RESUMEN
Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including ß-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. ß-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, ß-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, ß-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of ß-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a ß-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.
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Insuficiencia Cardíaca , Humanos , Calidad de Vida , Volumen Sistólico , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta/farmacología , Sistema Renina-Angiotensina , Antihipertensivos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéuticoRESUMEN
Stress substantially increases the risk of developing painful temporomandibular disorders (TMDs) by influencing the release of endogenous catecholamines. Propranolol, an antagonist of ß-adrenergic receptors, has shown potential in alleviating TMD-associated pain, particularly when the level of catecholamines is elevated. The aim of this study was to explore whether intra-articular propranolol administration is effective in diminishing temporomandibular joint (TMJ) pain during repeated stress situations. Additionally, we investigated the effect of repeated stress on the expression of genes encoding ß-adrenoceptors in the trigeminal ganglion. In the present study, rats were exposed to a stress protocol induced by sound, then to the administration of formalin in the TMJ (to elicit a nociceptive response), followed immediately afterward by different doses of propranolol, after which the analgesic response to propranolol was evaluated. We also assessed the levels of beta-1 and beta-2 adrenergic receptor mRNAs (Adrb1 and Adrb2, respectively) using reverse transcription-quantitative PCR (RT-qPCR). Our findings revealed that propranolol administration reduces formalin-induced TMJ nociception more effectively in stressed rats than in non-stressed rats. Furthermore, repeated stress decreases the expression of the Adrb2 gene within the trigeminal ganglion. The findings of this study are noteworthy as they suggest that individuals with a chronic stress history might find potential benefits from ß-blockers in TMD treatment.
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Propranolol , Articulación Temporomandibular , Ratas , Animales , Propranolol/efectos adversos , Articulación Temporomandibular/metabolismo , Ratas Wistar , Dolor , Catecolaminas/metabolismo , Catecolaminas/farmacología , Catecolaminas/uso terapéutico , Formaldehído/efectos adversos , Formaldehído/metabolismoRESUMEN
Human performance enhancing drugs (PEDs), frequently used in sport competitions, are strictly prohibited by the World Anti-Doping Agency (WADA). Biological samples collected from athletes and regular patients are continuously tested regarding the identification and/or quantification of the banned substances. Current work is focused on the application of a new analytical method, molecularly imprinted nanoparticles (nanoMIPs), to detect and determine concentrations of certain prohibited drugs, such as ß-blockers, in water and human urine samples. These medications are used in the treatment of cardiovascular conditions, negative effects of adrenaline (helping to relief stress), and hypertension (slowing down the pulse and softening the arteries). They can also significantly increase muscle relaxation and improve heart efficiency. The new method of the detection and quantification of ß-blockers is based on synthesis, characterization, and implementation of nanoMIPs (so-called plastic antibodies). It offers numerous advantages over the traditional methods, including high binding capacity, affinity, and selectivity for target molecules. Additionally, the whole process is less complicated, cheaper, and better controlled. The size and shape of the nanoMIPs is evaluated by dynamic light scattering (DLS) and transmission electron microscope (TEM). The affinity and selectivity of the nanoparticles are investigated by competitive pseudo enzyme-linked immunosorbent assay (pseudo-ELISA) similar to common immunoassays employing natural antibodies. To provide reliable results towards either doping detection or therapeutic monitoring using the minimal invasive method, the qualitative and quantitative analysis of these drugs is performed in water and human urine samples. It is demonstrated that the assay can detect ß-blockers in water within the linear range 1 nmol·L-1-1 mmol·L-1 for atenolol with the detection limit 50.6 ng mL-1, and the linear range 1 mmol·L-1-10 mmol·L-1 for labetalol with the detection limit of 90.5 ng·mL-1. In human urine samples, the linear range is recorded in the concentration range 0.1 mmol·L-1-10 nmol·L-1 for atenolol and 1 mmol·L-1-10 nmol·L-1 for labetalol with a detection limit of 61.0 ng·mL-1 for atenolol and 99.4 ng·mL-1 for labetalol.
RESUMEN
Fundamento: A cardiotoxicidade induzida por quimioterapia (CiC) é uma complicação importante entre os pacientes que recebem antraciclinas. Biomarcadores e parâmetros de imagem têm sido estudados por sua capacidade de identificar pacientes com risco de desenvolver essa complicação. O strain longitudinal global do ventrículo esquerdo (SLG-VE) tem sido descrito como um parâmetro sensível para detectar disfunção sistólica, mesmo na presença de fração de ejeção do ventrículo esquerdo (FEVE) preservada. Objetivo: avaliar o papel do SLG-VE como preditor de CiC. Métodos: O presente estudo consiste em uma análise post-hoc do estudo CECCY (Carvedilol for Prevention of ChemotherapyRelated Cardiotoxicity [Carvedilol para Prevenção da Cardiotoxicidade Relacionada à Quimioterapia]), que avaliou a prevenção primária de cardiotoxicidade com carvedilol durante quimioterapia com doxorrubicina em uma população com câncer de mama. Definiu-se cardiotoxicidade como uma redução >10% na FEVE. O SLG-VE foi obtido antes da quimioterapia em pacientes sem doença cardiovascular prévia ou anormalidades no ecocardiograma. Resultados: Trinta e um pacientes submetidos a estudo ecocardiográfico completo incluindo avaliação de SLG-VE antes da quimioterapia foram incluídos nesta análise. Um SLG-VE absoluto <16,9% antes da quimioterapia mostrou 100% de sensibilidade e 73% de especificidade para predizer cardiotoxicidade (AUC=0,85; IC 95% 0,6800,959, p<0,001). Nesta população, os valores de FEVE antes da quimioterapia não foram preditores de CiC (IC 95% 0,478 a -0,842, p=0,17). A associação de baixos níveis séricos de SLG-VE (<17%) e BNP (>17 pg/mL) dois meses após a quimioterapia aumentou a precisão para detectar CiC de início precoce (100% de sensibilidade, 88% de especificidade, AUC=0,94; IC 95% 0,7810,995, p<0,0001). Conclusões: Nossos dados sugerem que o SLG-VE é um possível preditor de cardiotoxicidade induzida por quimioterapia. São necessários estudos maiores para confirmar a relevância clínica desse parâmetro ecocardiográfico nesse cenário clínico. (AU)
Background: Chemotherapy-induced cardiotoxicity (ChC) is an important complication among patients receiving anthracyclines. Biomarkers and imaging parameters have been studied for their ability to identify patients at risk of developing ChC. Left ventricular global longitudinal strain (LV-GLS) is a sensitive parameter for detecting systolic dysfunction despite the presence of preserved left ventricular ejection fraction (LVEF). Objective: To evaluate the role of the LV-GLS as a predictor of ChC. Methods: This was a post-hoc analysis of the Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity trial, which evaluated the primary prevention of cardiotoxicity with carvedilol during doxorubicin chemotherapy in a population of patients with breast cancer. Cardiotoxicity was defined as a reduction ≥10% in LVEF. LV-GLS was determined before chemotherapy in patients with no prior cardiovascular disease or echocardiogram abnormalities. Results: Thirty-one patients for whom a complete echocardiography study including measurement of LV-GLS was performed before chemotherapy were included in this analysis. An absolute LV-GLS<16.9% before chemotherapy showed 100% sensitivity and 73% specificity for predicting cardiotoxicity (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.6800.959; p<0.001). In this population, LVEF values before chemotherapy did not predict ChC (95% CI, 0.478 to -0.842; p=0.17). The association of low LV-GLS (<17%) and brain-type natriuretic peptide serum levels (>17 pg/mL) at 2 months after chemotherapy increased the accuracy for detecting early-onset ChC (100% sensitivity, 88% specificity; AUC, 0.94; 95% CI, 0.7810.995; p<0.0001). Conclusions: Our data suggest that LV-GLS is a potential predictor of ChC. Larger studies are needed to confirm its clinical relevance in this clinical setting. (AU)
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Volumen Sistólico/efectos de los fármacos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Cardiotoxicidad/complicaciones , Tensión Longitudinal Global/efectos de los fármacos , Neoplasias de la Mama/diagnóstico , Ecocardiografía/métodos , Biomarcadores/análisis , Doxorrubicina/uso terapéutico , Antraciclinas/administración & dosificación , Quimioterapia/métodos , Carvedilol/toxicidad , Insuficiencia Cardíaca/prevención & controlRESUMEN
Memories of adverse events can be maladaptive when they lead to exaggerated fear, as observed in post-traumatic stress disorder (PTSD). Fear conditioning and fear sensitization are learning processes thought to play a role in fear-related disorders, and only few animal studies have evaluated the relationship between the associative and non-associative fear memory components on the development and maintenance of PTSD-like behavioral changes. Here we assessed the effects of a single dose of propranolol (10 mg/kg) or saline after fear memory retrieval on the long-term behavioral responses induced by severe stress in male rats. Animals were submitted to contextual fear conditioning (delayed shock group) or not (non-shock group) and underwent fear memory retrieval followed by propranolol or saline administration two weeks later. Rats were then evaluated in different behavioral tests to assess the expression of the conditioned fear response, anxiety-like and exploratory behaviors, and fear response after the presentation of unknown acoustic stimulus. Post-retrieval propranolol did not disrupt the subsequent expression of neither conditioned fear response nor the exploratory deficit and fear sensitization response, indicating that propranolol failed to mitigate long-term behavioral changes induced by severe stress in rats.
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Condicionamiento Psicológico/efectos de los fármacos , Conducta Exploratoria/efectos de los fármacos , Miedo/efectos de los fármacos , Propranolol/uso terapéutico , Trastornos por Estrés Postraumático/prevención & control , Animales , Condicionamiento Psicológico/fisiología , Estimulación Eléctrica/efectos adversos , Conducta Exploratoria/fisiología , Miedo/fisiología , Miedo/psicología , Masculino , Propranolol/farmacología , Ratas , Ratas Wistar , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/psicología , Estrés Psicológico/fisiopatología , Estrés Psicológico/prevención & control , Estrés Psicológico/psicologíaRESUMEN
In this study, we describe the experimental variables influencing enantioseparation of twelve ß-blockers when analyzed under polar-organic, reversed-phase and hydrophilic interaction liquid chromatography conditions on a column with immobilized amylose tris(3-chloro-5-methylphenylcarbamate) as chiral stationary phase. Regarding polar-organic mode, two component mobile phases consisting of methanol, ethanol or acetonitrile with the addition of basic additives such as diethylamine, triethylamine, mono-ethanolamine, ethylendiamine or trifluoroacetic acid/diethylamine mixture were evaluated. Studies of retention at different temperatures were also performed. In reversed-phase mode, mixtures consisting of methanol or acetonitrile with either aqueous boric acid-borate buffer or sodium hydrogen carbonate-carbonate buffer solutions were compared aiming to study the influence of organic modifier as well as buffer type and pH on resolution. In addition, a systematic evaluation of the retention factors of ß-blockers enantiomers in hydro-organic eluents containing acetonitrile in presence of diethylamine as additive was carried out by increasing progressively the water content, in order to check for retention dependencies indicative of the interplay of both hydrophilic interaction liquid chromatography and reversed-phase modes.
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Antagonistas Adrenérgicos beta/análisis , Antagonistas Adrenérgicos beta/aislamiento & purificación , Amilosa/análogos & derivados , Cromatografía Liquida , Cromatografía de Fase Inversa , Fenilcarbamatos/química , Acetonitrilos/química , Amilosa/química , Interacciones Hidrofóbicas e Hidrofílicas , Estereoisomerismo , Agua/químicaRESUMEN
Restricted-access nanoparticles (RANPs) were prepared from bovine serum albumin by coacervation. They have an average sized of 311 nm. They were characterized and used to capture the ß-blockers atenolol, metoprolol and propranolol from untreated biological samples. It is shown that both high protein affinity drugs (propranolol) and low protein affinity drugs (atenolol) could be rapidly extracted from plasma. This is revealed by kinetic and isothermal adsorption studies. On the other hand, almost all proteins from the sample were excluded. This demonstrates the efficiency of RANPs as restricted-access material. Sample preparation was carried out by solid phase microextraction using a probe obtained by the fixation of the RANPs at the end of a glass capillary. Atenolol (in concentrations from 100 to 1200 µg L-1), metoprolol (from 80 to 1000 µg L-1) and propranolol (from 15 to 200 µg L-1) were extracted from spiked plasma samples and analyzed by LC MS/MS without using a separation column. Correlation coefficients >0.99, good precision, accuracy, robustness, and lack of memory effects were observed for all of the analytes. The detection limits (at an S/N of 3) are 25.6, 14.6, and 3.8 µg L-1 for atenolol, metoprolol and propranolol, respectively. Ten samples can be simultaneously extracted within â¼15 min. Plasma samples of patients undergoing medical treatment were successfully analyzed with the method. Graphical abstract Schematic representation of a bovine serum albumin-based restricted access nanoparticle that exclude proteins from a human plasma sample but capture the small analytes.
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Antagonistas Adrenérgicos beta/sangre , Nanopartículas/química , Albúmina Sérica Bovina/química , Animales , Bovinos , Cromatografía Liquida , Humanos , Tamaño de la Partícula , Propiedades de Superficie , Espectrometría de Masas en TándemRESUMEN
INTRODUCTION: Although main antihypertensive drugs are able to efficiently reduce blood pressure, only a third of treated hypertensive patients achieve optimal blood pressure control. Extensive interpatient variability on drug metabolism and oral disposition of blood pressure lowering drugs can contribute to this failure in hypertension management. Areas covered: The aim of the present review is to update the knowledge on the features of hepatic metabolism of the main antihypertensive agents, including ß-blockers, calcium channel blockers, angiotensin receptor blockers, and angiotensin converting enzyme inhibitors. The factors that contribute to the large interindividual variability of main antihypertensive drugs are also covered. Expert opinion: The variability of plasma concentration of antihypertensive drugs due to the involvement of hepatic metabolism can contribute to the inadequate control of blood pressure in the daily clinical practice. Genotype screening of specific hepatic drug-metabolizing enzymes may contribute to optimize dose selection and to increase the rate of blood pressure control in patients treated with specific ß-blockers, calcium channel blockers, and angiotensin receptor blockers.
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Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/farmacocinética , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/farmacocinética , Antihipertensivos/farmacocinética , Antihipertensivos/farmacología , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/farmacocinética , Relación Dosis-Respuesta a Droga , Genotipo , HumanosRESUMEN
AIM: To examine the interference of ß-blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7, and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol, and propranolol for 30 days using an orogastric tube to hypertensive rats. METHOD: We collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme-linked immunosorbent assay (ELISA). On day 30 of treatment, the spontaneously hypertensive rats (SHR) were euthanized, and heart, liver, lung, and kidney tissues were biopsied. Proteins were isolated for determining the expression of CXCR-4, CXCR-7, GRK-2 (G protein-coupled receptors kinase 2), ß-arrestins (ß1-AR and ß2-AR), and nuclear factor kappa B (NFκB). RESULTS: We found that the study drugs modulated these proteins, and metoprolol and propranolol strongly affected the expression of ß1-AR (P = .0102) and ß2-AR (P = .0034). CONCLUSION: ß-blockers modulated tissue expression of the proteins and their interactions following 30 days of treatment. It evidences that this class of drugs can interfere with proteins of cell homing pathways.
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Antagonistas Adrenérgicos beta/farmacología , Antihipertensivos/farmacología , Movimiento Celular/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Animales , Atenolol/farmacología , Carbazoles/farmacología , Carvedilol , Quimiocina CXCL12/sangre , Modelos Animales de Enfermedad , Quinasa 2 del Receptor Acoplado a Proteína-G/metabolismo , Hipertensión/sangre , Hipertensión/fisiopatología , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Metoprolol/farmacología , Miocardio/metabolismo , FN-kappa B/metabolismo , Propanolaminas/farmacología , Propranolol/farmacología , Ratas Endogámicas SHR , Receptores CXCR/metabolismo , Receptores CXCR4/metabolismo , Transducción de Señal/efectos de los fármacos , beta-Arrestina 1/metabolismo , Arrestina beta 2/metabolismoRESUMEN
BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with ß-blockers remains controversial. OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). CONCLUSIONS: In this largest clinical trial of ß-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).
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Antagonistas Adrenérgicos beta/uso terapéutico , Antineoplásicos/efectos adversos , Cardiotoxicidad/diagnóstico por imagen , Cardiotoxicidad/prevención & control , Carvedilol/uso terapéutico , Adulto , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Cardiotoxicidad/epidemiología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: This review covers the pharmacokinetics and pharmacodynamic of ß-blockers, the rationale for their use, some recent controversies in its use for managing hypertension, as well as, the beneficial properties of the third-generation ß-blockers beyond hypertension. BACKGROUND: The efficacy and safety of ß-blockers in the treatment of hypertension and other cardiovascular diseases have been established during more than 50 years of clinical experience. Recent updates of clinical guidelines have downgraded the use of ß-blockers for the treatment of uncomplicated hypertension to second and third line therapy. It is a well-known fact that ß-blockers exhibit heterogeneous pharmacokinetic and pharmacodynamic properties that clearly influence their clinical efficacy and tolerability in the management of essential hypertension. Conventional nonvasodilating ß-blockers (atenolol and metoprolol) are inferior to first-line antihypertensive agents in terms of cardioprotection due to lower ability to reduce central blood pressure and its variability and the adverse effects on glycemic and lipid metabolism. CONCLUSION: New vasodilating ß-blockers, mainly carvedilol and nebivolol, show enhanced hemodynamic and metabolic properties, which probably result in a higher prevention of major cardiovascular events in hypertensive patients. Despite head-to-head clinical trials comparing the effects of vasodilating vs nonvasodilating ß-blockers on hard clinical endpoints are lacking, the current evidence suggests that third-generation ß-blockers are superior to conventional ß-blockers for the prevention of cardiovascular events in patients with essential hypertension. Moreover, beyond their antihypertensive properties, third-generation ß-blockers also have pleiotropic, antioxidant and antiinflammatory effects that warrant a "promissory new era" of this newly group.
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Antagonistas Adrenérgicos beta/uso terapéutico , Antihipertensivos/uso terapéutico , Hipertensión Esencial/tratamiento farmacológico , Antagonistas Adrenérgicos beta/efectos adversos , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Índice Glucémico/efectos de los fármacos , Humanos , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
INTRODUCTION: Growing evidence indicates that norepinephrine promotes cancer growth and metastasis whereas ß-blockers decrease these risks. This study aimed to examine the clinical impact of ß-blockers and other hypertensive drugs on disease recurrence and survival in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This study analyzed a cohort of 1274 consecutive patients who received definitive treatments for previously untreated HNSCC at our tertiary referral center between January 2001 and December 2012. Antihypertensive use was considered positive if patients were on medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilized to determine associations between antihypertensive drugs and recurrence, survival, and second primary cancer (SPC) occurrence. RESULTS: Hypertension itself was not a significant variable of recurrence and survival and no antihypertensive drug use affected SPC occurrence (all P > 0.1). After controlling for clinical factors, calcium-channel blocker use remained an independent variable for index cancer recurrence, and ß-blocker use was significantly associated with poor cancer-specific mortality, competing mortality, and all-cause mortality (all P < 0.05). ß-blocker use significantly affected competing and all-cause mortalities in normotensive patients, and calcium-channel blocker use affected index cancer recurrence in normotensive patients (all P < 0.05). CONCLUSIONS: Our data show that ß-blocker use is associated with decreased survival and calcium-channel blockers is associated with increased cancer recurrence in patients of HNSCC.
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Antagonistas Adrenérgicos beta/efectos adversos , Antihipertensivos/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Primarias Secundarias/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidad , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inducido químicamente , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Primarias Secundarias/inducido químicamente , Neoplasias Primarias Secundarias/diagnóstico , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
A method for the determination of five sedatives and 14 ß-blocker residues in swine, bovine and equine kidney was validated. Samples were extracted with acetonitrile and purified using dispersive solid phase extraction (d-SPE) with Celite 545 with subsequent analysis by LC-MS/MS. A simplified protocol was applied to validate the method scope extension to include new matrices. Parameters such as recovery, trueness, linearity (r2), relative standard deviation (RSD), decision limit (CCα) and method capability (CCß) were measured for the bovine and equine kidney matrices. The method was applied to the analysis of more than 300 real samples and is currently included in the Brazilian National Residue Control Plan.
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Antagonistas Adrenérgicos beta/metabolismo , Cromatografía Liquida/métodos , Hipnóticos y Sedantes/metabolismo , Riñón/metabolismo , Espectrometría de Masas en Tándem/métodos , Animales , Bovinos , Caballos , PorcinosRESUMEN
The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the ß-adrenergic receptor (ß-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the ß-AR. Retrospective cohort studies on the clinical outcomes of ß-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of ß-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving ß-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of ß-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of ß-blockers significantly reduced risk of breast cancer death among women with breast cancer.
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Antagonistas Adrenérgicos beta/uso terapéutico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Femenino , HumanosRESUMEN
OBJECTIVE: To evaluate the use of ß-blockers and to monitor heart rate in Mexican patients with coronary artery disease. METHODS: CLARIFY is an outpatients registry with stable CAD. A total of 33,283 patients from 45 countries were enrolled between November 2009 and July 2010 from which 1342 were Mexican patients. RESULTS: The mean HR pulse was 70 bpm (beats per minute). Patients in Mexico were compared with the remaining global CLARIFY population. Patients in Mexico had a higher incidence of acute myocardial infarction and percutaneous coronary intervention, and lower incidence of revascularization surgery compared with the remaining CLARIFY population. More often, Mexican patients presented with diabetes, but less often hypertension and stroke. These patients were split into three mutually exclusive groups of HR ≤ 60 (N=263), HR 61-69 (N=356) and HR ≥ 70 (N=722). Patients with elevated HR had a higher incidence of diabetes and higher diastolic blood pressure on average than those with controlled HR. Regarding the use of ß-blockers, they were used in 63.3% of patients, 2.7% showed intolerance or contraindication to treatment to monitor heart rate, and ivabradine was used in 2.3%. Out of approximately 849 patients receiving treatment of ß-blockers, 52.1% had ≥ 70 bpm HR. CONCLUSIONS: In a large proportion of Mexican patients with stable coronary disease the HR remain elevated, > 70 bpm, even with the use of ß-blockers; this requires further attention.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Enfermedad de la Arteria Coronaria/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Atención Ambulatoria , Femenino , Humanos , Estudios Longitudinales , Masculino , México , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Hypertension induces left-ventricular hypertrophy (LVH) by mechanisms involving oxidative stress and unbalanced cardiac matrix metalloproteinase (MMP) activity. We hypothesized that ß1-adrenergic receptor blockers with antioxidant properties (nebivolol) could reverse hypertension-induced LVH more effectively than conventional ß1-blockers (metoprolol) when used at doses that exert similar antihypertensive effects. Two-kidney one-clip (2K1C) hypertension was induced in male Wistar rats. Six weeks after surgery, hypertensive and sham rats were treated with nebivolol (10 mg kg(-1)day(-1)) or metoprolol (20 mg kg(-1)day(-1)) for 4 weeks. Systolic blood pressure was monitored weekly by tail-cuff plethysmography. LV structural changes and fibrosis were studied in hematoxylin/eosin- and picrosirius-stained sections, respectively. Cardiac MMP levels and activity were determined by in situ zymography, gel zymography, and immunofluorescence. Dihydroethidium and lucigenin-derived chemiluminescence assays were used to assess cardiac reactive oxygen species (ROS) production. Nitrotyrosine levels were determined in LV samples by immunohistochemistry and green fluorescence and were evaluated using the ImageJ software. Cardiac protein kinase B/Akt (AKT) phosphorylation state was assessed by Western blot. Both ß-blockers exerted similar antihypertensive effects and attenuated hypertension-induced cardiac remodeling. Both drugs reduced myocyte hypertrophy and collagen deposition in 2K1C rats. These effects were associated with lower cardiac ROS and nitrotyrosine levels and attenuation of hypertension-induced increases in cardiac MMP-2 levels and in situ gelatinolytic activity after treatment with both ß-blockers. Whereas hypertension increased AKT phosphorylation, no effects were found with ß-blockers. In conclusion, we found evidence that two ß1-blockers with different properties attenuate hypertension-induced LV hypertrophy and cardiac collagen deposition in association with significant cardiac antioxidant effects and MMP-2 downregulation, thus suggesting a critical role for ß1-adrenergic receptors in mediating those effects. Nebivolol is not superior to metoprolol, at least with respect to their capacity to reverse hypertension-induced LVH.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Benzopiranos/uso terapéutico , Etanolaminas/uso terapéutico , Hipertensión Renovascular/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Metoprolol/uso terapéutico , Animales , Antihipertensivos/uso terapéutico , Antioxidantes/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Regulación hacia Abajo , Riñón/irrigación sanguínea , Riñón/cirugía , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/uso terapéutico , Nebivolol , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Tirosina/análogos & derivados , Tirosina/análisis , Remodelación Ventricular/efectos de los fármacosRESUMEN
INTRODUCTION: Oral beta-blockers improve the prognosis of patients with acute myocardial infarction, while atrial fibrillation worsens the prognosis of this population. The reduction of atrial fibrillation incidence in patients treated with beta-blockers could at least in part explain the benefits of this drug. OBJECTIVE: To investigate the effect of beta-blockers on the incidence of atrial fibrillation in patients with acute myocardial infarction. METHODS: We analyzed 1401 patients with acute myocardial infarction and evaluated the occurrence or absence of atrial fibrillation, the use of oral beta-blockers and mortality during the first 24 hours. RESULTS: a) The use of beta-blockers was inversely correlated with the presence of atrial fibrillation (rho = 0.004; OR = 0.54). b) Correlations with mortality were as follows: 31.5% in patients with atrial fibrillation, 9.2% in those without atrial fibrillation (rho < 0.001; Odds Ratio = 4.52), and 17.5% in patients not treated with beta-blockers and 6.7% in those who received the drug (rho < 0.001; OR = 0.34). c) Adjusted Models: The presence of atrial fibrillation was independently correlated with mortality (OR = 2.48, rho = 0.002). The use of beta-blockers was inversely and independently correlated with mortality (OR = 0.53; rho = 0.002). The patients who used beta-blockers showed a lower risk of atrial fibrillation (OR = 0.59; rho = 0.029) in the adjusted model. CONCLUSION: The presence of atrial fibrillation and the absence of oral beta-blockers increased in-hospital mortality in patients with acute myocardial infarction. Oral beta-blockers reduced the incidence of atrial fibrillation, which might be at least partially responsible for the drug's benefit.