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We performed a prospective observational study and determined the number of standardized traumatic memories (NTRM) and PTSD symptom intensity in cardiac surgical patients at 1 day before surgery, and at 1 week and 6 months after the procedure. PTSD symptoms and NTRM were quantified using validated questionnaires. Metoprolol could be administered any time post-operatively.
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Metoprolol, a cardio-selective beta-adrenergic blocking agent, was studied in 25 patients to assess its effect on "non-specific" ST-segment and T-wave changes both at rest and during exercise. In two thirds of the patients with ST-T-abnormalities at rest, the changes disappeared completely after beta-blockade but reappeared during exercise in some of them. Only in 9 patients were the changes eliminated also during exercise implying that they were "functional", i.e., caused by increased sympathetic discharge. In those patients, where the ST-T-abnormalities were not affected at all by the beta-blockade, they were probably due to organic heart disease, whereas when they were reduced but not completely abolished, increased sympathetic tone as well as organic heart disease might be the cause. It is inferred that the diagnostic information is increased by studying the effect of beta-blockade not only at rest but also during exercise. Metoprolol seems to be well suited for the evaluation of "non-specific" ST-T-abnormalities, especially when non-selective beta-blockers should be avoided, e.g. in obstructive lung disease.
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ES was significantly decreased by beta-blocker therapy. According to the change in ES, DCM patients were classified into three groups, patients who improved, patients showing no change and patients who deteriorated. In the improvement and no-change groups, beta-blocker therapy induced a reduction in left ventricular dimensions and an associated increase in ejection fraction. However, in the deterioration group, left ventricular dimensions and ejection fraction were unchanged. There was a significant relationship between the change in left ventricular dimension at end-diastole and the change in ES.
Among 11 326 adults surviving a hospitalization for heart failure, 7976 received beta-blockers (atenolol, 38.5%; metoprolol tartrate, 43.2%; carvedilol, 11.6%; and other, 6.7%) during follow-up. The rate (per 100 person-years) of death during the 12 months after discharge varied by exposure and type of beta-blocker (atenolol, 20.1; metoprolol tartrate, 22.8; carvedilol, 17.7; and no beta-blockers, 37.0). After adjustment for confounders and the propensity to receive carvedilol, the risk of death compared with atenolol was higher for metoprolol tartrate (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.34) and no beta-blockers (HR, 1.63; 95% CI, 1.44-1.84) but was not significantly different for carvedilol (HR, 1.16; 95% CI, 0.92-1.44).
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The cost of reducing 1 mm of Hg blood pressure per day with nebivolol was 0.60, 0.70, and 1.06 INR, whereas that of metoprolol succinate was 0.93, 1.18, and 1.25 INR at their respective equivalent doses, hence significantly lower with the nebivolol group as compared to the metoprolol group (P < 0.05).
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To assess the role of physical activity, stress and treatment on BP variations in working hypertensives we used repeated self measurements of BP which are cheaper and more simple than ambulatory BP measurements but allow for a smaller number of measurements. 34 working hypertensives self measured daily life BP, at home and at workplace, 7 times a day, for at least one week, before and 6 weeks after beta-blockade with metoprolol 200 to 400 mg daily. They used a Spengler SP9 electronic sphygmometer and specified on 4 grades scales their physical activity and stress just before measurement. The time for self measurement of BP was settled according to occupations more than to clocktime. The equipment was standardized at each visit by measuring BP with a mercury manometer then with the electronic sphygmometer. There were no significant differences neither for SBP nor for DBP and the two measures correlate closely (r = 0.91), P = 0.0001). Analysis of variance on SBP exhibits the role of time (p (0.001) and stress (p (0.0001). Physical activity does not interfere (p = 0.19). There is no difference between work days and sundays (p = 0.17). Treatment effect was very strong (p (0.0001) but there was no interaction neither with physical activity nor stress. Analysis of variance on DBP exhibits similar results except that BP on workdays is significantly higher than on sundays (p = 0.03). We conclude that: Repeated self measurement of BP is able to display variation of BP with occupations and stress. Beta-blockade lowers BP but does not interfere with variability.
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Activity of human cytochrome P450 enzymes (CYPs) shows high inter-and intra-individual variability, which is determined by genetic and non-genetic factors. Using a combination of CYP-specific probe drugs, phenotyping cocktails allow simultaneous assessment of the activity of different CYP isoforms. The objective of this study was to characterize the phenotyping metrics of the Basel cocktail in healthy male subjects with induced and inhibited CYP activity.
Antihypertensive treatment for several years leads to regression in LVH in nearly all patients. In half of them the drug dosage can be reduced or the drug even discontinued. Weight loss may play an important part in this development.
Carvedilol (BM 14190) is a new potent and well-tolerated beta-adrenoceptor antagonist with vasodilating properties. Acute clinical studies have confirmed its efficacy as an antihypertensive agent. The present double-blind, randomized, metoprolol-controlled, long-term study reports the therapeutic results of carvedilol in essential hypertensive patients. Compared with placebo, carvedilol significantly reduces blood pressure after oral administration of 50 mg on a single and twice daily regimen. The antihypertensive effect was acute in onset, comparable in supine and standing position, and exercise-induced hypertension and tachycardia were significantly reduced. Indirect automatic 24 h blood pressure monitoring reliably confirmed clinic blood pressure and demonstrated a good antihypertensive effect of carvedilol after a single oral administration throughout daily activities and sleeping periods.
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Outpatient pain clinic in the northern Copenhagen area. Patients were referred by general practitioners or respondents to newspaper advertisements.
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Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading.
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To study side effects of drugs in preclinical as well as in postmarketing surveillance phase is very important. In our experiments the influence of metoprolol on carbohydrate- and lipid metabolism was investigated in male. Wistar rats. Metoprolol is a liposoluble beta1-selective adrenoceptor antagonists. We have calculated therapeutic dose which reduced heart frequency/min of the animals by 25%. This was 10 mg/kg. The blood glucose and triglyceride values of healthy rats are in the normal human domain. Blood glucose was high after the first metoprolol dose and increased further with continued treatment. Drug administration period comprised 16 days. At finishing experiments diminished glycogen content was measured which may be related to higher glucose output. In blood samples obtained one hour after last 16. metoprolol dose administration triglyceride values were high and HDL-C decreased. These data pertain to the development of a secondary hypertriglyceridaemia. Hyperglycemic and hypertriglyceridaemic responses were established with therapeutic doses regimen so they may be considered as unwanted effects.
The interaction between dextran sulfate (DS) with zwitterionic dipalmitoylphosphatidylcholine (DPPC) and negatively charged dipalmitoylphosphatidic acid monolayers at different surface pressures at air-liquid and liquid-liquid interfaces was studied using Langmuir-Blodgett (LB) and electrochemical techniques. The negatively charged DS can bind to phospholipids via calcium ions. To investigate the mechanism of the adsorption of DS on lipid monolayers, compression isotherms (pi-A) and capacitance-potential curves were measured, and a theoretical model was developed to interpret the capacitance data. The compression of lipid monolayers in the presence of DS led to a more condensed hybrid layer, removing the LE-LC phase transition of DPPC. Lower surface pressures improved the binding of DS on the lipid monolayers via calcium bridges due to the electrostatic attraction. Alternating current voltammetry and cyclic voltammetry were used to monitor the transfer of a cationic beta-blocker (metoprolol) across lipid monolayers in the absence and presence of the polyelectrolyte and to compare with the transfer of the standard probe, tetraethylammonium cation. Results showed a strong dependence on (i) the surface pressure, (ii) the applied potential, and, (iii) in the case of the hybrid layer, the charge of the phospholipid headgroup. Finally, results were also confirmed by attenuated total reflection Fourier transform infrared spectroscopy, performed after transferring lipid multilayers onto a solid substrate by the LB method.
Dose-related effects of ritodrine and ritodrine combined with metoprolol on urinary excretion rate were studied in anesthetized dogs. Urine production was abruptly reduced after a total dose of 4 micrograms.kg-1 of ritodrine. This effect could not be antagonized by metoprolol, although the ritodrine-induced decrease of mean arterial pressure and renal arterial blood flow was significantly inhibited. The possible role of fluid retention during tocolytic treatment, even with beta-adrenergic blockade, in the etiology of pulmonary edema is discussed with a review on recent literature.
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Although drug treatment of hypertension is associated with improved survival and decreased vascular complications, drug compliance is a major problem in the control of hypertension. All antihypertensive medications are associated with side effects; thus, it is a physician's responsibility to explain to each patient the side effects of the drugs he prescribes to treat hypertension, and to instill in the patient a sense of necessity for the treatment of hypertension. The choice of antihypertensive drug should be made based on each patient's lifestyle, overall health and ability to tolerate the drug. Ideally, the antihypertensive regimen should be simple, effective, convenient to take and have very few side effects.
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Organic micropollutants present in drinking water (DW) may cause adverse effects for public health, and so reliable analytical methods are required to detect these pollutants at trace levels in DW. This work describes the first green analytical methodology for multi-class determination of 21 pollutants in DW: seven pesticides, an industrial compound, 12 pharmaceuticals, and a metabolite (some included in Directive 2013/39/EU or Decision 2015/495/EU). A solid-phase extraction procedure followed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (offline SPE-UHPLC-MS/MS) method was optimized using eco-friendly solvents, achieving detection limits below 0.20 ng L(-1). The validated analytical method was successfully applied to DW samples from different sources (tap, fountain, and well waters) from different locations in the north of Portugal, as well as before and after bench-scale UV and ozonation experiments in spiked tap water samples. Thirteen compounds were detected, many of them not regulated yet, in the following order of frequency: diclofenac > norfluoxetine > atrazine > simazine > warfarin > metoprolol > alachlor > chlorfenvinphos > trimethoprim > clarithromycin ≈ carbamazepine ≈ PFOS > citalopram. Hazard quotients were also estimated for the quantified substances and suggested no adverse effects to humans. Graphical Abstract Occurrence and removal of multi-class micropollutants in drinking water, analyzed by an eco-friendly LC-MS/MS method.
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Merged analysis of amiodarone and metoprolol in the treatment of premature ventricular merge showed a comprehensive test results of Z=1.25, P=0.21, OR=1.18, 95%CI: 0.91-1.54; funnel plot analysis suggested the possible presence of publication bias. The comprehensive test of the incidence of adverse reactions in relation to the two drugs resulted in an OR of 1.96 (95%CI: 1.39-2.77), and funnel plot analysis also indicated publication bias.
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Noninfectious uveitis is usually managed by topical and systemic corticosteroids and in refractory cases by immunosuppressive drugs.
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The clinical efficacy of propranolol and metoprolol slow-release tablets (Durules) was compared in 20 patients with typical angina pectoris and concomitant hypertension. During a four-week run-in period all patients were given 80 mg propranolol b.i.d. in a single-blind fashion. Thereafter they were randomised in a double-blind fashion to treatment with either propranolol tablets, 80 mg b.i.d., or metoprolol Durules, 200 mg o.m. After four weeks, treatment was changed according to a cross-over design. The number of anginal attacks and nitroglycerin consumption were recorded by the patients in diary-cards. At the control visits, blood pressure was assessed in the supine and standing positions. No differences were found between the drugs as regards either antianginal or antihypertensive efficacy. Metoprolol Durules 200 mg o.m. are considered to be as effective as propranolol, 80 mg b.i.d. and may be preferred by some patients because of the simple dosage regimen.
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Due to the limited number of included trials, there is insufficient evidence to draw any conclusions about the effectiveness of cardiovascular prophylaxis in reducing mortality and cardiovascular events in people with AAA. Further good-quality randomised controlled trials that examine many types of prophylaxis with long-term follow-up are required before firm conclusions can be made.
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RMSSL increased strongly both following a short train of stimuli at 2.5 Hz and following catecholamine activation in trabeculae from MI with CHF, resulting in a decrease in Ftw in proportion to RMSSL. RyRS2808 phosphorylation was increased significantly in the left ventricle (LV; approximately 58%, P<0.05) but not in the RV (n.s.) in MI rats with CHF. FK506 tripled high frequency stimulation-induced RMSSL in nonfailing trabecula but did not further enhance RMSSL in failing trabecula. Isoproterenol increased RMSSL in nonfailing trabeculae only modestly despite a substantial increase in RyRS2808 phosphorylation in the RV (approximately 60%, P<0.05). Isoproterenol induced SL fluctuation without an increase in RV-RyRS2808 phosphorylation in failing trabeculae. Chronic beta-blockade decreased high frequency and catecholamine stimulation-induced RMSSL while RyRS2808 phosphorylation in the RV was indistinguishable from that in cMI.
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This was a randomized, multicentre, double-blind, placebo-controlled parallel group study. A total of 426 male and female patients with stable, effort-induced angina and documented coronary artery disease received either placebo or trimetazidine 20 mg three times daily in addition to metoprolol 50 mg twice daily. Treadmill exercise tests were performed at weeks (-1), 0, 4 and 12.
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After pretreatment with NGR1 or physiological saline, the rats were administered intraperitoneally with a mixture solution of cocktail probe drugs containing caffeine (10 mg/kg), tolbutamide (15 mg/kg), metoprolol (20 mg/kg), and dapsone (10 mg/kg). The bloods were then collected at a set of time-points for the ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis.
Once daily moexipril is a useful agent for the treatment of essential hypertension, which compares well with currently available options in terms of clinical efficacy and tolerability. In addition, clinical experience to date supports its use in postmenopausal women.
We did a prospective, randomised trial in 6614 patients aged 70-84 years with hypertension (blood pressure > or = 180 mm Hg systolic, > or = 105 mm Hg diastolic, or both). Patients were randomly assigned conventional antihypertensive drugs (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily) or newer drugs (enalapril 10 mg or lisinopril 10 mg, or felodipine 2.5 mg or isradipine 2-5 mg daily). We assessed fatal stroke, fatal myocardial infarction, and other fatal cardiovascular disease. Analysis was by intention to treat.
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Changes in thyroid hormone concentrations have the potential to significantly alter the extent of warfarin-induced anticoagulation. Clinicians must be aware of the need for close anticoagulation monitoring and dosage adjustment in patients receiving concomitant warfarin and methimazole. The full extent of this interaction may be delayed following a change in methimazole dose.