáveis. RESULTADOS: A idade média dos pac. foi de 64,1 ± 14,2 anos, com PAS 115,4 ± 15,3 mmHg, FC de 67,8 ± 9,4 bpm, peso 76,0 ± 17,0 kg e em ritmo sinusal (90,4%). Quanto ao tratamento, 93,3% estavam recebendo um bloqueador do SRA (52,9% IECA), todos recebiam betabloqueador (BB), sendo o carvedilol o mais prescrito (92,3%). Quanto às doses: 97,1% dos que recebiam um BRA estavam com dose abaixo da ideal; os que recebiam IECA 52,7% receberam dose otimizada. Quanto ao BB, em 76,0% foi possível prescrever as doses alvos. Nesse grupo de pac. a maioria com dose alvo do BB, pode-se observar que 36,5% apresentavam frequência cardíaca igual ou maior que 70 bpm em ritmo sinusal. CONCLUSÕES: Médicos cardiologistas habituados no tratamento da IC conseguem prescrever as doses-alvo de inibidores da ECA e BB para a maioria dos pac. Mesmo recebendo as doses preconizadas, cerca de um terço dos pac. persiste com FC acima de 70 bpm e deveria ter seu tratamento otimizado.

BACKGROUND: Heart failure (HF) is a syndrome that leads to poor outcome in advanced forms. The neurohormonal blockade modifies this natural history; however, it is often suboptimal. OBJECTIVE: The aim of this study is to assess at what percentage cardiologists used to treating HF can prescribe target doses of drugs of proven efficacy. METHODS: A total of 104 outpatients with systolic dysfunction were consecutively enrolled, all under stabilized treatment. Demographic and treatment data were evaluated and the doses achieved were verified. The findings are shown as percentages and correlations are made between different variables. RESULTS: The mean age of patients was 64.1 ± 14.2 years, with SBP =115.4 ± 15.3, HR = 67.8 ± 9.4 bpm, weight = 76.0 ± 17.0 kg and sinus rhythm (90.4%). As for treatment, 93.3% received a RAS blocker (ACEI 52.9%), all received beta-blockers (BB), the most often prescribed being carvedilol (92.3%). As for the doses: 97.1% of those receiving an ARB were below the optimal dose and of those who received ACEI, 52.7% received an optimized dose. As for the BB, target doses were prescribed to 76.0% of them. In this group of patients, most with BB target dose, it can be seen that 36.5% had HR > 70 bpm in sinus rhythm. CONCLUSION: Cardiologists used to treating HF can prescribe target doses of ACEI and BB to most patients. Even though they receive the recommended doses, about one third of patients persists with HR > 70 bpm and should have their treatment optimized.

Farmacovigilancia de interacciones medicamentosas en pacientes afiliados al sistema de salud de Colombia / Drug surveillance of medication interactions in patients affiliated to the health system in Colombia

Objetivos: determinar las posibles interacciones medicamentosas que generen problemas relacionados con medicamentos de seguridad, necesidad o efectividad, mediante la búsqueda activa en bases de datos de pacientes afiliados al Sistema General de Seguridad Social en Salud.Métodos: a partir de las bases de datos de dispensación de medicamentos deAudifarma S.A, a unos 3,7 millones de usuarios del país, se hizo una revisiónsistemática de estadísticas de una serie de medicamentos identificados porpresentar interacciones.Resultados: del total de pacientes que tomaban omeprazol se encontró que 12,3 porciento recibían concomitantemente hidróxido de magnesio mas aluminio; 1,7 porciento recibían ranitidina; 1,0 porciento sucralfato, además 0,3 porciento tomaban simultáneamente omeprazol+ sucralfato + hidróxido de magnesio y aluminio y 0,4 porciento omeprazol + ranitidina + hidróxido de magnesio y aluminio, que no potencian el efecto antiulceroso o pueden antagonizar sus acciones. También se halló que el 0,2 porciento de pacientes que tomaban verapamilo recibían al mismo tiempo digoxina o metil digoxina con riesgo de aumentar la toxicidad y antagonizar el efecto inotrópico. Todos los casos fueron notificados a los responsables de su atención sanitaria.Discusión: interacciones medicamentosas representan un riesgo potencial, el cual debe ser tenido en cuenta por los médicos prescriptores. La fármacovigilancia permite optimizar recursos y prevenir eventos adversos que puedan potencialmente causar morbilidad o letalidad. Se recomienda considerar la búsqueda en bases dedatos para reforzar los programas de vigilancia de uso de medicamentos en el país.

Objectives: to determine the possible medication interactions that generateproblems related to safety medications, needs or effectiveness, throughout theactive search in data bases of patients affiliated to the General Health System of Social Security. Methods: based on the data base from Audifarma S.A. in regards to the distribution of medications to 3.7 million of users in the country, a systematic review of thestatistics of a series of drugs identified for presenting interactions. Results: out of the total of patients that were taking omeprazol, it was found that 12.3% at the same time received magnesium hydroxide plus aluminum; 1.7%received ranitidine; 1.0% sucralfate, and also 0.3% were at the same time taking omeprazol + sucralfate+magnesium hydroxide and aluminum and 0.4% omeprazol + ranitidine+magnesium hydroxide and aluminum, which do not maximize the anti ulcerous effect or may antagonize its actions. It was also found that 0.2% of the patients was taking verapamil and at the same time received digoxin or methyl digoxin with the risk of increasing the toxicity and antagonizing its inotropic effect. All these cases were notified to those responsible for their sanitary attention. Discussion: medication interactions represent a potential risk, which has to be considered by the prescribing doctors. Drug surveillance allows the optimization of resources and the prevention of adverse events which may potentially cause mortality or be lethal. It is recommended that data bases be searched in order to reinforce the surveillance programs in relation to the use of medicines in the country.

Digitálicos: os resultados do DIG no século XXI / Digoxin: the results of the DIG study in the XXI century / Digitálicos: los resultados del DIG en el siglo XXI

Depois da divulgação de que não houve significância estatística na mortalidade geral do estudo DIG, a indicação dos digitálicos nos esquemas de tratamento da insuficiência cardíaca congestiva (ICC) reduziu drasticamente. Estudos post hoc, que reavaliaram os dados do DIG, indicaram que um aspecto não considerado neste ensaio multicêntrico exerce influência decisiva no prognóstico dos pacientes: a concentração sérica da digoxina. Em relação àqueles que receberam placebo, a mortalidade geral e a hospitalização foram reduzidas em pacientes com concentração de digoxina inferior a 0,9 ng/ml. No primeiro trabalho que avaliou a influência dos digitálicos em modelo experimental de ICC, verificamos em nosso laboratório que ratas com síndrome congestiva secundária a infarto do miocárdio têm a sobrevida prolongada sob tratamento com digitoxina. As informações atuais recomendam que os méritos dos digitálicos continuem a ser analisados para estabelecer adequadamente sua importância no tratamento da ICC.

After the report that there was no statistical significance in the general mortality of the DIG study, the indication of digoxin in the treatment regimens for congestive heart failure (CHF) drastically decreased. Post hoc studies that reassessed the DIG study data, indicated that an aspect that was not considered in this multicenter study has a critical influence on the prognosis of patients: the serum levels of digoxin. Regarding those that received a placebo, the general mortality and hospitalization were decreased in patients with a digoxin level < 0.9 ng/ml. At the first study that assessed the influence of digitalis in an experimental model of CHF, we verified in our lab that female rats with congestive syndrome secondary to myocardial infarction have a prolonged survival when undergoing treatment with digitoxin. The current information recommends that the merits of digoxin continue to be analyzed in order to adequately establish its importance in the treatment of CHF.

Después de la divulgación de que no hubo significancia estadística en la mortalidad general del estudio DIG, la indicación de los digitálicos en los esquemas de tratamiento de la insuficiencia cardíaca congestiva (ICC) se redujo drásticamente. Estudios post hoc, que reevaluaron los datos del DIG, indicaron que un aspecto no considerado en este ensayo multicéntrico ejerce influencia decisiva en el pronóstico de los pacientes: la concentración sérica de la digoxina. En relación a aquellos que recibieron placebo, la mortalidad general y la hospitalización fueron reducidas en pacientes con concentración de digoxina inferior a 0,9 ng/ml. En el primer trabajo que evaluó la influencia de los digitálicos en modelo experimental de ICC, verificamos en nuestro laboratorio que ratas con síndrome congestivo secundario a infarto de miocardio tienen la sobrevida prolongada bajo tratamiento con digitoxina. Las informaciones actuales recomiendan que los méritos de los digitálicos continúen a ser analizados para establecer adecuadamente su importancia en el tratamiento de la ICC.

Digoxin serum levels in patients with Chagas' cardiomyopathy and heart failure / Níveis séricos de digoxina em pacientes com insuficiência cardíaca secundária à cardiomiopatia da doença de Chagas

INTRODUCTION: The purpose of this study was to determine digoxin serum concentrations in patients with Chagas' cardiomyopathy with chronic heart failure, because little is known concerning this laboratory test in patients with this condition. METHODS: This study focuses on 29 (29 percent) out of 101 patients with chronic heart failure secondary to Chagas' cardiomyopathy receiving digoxin therapy. Digoxin was measured by the immune-enzymatic method. RESULTS: New York Heart Association Functional Class III/IV was noted in 13 (45 percent) patients. The mean potassium serum level was 4.3± 0.5mEq/L, mean creatinine serum levels 1.4± 0.3dg/100ml, and left ventricular ejection fraction 34.7± 13.8 percent. The median digoxin serum level was 1.27 (0.55; 1.79)ng/ml. Sixteen (55 percent) patients had digoxin serum levels higher than 1.0ng/ml. Abnormal digoxin serum levels were verified in 13 (45 percent) patients. Digoxin serum levels correlated moderately with creatinine serum levels (r = 0.39; p< 0.03) and negatively with sodium serum levels (r= -0.38; p= 0.03). CONCLUSIONS: Digoxin serum concentration should be measured in patients with Chagas' cardiomyopathy with chronic heart failure receiving digoxin therapy due to the potential for digoxin toxicity.

INTRODUÇÃO: O propósito deste trabalho foi o de determinar a concentração sérica de digoxina em pacientes com insuficiência cardíaca crônica secundária à cardiomiopatia da doença de Chagas porque pouco se conhece sobre os níveis séricos desse fármaco em pacientes com tal condição clínica. MÉTODOS: Foram recrutados 29 (29 por cento) de 101 pacientes com insuficiência cardíaca crônica secundária à cardiomiopatia da doença de Chagas, os quais estavam sendo tratados com digoxina. Essa droga foi medida no soro desses pacientes pelo método imunoenzimático. RESULTADOS: Treze (45 por cento) pacientes estavam no grau III/ IV da Sociedade Nova-Iorquina de Cardiologia. Os níveis séricos de potássio médio foram 4,3± 0,5 mEq/L, a creatinina sérica média 1,4± 0,3dg/100ml, e a fração de ejeção do ventrículo esquerdo 34.7± 13. 8 por cento. Os níveis séricos médios de digoxina foram 1,27 (0,55; 1,79)ng/ml. Dezesseis (55 por cento) pacientes apresentaram níveis séricos de digoxina > 1,0ng/ml. Níveis séricos anormais de digoxina foram observados em 13 (45 por cento) pacientes. Os níveis séricos de digoxina correlacionaram moderadamente com os de creatinina (r= 0,39; p< 0,03) e negativamente com os de sodium (r= -0,38; p= 0,03). CONCLUSÕES: Os níveis séricos de digoxina devem ser medidos em pacientes com insuficiência cardíaca crônica secundária à cardiomiopatia da doença de Chagas por causa do potencial para ocorrer toxicidade pela digoxina.

Digoxin's roles in heart failure patients: An overview / Los roles de digoxina en pacientes con insuficiencia cardíaca: Una revisión / Os papéis da digoxina em pacientes com insuficiência cardíaca: Uma revisão geral

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?.

Cardiovascular drugs in human mechanical nociception: digoxin, amlodipine, propranolol, pindolol and atenolol

Calcium channel blockers, β adrenergic receptor blockers and Na/K ATPase inhibitors are widely used drugs, mainly for cardiovascular diseases. Their pharmacological targets are not restricted to the cardivascular tissue, nociceptive system structures also express similar targets, which strongly suggests a direct effect on pain sensation. To evaluate the pain intensity changes in outpatient groups, who receive these drugs as a therapy, a cross-sectional sampled, randomized patient groups receiving the calcium channel blocker amlodipine for blood hypertension (n=45), β adrenergic receptor blockers (propranolol, atenolol or pindolol; n=40) for blood hypertension, or digoxin (n=40) for heart failure, were compared to an aparently healthy volunteers control group (n=60). A calibrated noxious pressure of 890 g/mm² was applied for 5 seconds on the patient’s sternum. Subjective pain intensity was reported by the visual analog scale (VAS, 0 to 10). Pain modulation system was evaluated by the application of a second stimulus with a 5 minutes delay. The analgesic effect of the β blockers group (propanolol, atenolol, pindolol) was dosage-dependant (-36.8 percent; P=0.0000003), without differences among them. The calcium channel blocker amlodipine showed lower pain scores (-50.6 percent; P=0.0000003) than β-receptor blockers (P=0.0000003). Digoxin presented the highest pain scores (+56.5 percent; P=0.0000003). All pain scores for the second stimulus were lower than the first stimulus and were differentially affected by β-blockers (atenolol, pindolol and propanolol) and calcium channel blocker (amlodipine), but not by digoxin. These results suggest the influence of widely clinically used cardiovascular drugs on nociception.

Los bloqueadores de los canales de calcio, los bloqueadores de los receptores β adrenérgicos y los inhibidores de la ATPasa Na/K son medicamentos ampliamente usados en enfermedades cardiovasculares. Sus blancos farmacológicos no se restringen al tejido cardiovascular, el sistema nervioso nociceptivo expresa blancos similares, lo que sugiere fuertemente un efecto directo en la sensación del dolor. El objetivo del presente estudio fue evaluar los cambios en la intensidad del dolor en grupos de pacientes ambulatorios que reciban estos medicamentos como terapia. Grupos aleatorios de pacientes que reciben el bloqueador de canales de calcio amlodipina contra la hipertensión arterial (n=45), bloqueadores de receptores β adrenérgicos (propranolol, atenolol or pindolol; n=40) contra la hipertensión arterial o digoxina (n=40) por insuficiencia cardíaca fueron comparados con un grupo control de voluntarios aparentemente sanos (n=60). A todos los grupos se les aplicó una presión nociva calibrada de 890 g/mm² durante 5 segundos sobre el esternón. El paciente reportó la intensidad subjetiva del dolor mediante la escala visual análoga (VAS). El sistema de modulación descendente del dolor fue evaluado mediante la aplicación del mismo estímulo 5 minutos después del primero. Se determinó un efecto analgésico en el grupo de β bloqueantes (propanolol, atenolol, pindolol) dosis dependiente (-36,8 por ciento; P=0,0000003) sin mostrar diferencias entre ellos. El bloqueador de canales de calcio amlodipina mostró un efecto analgésico (-50,6 por ciento; P=0,0000003) que fue mayor que el de los β bloqueantes (P=0,0000003). El grupo con digoxina expresó un efecto hiperalgésico (+56,5 por ciento; P=0,0000003). Todos los valores de dolor para el segundo estímulo fueron menores que para el primero y fueron diferencialmente afectados por los β bloqueantes (atenolol, pindolol and propanolol) y por la amlodipina pero no por la digoxina. Estos...

Comportamiento de la taquiarritmias cardíacas en los Cuidados Progresivos / Behavior of cardiac tachyrhythmia in the progressive care

Fundamento: Las arritmias cardíacas constituyen una importante causa de intervención en Unidades de Cuidados Intensivos y Coronarios. Objetivo: Conocer el comportamiento de las taquiarritmias cardíacas en estos servicios. Método: Se realizó un estudio descriptivo transversal a 87 pacientes ingresados con taquiarritmias cardíacas en los Servicios de Terapia Intensiva e Intermedia del Hospital Clínico Quirúrgico Docente «Amalia Simoni Argilagos¼ de la provincia de Camagüey desde enero de 2004 a diciembre de 2006. Las historias clínicas individuales y los protocolos de necropsia de los fallecidos constituyeron la fuente primaria de información. Resultados: La fibrilación auricular fue la arritmia más frecuente (70,1%) y la cardiopatía isquémica la causa identificada de mayor importancia (27,6%). El 75,8% de los enfermos presentó inestabilidad hemodinámica y en el 89,7% se utilizó como variante terapéutica los fármacos antiarrítmicos, la digoxina fue el antiarrítmico más usado. Conclusiones: Los fenómenos cardioembólicos constituyeron la complicación más importante y la propia arritmia la principal causa de muerte.

Background: Cardiac arrhythmias constitute an important intervention cause at the Intensive Care and Coronary Units. Objective: To know the behavior of cardiac tachyrhythmia in these services. Method: A cross-sectional descriptive study was carried out to 87 patients with cardiac tachyrhythmia admitted in the Intensive and Intermediate Therapy Services at "Amalia Simoni Argilagos" Educational Surgical Clinical Hospital of Camagüey province from January 2004 to December 2006. The individual medical histories and the dead necropsy protocols constituted the primary source of information. Results: The auricular fibrillation was the most frequent arrhythmia (70,1%) and the ischemic heart disease the identifying cause of greater importance (27,6%). The 75.8% of the sickpeople presented hemodynamic instability and in the 89.7% was utilized as therapeutic variant the antiarrhythmic drugs, the digoxin was the most antiarrhythmic used. Conclusions: The cardioembolic phenomena constituted the most important complication and the arrhythmia itself the main cause of death.

Pharmacokinetics of digoxin in children with congestive heart failure aggravated by other diseases / Farmacocinética de la digoxina en niños con insuficiencia cardiaca congestiva agravada por otras enfermedades

Objective. To determine individual digoxin level variations and the effect of some common diseases those aggravate congestive heart failure (CHF) on digoxin pharmacokinetics in children. Design. Digoxin pharmacokinetics was evaluated in 11 children with CHF and an additional disease, such as rheumatic fever, anemia or infections. Digoxin plasma levels were monitored in patients on multiple-dose regime. Setting. Third level pediatric hospital. Results. Pharmacokinetic parameters showed extensive variation; median values were: elimination half-life 42.0 hrs (8.3-77.0), volume of distribution 1.01 L/kg (0.654-6.25), and clearance 15.0 mL/kg/h (6.0-331.8), which differed from results in patients with only CHF, reported previously. Dosage schemes in use at the Cardiology Service produced the following results: 40.5% of patients reached therapeutic levels, 10.8% toxic levels and 48.6% sub-therapeutic levels. Conclusion. The range of dosage required in order to adjust individual treatments was very wide, leading us to the conclusion that therapeutic schemes for this population should be individualized based on their pharmacokinetic parameters, and therapeutic monitoring of drugs should be performed.

El objetivo del presente estudio es determinar el efecto de algunas enfermedades que agravan la insuficiencia cardiaca congestiva (ICC) sobre la farmacocinètica de digoxina en niños. Diseño. Se estudió la farmacocinètica de digoxina en 11 niños con ICC, agravada por otras enfermedades como fiebre reumática, anemia o infecciones. Posteriormente se llevó a cabo monitoreo de los niveles de digoxina mientras seguían un règimen de dosis múltiple. Lugar. Centro de atención de tercer nivel. Resultados. Los parámetros farmacocinèticos mostraron amplia variabilidad: los valores de las medianas fueron: vida media de eliminación 42.0 horas (8.3-77.0), volumen de distribución 1.01 L/kg (0.654-6.25), y depuración 15.0 mL/kg/h (6.0-331.8) los cuales son diferentes a los de los pacientes que únicamente padecen ICC previamente reportados. Con el esquema de dosis usado en el Servicio de Cardiología se encontraron los siguientes resultados: 40.5% de las muestras de pacientes alcanzaron niveles terapèuticos, 10.8% niveles tóxicos y 48.6% subterapèuticos. Conclusión. Debido a la variación en los parámetros farmacocinèticos individuales, ocasionados por las patologías que agravan la ICC, se recomienda individualizar los esquemas de dosificación a partir de criterios farmacocinèticos, sin prescindir del monitoreo terapèutico del fármaco.

Padrão de utilização clínica dos digitálicos: necessidade de reavaliação / Clinical Use of Digitalis. Need for Reassessment

Objetivo - Avaliar o padrão de utilização dos digitálicos, indicações de seu emprego e a freqüência de suspensão do fármaco em pacientes hospitalizados. Métodos - Foram estudados os prontuários de todos os pacientes internados nas enfermarias de medicina interna e especialidades médicas do Hospital de Clínicas de Porto Alegre. A coleta de dados foi realizada em 5 dias, sendo 3 no inverno e 2 no verão, mantendo um intervalo de pelo menos 2 semanas entre cada coleta. A presença de insuficiência cardíaca foi avaliada objetivamente através do escore proposto por Carlson e col. Resultados - De um total de 881 pacientes, 114 (13%) faziam uso de digoxina. A idade média ± DP desses pacientes foi de 66 ± 13 anos, sendo que 47% eram do sexo masculino. Dos pacientes que recebiam digoxina, 32% apresentavam escores compatíveis com insuficiência cardíaca definida ou possível; 26% apresentavam fibrilação ou flutter" atrial; 18% tinham insuficiência cardíaca e taquiarritmia supraventricular; e 24% não tinham indicação precisa segundo os critérios deste estudo. Oitenta e cinco por cento dos pacientes faziam uso prévio de digoxina e em 32% desses, a droga foi suspensa durante a internação. Considerando aqueles pacientes sem indicação para usar digitálicos, apenas 44% tiveram o tratamento com digoxina suspenso. Conclusão - De acordo com critérios contemporâneos, um percentual elevado de pacientes internados recebe digoxina sem indicação precisa. Estes dados sugerem que a reavaliação do uso de digitálicos deve ser incorporada à prática médica

Purpose - To evaluate the pattern of utilization of digitalis in an academic hospital. Methods - Clinical files of all patients admitted in medical wards at the Hospital de Clínicas de Porto Alegre were studied. Data were collected during five different days, three in the winter and two in the summer, keeping an interval of at least two weeks between each data collection. Heart failare diagnosis was evaluated objectively by means of a score proposed by Carlson et al. Results - From a total number of 881 patients, 114 (13%) were receiving digoxin. Mean age was 66 ± 13 years and 47% were males. Considering the patients who were taking digoxin, 32% presented scores compatible with definite or possible heart fuilare; 26% had atrial flutter or fibrillation; 18% had heart failare and supraventricular tachyarrhytmias; and in 24% no clear indications were found according to our criteria. Previous use of digoxin was found in 85% of the patients and 32% were withdrawn during the hospitalization. Considering just the patients who had no reason for using digoxin, only 44% had the drug withdrawn. Conclusion - According to current criteria, many hospitalized patients receive digoxin without a definite indication. These data suggest that reassessment of the use of digitalis should be incorporated into clinical practice