RESUMO
This study is based on the premise that the application of chemical synthesis strategies to structurally modify commercial drugs by complexation with biometals is a valid procedure to improve their biological effects. Our purpose is to synthesize a compound with greater efficacy than the original drug, able to enhance its antihypertensive and cardiac pharmacological activity. Herein, the structure of the coordination compound of Zn(II) and the antihypertensive drug olmesartan, [Zn(Olme)(H2O)2] (ZnOlme), is presented. After 8 weeks of treatment in SHR male rats, ZnOlme displayed a better blood pressure-lowering activity compared with olmesartan, with a noticeable effect even in the first weeks of treatment, while ZnCl2 showed similar results than the control. ZnOlme also reduced left ventricle (LV) weight and left ventricle/tibia length ratio (LV/TL), posterior wall thickness (PWT), and intraventricular septum in diastole (IVSd) suggesting its potential to prevent LV hypertrophy. Besides, ZnOlme reduced interstitial fibrosis (contents of collagen types I and III, responsible for giving rigidity and promoting vascular elasticity, respectively). The recovery of heart function was also evidenced by fractional shortening (diastolic left ventricular/systolic left ventricular) diameter determinations. Furthermore, ZnOlme increased the antioxidant capacity and prevented cardiac oxidative stress: it enhanced the reduction of reactive oxygen species generation, exerted a significant decrease in lipid peroxidation and enhanced glutathione contents in heart tissues compared to the control, Zn, and olmesartan treatments. Our results demonstrate that continuous oral administration of ZnOlme causes a better antihypertensive effect and grants enhancement of cardioprotection through antioxidant activity, in combination with hemodynamic improvement.
Assuntos
Anti-Hipertensivos , Hipertensão , Ratos , Animais , Masculino , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Ratos Endogâmicos SHR , Pressão Sanguínea , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Zinco/farmacologia , Zinco/uso terapêuticoRESUMO
There are few studies addressing duodenal inflammation. This study was designed to investigate the effects of a recently developed biotechnological product, a nano-formulation of olmesartan medoxomil (OM) - olmesartan medoxomil zeinmersomes (OMZ) - for the treatment of indomethacin-induced duodenitis in rats. Adult male Wistar rats were given indomethacin (10 mg/kg/day) for four weeks. They were divided into a positive control group (PC, untreated) and two groups treated orally with 3 mg/kg per day of OM or OMZ for the last two weeks of the 4-week indomethacin-treatment. At end of the four weeks, blood and duodenum were collected. Duodenal homogenate was used for measurement of levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, reduced glutathione (GSH), and cleaved caspase-3. Duodenal sections were stained with H&E. Gene expressions of nuclear factor kappa B (NF-κB p65), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) by RT-PCR, and protein expression of survivin by western blot were assessed. Plasma and duodenal olmesartan concentrations were measured by high performance liquid chromatography mass spectrometry. The duodenitis rats showed significantly higher duodenal levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and cleaved caspase-3, a significantly lower GSH level, and histopathological alterations. Moreover, they showed upregulated gene expressions of NF-κB p65 and Bax, downregulated gene expression of Bcl-2, decreased Bcl-2/Bax ratio, and lower protein expression of survivin. OMZ was more effective in protecting the duodenum from indomethacin-induced injuries compared to OM due to improved delivery, higher bioavailability, and better anti-inflammatory, antioxidant, and antiapoptotic effects. OMZ could be a better choice for hypertensive patients with non-steroidal anti-inflammatory drugs-induced duodenitis.
RESUMO
Resumen La diarrea crónica es una patología frecuente con un amplio diagnóstico diferencial. Presentamos el caso de un paciente con diarrea crónica secundaria a enterocolopatía por la toma prolongada de olmesartán. Se trata de una patología infradiagnosticada por desconocimiento de la entidad, pero que debe considerarse en base a la frecuencia de uso del grupo farmacológico. En nuestro caso, la buena evolución clínica tras la retirada del fármaco nos muestra la necesidad de considerarlo como causa directa del cuadro clínico. Un adecuado enfoque terapéutico en estos pacientes nos permitirá evitar pruebas complementarias, costos innecesarios y se traducirá en una mejora diagnóstica y del pronóstico de estos pacientes. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2203).
Abstract Chronic diarrhea is a common pathology with a broad differential diagnosis. We present the case of a patient with chronic diarrhea secondary to enteropathy due to prolonged consumption of olmesartan. This is an underdiagnosed pathology due to lack of knowledge regarding this entity, but it should be considered, given the frequency with which this pharmacological group is used. In our case, the favorable clinical progression after withdrawing the medication indicates the need to consider it as the direct cause of the clinical picture. An appropriate therapeutic approach to these patients will allow us to avoid complementary tests and unnecessary costs, and will translate into a better diagnosis and prognosis in these patients. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2203).
RESUMO
A drug-drug and drug-excipient interactions and compatibilities study was conducted for two fixed-dose combination (FDC) products containing olmesartan medoxomil (OLM)/hydrochlorothiazide (HCT) 20/12.5 mg and OLM/HCT 40/12.5 mg during their development including storage. The study consisted of the evaluation of samples retrieved during all stages of a real manufacturing process. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR), and contact angle techniques were applied to the samples to determine interactions and incompatibilities. Dissolution tests and long-term stability studies were conducted to evaluate dosage form performance. Results showed weak solid-state interactions able to obtain a eutectic mixture of OLM and HCT while microcrystalline cellulose (MC) impacted the thermal stability of both drugs. Reliable dissolution and long-term stability tests confirmed that the interactions observed were not considered incompatibilities because they were not influenced by the performance of the final products.
RESUMO
BACKGROUND: Angiotensin II is a potent activator of the Rho-kinase (ROCK) pathway, through which it exerts some of its adverse vasoconstrictor effects. Clinical evidence on the effects of blocking the angiotensin II receptor 1 on ROCK activity in hypertensive patients is scarce. OBJECTIVE: To demonstrate that ROCK activity in peripheral blood mononuclear cells (PMBCs) in patients with essential hypertension is reduced earlier than previously observed, along with blood pressure (BP) lowering on treatment with olmesartan. METHODS: Prospective pilot open study; 17 hypertensive patients were treated with progressive olmesartan doses starting with 20 mg qd. BP was measured at 3, 6 and 9 weeks after treatment initiation. If treatment failed to normalize BP after 3 weeks, olmesartan dose was increased to 40 mg qd, and if still hypertensive after 6 weeks, 12.5 mg of hydrochlorothiazide qd was added. ROCK activity was measured at baseline and 9 weeks after treatment as myosin phosphatase target subunit 1 phosphorylation (MYPT1-p/T ratio) in PBMC. RESULTS: Mean baseline BP was 162 ± 4.9/101 ± 2.4 mmHg. After 9 weeks of treatment, both systolic and diastolic BP were reduced by 41 and 22 mmHg, respectively (p<0.05). Mean pretreatment MYPT1- p/T ratio in PMBCs was significantly reduced by 80% after 9 weeks with olmesartan (p<0.01). CONCLUSION: Normotension achieved after 9 weeks in 82% of the patients treated with olmesartan was associated with a significant reduction of ROCK activity in PBMC.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Essencial/tratamento farmacológico , Imidazóis/administração & dosagem , Leucócitos Mononucleares/efeitos dos fármacos , Tetrazóis/administração & dosagem , Quinases Associadas a rho/metabolismo , Adulto , Regulação para Baixo , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/enzimologia , Hipertensão Essencial/fisiopatologia , Feminino , Humanos , Leucócitos Mononucleares/enzimologia , Masculino , Pessoa de Meia-Idade , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Fosforilação , Projetos Piloto , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Los Inhibidores de la enzima convertidora de angiotensina II (IECAs) y antagonistas de los receptores de angiotensina II (ARA II) son drogas usadas comúnmente en el manejo de hipertensión arterial, sin embargo, su uso en el embarazo está asociado con toxicidad fetal.1, 2 La acción de la angiotensina II requiere su unión a dos receptores; AT1, involucrado en el control de la tensión arterial y AT2, probablemente encargado del crecimiento fetal. 2 La angiotensina II es esencial en la hemodinamia sistémica y la filtración glomerular fetal y neonatal. La disminución de la perfusión placentaria por efecto hipotensor en el bloqueo del sistema renina angiotensina aldosterona materno puede determinar hipotensión fetal sistémica, disminución de la filtración glomerular, oligoamnios e insuficiencia renal, anormalidades tubulares, hipoplasia craneal y alto riesgo de muerte perinatal. 2 Reportamos el caso de prematuro de 30 semanas con oligohidramnios severo y exposición materna a olmesartan. Al nacimiento presentó dificultad respiratoria; imposibilidad de mantener una adecuada tensión arterial a pesar de los esfuerzos para conseguir mejorar su tono vascular; anuria sin respuesta a diuréticos; alteraciones craneales; alteraciones metabólicas severas con consecuencias fatales. El tratamiento de hipertensión materna con inhibidores de la enzima convertidora de angiotensina II y los antagonistas de los receptores de angiotensina II está asociada con toxicidad fetal por lo que su uso debe ser evitado durante el embarazo.
Angiotensin II converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARBs) are drugs for general use in the management of arterial hypertension, however their use in gestational hypertension is related to the Fetal toxicity. 1, 2 The action of angiotensin II requires its binding to two receptors; AT1, involved in the control of blood pressure and AT2, probably responsible for fetal growth.2 Angiotensin II is essential in systemic hemodynamics and fetal and neonatal glomerular filtration. The decrease in placental perfusion due to hypotensive effect in the blockade of the maternal rennin angiotensin aldosterone system can determine systemic fetal hypotension, decreased glomerular filtration, oligohydramnios and renal insufficiency, tubular abnormalities, cranial hypoplasia and high risk of perinatal death. 2 We report the case of prematurity of 30 weeks with a history of severe oligohydramnios and maternal exposure to olmesartan. At birth the patient presented in particular respiratory distress; inability to maintain adequate blood pressure despite efforts to improve your vascular tone; anuria without response to diuretics; cranial alterations; metabolic alterations with fatal consequences. The treatment of maternal hypertension with inhibitors of the angiotensin II convective enzyme and angiotensin II receptor antagonists is associated with fetal toxicity and should therefore be avoided during pregnancy
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Oligo-Hidrâmnio , Nascimento Prematuro , Insuficiência Renal , Angiotensina II , Exposição Materna , Hipertensão Induzida pela Gravidez , Desenvolvimento Fetal , Toxicidade , HipotensãoRESUMO
BACKGROUND: The aim of this study was to evaluate the effect of olmesartan medoxomil (Olme), an angiotensin II receptor antagonist, on oral mucositis (OM) experimental model. METHODS: Oral mucositis was induced in hamsters with 5-fluorouracil (5-FU; 60 mg/kg day 1 and 40 mg/kg day 2). Animals (n = 10/group) were pretreated with oral Olme (1, 5, or 10 mg/kg) or vehicle 30 minutes before 5-FU injection and daily, until day 10. Cheek pouch samples were subjected to histopathological and immunostaining analysis of IL-1ß, TNF-α, IL-10, TGF-ß, macrophage migration inhibitory factor (MIF), SOD, MMP-2 and FGF-2. In addition, IL-1ß and TNF-α levels were evaluated by ELISA. Myeloperoxidase activity (MPO), glutathione (GSH) and malondialdehyde (MDA) levels were investigated by spectroscopic UV/VIS analysis. Reverse transcriptase polymerase chain reactions (RT-PCRs) were used to quantify the expression of IL-1ß, TNF-α, NF-κBp65, MKP1 and ACE2. Inducible nitric oxide synthase (iNOS) and extracellular regulated kinase (ERK)1/2 protein levels were analysed by Western blot. RESULTS: Treatment with 10 mg/kg Olme reduced ulceration, inflammatory cell infiltration, MPO activity, MDA levels, iNOS and ERK1/2 proteins levels, MIF expression and TNF-α and IL-1ß of levels and gene expression. These findings were associated with a significant increase in the immunostaining of IL-10, FGF-2 and TGF-ß. In addition, gene expression of IL-1ß, TNF-α, NF-κBp65 MKP1 and ACE2 was decreased. CONCLUSION: Olmesartan at a dose of 10 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.
Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Olmesartana Medoxomila/farmacologia , Olmesartana Medoxomila/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Estomatite/tratamento farmacológico , Estomatite/metabolismo , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Cricetinae , Fluoruracila/efeitos adversos , Masculino , Mesocricetus , Modelos Animais , Estomatite/induzido quimicamenteRESUMO
BACKGROUND: Emerging evidence has shown a significant deficit in the control of hypertension (blood pressure <140/90 mmHg) among Hispanics or Latinos in about 65%. This study aims to determine the efficacy of the combination in fixed doses of olmesartan and amlodipine (20/5, 40/5, and 40/10 mg) in hypertensive patients treated in daily clinical practice by Colombian doctors. METHODS: This was an observational, retrospective, open-label, multi-center, non-comparative study. The primary outcome was a change in systolic and diastolic blood pressure from the baseline to week 12; the secondary outcome was the proportion of patients achieving a target blood pressure of <140/90 mmHg. Safety and tolerability were also evaluated. For analysis, a student t test was used for paired data, McNemar test, and ANCOVA. RESULTS: A total of 428 patients were enrolled from 16 centers in Colombia. At 12 weeks, patients' systolic blood pressure decreased in response to all three doses: by 27.75 ± 20.73 mmHg in 20/5 mg, 31.13 ± 22.23 mmHg in 40/5 mg, and 46.96 ± 20.15 mmHg in 40/10 mg (all p < 0.001). Furthermore, the diastolic blood pressure decreased by 14.19 ± 12.89 mmHg in 20/5 mg, 16.25 ± 10.87 mmHg in 40/5 mg, and 24.83 ± 10.41 mmHg in 40/10 mg (all p < 0.001). The percentage of patients achieving target blood pressure was 71.31% in 20/5 mg, 70.16% in 40/5 mg, and 63.33% in 40/10 mg. CONCLUSIONS: This study demonstrates the efficacy of the combination in fixed doses of olmesartan and amlodipine in the treatment of Colombian hypertensive patients.
Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Colômbia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
La diarrea es un efecto secundario habitual a la toma de fármacos, y en algunas ocasiones la enteropatía perdedora de proteínas tipo "sprue like" puede estar detrás de esta patología. El estudio de esta enfermedad puede suponer un desafío importante para el clínico, sobre todo en los casos que cursan con serología negativa para enfermedad celiaca. La atrofia vellositaria duodenal secundaria a la ingesta de micofenolato-mofetil y metotrexate es bien conocida y descrita desde hace tiempo, pero desde la inclusión en la posológica habitual de olmesartán como antihipertensivo de primera elección hemos objetivado un repunte importante de esta entidad. Debido al amplio uso de esta medicación, queremos poner de manifiesto esta enteropatía iatrogénica a través de dos casos clínicos ocurridos en nuestro hospital en 2014.(AU()
Diarrhea is a common side effect of medical treatment. "Sprue like" enteropathy may be behind this pathology. The study of this disease can be an important clinical challenge, especially in those cases with negative serology for celiac disease. Duodenal villous atrophy secondary to the intake of mycophenolate mofetil and methotrexate have been well known and described but since the inclusion of olmesartán as a first-line antihypertensive, we have seen an important rebound of this entity. Due to the wide use of this medication we want to report this iatrogenic effect through two clinical cases that occurred in our hospital in 2014.(AU)
Assuntos
Humanos , Masculino , Feminino , Doença Celíaca , Olmesartana Medoxomila , Atrofia , Diarreia , Insuficiência Renal , EnteropatiasRESUMO
A enteropatia induzida por olmesartana é uma entidade reconhecida recentemente como diagnóstico diferencial de atrofia vilosa. A apresentação clínica é semelhante à doença celíaca, porém a não resposta à retirada do glúten e sorologia antitransglutaminase negativa são chaves para o diagnóstico diferencial. A fisiopatologia é incerta, havendo especulações quanto à predisposição genética e mecanismo de ação da própria droga. A melhora clínica e histológica após a suspensão da medicação é a principal característica. Aqui reportamos um caso de enteropatia induzida por olmesartana de apresentação clínica aguda.(AU)
The olmesartan induced enteropathy is a recently recognized entity in the differential diagnosis of villous atrophy. The clinical presentation is similar to celiac disease, but transglutaminase negative sorology and noimprovement after gluten removal are key to the differential diagnosis. The pathophysiology is uncertain, withspeculations about genetic predisposition and the medication's mechanism of action itself. The clinical and histological improvement after drug discontinuation is the main feature. Here we report a case of Olmesartaninduced enteropathy with acute clinical presentation.(AU)
Assuntos
Humanos , Feminino , Idoso , Olmesartana Medoxomila/efeitos adversos , Enteropatias , Atrofia , Doença CelíacaRESUMO
Os sistemas multiparticulados são aqueles nos quais a dose do fármaco está dividida em pequenas unidades funcionais, tendo assim, uma série de vantagens sobre os sistemas monolíticos convencionais. Este trabalho teve por objetivo desenvolver formulações multiparticuladas de uso oral para fármacos anti-hipertensivos que serão utilizados na composição de associações. O material está dividido em seis capítulos, sendo inicialmente apresentada uma revisão da literatura a respeito da caracterização física destas pequenas unidades. Ensaios como análise granulométrica, morfologia, densidade, porosidade, avaliação de resistência mecânica e desintegração são os mais empregados para esta finalidade, possibilitando ao formulador conhecer os fatores de maior impacto relacionados às matérias primas e ao processo de fabricação no comportamento das formulações produzidas. Os demais capítulos seguem com o desenvolvimento dos sistemas multiparticulados, que foram embasados em diferentes delineamentos experimentais, seja pela utilização de planejamento fatorial fracionado ou projeto de mistura. Para o metoprolol, fármaco de alta solubilidade, foram produzidas formulações de liberação controlada, sendo a estratégia dividida em três etapas: (I) Produção de minicomprimidos revestidos, nos quais foram avaliadas diferentes combinações do polímero modulador de liberação; (II) otimização do perfil de liberação do fármaco, com avaliação de misturas das formulações produzidas na primeira etapa; (III) Processo de extrusão a quente, no qual diferentes proporções de fármaco e polímero hidrofóbico foram avaliadas. Para os fármacos hidroclorotiazida e olmesartana medoxomila, ambos de baixa solubilidade, a estratégia adotada foi a incorporação de uma dispersão dos fármacos e agentes solubilizantes em grânulos inertes obtidos por extrusão/revestimento. Adicionalmente, também foram produzidas formulações por extrusão a quente de diferentes proporções destes fármacos em polímero hidrofílico. De acordo com os resultados obtidos, foi possível obter formulações de minicomprimidos e grânulos com perfil de dissolução satisfatório, semelhantes aos apresentados pelos medicamentos adotados como referência. Em relação à extrusão a quente foi possível avaliar a influência do processo e polímeros empregados no perfil de dissolução dos grânulos produzidos
Multiparticulate systems are dosage forms in which dose is divided into small functional units presenting some advantages over monolithic conventional systems. The objective of this work was developing multiparticulate formulations for oral use containing antihypertensive drugs to be used in association. The thesis is divided into six issues, been first presented a literature review about physical characterization of multiparticulate systems. Granulometric analysis, morphology, density, porosity, mechanical strength and disintegration are the most used physical characterization tests, enabling formulator knowing the major impact factors related to raw materials and manufacturing process in the performance of the produced formulations. The other issues present the development of the multiparticulate systems based on different statistical experimental design, as fractional factorial design or mixture project. For metoprolol, a highly soluble drug, controlled release formulations were obtained, and the strategy was divided into three steps: (I) coated minitablets production, where different combinations of the controlled release polymer were analyzed; (II) drug release profile optimization, evaluating formulations mixtures produced in the first step; (III) hot melt extrusion process, where different drug: hydrophobic polymer ratios were evaluated. For hydrochlorothiazide and olmesartan medoxomil, both low soluble drugs, the strategy was incorporating a dispersion containing the drugs and solubilizing agents in inert granules obtained by extrusion/coating processes. Additionally, formulations containing different ratios of these drugs and hydrophilic polymers were produced by hot melt extrusion. According to the results, it was possible to obtain minitablets and granules with good dissolution profile, similar to the reference products. Regarding to hot melt extrusion, it was possible to evaluate the influence of process and polymers used in the dissolution profile of the produced granules
Assuntos
Preparações Farmacêuticas/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Olmesartana Medoxomila/administração & dosagem , Hidroclorotiazida/administração & dosagem , Hipertensão/complicações , Metoprolol/efeitos adversosRESUMO
OBJECTIVES: Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning. METHODS: Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF-1α mRNA expression, miR-21 expression and miR-210 expression were measured. RESULTS: Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF-1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. CONCLUSION: The results indicate that (1) the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1α, ...
Assuntos
Animais , Ratos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Imidazóis/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Tetrazóis/farmacologia , Modelos Animais de Doenças , Precondicionamento Isquêmico Miocárdico , Distribuição Aleatória , Ratos Endogâmicos SHRRESUMO
Se realizó un estudio multicéntrico, observacional, abierto no controlado para evaluar la eficacia de olmesartán en dosis de 20 y 40 mg administrados una vez al día en pacientes mexicanos con hipertensión arterial sistémica. Participaron 39 cardiólogos de 22 ciudades de la República Mexicana y se incluyeron a 350 pacientes (57% mujeres y 43% hombres), con edad promedio de 59.25 ± 13.53 años, rango de 24 a 92 años. Los valores promedio de la presión arterial sistólica en la visita inicial y final fueron de 152.8 ± 16.3 mmHg y 125.8 ± 10.9 mmHg y de la presión arterial diastólica fue 89.7 ± 11.3 mmHg y 77.0 ± 7.8 mmHg respectivamente. De acuerdo con la prueba t de Student, la disminución resultó estadísticamente significativa (p < 0.01). Para obtener estos resultados se administraron dosis de 20 mg en 36% de los pacientes y 40 mg en 64%. Se observó respuesta de eficacia global al tratamiento en 88% de los pacientes tratados. Se tomó como respuesta adecuada al tratamiento, presiones menores a 140/90 mmHg o reducción mayor a 10% de las cifras de tensión arterial, en relación con los valores basales al término de doce semanas de tratamiento. Se presentaron eventos adversos no significativos con tasa menor a 4.2% de los pacientes, la mayoría considerados como eventos adversos ya conocidos del medicamento. Podemos concluir que el uso de olmesartán probó ser un antihipertensivo eficaz y seguro en el tratamiento de la hipertensión arterial sistémica en pacientes mexicanos.
A multicentre, observational, open-label, non-controlled trial was performed to evaluate the efficacy of Olmesartan at doses of 20 and 40 mg administered once daily in Mexican patients with arterial hypertension. Thirty nine cardiologists from 22 cities of the Mexican Republic participated, 350 patients were included (57% women and 43% men), with mean age of 59.25 ± 13.53 years within a range of 24 to 92 years. The mean values of systolic blood pressure at the initial and final visit were 152.8 ± 16.3 mmHg and 125.8 ± 10.9 mmHg, and those for diastolic blood pressure were 89.7 ± 11.3 mmHg and 77.0 ± 7.8 mmHg, respectively. According to t Student's test, the reduction was statistically significant (p < 0.01). To achieve these results, doses of 20 mg were administered to 36% of patients and 40 mg to 64%. An efficacy response to treatment was observed in 88% of the patients treated. Blood pressures lower than 140/90 mmHg or a reduction greater than 10% of the blood pressure figures relative to baseline values at the end of twelve weeks of treatment were considered an adequate response to treatment. Non-significant adverse events occurred at a rate lower than 4.2% of patients. Most were considered as known adverse events of the drug. We can conclude that the use of Olmesartan, proved to be an effective and safe antihypertensive drug in the treatment of systemic arterial hypertension in Mexican patients.
RESUMO
Although the awareness and control of hypertension has increased, only 37% of hypertensive patients in the US achieve the conservative goal of <140/90 mmHg. Achieving optimal blood pressure (BP) control is the most important single issue in the management of hypertension, and in most hypertensive patients, it is difficult or impossible to control BP with one drug. Blocking two or more BP regulatory systems provides a more effective and more physiologic reduction in BP, and current guidelines have recommended the use of combination therapy as first-line treatment, or early in the management of hypertension. Fixed combination therapy is an efficacious, relatively safe, and may be cost-effective method of decreasing BP in most patients with essential hypertension. Similar to other combinations, fixed-dose combination tablets containing the dihydropyridine calcium channel blocker amlodipine and the angiotensin II receptor blocker olmesartan bring together two distinct and complementary mechanisms of action, resulting in improved BP control and potential for improved target organ protection relative to either class of agent alone.
Assuntos
Anlodipino/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Hipertensão/tratamento farmacológico , Imidazóis/administração & dosagem , Tetrazóis/administração & dosagem , Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Combinação de Medicamentos , Humanos , Imidazóis/uso terapêutico , Cooperação do Paciente , Comprimidos , Tetrazóis/uso terapêuticoRESUMO
FUNDAMENTO: As diretrizes nacionais e internacionais enfatizam a importância do tratamento eficaz da hipertensão arterial. Apesar disso, verificam-se baixos índices de controle e alcance das metas preconizadas, indicando que é importante planejar e implementar melhores estratégias de tratamento. OBJETIVO: Avaliar a eficácia de um tratamento, em escalonamento de doses, tendo como base a olmesartana medoxomila. MÉTODOS: Este é um estudo aberto, nacional, multicêntrico e prospectivo, de 144 pacientes com hipertensão arterial primária nos estágios 1 e 2, virgens de tratamento ou após período de washout de duas a três semanas para aqueles em tratamento ineficaz. Avaliou-se o uso da olmesartana medoxomila num algoritmo de tratamento, em quatro fases: (i) monoterapia (20 mg), (ii-iii) associada à hidroclorotiazida (20/12,5 mg e 40/25 mg) e (iv) adição de besilato de anlodipino (40/25 mg + 5 mg). RESULTADOS: Ao fim do tratamento, em escalonamento, 86 por cento dos sujeitos de pesquisa alcançaram a meta de pressão arterial (PA) < 130/85 mmHg. Ocorreram reduções na pressão arterial sistólica (PAS) e na pressão arterial diastólica (PAD) de, no máximo, -44,4 mmHg e -20,0 mmHg, respectivamente. A taxa dos respondedores sistólicos (PAS > 20 mmHg) foi de 87,5 por cento e diastólicos (PAD > 10 mmHg) de 92,4 por cento. CONCLUSÃO: O estudo se baseou em um esquema de tratamento semelhante à abordagem terapêutica da prática clínica diária e mostrou que o uso da olmesartana medoxomila, em monoterapia ou em associação a hidroclorotiazida e anlodipino, foi eficaz para o alcance de meta para hipertensos dos estágios 1 e 2.
BACKGROUND: The national and international guidelines emphasize the importance of the effective treatment of essenssial hypertension. Nevertheless, low levels of control are observed, as well as low attainment of the recommended goals, indicating that it is important to plan and implement better treatment strategies. OBJECTIVE: To evaluate the efficacy of a based treatment algorithm with olmesartan medoxomil. METHODS: This is an open, national, multicentric and prospective study of 144 patients with primary arterial hypertension, stages 1 and 2, naïve to treatment or after a 2-to-3 week washout period for those in whom treatment was ineffective. The use of olmesartan medoxomil was assessed in a treatment algorithm divided into 4 phases: (i) monotherapy (20 mg), (ii-iii) associated to à hydrochlorothiazide (20/12.5 mg and 40/25 mg) and (iv) addition of amlodipine besylate (40/25 mg + 5 mg). RESULTS: At the end of the phased-treatment, 86 percent of the study subjects attained the goal of BP < 130/85 mmHg. Maximum reductions in SAP and DAP were -44.4 mmHg and -20.0 mmHg, respectively. The rate of systolic responders (SAP > 20 mmHg) and of diastolic responders (DAP > 10 mmHg) was 87.5 percent and 92.4 percent, respectively. CONCLUSION: The study was based on a treatment regimen that was similar to the therapeutic approach in daily clinical practice and showed that the use of olmesartan medoxomil in monotherapy or in association with hydrochlorothiazide and amlodipine was effective in the attainment of the recommended goals for hypertension stage 1 and 2 hypertensive individuals.