Реферат
Resumo Fundamento Qualidade de imagem e dose de radiação são otimizadas com uma frequência cardíaca (FC) lenta e estável na realização de imagens de artérias coronárias durante a angiografia cardíaca por tomografia computadorizada (CCTA, do inglês cardiac computed tomography angiography) A segurança, a eficácia e o protocolo para a redução da FC com medicamento betabloqueador ainda não foi bem descrita em uma população de pacientes pediátricos. Objetivo Oferecer um protocolo de dose de metoprolol eficiente a ser usado em pacientes pediátricos externos durante a CCTA. Métodos Realizamos uma revisão retrospectiva de todos os pacientes pediátricos externos que receberam o metoprolol durante a CCTA. As características demográficas e clínicas foram resumidas e a redução média em FC foi estimada utilizando-se um modelo de regressão linear multivariada. As imagens foram avaliadas em uma escala de 1 a 4 (1= ideal). Resultados Um total de 78 pacientes externos passaram a uma CCTA com o uso de metoprolol. A média de idade foi de 13 anos, a média de peso foi de 46 kg, e 36 pacientes (46%) eram do sexo masculino. As doses médias de metoprolol foram 1,5 (IQR 1,1; 1,8) mg/kg, e 0,4 (IQR 0,2; 0,7) mg/kg para administrações orais e intravenosas, respectivamente. O produto dose-comprimento por exame foi de 57 (IQR 30, 119) mGy*cm. A redução média da FC foi 19 (IQR 12, 26) batimentos por minuto, ou 23%. Não foram relatadas complicações ou eventos adversos. Conclusão O uso de metoprolol num cenário de pacientes pediátricos externos para redução da FC antes de uma CCTA é seguro e eficiente. Pode-se reproduzir um protocolo de dose de metoprolol quando for necessário atingir uma FC mais lenta, garantindo tempos de aquisição mais rápidos, imagens mais claras e redução na exposição à radiação nessa população. (Arq Bras Cardiol. 2021; 116(1):100-105)
Abstract Background Image quality and radiation dose are optimized with a slow, steady heart rate (HR) when imaging the coronary arteries during cardiac computed tomography angiography (CCTA). The safety, efficacy, and protocol for HR reduction with beta blocker medication is not well described in a pediatric patient population. Objective Provide a safe and efficient metoprolol dose protocol to be used in pediatric outpatients undergoing CCTA. Methods We conducted a retrospective review of all pediatric outpatients who received metoprolol during CCTA. Demographic and clinical characteristics were summarized and the average reduction in HR was estimated using a multivariate linear regression model. Images were evaluated on a 1-4 scale (1= optimal). Results Seventy-eight pediatric outpatients underwent a CCTA scan with the use of metoprolol. The median age was 13 years, median weight of 46 kg, and 36 (46%) were male. The median doses of metoprolol were 1.5 (IQR 1.1, 1.8) mg/kg and 0.4 (IQR 0.2, 0.7) mg/kg for oral and intravenous administrations, respectively. Procedural dose-length product was 57 (IQR 30, 119) mGy*cm. The average reduction in HR was 19 (IQR 12, 26) beats per minute, or 23%. No complications or adverse events were reported. Conclusion Use of metoprolol in a pediatric outpatient setting for HR reduction prior to CCTA is safe and effective. A metoprolol dose protocol can be reproduced when a slower HR is needed, ensuring faster acquisition times, clear images, and associated reduction in radiation exposure in this population. (Arq Bras Cardiol. 2021; 116(1):100-105)
Тема - темы
Humans , Male , Child , Adolescent , Coronary Artery Disease , Metoprolol/adverse effects , Outpatients , Radiation Dosage , Retrospective Studies , Coronary Angiography , Computed Tomography Angiography , Heart RateРеферат
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
Тема - темы
Pharmaceutical Preparations/administration & dosage , Antihypertensive Agents/adverse effects , Olmesartan Medoxomil/administration & dosage , Hydrochlorothiazide/administration & dosage , Hypertension/complications , Metoprolol/adverse effectsРеферат
Objetivos Determinar los posibles resultados negativos asociados a la medicación mediante la metodología de búsqueda activa de posibles interacciones medicamentosas 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 de Audifarma S.A a unos 4 millones de usuarios del país, se hizo una revisión sistemática de estadísticas de una serie de medicamentos identificados por presentar interacciones de riesgo, dosis diferentes a las recomendadas o dispensación irregular. Los casos son socializados con las EPS responsables. Resultados Se encontró un caso de nefrotoxicidad por ácido zoledrónico; el 37,0 por ciento de los usuarios de clopidogrel recibían concomitantemente omeprazol, que reduce la efectividad del primero; el 29,9 por ciento de los pacientes que toman losartan están recibiendo dosis superiores a las recomendadas para su indicación; el 2,0 por ciento de los pacientes que toman metoprolol o verapamilo, los recibe simultáneamente, con riesgo de generar bradicardia sinusal, bloqueos auriculoventriculares o disfunción sistólica. Todos los casos fueron notificados a los responsables en la EPS que atienden estos pacientes. Discusión La farmacovigilancia activa permite optimizar recursos, prevenir eventos adversos que puedan potencialmente causar morbilidad importante o incluso letalidad o determinar problemas que podrían ser responsables del fracaso terapéutico. Este tipo de estrategia se anticipa a la aparición de posibles riesgos para el paciente por lo que se recomienda considerarla para reforzar los programas de vigilancia de uso de medicamentos en el país.
Objectives Determining negative results associated with medication through an active search of possible drug interactions in databases for patients affiliated to the Colombian general social security/health system. Methods Statistics related to Audifarma S.A. dispensation drug databases for about 4 million Colombian users were systematically reviewed for identifying drugs having known interactions involving risk, doses different from recommended ones or irregular dispensation. The pertinent health-care providing services were made aware of the above. Results There was one case of nephrotoxicity being caused by zoledronic acid. 37 percent of clopidogrel users concomitantly received omeprazole which reduces the former's effectiveness. 29.9 percent of patients who were taking losartan were receiving doses higher than the recommended ones. 2.0 percent of patients who were taking metoprolol or verapamil were simultaneously receiving them, at the risk of generating first-degree heart block, bradycardia, or systolic dysfunction. All these cases were notified to the pertinent health-care services. Conclusions Active pharmacosurveillance leads to resources being optimised, adverse events which can potentially cause morbidity or lethality being prevented or even determining problems which could be responsible for therapeutic failure. This type of strategy anticipates the appearance of possible risks for patients, meaning that drug use monitoring programmes in Colombia should be reinforced.
Тема - темы
Humans , Adverse Drug Reaction Reporting Systems , Drug-Related Side Effects and Adverse Reactions/epidemiology , Medication Systems/statistics & numerical data , National Health Programs/statistics & numerical data , Adverse Drug Reaction Reporting Systems/organization & administration , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/pharmacokinetics , Colombia , Diphosphonates/adverse effects , Drug Interactions , Imidazoles/adverse effects , Losartan/adverse effects , Medication Systems/organization & administration , Metoprolol/administration & dosage , Metoprolol/adverse effects , Metoprolol/pharmacokinetics , Omeprazole/administration & dosage , Omeprazole/pharmacokinetics , Retrospective Studies , Social Security , Software , Ticlopidine/administration & dosage , Ticlopidine/adverse effects , Ticlopidine/analogs & derivatives , Ticlopidine/pharmacokineticsТема - темы
Humans , Adrenergic beta-Antagonists/adverse effects , Perioperative Care/standards , Randomized Controlled Trials as Topic , Surgical Procedures, Operative/methods , Adrenergic beta-Antagonists/administration & dosage , Metoprolol/administration & dosage , Metoprolol/adverse effects , Myocardial Infarction/prevention & control , Perioperative Care/methods , Stroke/chemically inducedРеферат
In 102 cases of severe hypertension (DBP > or = 115 mm Hg), with or without acute complications, efficacy and safety of SL Nifedipine 10 mg (NIF), SL Captopril 25 mg (CAP), IV Metoprolol 15 mg (MET) and SL NIF + IV MET were studied in an inpatient trial. Maximum mean percent reduction in SBP was 13.3, 9.7, 15.7 and 19.9 and in DBP was 21.2, 13.9, 12.5 and 20.4 with NIF, CAP, MET and NIF + MET respectively. A safe DBP of < or = 110 mm Hg (Kaplan) was achieved in 90, 61, 72.2 and 95.2 percent of patients. A statistically significant fall in DBP was observed at 5 minutes with all regimens except CAP which was at 15 minutes. Mild side effects observed were palpitations and flushing (NIF n = 4), taste disturbances (CAP n = 3), heaviness of head (CAP n = 1) and giddiness (MET n = 2, NIF + MET n = 2). The trial data suggest that hypertensive crisis can be managed, without intensive care facility, with all four regimens; this implies significant cost containment.
Тема - темы
Acute Disease , Adolescent , Adult , Aged , Antihypertensive Agents/adverse effects , Blood Pressure/drug effects , Captopril/adverse effects , Cost-Benefit Analysis , Drug Therapy, Combination , Female , Humans , Hypertension/drug therapy , Male , Metoprolol/adverse effects , Middle Aged , Nifedipine/adverse effects , Safety , Treatment Outcome , Vasodilator Agents/adverse effectsРеферат
Thirty patients matched for age, parity, socioeconomic status and severity of pregnancy induced hypertension (PIH) were randomly allocated to treatment with metoprolol or methyldopa. The average fall in diastolic blood pressure was significant in the group treated with metoprolol as compared with the methyldopa group (p less than 0.01). There were 3 perinatal deaths in the methyldopa group and 1 in the metoprolol group; the mean birth weight of the babies was higher in cases treated with metoprolol. The results suggest metoprolol to be more efficacious with regard to control of hypertension and fetal outcome in cases of pregnancy induced hypertension.