RESUMEN
Atenolol, a cardioselective ß1-blocker, exhibits efficacy in treating cardiovascular diseases. We conducted a single-center, randomized, open, single-dose, 2-preparation, 2-cycle, 2-sequence, double-crossover trial with a 7-day washout period to investigate the pharmacokinetics, bioequivalence (BE), and safety of test and reference atenolol tablets (25 mg) in healthy Chinese volunteers. Forty-eight healthy participants were randomized into the fasting and fed arms. After administering a single oral dose of the test or reference formulation (25 mg), plasma atenolol concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were obtained from concentration-time profiles. In total, 23 and 24 individuals were included in the fasting and fed arms, respectively. The mean concentration-time profiles for both formulations were similar, and Cmax, AUC0-t, and AUC0-∞ were within the BE range of 80%-125%. Thirteen adverse events (AEs) were observed in 7 participants in the fasting arm; 1 withdrew from the trial early owing to an AE. In the fed arm, 20 AEs were observed in 8 participants, and none withdrew from the trial. All adverse reactions were grade I, with no serious AEs or deaths. Therefore, the 2 tablets are bioequivalent in healthy Chinese individuals under fasting and fed conditions, supporting their further clinical development.
Asunto(s)
Área Bajo la Curva , Atenolol , Estudios Cruzados , Ayuno , Voluntarios Sanos , Comprimidos , Equivalencia Terapéutica , Humanos , Atenolol/farmacocinética , Atenolol/administración & dosificación , Atenolol/efectos adversos , Masculino , Adulto , Femenino , Adulto Joven , Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos , Pueblo Asiatico , Administración Oral , Interacciones Alimento-Droga , China , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol has been suggested to significantly reduce rates of vascular events in this setting, though real-world evidence is limited. The aim of this study was to report our experience with celiprolol therapy in vEDS management. METHODS: Patients with a genetically confirmed diagnosis of vEDS who were referred for outpatient consultation at the Brescia University Hospital between January 2011 and July 2023 were included. At each visit, patients' medical history, results of vascular imaging, and office blood pressure measurements were recorded. Celiprolol therapy was progressively titrated to the maximum tolerated dose of up to 400 mg daily, according to the patients' tolerance. RESULTS: Overall, 26 patients were included. Female sex was prevalent (62%). Mean (SD) age was 37 (16) years. Follow-up duration was 72 (41) months. At the last follow-up visit, all patients were on celiprolol therapy, 80% of whom were taking the maximum recommended dose. The yearly risk of symptomatic vascular events was 8.8%, the majority of which occurred after reaching the maximum recommended dose of celiprolol. No significant predictor of symptomatic vascular events was identified among patients' clinical characteristics. CONCLUSION: In our cohort, rates of celiprolol use were high and the drug was well tolerated overall. Nonetheless, the risk of symptomatic vascular events remained nonnegligible. Future studies should identify reliable predictors of major adverse events and explore additional therapeutic strategies that could further lower the risk of life-threatening events in this population.
Asunto(s)
Celiprolol , Síndrome de Ehlers-Danlos , Humanos , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/tratamiento farmacológico , Síndrome de Ehlers-Danlos/complicaciones , Femenino , Masculino , Adulto , Persona de Mediana Edad , Celiprolol/efectos adversos , Resultado del Tratamiento , Factores de Riesgo , Factores de Tiempo , Italia/epidemiología , Adulto Joven , Medición de Riesgo , Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos , Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Estudios Retrospectivos , Presión Sanguínea/efectos de los fármacos , Síndrome de Ehlers-Danlos Tipo IVRESUMEN
BACKGROUND: Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost. MATERIALS AND METHODS: Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality. RESULTS: Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status. CONCLUSION: Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.
Asunto(s)
Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Hemodinámica/efectos de los fármacos , Metoprolol/administración & dosificación , Propanolaminas/administración & dosificación , Administración Intravenosa , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/economía , Angiografía por Tomografía Computarizada/economía , Angiografía Coronaria/economía , Análisis Costo-Beneficio/economía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Metoprolol/economía , Persona de Mediana Edad , Propanolaminas/economía , Estudios Prospectivos , Método Simple CiegoRESUMEN
PURPOSE: The aim of this study was to investigate the efficacy of esmolol on intraoperative hemodynamic and perioperative analgesic management. METHODS: Totally, 125 patients undergoing colectomy were randomly divided into three groups. Group S (saline group) was administered 0.75 mL/kg/h of normal saline for 5 min before anesthesia induction and maintenance of 0.25 mL/kg/h; Group E1 and Group E2 were administered 0.5 mg/kg and 1.0 mg/kg esmolol for 5 min before anesthesia induction, and maintained of 0.5 mg/kg/h and 2.0 mg/kg/h, respectively. Several parameters including indexes of hemodynamics variation (primary outcome), intra- and postoperative analgesic usage, and pain score were measured. RESULTS: Group E1 and Group E2 had significantly lower intubation response than Group S (P = 0.007, P = 0.001), and extubation response of Group E2 was significantly lower than Group S (P = 0.007). The opioid consumption in Group E1 and Group E2 was significantly lower than in Group S intraoperatively (P = 0.020 and 0.007). The incidence of postoperative adverse reactions among the three groups was not statistically significant (P = 0.368 and 0.772). CONCLUSION: Esmolol 0.5 mg/kg and 1.0 mg/kg infusion before intubation both can effectively inhibit the intubation response, while only maintenance with 2.0 mg/kg/h of esmolol can reduce the incidence of extubation response. At the same time, esmolol can decrease intraoperative opioid requirement without increasing the risk of adverse reactions. TRIAL REGISTRATION: ChiCTR1900024538 and the date of registration was July 15, 2019 at http://www.chictr.org.cn.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Colectomía , Hemodinámica/efectos de los fármacos , Dolor Postoperatorio/tratamiento farmacológico , Propanolaminas/administración & dosificación , Adulto , Anciano , Analgésicos Opioides/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios ProspectivosRESUMEN
The protective role of preoperative beta-blocker in patients undergoing non-cardiac surgery is unknown. We aimed to evaluate the effects of beta-blocker on perioperative myocardial injury in patients undergoing non-cardiac surgery. We consecutively enrolled 112 patients undergoing non-cardiac surgery. They were randomly allocated to receive bisoprolol or placebo given at least 2 days preoperatively and continued until 30 days after surgery. The primary outcome was incidence of perioperative myocardial injury defined by a rise of high-sensitive troponin-T (hs-TnT) more than 99th percentile of upper reference limit or a rise of hs-TnT more than 20% if baseline level is abnormal. Baseline characteristics were comparable between bisoprolol and placebo in randomized cohort Mean age was 62.5 ± 11.8 years and 76 (67.8%) of 112 patients were male. Among 112 patients, 49 (43.8%) underwent vascular surgery and 63 (56.2%) underwent thoracic surgery. The median duration of assigned treatment prior to surgery was 4 days (2-6 days). We did not demonstrate the significant difference in the incidence of perioperative myocardial injury [52.6% (30 of 57 patients) vs. 49.1% (27 of 55 patients), P = 0.706]. In addition, the incidence of intraoperative hypotension was higher in bisoprolol group than placebo group in patients undergoing non-cardiac surgery [70.2% (40 of 57 patients) vs. 47.3% (26 of 55 patients), P = 0.017]. We demonstrated that there was no statistically significant difference in perioperative myocardial injury observed between patients receiving bisoprolol and placebo who had undergone non-cardiac surgery.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Bisoprolol/administración & dosificación , Cardiopatías/prevención & control , Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos , Bisoprolol/efectos adversos , Método Doble Ciego , Cardiopatías/sangre , Humanos , Hipotensión/inducido químicamente , Complicaciones Posoperatorias/prevención & control , Procedimientos Quirúrgicos Operativos/efectos adversos , Tailandia , Troponina T/sangreRESUMEN
The purpose of the current studies was to develop ocular insert of betaxolol hydrochloride (BXH), using arabinoxylan (AX) as a film former. The inserts were prepared by sandwiching I mg of BXH between two films of AX. Six different formulations of ocular inserts were prepared in such a way that first three formulations contained varying concentrations of AX along with glycerol as plasticizer, whereas, rest of the formulations were added with 0.5mg of sodium alginate, sandwiched between two films of AX along with 1mg of BXH. Chemical compatibilities of the ingredients were assessed by using FTIR. Prepared ocular inserts were subjected to various physicochemical characterizations. The dissolution studies showed that ocular inserts containing sodium alginate with the AX showed sustained release effect better than the formulations with AX alone. Addition of sodium alginate resulted in inhibition of sudden release in initial phase and further sustained the release of drug from ocular inserts. Ocular inserts were pH compatible to the eyes as well as there was no interaction among the drug and excipients, suggesting that the selected excipients were suitable for the development of sustained release ocular inserts of BXH.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Alginatos , Betaxolol/administración & dosificación , Glicerol , Plantago , Xilanos , Administración Oftálmica , Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Betaxolol/farmacocinética , Preparaciones de Acción Retardada , Liberación de Fármacos , Glaucoma de Ángulo Abierto/tratamiento farmacológicoRESUMEN
BACKGROUND: Beta-blocking is important for critically ill patients. Although some patients are required to continue taking beta-blockers after they no longer need critical care, some of these patients have impaired swallowing abilities. Bisoprolol dermal patches have recently been introduced and appear to be a good alternative to oral bisoprolol tablets. However, it is still unclear whether the pharmacodynamics of such patches are affected by edema in patients who have experienced critical care. This study aimed to clarify the effects of systemic edema on beta-blocker absorption from dermal patches in critically ill patients. METHOD: Patients who exhibited tachycardia and impaired swallowing function after critical care were included in this study. They were assigned to either the edema group (nâ=â6) or no edema group (nâ=â6) depending on the presence/absence of edema in the lower extremities. A bisoprolol dermal patch was pasted onto each subject, and the blood bisoprolol concentration was checked at 8 timepoints over the next 24âhours. The area under the serum concentration time curve, maximum concentration observed (Cmax), and time of maximum concentration observed were also examined. RESULT: The mean blood bisoprolol concentrations of the 2 groups were not significantly different at 2, 4, 6, 8, 10, 12, 16, or 24âhours after the patch application. The area under the serum concentration time curve and maximum concentration observed were not different between the groups. The mean heart rates of the 2 groups were not significantly different at 6, 12, or 24âhours after the patch application (Student t test, Pâ=â.0588, Pâ=â.1080, and Pâ=â.2322, respectively). CONCLUSION: In this study, the blood concentration of bisoprolol and its heart rate-reducing effects after bisoprolol dermal patch application might not be affected by systemic edema in the lower extremities.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Bisoprolol/farmacocinética , Edema/metabolismo , Absorción Cutánea , Administración Cutánea , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/sangre , Anciano , Anciano de 80 o más Años , Bisoprolol/administración & dosificación , Bisoprolol/sangre , Estudios de Casos y Controles , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting. OBJECTIVES: The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19-associated ARDS. METHODS: A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography. RESULTS: Metoprolol administration was without side effects. At baseline, neutrophil content in BAL did not differ between groups. Conversely, patients randomized to metoprolol had significantly fewer neutrophils in BAL on day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 neutrophils/µl [Q1, Q3: 222, 1,346 neutrophils/µl] in the metoprolol and control groups, respectively; P = 0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO2:FiO2) significantly improved after 3 days of metoprolol treatment (median: 130 [Q1, Q3: 110, 162] vs median: 267 [Q1, Q3: 199, 298] at baseline and day 4, respectively; P = 0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5 ± 7.6 vs 21.9 ± 12.6 days; P = 0.17). CONCLUSIONS: In this pilot trial, intravenous metoprolol administration to patients with COVID-19-associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.
Asunto(s)
COVID-19/transmisión , Enfermedad Crítica/terapia , Metoprolol/administración & dosificación , Pandemias , Respiración Artificial/métodos , SARS-CoV-2 , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Adulto , Anciano , COVID-19/epidemiología , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge. Meeting this has resulted in changes to working practices and the impact on the management of patients with heart failure with reduced ejection fraction (HFrEF) is largely unknown. We performed a retrospective, observational study contrasting patients diagnosed with HFrEF attending specialist heart failure clinics at a UK hospital, whose subsequent period of optimisation of medical therapy was during the COVID-19 pandemic, with patients diagnosed the previous year. The primary outcome was the change in equivalent dosing of ramipril and bisoprolol at 6-months. Secondary outcomes were the number and type of follow-up consultations, hospitalisation for heart failure and all-cause mortality. In total, 60 patients were diagnosed with HFrEF between 1 December 2019 and 30 April 2020, compared to 54 during the same period of the previous year. The absolute number of consultations was higher (390 vs 270; p = 0.69), driven by increases in telephone consultations, with a reduction in appointments with hospital nurse specialists. After 6-months, we observed lower equivalent dosing of ramipril (3.1 ± 3.0 mg vs 4.4 ± 0.5 mg; p = 0.035) and similar dosing of bisoprolol (4.1 ± 0.5 mg vs 4.9 ± 0.5 mg; p = 0.27), which persisted for ramipril (mean difference 1.0 mg, 95% CI 0.018-2.09; p = 0.046) and bisoprolol (mean difference 0.52 mg, 95% CI -0.23-1.28; p = 0.17) after adjustment for baseline dosing. We observed no differences in the proportion of patients who died (5.0% vs 7.4%; p = 0.59) or were hospitalised with heart failure (13.3% vs 9.3%; p = 0.49). Our study suggests the transition to telephone appointments and re-deployment of heart failure nurse specialists was associated with less successful optimisation of medical therapy, especially renin-angiotensin inhibitors, compared with usual care.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Bisoprolol/administración & dosificación , COVID-19 , Insuficiencia Cardíaca/tratamiento farmacológico , Ramipril/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Bisoprolol/efectos adversos , Enfermedad Crónica , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Ramipril/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Vaccination plays an important role in the fight against SARS-CoV-2 to minimie the spread of coronavirus disease 2019 (COVID-19) and its life-threatening complications. Myocarditis has been reported as a possible and rare adverse consequence of different vaccines, and its clinical presentation can range from influenza-like symptoms to acute heart failure. We report a case of a 30-year-old man who presented progressive dyspnea and constrictive retrosternal pain after receiving SARS-CoV-2 vaccine. Cardiac magnetic resonance and laboratory data revealed typical findings of acute myopericarditis.
Asunto(s)
Aspirina/administración & dosificación , Vacuna BNT162 , Bisoprolol/administración & dosificación , COVID-19 , Miocarditis , Prednisolona/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Adulto , Antiinflamatorios/administración & dosificación , Vacuna BNT162/administración & dosificación , Vacuna BNT162/efectos adversos , COVID-19/diagnóstico , COVID-19/prevención & control , Forma MB de la Creatina-Quinasa/sangre , Electrocardiografía/métodos , Humanos , Imagen por Resonancia Cinemagnética/métodos , Masculino , Miocarditis/sangre , Miocarditis/etiología , Miocarditis/fisiopatología , Miocarditis/terapia , SARS-CoV-2 , Resultado del Tratamiento , Troponina I/sangreRESUMEN
Importance: Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH. Objective: To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy. Design, Setting, and Participants: This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020. Interventions: Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment. Main Outcomes and Measures: The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score. Results: Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, -4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, -5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups. Conclusions and Relevance: In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy. Trial Registration: ClinicalTrial.gov Identifier: NCT02342275.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Atenolol/uso terapéutico , Hemangioma Capilar/tratamiento farmacológico , Propranolol/uso terapéutico , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Antagonistas Adrenérgicos beta/administración & dosificación , Atenolol/administración & dosificación , China , Femenino , Humanos , Lactante , Masculino , Propranolol/administración & dosificación , Estudios ProspectivosRESUMEN
BACKGROUND: To the best of our knowledge, there is no study that has conducted a review investigating the clinical efficacy and safety of bisoprolol combined with trimetazidine on chronic heart failure (CHF) patients with chronic obstructive pulmonary disease (COPD). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of bisoprolol combined with trimetazidine on CHF patients with COPD. METHODS: Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library will be searched in April 2021 by 2 independent reviewers. For search on PubMed, the following search terms will be used: "trimetazidine, bisoprolol, chronic heart failure, chronic obstructive pulmonary disease." In order to achieve a consistency of extracted items, the data extractors will extract data from a sample of eligible studies. The outcomes include all-cause mortality and hospitalization for cardiac or/and respiratory causes; left ventricular structure and function; and functional scores. Review Manager software (v 5.4; Cochrane Collaboration) will be used for the meta-analysis. Two independent reviewers will assess the risk of bias of the included studies at study level. Any disagreements will be discussed and resolved in discussion with a third reviewer. RESULTS: The results of our review will be reported strictly following the PRISMA criteria. CONCLUSIONS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/ZWPRB.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Bisoprolol/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Trimetazidina/administración & dosificación , Vasodilatadores/administración & dosificación , Enfermedad Crónica , Quimioterapia Combinada , Insuficiencia Cardíaca/complicaciones , Humanos , Metaanálisis como Asunto , Estudios Observacionales como Asunto , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Caffeine poisoning may cause life-threatening arrhythmias and hemodynamic failure. We aimed to investigate the toxicokinetics (TK), toxicodynamics (TD) and TK/TD relationships of caffeine in a case of poisoning. CASE REPORT: A 47-year-old male ingested pure anhydrous caffeine powder (70 g) in a suicide attempt. He developed agitation, tachycardia, and two episodes of ventricular fibrillation treated with defibrillation and tracheal intubation. He was successfully managed using intravenous infusions of esmolol and norepinephrine. METHODS: We modelled the time-course of plasma caffeine concentration (TK study using online liquid chromatography-tandem mass spectrometry), the time-course of blood lactate concentration and infusion rates of esmolol and norepinephrine (TD studies) and the TK/TD relationships. RESULTS: Caffeine TK was of first-order peaking at 258 mg/L with an elimination half-life of 46.2 h and clearance of 2.2 L/h. Caffeine-related effects on blood lactate (peak, 10 mmol/L at 1.25 h postingestion) were described by a Bateman-type equation (formation rate, 0.05 mmol/mg.h; elimination rate, 0.9 mmol/mg.h). Esmolol and norepinephrine infusion rates to reverse caffeine-related cardiovascular effects (peaks at 51-h postingestion) fitted well with a sigmoidal Emax model (EC50, 180.0 and 225.9 mg/L, respectively; Hill coefficient, 10.0). CONCLUSION: Massive caffeine ingestion is characterized by prolonged caffeine elimination. TK/TD relationships are helpful to quantify caffeine-related catecholaminergic effects.
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Cafeína/envenenamiento , Estimulantes del Sistema Nervioso Central/envenenamiento , Frecuencia Cardíaca/efectos de los fármacos , Intento de Suicidio , Taquicardia/inducido químicamente , Fibrilación Ventricular/inducido químicamente , Administración Oral , Agonistas alfa-Adrenérgicos/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Cafeína/administración & dosificación , Cafeína/farmacocinética , Cardiotoxicidad , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/farmacocinética , Cardioversión Eléctrica , Semivida , Humanos , Hiperlactatemia/inducido químicamente , Infusiones Intravenosas , Intubación Intratraqueal , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Norepinefrina/administración & dosificación , Polvos , Propanolaminas/administración & dosificación , Taquicardia/diagnóstico , Taquicardia/fisiopatología , Taquicardia/terapia , Resultado del Tratamiento , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/terapiaRESUMEN
BACKGROUND: Bisono® is the world's first transdermal formulation of a bisoprolol, which is approved for the treatment of hypertension in Japan. We aimed to investigate the usefulness of this formulation in patients who were admitted to our hospital with cardiac symptoms suggestive of acute coronary syndrome or an acute exacerbation of heart failure. METHODS: This study involved a retrospective survey of medical records from September 1, 2017 to April 30, 2018 obtained from the Cardiovascular Center of Kyoto Katsura Hospital. The clinical data of patients on admission who had received a transdermal formula of bisoprolol (Bisono® tape) were retrieved; their blood pressure and heart rate data were analyzed in relation to the doses of Bisono® tape administered. RESULTS: Sixty-three patients received the Bisono® tape. Their final diagnoses included acute myocardial infarction, an exacerbation of heart failure, and atrial fibrillation. While there was no significant correlation observed between the administered doses of the drug and reduction in blood pressure achieved within 24 h after admission, there was a significant (p < 0.05) correlation between the doses of Bisono®tnd reduction in the heart rate within 24 h after admission (ΔHR0-24 h). Only one patient who received 8 mg of Bisono® exhibited temporal bradycardia (heart rate < 50 bpm). CONCLUSION: The transdermal formulation of bisoprolol may be useful for the early introduction of ß-blockers in patients admitted with cardiac symptoms associated with myocardial ischemia or heart failure. However, caution should be exercised because of the possible risk of hypotension.
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Síndrome Coronario Agudo/tratamiento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Bisoprolol/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Enfermedad Aguda , Administración Cutánea , Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/diagnóstico , Bisoprolol/uso terapéutico , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Estudios Retrospectivos , Tiempo de Tratamiento , Parche Transdérmico , Resultado del TratamientoRESUMEN
BACKGROUND: Coronary CT angiography (CCTA) is increasing seen as a first line investigation in patients with suspected coronary artery disease. Heart-rate control improves the image quality and diagnostic accuracy of CCTA. Typically, beta-blockers are administered to induce sinus bradycardia. Sinus bradycardia may also be induced by ivabradine. We hypothesized that in a real-world population ivabradine would be an effective alternative to metoprolol at heart rate lowering for CCTA. METHODS: This was a retrospective analysis of consecutive patients who were exposed to an ivabradine-based (IB) versus a metoprolol-only (MO) protocol to achieve a target heart rate = 65bpm. Hemodynamic responses to both strategies were compared along with differences in cost and the time expired from medication administration to CCTA. RESULTS: 5955 consecutive patients were included in the analysis: 3211 were imaged during an era of a metoprolol only strategy (MO) and 2744 CCTA following an ivabradine based (IB) strategy. 2676 patients had heart rates >65 and received heart-rate lowering medication: 1958 patients had MO, and 718 received IB protocol. Target heart rate of = 65bpm was achieved in 77% of MO and 89% of IB patients (p < 0.01). The time from initial medication administration to CCTA was longer in the IB versus MO patients (77 versus 48 min, p < 0.01). CONCLUSIONS: Introduction of a novel single dose ivabradine-based protocol to control heart rate for CCTA was more successful in achieving target heart rate than a metoprolol-only strategy. The use of ivabradine however incurred a 1.6-fold increase in the time delay from medication administration and imaging compared to a metoprolol only protocol.
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Fármacos Cardiovasculares/administración & dosificación , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Frecuencia Cardíaca/efectos de los fármacos , Ivabradina/administración & dosificación , Tomografía Computarizada Multidetector , Pruebas en el Punto de Atención , Administración Oral , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Anciano , Femenino , Humanos , Masculino , Metoprolol/administración & dosificación , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo , Flujo de TrabajoRESUMEN
The practice of prescribing ß-blockers to lower blood pressure and mitigate perioperative cardiovascular events has been questioned because of reports of an increased risk of stroke. The benefit of ß-blocker therapy primarily relies on preventing activation of cardiac ß1-adrenergic receptors (ARs). However, we reported that ß1ARs also mediate vasodilator responses of rat cerebral arteries (CAs), implying that ß-blockers may impair cerebral blood flow under some conditions. Here, we defined the impact of metoprolol (MET), a widely prescribed ß1AR-selective antagonist, on adrenergic-elicited diameter responses of rat CAs ex vivo and in vivo. MET (1-10 µmol/l) prevented ß1AR-mediated increases in diameter elicited by dobutamine in cannulated rat CAs. The ß1AR-mediated dilation elicited by the endogenous adrenergic agonist norepinephrine (NE) was reversed to a sustained constriction by MET. Acute oral administration of MET (30 mg/kg) to rats in doses that attenuated resting heart rate and dobutamine-induced tachycardia also blunted ß1AR-mediated dilation of CAs. In the same animals, NE-induced dilation of CAs was reversed to sustained constriction. Administration of MET for 2 weeks in drinking water (2 mg/ml) or subcutaneously (15 mg/kg per day) also resulted in NE-induced constriction of CAs in vivo. Thus, doses of MET that protect the heart from adrenergic stimulation also prevent ß1AR-mediated dilation of CAs and favor anomalous adrenergic constriction. Our findings raise the possibility that the increased risk of ischemic stroke in patients on ß-blockers relates in part to adrenergic dysregulation of cerebrovascular tone. SIGNIFICANCE STATEMENT: ß-Blocker therapy using second-generation, cardioselective ß-blockers is associated with an increased risk of stroke, but the responsible mechanisms are unclear. Here, we report that either acute or chronic systemic administration of a cardioselective ß-blocker, metoprolol, mitigates adrenergic stimulation of the heart as an intended beneficial action. However, metoprolol concomitantly eliminates vasodilator responses to adrenergic stimuli of rat cerebral arteries in vivo as a potential cause of dysregulated cerebral blood flow predisposing to ischemic stroke.
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Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Cardiotónicos/farmacología , Arterias Cerebrales/efectos de los fármacos , Metoprolol/farmacología , Receptores Adrenérgicos beta 1/metabolismo , Vasodilatación , Agonistas de Receptores Adrenérgicos beta 1/farmacología , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos , Animales , Cardiotónicos/administración & dosificación , Cardiotónicos/efectos adversos , Arterias Cerebrales/fisiología , Dobutamina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Metoprolol/administración & dosificación , Metoprolol/efectos adversos , Norepinefrina/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Open abdominal surgery is frequently related to excessive inflammation and a compromised intestinal barrier, leading to poor clinical outcomes. The administration of beta-1 blocker has been shown to effectively reduce inflammation and preserve intestinal barrier function in patients with sepsis, shock, or other critical illnesses. The underlying mechanism of these effects may be associated with the autonomic nervous system's activation via cholecystokinin receptors. This study aimed to investigate the effect of beta-1 blocker on systemic and local inflammatory responses and the intestinal barrier function in the context of open abdominal surgery. METHODS: A rat model of open abdominal surgery was induced through peritoneal air exposure for 3 hours and treated via gavage with the beta-1 blocker, metoprolol, or saline. Cholecystokinin-receptor antagonists were administered before the metoprolol treatment. Peritoneal lavage fluid, serum, and tissues were collected 24 hours after surgery to determine systemic and local inflammation and intestinal integrity. RESULTS: The intervention with metoprolol significantly reduced serum tumor necrosis factor-alpha and interleukin-6 (P < .05) and peritoneal interleukin-6 (P < .01) compared with those of animals treated with saline. The intestinal myeloperoxidase indicating the influx of neutrophils was also significantly prevented by the administration of metoprolol (P < .05). Above all, this intervention resulted in a significant decrease in serum D-lactate and intestinal fatty acid-binding protein, intestinal permeability, bacterial translocation, and Chiu's score for intestinal mucosa injury (P < .05). However, the anti-inflammatory and intestinal integrity protective effects of metoprolol were prevented by the blockage of cholecystokinin receptors (P < .05). CONCLUSION: Our data indicate that beta-1 blocker reduces systemic and local inflammatory responses and preserves intestinal barrier function after open abdominal surgery through a mechanism that depends on cholecystokinin receptors. Clinically, these findings imply that perioperative intervention with a beta-1 blocker may be an effective new therapy to enhance recovery after open abdominal surgery.
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Abdomen/cirugía , Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Antiinflamatorios/farmacología , Mucosa Intestinal/efectos de los fármacos , Cuidados Posoperatorios , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Citocinas/sangre , Citocinas/metabolismo , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Modelos Animales de Enfermedad , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Metoprolol/farmacología , Permeabilidad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , RatasRESUMEN
OBJECTIVE: The effect of early intravenous (IV) beta-blockers (BBs) administration in patients undergoing primary percutaneous coronary intervention (pPCI) on ST-segment deviation is unknown. We undertook a prespecified secondary analysis of the Early Beta-blocker Administration before primary PCI in patients with ST-elevation Myocardial Infarction (EARLY-BAMI) trial to investigate the effect of early IV BB on ST-segment deviation. METHODS: The EARLY-BAMI trial randomised patients with ST-elevation myocardial infarction (STEMI) to IV metoprolol (2×5 mg bolus) or matched placebo before pPCI. The prespecified outcome, evaluated by an independent core laboratory blinded to study treatment, was the residual ST-segment deviation 1 hour after pPCI (ie, the percentage of patients with >3 mm cumulative ST deviation at 1 hour after pPCI). RESULTS: An ECG for the evaluation of residual ST-segment deviation 1 hour after pPCI was available in 442 out of 683 randomised patients. The BB group had a lower heart rate after pPCI compared with placebo (71.2±13.2 vs 74.3±13.6, p=0.016); however, no differences were noted in the percentages of patients with >3 mm cumulative ST deviation at 1 hour after pPCI (58.6% vs 54.1%, p=0.38, in BB vs placebo, respectively) neither a significant difference was found for the percentages of patients in each of the four prespecified groups (normalised ST-segment; 1-3 mm; 4-6 mm;>6 mm residual ST-deviation). CONCLUSIONS: In patients with STEMI, who were being transported for primary PCI, early IV BB administration did not significantly affect ST-segment deviation after pPCI compared with placebo. The neutral result of early IV BB administration on an early marker of pharmacological effect is consistent with the absence of subsequent improvement of clinical outcomes.
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Electrocardiografía/efectos de los fármacos , Metoprolol/administración & dosificación , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio con Elevación del ST/terapia , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/diagnóstico , Resultado del TratamientoRESUMEN
Background Intravenous high-dose glucagon is a recommended antidote against beta-blocker poisonings, but clinical effects are unclear. We therefore investigated hemodynamic effects and safety of high-dose glucagon with and without concomitant beta-blockade. Methods and Results In a randomized crossover study, 10 healthy men received combinations of esmolol (1.25 mg/kg bolus+0.75 mg/kg/min infusion), glucagon (50 µg/kg), and identical volumes of saline placebo on 5 separate days in random order (saline+saline; esmolol+saline; esmolol+glucagon bolus; saline+glucagon infusion; saline+glucagon bolus). On individual days, esmolol/saline was infused from -15 to 30 minutes. Glucagon/saline was administered from 0 minutes as a 2-minute intravenous bolus or as a 30-minute infusion (same total glucagon dose). End points were hemodynamic and adverse effects of glucagon compared with saline. Compared with saline, glucagon bolus increased mean heart rate by 13.0 beats per minute (95% CI, 8.0-18.0; P<0.001), systolic blood pressure by 15.6 mm Hg (95% CI, 8.0-23.2; P=0.002), diastolic blood pressure by 9.4 mm Hg (95% CI, 6.3-12.6; P<0.001), and cardiac output by 18.0 % (95% CI, 9.7-26.9; P=0.003) at the 5-minute time point on days without beta-blockade. Similar effects of glucagon bolus occurred on days with beta-blockade and between 15 and 30 minutes during infusion. Hemodynamic effects of glucagon thus reflected pharmacologic glucagon plasma concentrations. Glucagon-induced nausea occurred in 80% of participants despite ondansetron pretreatment. Conclusions High-dose glucagon boluses had significant hemodynamic effects regardless of beta-blockade. A glucagon infusion had comparable and apparently longer-lasting effects compared with bolus, indicating that infusion may be preferable to bolus injections. Registration Information URL: https://www.clinicaltrials.gov; Unique identifier: NCT03533179.
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Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Glucagón/administración & dosificación , Hemodinámica/efectos de los fármacos , Hormonas/administración & dosificación , Propanolaminas/administración & dosificación , Adulto , Estudios Cruzados , Dinamarca , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Masculino , Método Simple Ciego , Adulto JovenRESUMEN
Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S-metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.001). The natural log of CLo was lower with an AS of 1 (7.6 ± 0.4 mL/minute) vs. 2-2.25 (8.3 ± 0.6 mL/minute; P = 0.012), similar between an AS of 1 and 1.25-1.5 (7.8 ± 0.5 mL/minute; P = 0.702), and lower with an AS of 1.25-1.5 vs. 2-2.25 (P = 0.03). There was also a greater reduction in heart rate with metoprolol among study participants with AS of 1 (-10.8 ± 5.5) vs. 2-2.25 (-7.1 ± 5.6; P < 0.001) and no significant difference between those with an AS of 1 and 1.25-1.5 (-9.2 ± 4.7; P = 0.095). These data highlight linear trends among CYP2D6 AS and metoprolol PK and PD, but inconsistencies with the phenotypes assigned by AS based on the current standards. Overall, this case study with metoprolol suggests that utilizing CYP2D6 AS, instead of collapsing AS into phenotype categories, may be the most precise approach for utilizing CYP2D6 pharmacogenomics in clinical practice.