Trombolisis endovenosa post reversión de acenocumarol con complejo de protrombina: caso clínico / Intravenous thrombolysis after reversion of acenocoumarol anticoagulation: report of one case

We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.

Circulating microparticles and central blood pressure according to antihypertensive strategy

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Massa Ventricular e Tamanho Atrial em Diabéticos Hipertensos em Uso de Losartana ou Benazepril / Ventricular Mass and Atrial Size in Diabetic Hypertensive Patients Using Losartan or Benazepril

Fundamentos: Diabéticos hipertensos apresentam maior probabilidade de desenvolverem hipertrofia ventricular esquerda e fibrilação atrial. Evidências sugerem que bloqueadores do sistema renina-angiotensina-aldosterona devem ser usado neste grupo de pacientes. Objetivo: Avaliar se há diferença entre os efeitos do inibidor da enzima conversora de angiotensina benazepril e do bloqueador de receptor de angiotensina losartana sobre o tamanho atrial esquerdo, a massa ventricular, quando associados ao tratamento de pacientes hipertensos diabéticos em uso de anlodipino. Métodos: Foram randomizados em dois grupos para associação de losartana ou benazepril 34 pacientes hipertensos e diabéticos tipo 2 do serviço de clínica médica da Universidade do Estado do Rio de Janeiro, após período de 6 semanas apenas com anlodipino. Ao início e ao término do tratamento combinado, os pacientes foram submetidos a ecocardiograma para medidas de cavidades, espessuras parietais e fluxos. Resultados: Houve redução da massa ventricular esquerda indexada no grupo losartana de 81,1 ± 23,5 para 76,9 ± 23,8 g/m² (p = 0,044), sem diferença no grupo benazepril (de 81,8 ± 10,8 para 79,7 ± 12,1; p = 0,520). O diâmetro atrial esquerdo foi menor ao final de 12 semanas (p = 0,034) no grupo losartana, no qual variou de 2,12 ± 0,23 para 2,03 ± 0,22 cm/m² (p = 0,103), quando comparado ao grupo benazepril, no qual variou de 2,12 ± 0,30 para 2,23 ± 0,29 cm/m² (p = 0,064). Conclusão: A combinação losartana e anlodipino foi melhor que a combinação benazepril e anlodipino para redução de massa ventricular esquerda e tamanho do átrio esquerdo nesta amostra de hipertensos diabéticos tipo 2

Background: Hypertensive diabetic patients are more likely to develop left ventricular hypertrophy and atrial fibrillation. Evidence suggests that renin-angiotensin-aldosterone system blockers should be used in this group of patients. Objective: To evaluate if there are differences between the effects of angiotensin-converting enzyme benazepril and the angiotensin-receptor blocker losartan on left atrial size and ventricular mass when associated to the treatment of diabetic hypertensive patients using amlodipine. Methods: 34 hypertensive type-2 diabetic outpatients from the Internal Medicine service of Universidade do Estado do Rio de Janeiro were randomized into two groups, after a period of 6 weeks receiving only amlodipine, to receive losartan or benazepril. At the beginning and end of the combined treatment, patients were submitted to echocardiography for cavity assessment, wall thickness and flow measurements. Results: There was reduction in left ventricular mass index in the losartan group (from 81.1 ± 23.5 to 76.9 ± 23.8 g/m²; p = 0.044), with no difference in the benazepril group (from 81.8 ± 10.8 to 79.7 ± 12.1 g/m²; p = 0.520). The left atrial diameter index was lower at 12 weeks (p=0.034) in the losartan group, which ranged from 2.12 ± 0.23 to 2.03 ± 0.22 cm/m² (p = 0.103) when compared to the benazepril group, which ranged from 2.12 ± 0.30 to 2.23 ± 0.29 cm/m² (p = 0.064). Conclusion: The losartan and amlodipine combination was better than the benazepril and amlodipine combination for left ventricular mass and left atrial size reduction in this sample of type 2 diabetic hypertensive patients

Comparação dos efeitos do benazepril e da losartana sobre a função endotelial e a rigidez arterial em pacientes diabéticos com hipertensão não controlada por anlodipino / Comparison of benazepril and losartan on endothelial function and vascular stiffness in hypertensive diabetic patients with hypertension not controlled by amlodipine

Em pacientes hipertensos e diabéticos, o sistema renina-angiotensina-aldosterona está relacionado com disfunção endotelial, rigidez vascular e aterosclerose. As principais medicações disponíveis para a inibição desse sistema são os inibidores da enzima conversora de angiotensina e os bloqueadores do receptor AT1 de angiotensina. A maioria das diretrizes internacionais faz as mesmas recomendações para as duas classes, mas diferenças no seu mecanismo de ação podem ter relevância clínica. O objetivo principal foi comparar benazepril e losartana em pacientes hipertensos e diabéticos com pressão arterial não controlada por anlodipino, analisando parâmetros inflamatórios (proteína C reativa), da função endotelial (através da dilatação mediada por fluxo da artéria braquial) e de rigidez vascular (através da velocidade da onda de pulso e das pressões aórticas). O objetivo secundário foi, através de uma análise post-hoc, pesquisar se há interação entre as estatinas e os inibidores do sistema renina-angiotensina-aldosterona. Pressão arterial, função endotelial e rigidez vascular foram comparados entre usuários e não-usuários de estatina. Os dados estão apresentados como mediana (intervalo interquartil). Os resultados principais mostraram que o grupo benazepril apresentou menor proteína C reativa [0,38 (0,15-0,95) mg/dl vs 0,42 (0,26-0,59) mg/dl, p=0,020]. Houve, ainda, uma leve melhora da dilatação mediada por fluxo da artéria braquial no grupo benazepril (aumento 45%, p=0,057) em comparação com o grupo losartana (aumento 19%, p=0,132). Não houve diferença na velocidade da onda de pulso [8,5 (7,8-9,4) m/s vs 8,5 (7,0-9,7) m/s, p=0,280] e na pressão aórtica sistólica [129 (121-145) mmHg vs 123 (117-130) mmHg, p=0,934] entre os grupos benazepril e losartana...

In hypertensive diabetic patients, the renin-angiotensin-aldosterone system is related to endothelial dysfunction, vascular stiffness and atherosclerosis. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are two of the most important medications that inhibit this system. Most international guidelines recommend them interchangeably, albeit small differences may have clinical relevance. The main objective was to compare inflammatory parameters (by C-reactive protein), endothelial function (by flow-mediated vasodilation) and vascular stiffness (by pulse wave velocity and aortic pressures) between benazepril and losartan in hypertensive diabetic patients whose blood pressure was not controlled by amlodipine. The secondary objective was a post-hoc analysis to study possible synergism between statins and renin-angiotensin-aldosterone system inhibitors. Blood pressure reduction, endothelial function and vascular stiffness were compared between patients using or not statins. Main results showed that C-reactive protein had lower values in benazepril group [0.38 (0.15-0.95) mg/dl vs 0.42 (0.26-0.59) mg/dl, p=0.020]. There was a slightly higher flow-mediated vasodilation response in benazepril group (45% of increase, p=0.057) than in losartan group (19% of increase, p=0.132). Aortic systolic blood pressure [129 (121-145) mmHg vs 123 (117-130) mmHg, p=0.934] and carotid-femoral pulse wave velocity [8.5 (7.8-9.4) m/s vs 8.5 (7.0-9.7) m/s, p=0.280] were the same between groups. Secondary results showed that patients using statins had greater reduction in mean systolic blood pressure in 24 hour monitoring [134 (120-146) mmHg to 122 (114-135) mmHg, p=0.007] than patients not using statins [137 (122-149) mmHg to 128 (122-140) mmHg, p=0.362]. Patients using statins had higher flow-mediated vasodilation response [6.5% (5.1-7.1) to 10.9% (7.3-12.2), p=0.003] than those not using statins [7.5% (6.0-10.2) to 8.3% (7.5-9.9), p=0.820]...

Papel de la adrenomedulina cerebelosa en la regulación de la presión arterial / Role of cerebelar adrenomedullin in blood pressure regulation

La adrenomedulina (AM) es un péptido ubicuo de 52 residuos de aminoácidos que cumple funciones importantes en la regulación de la función cardiovascular (CDV). La AM ejerce sus acciones a través de su unión con tres subtipos de receptores, el receptor del péptido relacionado al gen de la calcitonina tipo 1 (CGRP1), el receptor de AM tipo 1 (AM1) y tipo 2 (AM2). El CGRP1 está formado por el receptor similar al receptor de calcitonina (CRLR) y la proteína que modifica la actividad del receptor tipo 1 (RAMP1). El AM1 por el CRLR+RAMP2 y el AM2 por el CRLR+RAMP3. A nivel del sistema nervioso central, la AM y sus receptores se localizan en diversas regiones, incluyendo el cerebelo. Se ha demostrado marcados incrementos en la densidad de los sitios de unión para la AM en el cerebelo durante la hipertensión, lo que sugiere un papel del sistema adrenomedulinérgico cerebeloso en la regulación de la presión arterial (PA). En el presente estudio se evaluó la participación de la AM cerebelosa en la regulación de la PA. Nuestros hallazgos muestran la existencia de desregulación de los componentes del sistema AM cerebeloso durante la hipertensión, ya que se encontró una reducida expresión de CRLR, RAMP1 y RAMP3 y una incrementada expresión de la AM y RAMP2 en el vermis de cerebelo de ratas hipertensas (SHR), cuando se comparó con las ratas controles, Wistar Kyoto (WKY), de 8 y 16 semanas de edad. La reducción de la PA mediante el tratamiento crónico con valsartán (60mg/Kg/día,p.o.) revirtió las desregulación de la AM y los componentes de su receptor, observados en las ratas SHR. El papel de las especies reactivas de oxígeno (EROS) en la acción de la AM cerebelosa quedó evidenciado, ya que la AM fue capaz de reducir la actividad de las tres enzimas antioxidantes, superóxiodo dismutasa (SOD), catalasa (CAT) y glutatión peroxidasa (GPx), en las ratas WKY y Sprague - Dawley (SD). Aún mas, nuestros hallazgos mostraron claramente el efecto antagónico entre la AM y la ANG II sobre la actividad de las enzimas antioxidantes inducida por la ANG II. El efecto de la AM sobre las enzimas antioxidantes no se manifestó en la ratas hipertensas, sin embargo el mismo fue restaurado mediante la disminución de la presión arterial con la administración crónica de dos antihipertensivos de mecanismo de acción distintos como la amlodipina (5mg/Kg/día,p.o) o el valsartán (60mg/Kg/día,p.o), lo que sugiere una relación entre la hipertensión y ausencia del efecto de AM en la ratas SHR. Al evaluar la posible vía de señalización que media la acción de la AM y el antagonismo con la ANG II sobre la actividad de las enzimas antioxidantes, demostramos que no existe una vía final común para dicho antagonismo, siendo la proteína quinasa A (PKA) y los 3 subtipos de receptores CGRP1, AM1 y AM2 los que median la acción de la AM, mientras que la acción de la ANG II se encuentra mediada a través de una vía que involucra la PKC/NAD(P)H oxidasa. Los hallazgos demuestran el antagonismo entre la AM y la ANG II en la regulación del estrés oxidativo en el cerebelo y ratifican la desregulación de la señalización de la AM mediada por EROs durante la hipertensión. Al evaluar las vías de señalización intracelular que median la acción de la AM en el cerebelo, demostramos que la AM es capaz de activar a las ERK, la producción de GMPc y NO a través de la estimulación del receptor AM1, y del AMPc a través de los tres subtipos de receptores de AM, lo que apoya que en el cerebelo la AM ejerce acciones a través de diversas vías de señalización como lo son NO/GMPc, AC/AMPc/PKA y/o ERK. El posible papel funcional de la AM in vivo fue inequívoco, ya que se demostró que la microinyección de AM en el vermis cerebeloso produjo una respuesta hipotensora profunda en las ratas SHR pero no en las normotensas. El hecho que la microinyección de AM en el vermis cerebelar en las ratas SD, WKY y SHR disminuyó significativamente la respuesta presora frente al estrés simpatoadrenal inducido por el estímulo eléctrico plantar, sugiere que la acción hipotensora está mediada a través de la regulación del eflujo simpático e indica un posible papel de la AM en la regulación de la respuesta CDV frente al estrés. En conjunto, nuestros resultados demuestran la existencia de un sistema adrenomedulinérgico funcional en el cerebelo, e indican por primera vez, que la AM cumple un papel importante en la regulación de la PA durante la hipertensión y el estrés.

comparative study of the management of stage 2 hypertension by combined therapy with losartan, amlodipine and hydrochlorothiazide

The most effective and accurate treatment of hypertensive patients reduces cardiovascular events and improves the quality of life. This study compared the efficacy and safety of combined [combination therapy] with an angiotensin-receptor blocker [ARB] a calcium-channel blocker [CCB] [Losartan / Amloidipine 50/10mg] vs maximal combination doses of ARB with hydrochlorothiazide [Losartan /HCTZ 100/25 mg] and maximal combination doses of CCB with HCTZ [Amlodipine /HCTZ 10/25 mg] in the management of stage 2 hypertension. This randomized clinical trial [RTC] comprised 478 hypertensive patients with mean age 50.5 +/- 5.21 years, and took place between January 2010 and December 2011 in Vasei Hospital clinic in Sabzevar. Antihypertensive drugs were washed out after 5 days of discontinuation of drugs and the patients with mean blood pressure in sitting position >/= 160 and <200 mmHg in systole and >/= 100 and <110 mmHg in diastole were randomized into three groups: Losartan / Amlodipine 50/10 mg [n =164], Losartan / HCTZ 100/25 mg [n =155] and Amlodipine / HCTZ 10/25 mg [n =159]. The end point was reaching the blood pressure below 140/90 within 56 days of treatment in each group. There was a significant difference in systolic blood pressure reductions between treatment groups [P<0.001] and also there was a significant difference between groups in reducing diastolic blood pressure [P<0.01]. The highest systolic and diastolic blood pressure reduction respectively was found in Amlodipine/losartane and losartane/HTCZ group. The ANCOVA analysis revealed that only treatment regimen had a significant effect [P=0.01] and other factor including Age, Gender, Diabetes Mellitus, Smoking and High serum cholesterol didn't have significant effect on blood pressure reduction. ARB/CCB combination therapy reduced blood pressure more effectively than the maximal doses of ARB or CCB with HCTZ in stage 2 hypertensive patients within this period of study

Combinação de anlodipino e enalaprila em pacientes hipertensos com doença coronariana / Combination of amlodipine and enalapril in hypertensive patients with coronary disease / Combinación de amlodipino y enalapril en pacientes hipertensos con enfermedad coronaria

FUNDAMENTO: Pacientes (pts) com doença coronariana (DAC) estável podem se beneficiar de menor pressão arterial (PA), conforme estudos recentes. OBJETIVO: Avaliar a eficácia e a tolerabilidade da combinação fixa anlodipino + enalaprila, comparada a anlodipino na normalização da PA diastólica (PAD) (< 85 mmHg), em pts com DAC e HAS. MÉTODOS: Estudo duplo-cego, randomizado, com dois grupos de pts com PAD > 90 e <110 mmHg e DAC. Excluímos os com FEVE < 40%; sintomas de insuficiência cardíaca ou angina classe III e IV; doenças graves e PAD > 110 mmHg durante o wash-out de quatro semanas, em uso só de atenolol. Após wash-out randomizamos para combinação (A) ou anlodipino (B) e seguimos de quatro em quatro semanas até 98 dias. As doses (mg) iniciais foram, respectivamente: A- 2,5/10 e B- 2,5, sendo incrementadas se PAD> 85mmHg, nas visitas. Estatística com χ2, Fischer e análise de variância, para p< 0,05. RESULTADOS:de 110 pts selecionados, randomizamos 72 (A= 32, B= 40). As reduções da PAD e da PA sistólica (PAS) foram intensas (p< 0,01), mas sem diferenças entre os grupos em mmHg: PAS, A (127,7 ± 13,4) e B (125,3 ± 12,6) (p= 0,45) e PAD, A (74,5 ± 6,7 mmHg) e B (75,5 ± 6,7 mmHg) (p= 0,32). Houve menos edema de membros inferiores no A (7,1% vs 30,6%, p=0,02) no 98º dia. CONCLUSÃO: A combinação fixa de enalaprila com anlodipino, tal qual anlodipino isolado, em pts com DAC e HAS estágios I e II foi eficaz na normalização da pressão, adicionando bloqueio ao sistema renina-angiotensina.

BACKGROUND: Patients (pts) with stable coronary artery disease (CAD) can benefit from a decrease in the blood pressure (BP), according to recent studies. OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP) (<85 mmHg), in pts with CAD and systemic arterial hypertension (SAH). METHODS: Double-blind and randomized study, with two groups of pts with DAP >90 and <110 mmHg and CAD. Patients with left ventricular ejection fraction (LVEF) < 40%, symptoms of heart failure or angina class III and IV, severe diseases and DAP >110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A) or amlodipine (B) and were followed every four weeks up to 98 days. The initial doses (in mg) were, respectively: A- 2.5/10 and B- 2.5; the doses were increased when DAP > 85mmHg, at the visits. Statistical analysis was carried out with χ2, Fischer and analysis of variance, for p< 0.05. RESULTS: Of the 110 selected pts, 72 (A= 32, B= 40) were randomized. The decreases in DAP and systolic arterial pressure (SAP) were significant (p< 0.01), but with no difference between the groups in mmHg: SAP, A (127.7 ± 13.4) and B (125.3 ± 12.6) (p= 0.45) and DAP, A (74.5 ± 6.7 mmHg) and B (75.5 ± 6.7 mmHg) (p= 0.32). Group A presented a lower incidence of lower-limb edema: (7.1% vs 30.6%, p=0.02) on the 98th day of follow-up. CONCLUSION: The fixed combination of enalapril and amlodipine, as well as isolated amlodipine, was effective in the normalization of BP in pts with CAD and SAH stages I and II, adding blockage of the renin-angiotensin system.

FUNDAMENTO: Pacientes (pts) con enfermedad coronaria (EAC) estable pueden beneficiarse con una menor presión arterial (PA), de acuerdo con estudios recientes. OBJETIVO: Evaluar la eficacia y la tolerancia de la combinación fija amlodipino + enalapril, comparada a el amlodipino en la normalización de la PA diastólica (PAD) (< 85 mmHg), en pts con EAC y HAS. MÉTODOS: Estudio doble ciego, randomizado, con dos grupos de pts con PAD >90 y <110 mmHg y EAC. Excluimos a los pts con FEVI < 40%; síntomas de insuficiencia cardiaca o angina clase III y IV; enfermedades graves y PAD >110 mmHg durante el wash-out de cuatro semanas, en uso sólo de atenolol. Después del wash-out randomizamos para combinación (A) o amlopidino (B) y seguimos de cuatro en cuatro semanas hasta 98 días. Las dosis (mg) iniciales fueron, respectivamente: A- 2,5/10 y B- 2,5, siendo incrementadas si PAD> 85mmHg, en las visitas. Estadística con χ2, Fischer y análisis de varianza, para p< 0,05. RESULTADOS: De un total de 110 pts seleccionados, randomizamos a 72 (A= 32, B= 40). Las reducción de la PAD y de la PA sistólica (PAS) fueron intensas (p< 0,01), pero sin diferencias entre los grupos en mmHg: PAS, A (127,7 ± 13,4) y B (125,3 ± 12,6) (p= 0,45) y PAD, A (74,5 ± 6,7 mmHg) y B (75,5 ± 6,7 mmHg) (p= 0,32). Se registró menos edema de miembros inferiores en el A (7,1 por ciento vs 30,6%, p=0,02) en el 98º día. CONCLUSIÓN: La combinación fija de enalapril con amlodipino, tal como el amlodipino aislado, en pts con EAC y HAS estadios I y II fue eficaz en la normalización de la presión, agregando un bloqueo al sistema renina-angiotensina.

Comparison of Losartan and Amlodipine in hypertensive type-II diabetic patients

The present study assesses whether Losartan and Amlodipine, alone or in combination, prevent microalbuminuria in hypertensive type II diabetic patients. Department of pharmacology, Basic Medical Sciences Institute [BMSI], Jinnah Post Graduate Medical Centre, Karachi from June 2006 to January 2007. In this study 60 hypertensive diabetic patients were divided into 3 groups having 20 each. Group 'N' patients were kept as control, group 'A' patients were treated with Losartan, 50 mg once daily, group 'B' with Amlodipine 10 mg once daily and Group 'C' patients were given a combination of both the drugs i.e. tab losartan and tab amlodipine. Tablet Glibenclamide 5 mg was given according to the glicemic control. Although all the three groups showed a comparable effect in lowering both the systolic and diastolic blood pressure but the effect on proteinuria was variable. Losartan treated patients in Group 'A' shows marked reduction of proteinuria but non-significant change in creatinine clearance. In Group 'B' the patients who were treated with Amlodipine showed significant reduction in creatinine clearance, but non-significant change in proteinuria and Group 'C' patients showed countable reduction in proteinuria but a non-significant increase was observed in creatinine clearance. The results suggest that in hypertensive type II diabetic patients Losartan is worthwhile reducing both systolic and diastolic blood pressure and proteinuria significantly

Estudo `LOTHAR`: avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e losartana no tratamento da hipertensão arterial primária / The `LOTHAR` study: evaluation of efficacy and tolerability of the fixed combination of amlodipine and losartan in the treatment of essential hypertension

OBJETIVO: O estudo LOTHAR avaliou a eficácia, tolerabilidade e os efeitos metabólicos em médio e longo prazo (um ano) da combinação fixa de anlodipino e losartana versus anlodipino e losartana isoladamente. MÉTODOS: Estudo multicêntrico brasileiro, randomizado, duplo-cego e comparativo realizado com 198 pacientes com hipertensão arterial primária em estágios 1 e 2. RESULTADOS: A combinação fixa apresenta alta eficácia anti-hipertensiva que se mantém em longo prazo com percentual reduzido de escape do controle pressórico, inferior a dos dois regimes monoterápicos de comparação. Em longo prazo, mais de 60 por cento dos pacientes tratados com a combinação fixa permaneceram com níveis da PAD < 85 mmHg e o efeito anti-hipertensivo quando avaliado pela MAPA persistiu nas 24 horas com relação vale-pico de 76,7 por cento. A freqüência de eventos adversos foi bastante reduzida neste grupo sendo a incidência em longo prazo de edema de membros inferiores cerca de quatro vezes menor que a observada com o anlodipino isolado. A combinação fixa não alterou os metabolismos da glicose e dos lípides tanto em médio quanto em longo prazos. CONCLUSAO: Estes resultados nos permitem afirmar que a combinação de anlodipino e losartana, a primeira combinação fixa de um antagonista dos canais de cálcio e um bloqueador do receptor da angiotensina II disponível no mercado farmacêutico constitui-se em excelente opção para o tratamento da hipertensão arterial em larga gama de pacientes hipertensos.

Desenvolvimento de teste de dissolução e estudo comparativo de comprimidos e cápsulas magistrais contendo anlodipino / Development of dissolution test and comparative study of tablets and compounded capsules containing amlodipine

O anlodipino é um fármaco amplamente utilizado para o tratamento da hipertensão arterial e da angina, e encontra-se disponível, no mercado brasileiro, sob a forma de comprimidos e cápsulas magistrais.O presente estudo objetivou desenvolver as condições para o teste de dissolução, bem como realizar estudo comparativo visando avaliar a intercambiabilidade de alguns produtos contendo o fármaco por meio de testes físicos e físico-químicos, tais como:variação de peso, desintegração, dureza, friabilidade, identificação, teor, uniformidade de conteúdo, teste e perfil de dissolução.No desenvolvimento do método de dissolução, diversas condições foram testadas e os seguintes parâmetros foram considerados satisfatórios:ácido clorídrico 0,01N (500 mL, a 37graus C mais ou menos 0,5 graus C) como meio de dissolução, aparato cesta e pá, respectivamente para cápsulas e comprimidos, e rotação de 50 rpm.Realizou-se estudo comparativo de cápsulas manipuladas por cinco diferentes farmácias, denominadas de A, B, C, D e E;bem como de comprimidos obtidos de cinco laboratórios produtores diferentes, denominados de F, G, H, I e J. Os produtos B (cápsula) e H (comprimido) foram reprovados nos teste de uniformidade de conteúdo e dureza, respectivamente.Todos os demais produtos apresentaram resultados satisfatórios nos testes a que foram submetidos.

Multicentric, clinical trial of S-Amlodipine 2.5 mg versus Amlodipine 5 mg in the treatment of mild to moderate hypertension--a randomized, double-blind clinical trial.

OBJECTIVE: To compare the efficacy and tolerability of 2.5 mg of S-Amlodipine with 5 mg of Amlodipine in the treatment of mild to moderate hypertension in a double blind, double dummy, randomized, comparative clinical trial. METHOD AND MATERIALS: Two hundred OPD patients (97 women and 103 men) with mean age 53.4 +/- 5.58 years, with stage I and stage 2 hypertension were enrolled for the study after obtaining informed written consent. Twelve patients were dropped out as lost to follow up. Ninety seven patients in the S-Amlodipine 2.5 mg treatment group and ninety one patients in the Amlodipine 5 mg treatment group completed the study. Those with a history of angina pectoris, myocardial infarction or recent cerebrovascular accident in the past six months and those with stage 3 and stage 4 hypertension were excluded from the study. Those showing a history of secondary hypertension were also excluded from the study. For the first two weeks all patients received dummy tablets of both S-Amlodipine and Amlodipine, as a wash out therapy and to get the actual blood pressure reading. After two weeks, enrolled patients received a preparation containing either S-Amlodipine (containing 2.5 mg of S-Amlodipine) and dummy tablets of Amlodipine or Amlodipine besylate (containing 5 mg of racemic Amlodipine) and dummy tablets of S-Amlodipine once daily for a period of six weeks. RESULTS: The results were analyzed by Student's 't' test The reduction in the average systolic and diastolic blood pressure, in the standing, supine and sitting postures in the S-Amlodipine group as well as in the Amlodipine group after six weeks of treatment was highly significant (P < or = 0.0001). The baseline values for average systolic blood pressure in standing, supine and sitting positions in the S-Amlodipine 2.5 mg treatment group were found to be 164.12 +/- 10.28, 165.72 +/- 10.88 and 165.24 +/- 10.66 mm of Hg respectively, which after treatment of six weeks changed to 144.9 +/- 7.4, 146.04 +/- 8.56 and 145.36 +/- 8.32 mm of Hg. The baseline values for average systolic blood pressure in standing, supine and sitting positions in the Amlodipine 5 mg treatment group were found to be 164.57 +/- 10.36, 166.47 +/- 10.58 and 165.81 +/- 10.54 mm of Hg respectively, which after treatment of six weeks changed to 154.42 +/- 6.33, 147.23 +/- 7.11 and 146.57 +/- 7.54 mm of Hg. The baseline values for average diastolic blood pressure in standing, supine and sitting positions in the S-Amlodipine 2.5 mg treatment group were found to be 99.63 +/- 6.22, 101.13 +/- 7.18 and 100.59 +/- 6.6 mm of Hg respectively, which after treatment of six weeks changed to 86.0 +/- 4.70, 87.18 +/- 5.20 and 86.27 +/- 5.68 mm of Hg. While the baseline values for average diastolic blood pressure in standing, supine and sitting positions in the Amlodipine 5 mg treatment group were found to be 98.95 +/- 5.54, 100.86 +/- 6.71 and 100.38 +/- 6.38 mm of Hg respectively, which after treatment of six weeks changed to 86.19 +/- 4.77, 87.52 +/- 5.44 and 87.33 +/- 5.98 mm of Hg. However the difference in the average reduction in systolic and diastolic blood pressures, in the two treatment groups, in the sitting, supine and the standing positions was not found to be statistically significant (p > 0.1) (CI = 0.95). There was no statistically significant change in the levels of serum creatinine, SGOT, SGPT, HDL, LDL, triglyceride and total cholesterol in patients receiving Amlodipine 5 mg. The reduction in total cholesterol as well as triglyceride level in the S-Amlodipine 2.5 mg treatment group was found to be greater but it failed to show any statistically significant difference. CONCLUSION: S-Amlodipine 2.5 mg is found to be equivalent in its efficacy and tolerability when compared to Amlodipine 5 mg in the treatment of mild to moderate hypertension.

Efficacy and safety of losartan-amplodipine combination--an Indian postmarketing surveillance experience.

The present study was conducted among 719 patients enrolled by 109 doctors to evaluate the efficacy and tolerability of the combination of losartan potassium and amlodipine besylate in Indian patients with mild to moderate hypertension. Out of them 11 patients were dropped out. Of these 708 patients 643 patients received once daily dosage of the combination whereas 10 patients received 1/2 daily, 13 patients received 1 1/2 daily and 42 patients received 1 twice daily dosage of the combination. The mean SBP in the study was 172.89 +/- 19.18 mm Hg baseline. After the 10-day treatment, the mean SBP had significant reduction ie, 13.1% from basal and at the end of day 20 of the treatment, the reduction was 19.13% from the baseline which was significant. Similarly mean DBP was 105.42 +/- 10.85 mm Hg at baseline. After treatment, the mean DBP had significant reduction. After 10- day treatment, there was 12.7% reduction from the baseline and at the end of the treatment ie, after day 20, the reduction was 17.70% from basal, which was significant. Global evaluation of efficacy was done by the physicians; 93.8% of the cases had excellent to good response and 4.9% patients had fair response. Details of any adverse event reported or noted during the treatment with the combination were recorded in the appropriate section of the case record form, whether considered treatment related or not, as reported by the patients. The severity of an adverse event was graded on a 3-point scale as mild, moderate and severe. The most common side-effects reported were oedema of feet (5.08%), ankle oedema (1.98%). Remaining adverse events included some cardiovascular events such as palpitations, gastro-intestinal events such as constipation, miscellaneous events, muscular pain, weakness, generalised swelling, etc. CNS events included giddiness, headache, insomnia, etc.

Hipertensión pulmonar e infección por VIH: comunicación de un caso / Pulmonary hypertension and HIV infection: 1 case report

Pulmonary hypertension associated to HIV infection has been reported in the literature with increased frequency. Apparently, this condition has a faster clinical evolution and a higher mortality than primary pulmonary hypertension. The pathogenic mechanisms of HIV associated pulmonary hypertension and the influence of its treatment on patientÕs evolution are not well known. We report a 32 years old homosexual male that developed a severe dyspnea in a period of 2 months. Echocardiogram demonstrated right ventricular dilatation and a systolic pulmonary artery pressure of 86 mm Hg. No other causes for pulmonary hypertension were found. Antiviral therapy and vasodilator treatment with a calcium channel blocker were started and the patient had an important subjective clinical improvement

Antagonistas dos canais de cálcio na insuficiência cardíaca congestiva / Calcium channel blockers in heart failure

A utilizaçäo dos antagonistas dos canais de cálcio no tratamento da disfunçäo ventricular esquerda e da insuficiência cardíaca congestiva tem sido proposta, principalmente, por seu potente efeito vasodilatador.Entretanto, a despeito da base teórica, os resultados dos estudos que exploram seu benefício nessas circunstância clínicas näo têm sido animadores.Talvez, porque os antagonistas dos canais de cálcio podem promover depressäo da contralidade, ativaçäo do sistema neuro-hormonal e alteraçäo desfavorável nos marcadores autonômicos.Os diidropiridínicos de primeira geraçäo demonstram efeitos deletérios sobre as condições hemodinâmicas e o estado clínico.O diltiazem acrescentou prejuízo, quando utilizado em disfunçäo sistólica devida a doença arterial coronária.O verapamil, que näo é utilizado em insuficiência cardíaca congestiva sistólica, monstrou ser benéfico na disfunçäo diastólica ventricular esquerda, como a nisoldipina.Esta última e a nicardipina näo foram consideradas seguras para uso em pacientes com insuficiência cardíaca congestiva moderada a grave.A felopidina näo apresentou diferença de resultados, em relaçäo à mortalidade e a tolerância ao esforço, quando comparada ao grupo placebo.Entretanto, a amlodipina demonstrou uma reduçäo significativa da mortalidade, em pacientes com insuficiência cardíaca congestiva secundária à cardiomiopatia näo isquêmica.Portanto, há que ser cauteloso na utilizaçäo dos antagonistas dos canais de cálcio de primeira geraçäo e considerar o benefício terapêutico demonstrado pela amlodipina, quando adicionada ao tratamento padräo da insuficiência cardíaca congestiva.

Hipertrofia ventricular izquierda regresión con lisinopril vs. amlodipino

Objetivo: la hipertrofia ventricular izquierda secundaria a hipertensión conlleva enfermedad coronaria, arritmia, falla cardíaca y muerte súbita. Se ha reportado regresión con el tratamiento farmacológico. Nosotros cuantificamos la respuesta a inhibidores ECA y calcioantagonistas, comparando su eficacia. Diseño:experimento clínico controlado, aleatorizado, ciego. Marco de referencia: Hospital Universitario San Juan de Dios de Bogotá, servicio de consulta externa, programa riesgos cardiovasculares. Pacientes: se seleccionaron los pacientes teniendo como criterios; hipertensión arterial (HTA) de recientes diagnóstico y sin medicación, sin enfermedad cardiovascular concomitante, no obesos ni atletas, entre octubre 1994 y junio 1997. Intervención: asignación aleatoria a tratamiento con lisinopril y amlodipino. Medición: ecocardiografía bidimensional al inicio y seis meses despúes de tratamiento farmacológico. Resultados: de 35 pacientes seleccionados, 30 finalizaron el estudio, los grupos fueron homogéneos, en cuanto a edad, peso, talla y cifras de presión arterial. Encontramos una prevalencia de 30 por ciento para hipertrofia y una regresión de 15.64 gr/m² en el grupo de lisinopril (10.6 por ciento) y 4.6 gr.m²(3.65 por ciento) en el grupo de amlodipino, diferencias no significativas. Control de presión arterial adecuada en ambos grupos de 150/104 al inicio a 140/84 en el grupo A y 159/105 a 139/84 en el grupo B, eficacia comparable. Conclusión: aunque hubo control adecuado de la presión arterial y regresión de la hipertrofia en más de 60 por ciento de los pacientes en ambos grupos, las diferencias no fueron estadísticamente significativas

Lisinopril vs amlodipina en la hipertension arterial esencial leve a moderada / Amlodipine vs lisinopril in the moderate a light essential artery hypertension

La hipertención arterial (HTA) es un importante factor de riesgo de enfermedad cardiovascular (FR-ECV); este riesgo se potencia por la presencia de otros FR-ECV. Treinta pacientes con presión arterial diastólica (PAD) entre 95 y 115 mmHg, fueron administrados a un ensayo clínico doble ciego con asignación aleatoria a recibir 5 mg diarios en la mañana de Lisinopril (LIS) o de Amlodipina (AML) y placebo de la otra droga. El tratamiento se mantenía durante 21 semanas y se aumentaba a 10 ó 20 mg/día en las semanas 3 y 6 si se obtenía PAD mayor e igual mmHg. La edad promedio en el grupo AML fue 39 años vs 43 años en el grupo LIS; es sexo masculino predominó en el grupo AML (71 por ciento) vs 31 por ciento). No hubo diferencias estadísticamente significativas en la presión arterial al inicio del estudio. Culminaron el estudio 21 pacientes: 8 en el grupo AML y 13 en el grupo LIS. No hubo variaciones significativas en las pruebas de laboratorio. La reducción en la presión arterial sistólica (PAS) y PAD fue estadísticamente significativa en la semana 21 respecto al inicio tanto para el grupo LIS como AML: para la PAS, de 15 a 20 mmHg enel grupo AML y de 11 a 16 mmHg en el grupo LIS; para la PAD, de 9 a 12 mmHg en el grupo AML y de 5 a 13 mmHg en el grupo LIS. Al final del estudio no hubo diferencias estadísticamente significativas en la presión arterial entre ambos grupos. El 100 por ciento de los pacientes del grupo AML y el 62 por ciento del grupo LIS presentaron algún tipo de efecto secundario. Se logró la reducción significativa en la presión arterial con LIS o AML luego de 21 semanas de tratamiento. La meta de control de presión arterial (PAD<90 mmHg) al final del estudio o al menos una reducción de 10 mmHg respecto al momento inicial) se logró, tomando en cuenta todas las posiciones de medición, en 62 por ciento del grupo LIS y 25 por ciento del grupo AML. En nuestro estudio, pacientes latinoamericanos presentaron reducción de presión arterial con LIS y AML similares a las obtenidas en estudios con pacientes blancos. Sin embargo, la prevalencia de efectos secundarios fue mayor, sobre todo con AML, pareciendo estar en proporción directa con la dosis y duración del tratamiento

Cambios hemodinámicos en la función sistólica, diastólica y la circulación periférica inducidas por amlodipina en pacientes con hipertensión arterial esencial asociada con disfunción ventricular izquierda / Hemodynamic changes in systolic and diastolic function and in the peripheral circulation induced by amlodipine in patients with essencial hypertension with left ventricular dysfunction

La hipertensión arterial afecta la función y la estructura cardiovascular, con hipertrofia y disfunción ventricular frecuentes, en especial en pacientes con cardiopatía isquémica asociada. Evaluamos 20 pacientes entre 40 y 70 años de edad, con diagnóstico de hipertensión esencial (presión arterial diastólica entre 95 y 115 mmHg) asociada a disfunción ventricular (fracción de eyección ó 45 por ciento). Se estudiaron por angiografía radioisotópica la función sistólica, la función diastólica y la circulación periférica en las siguientes etapas: A) al final del período lavado-placebo (pretratamiento); B) en fase aguda, a las 6 horas de amlodipina (10 mg) por vía oral; C) en fase crónica, al final de 8 semanas de igual tratamiento con monodosis. El tratamiento en fase aguda y crónica mostró una disminución significativa de la presión arterial sistólica, diastólica y de la resistencia periférica total (en un 15 por ciento, 14 por ciento y 20 por ciento respectivamente). El pico de llenado del ventrículo izquierdo basal fue 1,9 ñ 0,4 (VFD/S), mejorando un 21 por ciento en el tratamiento crónico en reposo y 17 por ciento durante el ejercicio ergométrico, lo que evidenció una mejoría de la función diastólica del ventrículo izquierdo (p<0,01). El volumen de fin de sístole o residual, aumentado como expresión de la falla de bomba, disminuyó en 15 y 19 por ciento en reposo y esfuerzo. En el pretratamiento los parámetros hemodinámicos muestran disfunción ventricular sistólica y diastólica del ventrículo izquierdo con compromiso del ventrículo derecho, tanto en reposo como en esfuerzo, con disminución de la reserva cardíaca. El efecto vasodilatador de la amlodipina, con disminución de la poscarga, produjo efectos hemodinámicos favorables, tanto en el control de la hipertensión arterial como en la mejoría de la disfunción biventricular asociada