OBJECTIVETo study the pharmacokinetics of propranolol and metoprolol in rats after acute exposure to high altitude.

METHODSWistar rats were randomly assigned into 4 groups for treatment with intragastric administration of propranolol or metoprolol after acute exposure to high altitude (4010 m) or normal altitude (50 m). Venous blood samples were collected from the rats at different time points after drug administration to determine the drug concentrations in the plasma and plasma ultrafiltrate using liquid chromatography-mass spectrometry (LC-MS/MS).

RESULTSThe protein binding rate of propranolol was significantly increased but that of metoprolol remained unchanged after acute exposure to high altitude. Compared with the rats exposed to normal altitude, the rats with acute exposure to high altitude showed significant alterations in the pharmacokinetic parameters of the drugs, shown by increased Cmax and AUC, prolonged t1/2 and MRT, and lowered Clz/F of propranolol, and by increased Tmax and prolonged t1/2 and MRT of metoprolol without obvious changes of the parameters of the compartmental model.

CONCLUSIONSignificant changes in the pharmacokinetics of propranolol and metoprolol occur in rats after acute exposure to high altitude possibly in relation to, apart from the changes in plasma protein binding ratio and blood gas, alterations in metabolic enzyme activities, increased blood viscosity, and species and general conditions of the animals.

Altitude ; Animals ; Chromatography, Liquid ; Metoprolol ; pharmacokinetics ; Propranolol ; pharmacokinetics ; Protein Binding ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry

Adrenergic beta-Antagonists ; analysis ; Analgesics, Opioid ; analysis ; Chromatography, High Pressure Liquid ; methods ; Humans ; Metoprolol ; analysis ; Tramadol ; analysis

OBJECTIVETo investigate the value of metoprolol injection at dobutamine-atropine stress echocardiography (DASE) for detection of coronary artery disease (CAD).

METHODSDASE was performed in 72 patients with suspected CAD. All the patients received rapid metoprolol injection immediately after getting peak heart rate at DASE (DASE-Meto) and were subjected to coronary angiography (CAG) within two weeks. Regional wall motion and haemodynamic parameters at peak heart rate during DASE and after metoprolol injection were analyzed, and DASE and DASE-Meto results were compared with CAG.

RESULTSThere were 35 patients with CAG positive and 37 negative. The sensitivity, specificity, accuracy and positive and negative predictive values of DASE for detecting CAD were 65.7%, 86.5%, 76.4%, 82.1% and 84.6%, respectively. There were 10 patients with positive result at CAG undetected by DASE but observed regional wall motion abnormality (RWMA) after metoprolol injection. So the sensitivity, specificity, accuracy and positive and negative predictive values of DASE-Meto for detecting CAD were 94.3%, 83.8%, 88.9%, 72.7%, 93.9%, respectively. After metoprolol injection, the symptoms caused by the medicine used in detection were alleviated soon and recovery time was shortened.

CONCLUSIONThe use of metoprolol at DASE can improve the accuracy and security of CAD detection.

Aged ; Coronary Disease ; diagnostic imaging ; Echocardiography, Stress ; methods ; Female ; Humans ; Male ; Metoprolol ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity

OBJECTIVE: To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease. METHODS: The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes. RESULTS: In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them. CONCLUSIONS CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.
Adrenergic beta-Antagonists ; Chromatography, Liquid ; Coronary Artery Disease ; Cytochrome P-450 CYP2D6 ; Genotype ; Humans ; Metoprolol ; Tandem Mass Spectrometry

Cardiovascular and central nervous system (CNS) toxicity, including tachydysrhythmia, agitation, and seizures, may arise from cocaine or bupropion use. We report acute toxicity from the concomitant use of cocaine and bupropion in a 25-year-old female. She arrived agitated and uncooperative, with a history of possible antecedent cocaine use. Her electrocardiogram demonstrated tachycardia at 130 beats/min, with a corrected QT interval of 579 ms. Two doses of 5 mg intravenous metoprolol were administered, which resolved the agitation, tachydysrhythmia, and corrected QT interval prolongation. Her comprehensive toxicology screen returned positive for both cocaine and bupropion. We believe clinicians should be aware of the potential for synergistic cardiovascular and CNS toxicity from concomitant cocaine and bupropion use. Metoprolol may represent an effective initial treatment. Unlike benzodiazepines, metoprolol directly counters the pharmacologic effects of stimulants without respiratory depression, sedation, or paradoxical agitation. A lipophilic beta-blocker, metoprolol has good penetration of the CNS and can counter stimulant-induced agitation.
Adult ; Benzodiazepines ; Bupropion ; Central Nervous System ; Cocaine ; Dihydroergotamine ; Electrocardiography ; Female ; Humans ; Metoprolol ; Respiratory Insufficiency ; Seizures ; Tachycardia ; Toxicology

OBJECTIVES: The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs. METHODS: A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia. RESULTS: A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine). CONCLUSIONS There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.
Humans ; Aged ; Cholinergic Antagonists/adverse effects* ; Outpatients ; Metoprolol ; Alprazolam ; Eszopiclone ; Nifedipine ; Sleep Initiation and Maintenance Disorders ; Risk Factors

BACKGROUND: Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS. METHODS: This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics. RESULTS: A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013). CONCLUSIONS Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.
Adolescent ; Child ; Humans ; Metoprolol/therapeutic use* ; Postural Orthostatic Tachycardia Syndrome/drug therapy* ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left

OBJECTIVETo investigate the effect of metoprolol on the expression of G protein-coupled receptor kinases 2 (GRK2) in lymphocyte of advanced elderly patients with chronic heart failure.

METHODS32 elderly patients with chronic heart failure were divided into control group and metoprolol group, 16 each. Conventional therapy was used in the control group, conventional therapy plua metoprolol was used in metoprolol group. The treatment courses were 8 weeks in both groups.

RESULTSLeft ventricular end-diastolic diameter and left ventricular ejection fraction were not different between the two groups. Lymphocyte GRK2 mRNA level in metoprolol group was lower than that in control group.

CONCLUSIONMetoprolol can inhibit the expression of GRK2 in lymphocyte of advanced elderly patients with chronic heart failure.

Aged, 80 and over ; Chronic Disease ; G-Protein-Coupled Receptor Kinase 2 ; blood ; genetics ; metabolism ; Heart Failure ; metabolism ; Humans ; Lymphocytes ; metabolism ; Metoprolol ; pharmacology

OBJECTIVEThis study was designed to compare the short-term and long-term effects of oral rehydration salts, oral rehydration salts plus metoprolol or oral rehydration salts plus midodrine hydrochloride on the treatment of postural tachycardia syndrome (POTS) in children.

METHODA total of 118 children with POTS were divided into oral rehydration salts group (n = 39), metoprolol group (oral rehydration salts plus metoprolol, n = 10) or midodrine hydrochloride group (oral rehydration salts plus midodrine hydrochloride, n = 69). The patients were followed up in clinics or over telephone for 3 - 18 months, with a mean of (11.7 ± 4.1) months. The symptom scores were recorded before treatment, after 3 months and at the end of the follow-up. Reduction of the score by 2 points or more was considered that the treatment was effective. The effective rate in 3 months was applied to evaluate short-term effects of 3 different therapies by chi-square test. Taking futility as events, Kaplan-Meier curves were drawn to compare long-term effects of the 3 different therapies in treating POTS in children.

RESULTNo significant differences among the 3 groups were found in sex, age, body height, weight, the symptom scores before treatment or hemodynamic variables. Oral rehydration salts, metoprolol and midodrine hydrochloride improved clinical symptoms after 3 months. The symptom scores of the 3 groups before treatment and after 3 months were 2.4 ± 3.2 vs. 5.5 ± 2.9, 2.2 ± 3.0 vs. 6.1 ± 3.0 and 1.9 ± 1.6 vs. 5.9 ± 2.7, respectively. The difference was significant (P < 0.05). Descending order of the short-term effective rate was 91.3% in midodrine hydrochloride group, 80.0% in metoprolol group and 74.4% in oral rehydration salts group. The difference was significant (χ(2) = 5.85, P < 0.05). All the 3 different therapies improved clinical symptoms at the end of follow-up. The symptom scores were 2.6 ± 3.2 vs. 5.6 ± 2.9, 2.5 ± 3.1 vs. 6.1 ± 3.0 and 2.2 ± 2.1 vs. 6.0 ± 2.7, respectively. (P < 0.05). The result of the Kaplan-Meier curves showed that the long-term effect of midodrine hydrochloride was significantly superior to metoprolol group and oral rehydration salts group (P < 0.05). There was no significant difference between the latter two groups.

CONCLUSIONOral rehydration salts plus midodrine hydrochloride or plus metoprolol improved the efficacy of drugs in children with POTS. And the efficacy of midodrine hydrochloride was superior to that of metoprolol.

Adolescent ; Child ; Female ; Humans ; Male ; Metoprolol ; therapeutic use ; Midodrine ; therapeutic use ; Postural Orthostatic Tachycardia Syndrome ; drug therapy ; Prospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of amiodarone and metoprolol in the treatment of ventricular premature beats.

METHODSControlled randomized clinical trials from 1999 through 2009 were retrieved in China HowNet, VIP Web, Pubmed home. Using Rev Man4.2 software provided by Cochrane Collaboration, Meta-analysis was conducted of 30 articles meeting the inclusion criteria involving a total of 1188 patients.

RESULTSMerged 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.

CONCLUSIONSThe total response rate of amiodarone does not seem to be superior to metoprolol in the treatment of premature ventricular contractions, and amiodarone is associated with higher incidence of adverse reactions.

Amiodarone ; adverse effects ; therapeutic use ; Drug Therapy, Combination ; Humans ; Metoprolol ; adverse effects ; therapeutic use ; Treatment Outcome ; Ventricular Premature Complexes ; drug therapy