Correspondência de teor de dissulfeto de captopril com odor de enxofre em comprimidos de captopril 25 mg, provenientes de farmácias públicas (postos de saúde) e drogarias comerciais / Correspondence of captopril disulfide content with sulfur odor in 25 mg captopril tablets from public pharmacies (health clinics) and commercial drugstores

Introdução: O captopril (CP) é o medicamento de escolha para o tratamento da hipertensão arterial. Sua degradação leva à formação do dímero dissulfeto de captopril (DSCP), este associado a um odor forte no medicamento, podendo causar abandono do tratamento pelo paciente. Objetivo: Determinar DCSP, associar a percepção olfativa de odor de enxofre desprendido do produto e realizar a avaliação de bula de comprimidos de captopril 25 mg distribuídos pelos setores público e privado. Método: Foi verificado o desempenho do método de determinação do CP e DSCP pela Farmacopeia Brasileira 6a ed. por HPLC (DAD). Foram analisados 13 produtos de comprimidos de captopril 25 mg, sendo dois provenientes do setor público de lotes diferentes e mesmo fabricante e 11 do setor privado de diferentes fabricantes e lotes. Foram avaliados aspectos do comprimido quanto à percepção de odor, determinação de peso, identificação e teor de CP e de DSCP e análise do conteúdo da bula. Resultados: Dentre os 13, o medicamento vencido apresentou 4,4% de DSCP, os demais estavam de acordo com a especificação. Verificouse  correspondência do odor de enxofre perceptível com teor de DSCP acima de 0,5%. Considerando os textos de bula sobre odor de enxofre, as constatações foram: nenhuma informação (três produtos), odor característico (dois), leve odor de enxofre (um), leve odor de enxofre sem diminuir a eficácia (sete). Conclusões: As amostras apresentaram resultados satisfatórios para os ensaios realizados. Verificou-se falta de homogeneidade nas informações das bulas sobre o odor dos comprimidos. A percepção do paciente quanto ao odor de enxofre, mesmo dentro do limite tolerado de DSCP, pode levar a não aceitação do medicamento e consequente não adesão ao tratamento da hipertensão, além de gerar prejuízos ao SUS.

Introduction: Captopril (CP) is the drug of choice for the treatment of hypertension. Its degradation leads to the formation of captopril disulfide dimer (DSCP), associated with a strong odor in the drug, which can cause the patient abandonment of treatment. Objective: To determine DCSP, associate the olfactory perception of the sulfur odor given off by the product and carry out the evaluation of the package insert for captopril 25 mg tablets distributed in the public and private sectors. Method: The performance of CP and DSCP determination method of the Brazilian Pharmacopoeia 6 ed was verified by HPLC (DAD). Thirteen products of 25 mg captopril tablets were analyzed, 2 of which came from the public sector from different batches and the same manufacturer: the other 11 came from the private sector from different batches and manufacturers. The samples were analyzed regarding appearance, odor perception, identification, weight determination, CP and DSCP content (by HPLC) and package insert content. Results: Among the 13, the expired drug had 4.4% DSCP; the others were in accordance with the specification. Correspondence of perceptible sulfur odor was established for drugs with DSCP content above 0.5%. Considering the texts on sulfur odor in the package inserts, the findings were: none information (3 products), characteristic odor (2), slight sulfur odor (1), slight sulfur odor without decreasing effectiveness (7). Conclusions: The samples showed satisfactory results for the tests performed. There was a lack of homogeneity in the information in the package inserts about odor of the tablets. The patient's perception of sulfur odor, even within the tolerated limit of DSCP, can lead to non-acceptance of the drug and consequent non- adherence to the treatment of hypertension, in addition to causing damage to the SUS.

Re-evaluation of the diagnostic value and optimal cutoff point of captopril challenge test in diagnosis of primary aldosteronism / 中华内科杂志

Objective:The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA).Methods:This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy.Results:A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUC ROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions:CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

Reversible regulation of enzyme-like activity of molybdenum disulfide quantum dots for colorimetric pharmaceutical analysis / 药物分析学报

Regulating the catalytic activity of nanozymes is significant for their applications in various fields.Here,we demonstrate a new strategy to achieve reversible regulation of the nanozyme's activity for sensing purpose.This strategy involves the use of zero-dimensional M0S2 quantum dots(MQDs)as the building blocks of nanozymes which display very weak peroxidase(POD)-like activity.Interestingly,such POD-like activity of the MQDs largely enhances in the presence of Fe3+while diminishes with the addition of captopril thereafter.Further investigations identify the mechanism of Fe3+-mediated aggregation-induced enhancement of the POD-like activity and the inhibitory effect of captopril on the enhance-ment,which is highly dependent on their concentrations.Based on this finding,a colorimetric method for the detection of captopril is developed.This sensing approach exhibits the merits of simplicity,rapidness,reliability,and low cost,which has been successfully applied in quality control of captopril in pharmaceutical products.Moreover,the present sensing platform allows smartphone read-out,which has promising applications in point-of-care testing devices for clinical diagnosis and drug analysis.

Role of dexamethasone/captopril co-loaded immunoliposome-nanoparticle hybrids on the regulation of macrophage polarization in mice with glomerulonephritis / 药学学报

In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.

Captopril oral solution for pediatric use: formulation, stability study and palatability assessment in vivo

Abstract he aim of this work was to develop an oral solution of captopril at 5 mg/mL preservative-free. Two formulations were prepared, one containing sweetener (formulation 1) and the other without this excipient (formulation 2). The results found of validation parameters from analytical method performed by HPLC for captopril were, linearity 0.9998, the limit of detection 15.71 µg/mL, the limit of quantification 47.60 µg/mL, repeatability 1.05%, intermediate precision 2.42%, accuracy intraday 101,53%, accuracy inter-day 99.85%. Moreover, the results found for captopril disulfide were, linearity 0.9999, limit of detection 0.65 µg/mL, limit of quantification 1.96 µg/mL, repeatability 2.28%, intermediate precision 1.51%, accuracy intraday 101.36%, accuracy inter-day 100.29%. The appearance of formulations was clear and colorless, pH measures were 3.12 and 3.04, dosage of captopril and captopril disulfide were 99.45% and 99.82%, 0.24% and 0.12% for formulation 1 and formulation 2, respectively. The stability study demonstrated that the concentration of captopril and captopril disulfide in the formulations was > 90% and below 3%, respectively. The in vivo palatability study in animals and humans showed that Formulation 1 containing the sweetener had better acceptance. Thus, the sweetener was able to improve the unpleasant taste of the formulation

Role of ACE and ACE-2 in abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart

Abstract Ischemic heart disease is the leading cause of death in postmenopausal women. The activity of heart ACE increases whereas the activity of ACE-2 decreases after menopause. The present study was designed to investigate the role of ACE and ACE-2 in the abrogated cardioprotective effect of IPC in OVX rat heart. The heart was isolated from OVX rat and mounted on Langendorff's apparatus for giving intermittent cycles of IPC. The infarct size was estimated using TTC stain, and coronary effluent was analyzed for LDH, CK-MB, and nitrite release. IPC induced cardioprotection was significantly attenuated in the ovariectomized rat heart as compared to the normal rat heart. However, this attenuated cardioprotection was significantly restored by perfusion of DIZE, an ACE-2 activator, and captopril, an ACE inhibitor, alone or in combination noted in terms of decrease in myocardial infarct size, the release of LDH and CK-MB, and also increase in the release of NO as compared to untreated OVX rat heart. Thus, it is suggested that DIZE and captopril, alone or in combination restore the attenuated cardioprotective effect of IPC in OVX rat heart which is due to an increase in ACE-2 activity and decrease in ACE activity after treatment.

Inhibition of diabetes mellitus-induced knee joint injury in rats by a combination of metformin and captopril / Inhibición de la lesión de la articulación de la rodilla inducida por diabetes mellitus en ratas mediante una combinación de metformina y captopril

SUMMARY: Osteoarthritis (OA) is an inflammatory disease that damages the joints and affects millions of people worldwide. The potential inhibitory effects of the antidiabetic drug metformin combined with captopril, the angiotensin-converting enzyme inhibitor, on diabetes-induced damage to the knee joint articular cartilage associated with the inhibition of glycemia, dyslipidemia, and inflammation has not been investigated before. Therefore, we induced diabetes in rats using high carbohydrate and fat diets and a single injection of streptozotocin (50 mg/kg). The protective group of rats was pre-treated with combined daily doses of metformin (Met; 200 mg/kg body weight) and captopril (Cap; 150 mg/kg body weight) for 14 days before diabetic induction and continued on metformin and resveratrol until the end of the experiment at week 12. Harvested tissues obtained from knee joints were prepared for basic histology staining with haematoxylin and eosin (H&E) and examined under light microscopy. Representative H&E images showed that OA was developed in the diabetic rats as demonstrated by a profound damage to the knee joints such as irregular eroded and a sharp decrease in the thickness of the articular cartilage surface and abnormal remodeling of the subchondral bone that were substantially ameliorated by Met+Cap. Met+Cap also significantly (p< 0.05) reduced blood levels of glucose, glycated hemoglobin (HbA1c), dyslipidemia, and the inflammatory biomarkers, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) induced by diabetes. In addition, a significant (p≤ 0.0014) correlation between the articular cartilage thickness and the blood levels of glucose, HbA1c, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), and hs-CRP were observed. Thus, we demonstrate that Met+Cap effectively protect the knee joint against injuries induced secondary to diabetes in rats, possibly due to the inhibition of glycemia, dyslipidemia, and biomarkers of inflammation.

RESUMEN: La osteoartritis (OA) es una enfermedad inflamatoria que daña las articulaciones y afecta a millones de per- sonas en todo el mundo. No se han investigado los posibles efectos inhibidores del fármaco antidiabético metformina combinado con captopril, el inhibidor de la enzima convertidora de angiotensina, sobre el daño inducido por la diabetes en el cartílago articular de la articulación de la rodilla asociado con la inhibición de la glucemia, dislipidemia e inflamación. En este estudio fue inducida la diabetes en ratas con dietas altas en carbohidratos y grasas y una sola inyección de estreptozotocina (50 mg / kg). El grupo protector de ratas se pretrató con dosis diarias combinadas de metformina (Met; 200 mg / kg de peso corporal) y captopril (Cap; 150 mg / kg de peso corporal) durante 14 días antes de la inducción diabética. El tratamiento se continuó con metformina y resveratrol hasta el final del experimento en la semana 12. Los tejidos obtenidos de las articulaciones de la rodilla se prepararon para la tinción de histología básica con hematoxilina y eosina (H&E) y se examinaron con microscopía óptica. Imágenes representativas de H&E mostraron que la OA se desarrolló en las ratas diabéticas, como lo evidencia un daño profundo en las articulaciones de la rodilla, como la erosión irregular y una fuerte disminución en el grosor de la superficie del cartílago articular y remodelación anor- mal del hueso subcondral que fueron mejorados sustancialmente por Met + Cap. Met + Cap. También redujo significativamente (p <0.05) los niveles sanguíneos de glucosa, hemoglobina glicosilada (HbA1c), dislipidemia y los biomarcadores inflamatorios, proteína C reactiva de alta sensibilidad (hs-CRP), interleucina-6 (IL-6), y factor de necrosis tumoral alfa (TNF-α) inducido por diabetes. Además, una correlación significativa (p≤ 0,0014) entre el grosor del cartílago articular y los niveles sanguíneos de glucosa, HbA1c, triglicéridos (TG), lipoproteínas-colesterol de baja densidad (LDL- C), lipoproteínas de alta densidad-colesterol (HDL-C) ) y hs-CRP. Así, demostramos que Met + Cap protege eficazmente la articulación de la rodilla contra lesiones inducidas por diabetes en ratas, posiblemente debido a la inhibición de la glicemia, dislipidemia y biomarcadores de inflamación.

Effect of captopril pretreatment on the dentin bonding durability of self-etch adhesive / 浙江大学学报·医学版

To investigate the effect of captopril on the dentin bonding durability of self-etch adhesive. Different concentrations of captopril ethanol solutions or captopril ethanol/water solutions were prepared to pretreat dentin as primer for the self-etch adhesives. The surface morphology of the dentin was observed with scanning electron microscopy (SEM). Based on the morphology analysis, the pretreatment condition was selected and two self-etch adhesives were employed to evaluate the improvement effect of the captopril pretreatment on the dentin bonding durability. : SEM showed that the pretreatment of captopril ethanol solutions and captopril ethanol/water solutions were able to remove the smear lay and partially expose collagen matrix. According to the SEM results, the pretreating condition of captopril ethanol/water solution with the pretreating time of was selected for further dentin bonding study. For Clearfil SEBOND system, the immediate bonding strength increased from to  (0.05]. For Clearfil S BOND system, there was no significant difference in the immediate bonding strength between the experimental group [(4.07) MPa] and the control group[(4.11) MPa]. But after one-year aging, the bonding strength of the experimental group was higher than that of the control group <0.05]. : The pretreatment with captopril ethanol/water solution increases the dentin bonding strength of the self-etch adhesive systems and also improves the bonding durability.

Clinical value of captopril test in noninvasive diagnosis of aldosterone-producing adenoma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical characteristics of aldosterone-producing adenoma (APA) subtypes in primary aldosteronism (PA) and the application value of captopril challenge test (CCT) in adenomas. And to find out the clinically specific non-invasive index for identifying APA subtypes from PA.@*METHODS@#The clinical data of hospitalized patients with hypertension were retrospectively collected. All the patients were conducted with the CCT and 90 patients with PA were confirmed. Among them, 34 patients were confirmed to have APA by surgery. The clinical indicators of the two groups of patients including plasma aldosterone concentration (PAC), aldosterone inhibition rate (%), and aldosterone to renin ratio (ARR) before and after the CCT were compared, the receiver operating characteristic (ROC) curves for the relevant indicators before and after the CCT drawn, and the areas under the curve (AUC) compared. The ROC curves were used to analyze the efficiency of the different CCT diagnostic criteria for diagnosing APA.@*RESULTS@#Compared with the PA group, the duration of hypertension was shorter, the incidence of hypokalemia was higher, and the average serum potassium level was lower when APA was diagnosed. There were no significant differences in blood pressure level, gender, serum sodium and body mass index between the two groups. Compared with PA population, APA group had higher PAC and ARR whether before or after the CCT, but lower plasma renin concentration (PRC). In APA patients, the mean degree of PAC declined after CCT was approximately 5.7%, but 5% with that of PA. As for diagnosing, ARR before or after CCT had diagnostic value for APA, in which the ARR cut-off point was 7.12, which yielded a sensitivity and specificity of 35.85% and 77.78%. The cut-off point of ARR after CCT was 4.23, with a sensitivity of 71.43% and specificity of 62.22%. For the diagnosis, the ARR before and after CCT were of no significant difference. However, the diagnostic specificity of ARR>7.12 combined with hypokalemia was up to 80%.@*CONCLUSION@#ARR before or after CCT have clinical value for the diagnosis of APA from PA, when combined with hypokalemia yielded high specificity.

COVID-19 y su asociación con los inhibidores de la enzima convertidora de angiotensina y los antagonistas de los receptores para angiotensina II / COVID-19 and its Association with Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Antagonists

Resumen En la pandemia de COVID-19 que se ha presentado en México y en el mundo, y que ya ha infectado alrededor de 7 millones de personas, las comorbilidades que se han asociado a esta enfermedad en orden de importancia son: hipertensión, diabetes mellitus, obesidad, enfermedad pulmonar obstructiva crónica, enfermedad cardiovascular, insuficiencia renal crónica, tabaquismo e inmunosupresión, y la hipertensión arterial es un rasgo característico en todas ellas. La enzima convertidora de angiotensina-2 (ACE2), es el receptor funcional para el SARS-CoV-2. Este virus, tiene una proteína llamada espiga (proteína S) que reconoce a la ACE2 como su receptor para ingresar a las células. La ACE2 es una proteína de la membrana plasmática y se encuentra expresada en las células alveolares tipo I y II, células epiteliales, fibroblastos, células endoteliales y macrófagos. El tratamiento con inhibidores de la enzima convertidora de angiotensina (ACEi) o con antagonistas del receptor a angiotensina II (ARBs) aumentan notablemente la expresión de ACE2. Por lo tanto, en pacientes con estas patologías y tratados con estos medicamentos, se podría incrementar el riesgo de desarrollar la COVID-19 en forma severa y fatal. Cabe destacar que los pacientes con mayor mortalidad por la COVID-19 en México son los que presentan hipertensión, diabetes mellitus, obesidad y los mayores de 65 años. Por todo lo anterior, podríamos sugerir que, durante la etapa crítica de la pandemia por SARS-CoV-2, a los pacientes, particularmente en personas de edad avanzada, con hipertensión o con diabetes mellitus y obesidad que cursan con hipertensión y si su tratamiento es con ACEi o con ARBs, se les debería modificar a medicamentos alternativos como los bloqueadores de los canales de Ca2+ tipo L (amlodipino), que hasta el momento no han sido asociados con la ACE2.

Abstract Worldwide, over 7 million people have been infected due to the pandemic of COVID-19. The comorbidities associated to this disease are: hypertension, diabetes mellitus, obesity, obstructive pulmonary disease (COPD), cardiovascular disease, chronic renal failure, smoking, immunosuppression, and hypertension. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2. This virus has an S protein that recognizes ACE2 as its receptor to enter the cell. ACE2 is a plasmatic protein expressed in alveolar cells type I, II, fibroblasts, endothelial cells and macrophages. Treatment with inhibitors of the angiotensin-converting enzyme (ACEi) or the receptor antagonist for angiotensin II (ARBs) notably increase the expression of ACE2. Therefore, in patients with these pathologies and treated with these medicines, the risk of developing the COVID-19 in a severe and fatal way could be increased. In Mexico, the major mortality due to COVID-19 is related to hypertension, diabetes mellitus, obesity and being over 65 years of age. Therefore, we suggest that during the SARS-CoV-2 pandemic, patients with hypertension treated with ACEi or ARBs, should receive alternative treatments such as L-type Ca2+ channel blockers (amlodipine) that have not been associated with ACE2 until now.

Caracterización de las Crisis Hipertensivas en adultos de la Emergencia del Hospital José Félix Valdivieso, Enero 2016 a Diciembre 2018 / Hypertensive Crisis Characterization in adults in the Emergency Department of Hospital José Felix Valdivieso, Januay 2016- December 2018

INTRODUCCIÓN: La crisis hipertensiva es considerada una complicación aguda de la Hipertensión Arterial Sistémica, y contribuye a las 9.4 millones de muertes anuales estimadas, asociadas a la misma. La morbilidad que ocasionan es otro problema de importancia. Los datos a nivel local son escasos, por lo que conocer las características clínico-epidemiológicas de las crisis hipertensivas reviste gran importancia. El objetivo de este estudio fue caracterizar las Crisis hipertensivas en adultos de la Emergencia del Hospital José Félix Valdivieso Santa Isabel, periodo enero 2016 a diciembre 2018. METODOLOGÍA: Se trató de un estudio descriptivo, transversal, con un universo de 151 pacientes diagnosticados con crisis hipertensiva en el Hospital José Félix Valdivieso entre enero 2016 y diciembre 2018, realizando un muestreo aleatorio simple se obtuvo 122 pacientes. Se recolectó la información mediante revisión de las historias clínicas. Se procesaron los datos mediante Excel 2016, para posteriormente interpretarlos mediante tablas y gráficos. RESULTADOS: El 57% de los pacientes fue de sexo femenino, el grupo de edad de 40 a 65 años que representa el 49% de la muestra, 67% tuvieron un nivel de instrucción primaria, 65% fueron de una procedencia rural. En cuanto a la presencia de factores de riesgo conocidos para crisis hipertensivas, el 50% de la población tuvo sobrepeso, el 70% hipertensión arterial previa. Según el tipo de crisis hipertensiva, el 93% fueron urgencia hipertensivas, en las emergencias hipertensivas el órgano afecto con mayor frecuencia fue el cerebro con 89%. La manifestación clínica más frecuente fue cefalea con un 59%, seguida de sintomatología neurológica.. En cuanto al manejo la terapéutica inicial fue Captopril en el 61%. CONCLUSIÓN: La mayor parte de pacientes afectados fueron del sexo femenino, adultos de edad media. La mayoría de la muestra tuvo antecedentes de sobrepeso u obesidad. El 70% de la población tenia diagnóstico previo de Hipertensión Arterial, y de ellos solamente el 80% tomaba fármacos antihipertensivos. La mayoría de crisis fueron urgencias hipertensivas, en las emergencias hipertensivas el órgano diana más afectado fue el cerebro. El medicamento que se administró con mayor frecuencia en el manejo inicial de la crisis hipertensiva fue captopril. No se registró mortalidad en ese estudio.(au)

BACKGROUND: Hypertensive crisis is considered an acute complication of Hypertension, causing 9.4 million deaths annually. Another important problem is the resulting morbidity. Locally, data is limited, that is the importance of presenting the clinical and epidemiological characteristics of hypertensive crisis. The aim of this study was characterizing hypertensive crisis in adults, in Hospital José Félix Valdivieso, Santa Isabel, from January 2016 to December 2018. METHODS: Descriptive, cross-sectional study, the study universe were 151 patients diagnosed with hypertensive crisis in Hospital José Félix Valdivieso from January 2016 to December 2018, by simple random sampling we picked 122 patients. The information was obtained from the patient's medical chart. The data was processed using Excel 2016, and later interpreted using tables and charts. RESULTS: 57% of the sample were female, 49% had between 40 to 65 years of age, 67% had primary education, 65% came from rural areas. About risk factors; 50% of the population was overweight, 70% had previous diagnosis of hypertension. About the type of hypertensive crisis; 93% were hypertensive urgencies, the most commonly affected organ in hypertensive emergencies was the brain, in 89% of the cases. Headache, was the most frequent symptom(59%), followed by neurological symptoms. Captopril was used as initial treatment in 61% of the cases. CONCLUSION: The majority of affected patients were female, middle aged adults. Most of the sample had overweight or obesity. 70% of the population had previous diagnosis of hypertension, of this patients only 80% had hypertensive treatment. Most of the crisis were hypertensive urgencies, in hypertensive emergencies the most commonly affect organ was the brain. Captopril was used in most of the cases for initial treatment. This study didn't registered any deaths.(au)

Value of non-contrast-enhanced MR angiography combined with captopril renal scintigraphy in the diagnosis of renovascular hypertension / 中华核医学与分子影像杂志

Objective@#To evaluate the clinical value of non-contrast-enhanced MR angiography (NCE-MRA) combined with captopril renal scintigraphy (CRS) in the diagnosis of renovascular hypertension (RVH).@*Methods@#A total of 52 patients (33 males, 19 females; age: (54.5±16.3) years) with highly suspected RVH between January 2018 and October 2018 from Henan Provincial People′s Hospital were retrospectively analyzed. The examination data of NCE-MRA, basic renal dynamic imaging, CRS and digital subtraction angiography (DSA) were collected and reviewed. The renal artery stenosis (RAS) rate≥70% was the criterion for RVH diagnosed by DSA, which was considered as the gold standard. The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of NCE-MRA, CRS and NCE-MRA+ CRS were determined. The consistency between NCE-MRA and DSA was analyzed by Kappa test. The differences of diagnostic efficiencies between CRS and NCE-MRA + CRS were compared by χ2 test or Fisher exact test.@*Results@#There was a high consistency between NCE-MRA and DSA in the diagnosis of RVH (Kappa=0.81, 95% CI: 0.62-0.96; P<0.01). The diagnostic sensitivity, specificity, accuracy, PPV and NPV of NCE-MRA were 88.89%(24/27), 92.00%(23/25), 90.38%(47/52), 92.31%(24/26), and 88.46%(23/26) respectively, those of CRS were 81.48%(22/27), 72.00%(18/25), 76.92%(40/52), 75.86%(22/29) and 78.26%(18/23) respectively, and those of NCE-MRA+ CRS were 74.07%(20/27), 100%(25/25), 86.54%(45/52), 100%(20/20) and 78.12%(25/32) respectively. Compared with CRS, the specificity (P=0.01) and PPV (P=0.03) of NCE-MRA+ CRS in the diagnosis of RVH were increased.@*Conclusion@#NCE-MRA and CRS are effective in the diagnosis of RVH, and the combination of two methods can significantly improve the diagnostic specificity and PPV than CRS alone.

Value of non-contrast-enhanced MR angiography combined with captopril renal scintigraphy in the diagnosis of renovascular hypertension / 中华核医学与分子影像杂志

Objective To evaluate the clinical value of non-contrast-enhanced MR angiography (NCE-MRA) combined with captopril renal scintigraphy (CRS) in the diagnosis of renovascular hypertension (RVH).Methods A total of 52 patients (33 males,19 females;age:(54.5±16.3) years) with highly suspected RVH between January 2018 and October 2018 from Henan Provincial People's Hospital were retrospectively analyzed.The examination data of NCE-MRA,basic renal dynamic imaging,CRS and digital subtraction angiography (DSA) were collected and reviewed.The renal artery stenosis (RAS) rate ≥70％ was the criterion for RVH diagnosed by DSA,which was considered as the gold standard.The diagnostic sensitivity,specificity,accuracy,positive predictive value (PPV) and negative predictive value (NPV) of NCE-MRA,CRS and NCE-MRA+CRS were determined.The consistency between NCE-MRA and DSA was analyzed by Kappa test.The differences of diagnostic efficiencies between CRS and NCE-MRA + CRS were compared by x2 test or Fisher exact test.Results There was a high consistency between NCE-MRA and DSA in the diagnosis of RVH (Kappa=0.81,95％ CI:0.62-0.96;P＜0.01).The diagnostic sensitivity,specificity,accuracy,PPV and NPV of NCE-MRA were 88.89％(24/27),92.00％(23/25),90.38％ (47/52),92.31％(24/26),and 88.46％(23/26) respectively,those of CRS were 81.48％(22/27),72.00％ (18/25),76.92％ (40/52),75.86％ (22/29) and 78.26％ (18/23) respectively,and those of NCE-MRA+CRS were 74.07％(20/27),100％(25/25),86.54％(45/52),100％(20/20) and 78.12％ (25/32) respectively.Compared with CRS,the specificity (P =0.01) and PPV (P =0.03) of NCE-MRA+CRS in the diagnosis of RVH were increased.Conclusion NCE-MRA and CRS are effective in the diagnosis of RVH,and the combination of two methods can significantly improve the diagnostic specificity and PPV than CRS alone.

Captopril renal scintigraphy in diagnosis of renovascular hypertension and the impact of plasma renin activity / 中国医学影像技术

Objective: To observe the diagnostic efficiency of Captopril renal scintigraphy (CRS) for renovascular hypertension (RVH) and the impact of plasma renin activity (PRA). Methods: Plasma levels of PRA, angiotensin Ⅱ (AngⅡ) and aldosterone (ALD) in peripheral blood in orthostatic position and supine position of 35 RVH patients who underwent basic renal scintigraphy and CRS examination were retrospectively analyzed. According to CRS, the patients were divided into positive group and negative group. The levels of PRA, AngⅡ and ALD were analyzed. ROC curve was used to analyze PRA and obtain the minimum threshold. Results: There were 24 cases in positive group and 11 cases in negative group. The orthostatic position PRA in positive group was significantly higher than that in negative group (Z=3.11,P0.05). ROC curve analysis showed that the area under the curve was 0.84. When the threshold point of PRA was 2.47 ng/(ml·h), the sensitivity and specificity were 83.33% and 81.82%, respectively. Conclusion: Orthostatic position PRA is an important impact factor of diagnostic sensitivity of CRS for RVH. Combining with orthostatic position plasma PRA can improve the value of CRS for diagnosis and treatment of RVH.

Preformulation of a liquid dosage formulation of captopril for pediatric use: drug-excipient compatibility and stability studies

Currently, medications used in children are typically modified from pharmaceutical dosage forms designed for adults. Captopril is widely adapted to liquid formulations for use in hospitals. Its stability in the aqueous medium is reduced since it undergoes oxidation producing captopril disulfide (its main metabolite). The aim of this formulation study was to suggest favorable conditions for the development of a stable captopril formulation. The compatibility between the drug and excipients was evaluated by differential scanning calorimetry analysis (DSC). For studies in solution, different formulations were prepared according to a factorial design varying EDTA concentration, water purity and pH. The resultant formulations were stored at 60°C and analyzed over a twelve-day period using HPLC. The DSC curves obtained suggested, although not conclusive to elucidation, interactions of captopril with citric acid and sucralose. The stability study of these solutions revealed that the variables significantly influenced captopril content, which degraded at zero order kinetics and rates differing by a factor of up to 7 times, where pH proved the most influential factor. Interactions between variables were observed. Therefore, development of a stable captopril formulation is feasible provided EDTA and a buffering agent is used at suitable concentrations (0.08% and pH 3.85).

Medicamentos de referência, genérico e similar: avaliação da qualidade dos comprimidos de captopril e enalapril / Reference, generic and similar medicines: quality assessment of captopril and enalapril tablets

Este trabalho objetivou analisar a qualidade dos comprimidos e a relação entre os medicamentos de referência, genéricos e similares. Para estudo e coleta de dados, foram realizados testes físicos e físico-químicos de acordo com a farmacopéia brasileira 5º edição 2010. Os produtos analisados apresentaram resultados satisfatórios quanto aos aspectos visuais, teste de vazamento, determinação de peso médio em formas farmacêuticas sólidas, determinação de resistência mecânica através dos testes de dureza e friabilidade e teste de desintegração, demonstraram qualidade conforme com devidas especificações, estando adequados para o consumo.

Effects of captopril on Klotho protein in hypertensive rats / 西安交通大学学报(医学版)

Objective: To evaluate the effects of captopril on Klotho protein and related inflammatory factors in the model of hypertensive SD rats. Methods: Eighteen SD rats were randomly divided into normal group, hypertensive model group and captopril experimental group, respectively. N'-nitro-L-arginine (L-NNA) was used by gavage in SD rats to make the hypertensive model. After successful establishment of the model, the experimental group was given captopril for treatment of hypertension, and the normal group and hypertension group were given an equal volume of normal saline by gavage in the SD rats. Blood pressure changes were measured by tail arteries of the SD rats. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma levels of Klotho protein, thromboxane (TXA2), and endothelin (ET). The level of nitric oxide (NO) was measured by nitrate reductase method. The content of malondialdehyde (MDA) was measured by TBA method, and the activity of superoxide dismutase (SOD) was measured by WST-1 method. The pathological changes of HE stained vascular wall in thoracic aorta of each group were observed. The vascular endothelial cell injury was evaluated by measuring the expression of CD31 by immunohistochemistry (IHC). Results: Compared with those in the normal group, the contents of TXA2, ET and MDA in the model group were significantly higher (P<0.05), while the content of Klothoprotein and NO and SOD activities were lower (P<0.05). Compared with those in the model group, the contents of TXA2, ET and MDA in the captopril group were significantly decreased (P<0.05), and the Klotho protein content, NO content and SOD activity were higher (P<0.05). The results of HE staining showed that the aortic vascular fibrosis and disorder in the model group and the aorticl wall were thicker than those in the normal group. The vessel wall was significantly thinner in the treatment group than in the model group. The results of IHC showed that the aortic endothelial cells in the model group were damaged and shedding. The vascular endothelial cells in the controlled group were increased and gradually repaired. Conclusion: Captopril can reduce the stress response of endothelial cells and repair the vascular endothelium, which can improve vascular endothelial function and increase Klotho protein level.

Vía aérea difícil no prevista secundaria a consumo de inhibidores de la enzima convertidora de angiotensina. Reporte de caso / Unexpected difficult airway management due to the use of ACE inhibitors: case report

Abstract Angioedema induced by the use of angiotensin converting enzyme (ACE) inhibitors is an uncommon but life-threatening complication, especially when the airway is affected, creating unexpected difficult airway management. A prompt differential diagnosis with anaphylactic shock is critical, given that adrenaline treatment does not improve angioedema. We report a case of angioedema induced by ACE inhibitor following in-hospital administration of captopril, with almost impossible intubation, and secondary aspiration during airway management. Angioedema was erroneously treated, because it was mistakenly considered to be an anaphylactic reaction, and it could have ended in death.

Resumen El angioedema es una complicación poco frecuente relacionada con el uso de inhibidores de la enzima convertidora de angiotensina, pero potencialmente mortal, especialmente en el caso de afectar a la vía aérea, generando vías aéreas difíciles no previstas. Es de vital importancia realizar un rápido diagnóstico diferencial del cuadro con el shock anafiláctico, dado que el tratamiento con adrenalina, no mejora el angioedema. Presentamos un caso de angioedema tras administración intrahospitalaria de Captopril a un paciente sano, sin vía aérea difícil prevista, generando una intubación casi imposible y broncoaspiración secundaria durante el manejo de la vía aérea. El cuadro clínico se desencadenó por la confusión del angioedema, con una reacción anafiláctica, realizándose un tratamiento inapropiado. Las consecuencias del mismo pudieron ser mortales.

Formula Optimization of Captopril Timing Osmotic Pump Tablets / 中国药房

OBJECTIVE:To optimize the formula of Captopril timing osmotic pump tablets. METHODS:Using accumulative release rate (Q) as index, single factor test was used to investigate the effects of blocking layer coating weight gain, semipermeable membrane coating weight gain,the type of polyepoxide (PEO),the amount of PEO (3 × 105) and HPMC in drug bearing layer,the amount of PEO (7 × 106) and NaCl in booster layer on drug release of Captopril timing osmotic pump tablets. Based on single factor investigation,using comprehensive score of release behavior(L)as index,the amount of PEO(3×105)and HPMC in drug bearing layer,the amount of PEO(7×106)and NaCl in booster layer as factors,L9(43)orthogonal test was used to optimize the formula of tablet core validation test was conducted. RESULTS:The optimal formula of tablet core included PEO(3× 105)71 mg and HPMC 15 mg in drug bearing layer,PEO(7×106)61 mg and NaCl 18 mg in booster layer,coating weight gain 7％ and semipermeable membrane coating weight gain 10％ in blocking layer. The osmotic pump tablet prepared by optimized formula released after 4 h;in vitro drug release regression equation was Q=5.118t-21.441(R2=0.9956),which was in line with zero-order release characteristics. CONCLUSIONS:The optimal formula is stable,feasible and controllable in quality,and can provide reference for further development of Captopril timing osmotic pump tablets.

Analysis of curative effect by Captopril in Henoch-Sch(o)nlein purpura nephritis characterized by mild proteinuria / 中华实用儿科临床杂志

Objective To explore the activation of renin-angiotensin system (RAS),efficiency and safety of Captopril,and the predictor of therapeutic activity for Henoch-Sch(o)nlein purpura nephritis (HSPN) characterized by mild proteinuria.Methods A total of 71 children who were hospitalized in Children's Hospital Affiliated to Capital Institute of Pediatrics from July 2014 to January 2017 were involved,with the diagnosis of HSPN and the characteristic of mild proteinuria.The cases were divided into 2 groups,one as Captopril group,the other as case control group.The patients were followed up for 6 months.Forty healthy children were assigned as healthy control group.Blood pressure,urinary protein excretion,levels of urinary angiotensinogen (AGT) and transforming growth factor β1 (TGF-β1),and the side effects of Captopril were surveyed.The therapeutic effects of these groups were analyzed by Kaplan-Meier survival curve.Results (1) Clinical characteristics:in the 71 cases,43 cases were male,28 cases were female,aged from 3 years to 14 years and 7 months.A total of 32 cases (45.1％) had manifested with isolated proteinuria,39 cases (54.9％) were with hematuria and proteinuria.The volume of 24 hours' urinary protein was 4.2-23.5 mg/(m2 · h) [median 9.6(7,12) mg/(m2 · h)] at the beginning.(2) The level of urinary AGT:the levels of urinary AGT in the children with HSPN were significantly higher than those of the healthy control group(Z =-3.010,P =0.003).(3) Curative effect:there was no significant difference in age,disease staging,mean arterial pressure(MAP),levels of urinary of proteinuria and estimated glomerular filtration rate (eGFR) between the patients with or without Captopril.The proteinuria was relieved in 88.57％ cases of Captopril group(35 cases),and the proportion was 80.55％ in the case control group(36 cases),and there was no significant difference between the 2 groups.The levels of proteinuria were decreased significantly in the children of Captopfil group 2 months after the enrollment,and there was a statistical significance (Z =2.010,P =0.044).But in the patients of each group,the levels of urinary protein excretion (Z =-2.127,P=0.030;Z=-2.639,P=0.010),TGF-β1(Z=-2.126,P=0.030;Z=-2.058,P=0.040) at theonset were significantly higher in the children with persistent proteinuria compared to those with remission of proteinuria completely,and there was a statistical significance.(4)Side effect:among 35 cases with therapy of Captopril,4 cases (11.42％) were verified to have adverse reaction (hypotension,dry cough and abnormal renal function),with mild symptom.Conclusion The overall prognosis of children of HSPN presenting as mild proteinuria are not improved completely by Captopril.The occurrence of adverse effects for Captopril is seldom and less severe.The level of urinary protein excretion,TGF-31 and AGT at the onset have some relevance with the prognosis of the patients of HSPN.