- Graphene Oxide/Polyethylene Glycol-Stick for Thin Film Microextraction of β-Blockers from Human Oral Fluid by Liquid Chromatography-Tandem Mass Spectrometry. [Journal Article]Molecules 2019; 24(20)M
- A wooden stick coated with a novel graphene-based nanocomposite (Graphene oxide/polyethylene glycol (GO/PEG)) is introduced and investigated for its efficacy in solid phase microextraction techniques. The GO/PEG-stick was prepared and subsequently applied for the extraction of β-blockers, acebutolol, and metoprolol in human oral fluid samples, which were subsequently detected by liquid chromatogr…
A wooden stick coated with a novel graphene-based nanocomposite (Graphene oxide/polyethylene glycol (GO/PEG)) is introduced and investigated for its efficacy in solid phase microextraction techniques. The GO/PEG-stick was prepared and subsequently applied for the extraction of β-blockers, acebutolol, and metoprolol in human oral fluid samples, which were subsequently detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). Experimental parameters affecting the extraction protocol including sample pH, extraction time, desorption time, appropriate desorption solvent, and salt addition were optimized. Method validation for the detection from oral fluid samples was performed following FDA (Food and Drug Administration) guidelines on bioanalytical method validation. Calibration curves ranging from 5.0 to 2000 nmol L-1 for acebutolol and 25.0 to 2000 nmol L-1 for metoprolol were used. The values for the coefficient of determination (R2) were found to be 0.998 and 0.996 (n = 3) for acebutolol and metoprolol, respectively. The recovery of analytes during extraction was 80.0% for acebutolol and 62.0% for metoprolol, respectively. The limit of detections (LODs) were 1.25, 8.00 nmol L-1 for acebutolol and metoprolol and the lower limit of quantifications (LLOQ) were 5.00 nmol L-1 for acebutolol and 25.0 nmol L-1 for metoprolol. Validation experiments conducted with quality control (QC) samples demonstrated method accuracy between 80.0% to 97.0% for acebutolol and from 95.0% to 109.0% for metoprolol. The inter-day precision for QC samples ranged from 3.6% to 12.9% for acebutolol and 9.5% to 11.3% for metoprolol. Additionally, the GO/PEG-stick was demonstrated to be reusable, with the same stick observed to be viable for more than 10 extractions from oral fluid samples.
- CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study. [Journal Article]J Cardiothorac Vasc Anesth 2019JC
- CONCLUSIONS: The PREEMPTIVE pilot study is the first perioperative pilot trial to provide essential information for the design of a future, large-scale trial comparing CYP2D6 genotype-guided metoprolol management with a nontailored strategy in terms of managing AF. In addition, secondary outcomes regarding implementation, clinical benefit, safety, and cost-effectiveness in patients undergoing cardiac surgery will be examined.
- Expectoration of bronchial casts in association with Ramipril treatment. [Journal Article]Cardiol Young 2019; :1-2CY
- We report of a 26-year-old female patient who was referred to our centre with congestive heart failure (CHF). Acute myocarditis with a high Parvovirus B19 virus load was diagnosed by myocardial biopsy. CHF improved after start of ramipril 5 mg/d, metoprolol, diuretics, immunoglobins, and a 24-hour infusion of levosimendan. Soon after initiation of medical therapy, the patient started to expectora…
We report of a 26-year-old female patient who was referred to our centre with congestive heart failure (CHF). Acute myocarditis with a high Parvovirus B19 virus load was diagnosed by myocardial biopsy. CHF improved after start of ramipril 5 mg/d, metoprolol, diuretics, immunoglobins, and a 24-hour infusion of levosimendan. Soon after initiation of medical therapy, the patient started to expectorate bronchial casts with varying frequencies (three times per week to five times daily). Thorough pneumological workup, including histology of the casts, microbiology, and a CT scan of the lungs, did not reveal any cause for bronchial cast formation. Inhalative corticoids were started without any benefit. Two years later, cardiac catheterisation demonstrated normalised left ventricular function. LV end-diastolic pressure, however, was still elevated at 14 mmHg. Endomyocardial biopsies at this time were negative for virus genome. Finally, we changed afterload reduction therapy from ramipril to candesartan. Within 24 hours, expectoration of bronchial casts terminated. Four weeks later, re-exposition to ramipril prompted immediate re-appearance of cast formation, which again stopped with switching back to candesartan. Finally, we were to prove that treatment with ramipril resulted in bronchial cast formation in this patient.
- Neonatal effects of intrauterine metoprolol/bisoprolol exposure during the second and third trimester: a cohort study with two comparison groups. [Journal Article]J Hypertens 2019JH
- CONCLUSIONS: Long-term intrauterine exposure to metoprolol or bisoprolol may increase the risk of being born small-for-gestational-age. It is still a matter of debate to which extent maternal hypertension contributes to the lower birth weight. Serious neonatal symptoms are rare. Altogether, metoprolol and bisoprolol are well tolerated treatment options, but a case-by-case decision on close neonatal monitoring is recommended.
- Physiologically Based Pharmacokinetic Modelling to Identify Pharmacokinetic Parameters Driving Drug Exposure Changes in the Elderly. [Journal Article]Clin Pharmacokinet 2019CP
- CONCLUSIONS: The progressive decrease in hepatic and renal blood flow, as well as glomerular filtration, rate led to a reduced clearance driving exposure changes in the healthy elderly, independent of the drug.
- The Effect of Antiarrhythmic Drugs on the Beat Rate Variability of Human Embryonic and Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. [Journal Article]Sci Rep 2019; 9(1):14106SR
- Embryonic stem cell (ESC) derived tissue is a promising tool to be used in different clinical, preclinical and also scientific settings, for example as in vivo biological pacemaker, preclinical drug safety screening tool or ultimately as part of a cell replacement therapy. However, before ESC derived tissue can be used routinely for these purposes in humans, further studies are needed. In this co…
Embryonic stem cell (ESC) derived tissue is a promising tool to be used in different clinical, preclinical and also scientific settings, for example as in vivo biological pacemaker, preclinical drug safety screening tool or ultimately as part of a cell replacement therapy. However, before ESC derived tissue can be used routinely for these purposes in humans, further studies are needed. In this context, the aims of the present study were to examine the effect of antiarrhythmic drugs on human ESC (hESC) und human induced pluripotent stem cell (hiPSC) derived cardiomyocytes by analyzing the beat rate variability (BRV), which can be considered as the in vitro equivalent of the heart rate variability (HRV) in vivo. Short-term recordings of extracellular field potentials of spontaneously beating cardiomyocytes derived from hESCs and hiPSCs were made using Microelectrode Arrays (MEA). The effect of Flecainide, Ivabradine and Metoprolol was tested. The offline analysis of the BRV was mainly focused on time domain methods. Additionally a non-linear analysis method was used. The evaluation of the Poincaré-Plots of the measurements without pharmacological intervention revealed that the vast majority of the scatter plots have a similar, ellipsoid shape. Flecainide and Ivabradine influenced BRV parameters significantly, whereas Metoprolol did not alter the BRV markedly. We detected remarkable similarities between the BRV of hESC and hiPSC derived cardiomyocytes in vitro and the HRV in vivo. The effect of antiarrhythmic drugs on spontaneously beating cardiomyocytes derived from hESC and hiPSC was generally consistent with clinical experiences and also with our previous study based on murine ESC derived cardiomyocytes. In conclusion, our study points out the great potential of hESC and hiPSC derived tissue to be used routinely for many different applications in medicine and science.
- The Role of Metoprolol and Enalapril in the Prevention of Doxorubicin-induced Cardiotoxicity in Lymphoma Patients. [Randomized Controlled Trial]Anticancer Res 2019; 39(10):5703-5707AR
- CONCLUSIONS: A total of 47 patients completed the follow-up and 21 patients died, none due to cardiotoxicity events. Clinical signs of heart failure were not seen in any patients and no statistically significant differences between baseline and 10-year findings were seen for echocardiographic variables. No evidence of long-term cardiotoxicity was seen and nor metoprolol or enalapril offered an additional benefit.
- Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing non-cardiac surgery. [Journal Article]Cochrane Database Syst Rev 2019; 9:CD013438CD
- CONCLUSIONS: The evidence for early all-cause mortality with perioperative beta-blockers was uncertain. We found no evidence of a difference in cerebrovascular events or ventricular arrhythmias, and the certainty of the evidence for these outcomes was low and very low. We found low-certainty evidence that beta-blockers may reduce atrial fibrillation and myocardial infarctions. However, beta-blockers may increase bradycardia (low-certainty evidence) and probably increase hypotension (moderate-certainty evidence). Further evidence from large placebo-controlled trials is likely to increase the certainty of these findings, and we recommend the assessment of impact on quality of life. We found 18 studies awaiting classification; inclusion of these studies in future updates may also increase the certainty of the evidence.
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- Perioperative beta-blockers for preventing surgery-related mortality and morbidity in adults undergoing cardiac surgery. [Journal Article]Cochrane Database Syst Rev 2019; 9:CD013435CD
- CONCLUSIONS: We found no evidence of a difference in early all-cause mortality, myocardial infarction, cerebrovascular events, hypotension and bradycardia. However, there may be a reduction in atrial fibrillation and ventricular arrhythmias when beta-blockers are used. A larger sample size is likely to increase the certainty of this evidence. Four studies awaiting classification may alter the conclusions of this review.