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Fundamental & Clinical Pharmacology Dec 2022Depression is common among people with cardiovascular diseases. Therefore, the combined use of antidepressants and cardiovascular drugs is very common, which increases...
Depression is common among people with cardiovascular diseases. Therefore, the combined use of antidepressants and cardiovascular drugs is very common, which increases the possibility of drug interaction. Simultaneously compare the effects of duloxetine and fluoxetine on metoprolol metabolism, and provide evidence-based guidance for medication safety. Sprague-Dawley rats were randomly divided into three groups: group A (10.3 mg/kg metoprolol alone), group B (10.3 mg/kg metoprolol + 6.2 mg/kg fluoxetine), and group C (10.3 mg/kg metoprolol + 6.2 mg/kg duloxetine). Tail vein blood was collected and subjected to the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection. Moreover, in vitro inhibition of fluoxetine and duloxetine were assessed by incubating liver microsomes and CYP2D6.1 with metoprolol. In in vivo study, the administration of fluoxetine or duloxetine significantly increased the AUC and AUC of metoprolol (P < 0.05). Differences between fluoxetine and duloxetine in plasma concentration were also investigated, and their pharmacokinetic parameters such as AUC and AUC were significantly distinct (P < 0.05). In vitro, fluoxetine and duloxetine inhibited the metabolism of metoprolol via mixed competitive mechanism of cytochrome P450. IC values of fluoxetine and duloxetine were 12.86 and 2.51 μM, respectively. Moreover, the metabolism rate of metoprolol was inhibited to 19.62% and 17.14% in recombinant human CYP2D6.1 by fluoxetine and duloxetine, respectively. Duloxetine showed a more significant inhibitory potential compared to fluoxetine in vitro, but the main pharmacokinetic parameters of fluoxetine and duloxetine revealed differences in inhibiting metoprolol metabolism in vivo.
Topics: Rats; Animals; Humans; Fluoxetine; Metoprolol; Duloxetine Hydrochloride; Cytochrome P-450 CYP2D6; Chromatography, Liquid; Tandem Mass Spectrometry; Rats, Sprague-Dawley
PubMed: 35510497
DOI: 10.1111/fcp.12795 -
Pharmacoepidemiology and Drug Safety Jun 2018Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this...
PURPOSE
Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug-drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.
METHODS
We performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (≥60 years) who had ever been prescribed metoprolol and had a first co-prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co-prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).
RESULTS
Combinations of metoprolol-paroxetine/fluoxetine, metoprolol-citalopram, and metoprolol-mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol-citalopram, metoprolol-paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77-1.48; OR = 0.87, 95% CI:0.57-1.33, respectively). In comparison with metoprolol-mirtazapine, metoprolol-paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01-2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03-2.53).
CONCLUSION
Paroxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.
Topics: Aged; Aged, 80 and over; Citalopram; Cohort Studies; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Drug Prescriptions; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Metoprolol; Middle Aged; Mirtazapine; Netherlands; Paroxetine
PubMed: 29575226
DOI: 10.1002/pds.4422 -
Basic Research in Cardiology Jun 2023Whereas prior experiments in juvenile pigs had reported infarct size reduction by intravenous metoprolol early during myocardial ischaemia, two major clinical trials in...
Whereas prior experiments in juvenile pigs had reported infarct size reduction by intravenous metoprolol early during myocardial ischaemia, two major clinical trials in patients with reperfused acute myocardial infarction were equivocal. We, therefore, went back and tested the translational robustness of infarct size reduction by metoprolol in minipigs. Using a power analysis-based prospective design, we pretreated 20 anaesthetised adult Göttingen minipigs with 1 mg kg metoprolol or placebo and subjected them to 60-min coronary occlusion and 180-min reperfusion. Primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was a secondary endpoint. There was no significant reduction in infarct size (46 ± 8% of area at risk with metoprolol vs. 42 ± 8% with placebo) or area of no-reflow (19 ± 21% of infarct size with metoprolol vs. 15 ± 23% with placebo). However, the inverse relationship between infarct size and ischaemic regional myocardial blood flow was modestly, but significantly shifted downwards with metoprolol, whereas ischaemic blood flow tended to be reduced by metoprolol. With an additional dose of 1 mg kg metoprolol after 30-min ischaemia in 4 additional pigs, infarct size was also not reduced (54 ± 9% vs. 46 ± 8% in 3 contemporary placebo, n.s.), and area of no-reflow tended to be increased (59 ± 20% vs. 29 ± 12%, n.s.).Infarct size reduction by metoprolol in pigs is not robust, and this result reflects the equivocal clinical trials. The lack of infarct size reduction may be the result of opposite effects of reduced infarct size at any given blood flow and reduced blood flow, possibly through unopposed alpha-adrenergic coronary vasoconstriction.
Topics: Animals; Metoprolol; Myocardial Infarction; Myocardial Ischemia; Myocardium; Swine; Swine, Miniature
PubMed: 37289247
DOI: 10.1007/s00395-023-00993-4 -
Environmental Toxicology Dec 2023Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental...
Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental matrices globally. The dwindling in the biodiversity of useful insects owing to increasing presence of environmental chemicals is currently a great interest to the scientific community. In the current research, the toxicological impact of ecologically relevant concentrations of metoprolol at 0, 0.05, 0.1, 0.25, and 0.5 μg/L on Nauphoeta cinerea nymphs following exposure for 42 consecutive days was evaluated. The insects' behavior was analyzed with automated video-tracking software (ANY-maze, Stoelting Co, USA) while biochemical assays were done using the midgut, head and fat body. Metoprolol-exposed nymphs exhibited significant diminutions in the path efficiency, mobility time, distance traveled, body rotation, maximum speed and turn angle cum more episodes, and time of freezing. In addition, the heat maps and track plots confirmed the metoprolol-mediated wane in the exploratory and locomotor fitness of the insects. Compared with control, metoprolol exposure decreased acetylcholinesterase activity in insects head. Antioxidant enzymes activities and glutathione level were markedly decreased whereas indices of inflammation and oxidative injury to proteins and lipids were significantly increased in head, midgut and fat body of metoprolol-exposed insects. Taken together, metoprolol exposure induces neurobehavioral insufficiency and oxido-inflammatory injury in N. cinerea nymphs. These findings suggest the potential health effects of environmental contamination with metoprolol on ecologically and economically important nontarget insects.
Topics: Animals; Metoprolol; Acetylcholinesterase; Oxidative Stress; Antioxidants; Cockroaches
PubMed: 37584562
DOI: 10.1002/tox.23934 -
Current Medical Research and Opinion Sep 2018Extensive clinical experience on metoprolol has been gained in different cardiovascular conditions. (Review)
Review
BACKGROUND
Extensive clinical experience on metoprolol has been gained in different cardiovascular conditions.
REVIEW
This paper discusses the use of metoprolol, with a focus on the extended-release formulation, in clinical practice in the light of existing evidence and current recommendations. This is a narrative review based on existing evidence and clinical experience of the author. Evidence on the use of metoprolol in heart failure, ischemic artery disease, arterial hypertension, and atrial fibrillation is well-established.
CONCLUSIONS
Metoprolol still appears to be a suitable pharmacological option in different cardiovascular conditions. Research on this molecule is still active and new, promising settings of use are being explored and may provide relevant results in the years to come.
Topics: Adrenergic beta-1 Receptor Antagonists; Cardiovascular Diseases; Delayed-Action Preparations; Humans; Metoprolol; Treatment Outcome
PubMed: 29781321
DOI: 10.1080/03007995.2018.1479245 -
Indian Heart Journal 2022Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid ventricular rate (AF-RVR) in the emergency department.
OBJECTIVES
To compare the efficacy of intravenous diltiazem and metoprolol for rate control and safety with respect to development of hypotension and bradycardia in patients with AF-RVR.
METHODS
For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane databases, and the clinicaltrials.gov registry between database inception and 30th May 2021. Articles were included if they compared efficacy and safety of diltiazem versus metoprolol in critically ill adult patients hospitalized with AF-RVR. Outcome measures were achievement of rate control, development of new hypotension, and bradycardia after drug administration.
RESULTS
Of 86 records identified, 14 were eligible, all of which had a low to moderate risk of overall bias. The meta-analysis (Mantel-Haenszel, random-effects model) showed that diltiazem use was associated with increased achievement of rate control target compared to metoprolol [14 studies, n = 1732, Odds Ratio (OR): 1.92; 95% Confidence Intervals (CI):1.26 to 2.90; I = 61%]. In the pooled analysis, no differences were seen in hypotension using diltiazem vs metoprolol [12 studies, n = 1477, OR: 0.96; 95% CI:0.61 to 1.52; I = 35%] or bradycardia [9 studies, n = 1203, OR: 2.44; 95% CI: 0.82 to 7.31; I = 48%].
CONCLUSIONS
Intravenous diltiazem is associated with increased achievement of rate control target in patients with AF-RVR compared to metoprolol, while both medications are associated with similar incidence of hypotension and bradycardia.
Topics: Adult; Humans; Diltiazem; Atrial Fibrillation; Metoprolol; Bradycardia; Hypotension; Heart Rate
PubMed: 36334652
DOI: 10.1016/j.ihj.2022.10.195 -
Medicine Sep 2022This meta-analysis aimed to systematically and comprehensively assess the effectiveness and safety of wenxin granule (WXG) and metoprolol in the treatment of elderly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to systematically and comprehensively assess the effectiveness and safety of wenxin granule (WXG) and metoprolol in the treatment of elderly patients with coronary heart disease (CHD) and arrhythmia.
METHODS
We searched the electronic databases of the Cochrane Library, PUBMED, EMBASE, CNKI, Wangfang, and CBM from initiation to May 1, 2022, and selected a set of clinical indicators for WXG and metoprolol for CHD and arrhythmia. The methodological quality of the included studies was analyzed using the Cochrane risk-of-bias tool. Data were pooled using a fixed-effects or random-effects model, and a meta-analysis was conducted.
RESULTS
Eight randomized controlled trials involving 722 patients with CHD and arrhythmia were included. Our findings showed that WXG and metoprolol showed better effects than metoprolol alone on electrocardiogram change (odds ratio [OR] = 7.21, 95% confidence interval [CI] [1.48, 35.07]), clinical symptom improvement (OR = 5.83, 95% CI [1.52, 22.35]), overall clinical effect (OR = 5.51, 95% CI [2.65, 11.44], P < .001), atrial premature beat (mean difference [MD] = -109.85, 95% CI [-171.25, -48.46], P < .001), ventricular premature beat (MD = -195.43, 95% CI [-334.09, -56.77], P < .001), borderline premature beat (MD = -42.92, 95% CI [-77.18, -8.67], P = .01), short-burst ventricular tachycardia (MD = -35.98, 95% CI [-39.66, -32.30], P < .001), ST segment reduction (MD = -0.47, 95% CI [-0.54, -0.40], P < .001), ST segment decrease duration (MD = -0.76, 95% CI [-0.95, -0.57], P < .001). However, no significant differences were observed in adverse reactions (OR = 0.54, 95% CI [0.27, 1.09], P = .09).
CONCLUSION
Compared to metoprolol alone, WXG and metoprolol can more effectively manage patients with CHD and arrhythmia. However, additional large-scale, multicenter, rigorous, and high-quality randomized controlled trials are warranted to verify the present findings.
Topics: Aged; Coronary Disease; Drugs, Chinese Herbal; Humans; Metoprolol; Multicenter Studies as Topic; Ventricular Premature Complexes
PubMed: 36107542
DOI: 10.1097/MD.0000000000030250 -
The Journal of the Association of... Jun 2017The process of drug discovery and development today encompass a myriad of paths for bringing a new therapeutic molecule that has minimal adverse effects and of optimal... (Review)
Review
BACKGROUND
The process of drug discovery and development today encompass a myriad of paths for bringing a new therapeutic molecule that has minimal adverse effects and of optimal use to the patient. Chirality was proposed in the direction of providing a purer and safer form of drug [Ex- cetrizine and levocetrizine]. Decades have passed since the introduction of this concept and numerous chiral molecules are in existence in therapeutics, yet somehow this concept has been ignored. This review aims to rediscover the ignored facts about chirality, its benefits and clear some common myths considering the example of S-Metoprolol in the management of Hypertension and other cardiovascular diseases.
METHODS
Relevant articles from Pubmed, Embase, Medline and Google Scholar were searched using the terms "Chiral", "Chirality", "Enantiomers", "Isomers", "Isomerism", "Stereo-chemistry", and "S-Metoprolol". Out of 103 articles found 17 articles mentioning in general about the concept of chirality and articles on study of S-metoprolol in various cardiovascular diseases were then reviewed.
RESULTS
Many articles mention about the importance of chirality yet the concept has not been highlighted much. Clear benefits with chiral molecules have been documented for various drug molecules few amongst them being anaesthetics, antihypertensives, antidepressants. Benefits of S-metoprolol over racemate are also clear in terms of responder rates, dose of administration and adverse effects profile in various cardiovascular diseases.
CONCLUSIONS
Chirality is a good way forward in providing a new drug molecule which is safe with lesser pharmacokinetic and pharmacodynamics variability, lesser side effects and more potent action. S-metoprolol is chirally pure form of racemate metoprolol and has lesser side effects, is safer in patients of COPD and Diabetes who also have hypertension and comparable responder rates at half the doses when compared to racemate.
Topics: Adrenergic beta-1 Receptor Antagonists; Cardiovascular Diseases; Drug Design; Humans; Metoprolol; Stereoisomerism; Structure-Activity Relationship
PubMed: 28782316
DOI: No ID Found -
Journal of Healthcare Engineering 2022In China, the incidence of arrhythmia has also increased to approximately 20% of all cardiovascular diseases. The incidence of cardiovascular diseases in China has...
In China, the incidence of arrhythmia has also increased to approximately 20% of all cardiovascular diseases. The incidence of cardiovascular diseases in China has certain characteristics, which are generally low in the south and high in the north, and they tend to be younger and growing. Permanent pacemaker implantation is currently the most effective means of treating arrhythmia and preventing sudden death. To explore the clinical application value of metoprolol in patients after permanent pacemaker implantation. Ninety patients with permanent dual-chamber pacemaker implantation in our hospital are selected and divided into a metoprolol group and a control group according to whether metoprolol is used one week after the operation and 45 patients in each group. After one postoperative week, the LVEF%, LVEDd, LAD, and E/A of the metoprolol and the control groups had no statistically significant differences ( > 0.05). Twelve months postoperatively, the E/A of the metoprolol group is higher than that of the control group ( < 0.05), and LVEDd and LAD are lower than those of the control group ( < 0.05). The NT-proBNP and hs-CRP levels between the metoprolol and control groups had no significant differences ( > 0.05) in the values recorded immediately postoperatively. The NT-proBNP of the metoprolol group is lower than that of the control group ( < 0.05) at 12 months following pacemaker implantation. At one week after surgery, QTd, Pd, and Tp-Te are not significantly different ( > 0.05) between the metoprolol group and the control group, whereas the QTd and Pd times in the metoprolol group are lower than those in the control group ( < 0.05) at the 12-month follow-up. At one week postoperatively, the SDNN, SDANN, and RMSSD between the metoprolol and control groups did not show any statistically significant differences ( > 0.05). The SDANN of the metoprolol group is higher than that in the control group ( < 0.05) in the 12-month evaluation. One week after the operation, the serum IL-6 and TNF- levels are not significantly different between the metoprolol and control groups ( > 0.05). At 12 months after surgery, the serum IL-6 and TNF- levels in the metoprolol group are lower than those in the control group ( < 0.05). The incidence of adverse events in the metoprolol group is 9.30% lower than 26.83% in the control group within 12 months after the operation ( < 0.05). The use of metoprolol in patients with permanent pacemaker implantation after surgery can reduce the expansionary remodeling of the left atrium and have less impact on the QT-dispersion and Pd time.
Topics: Arrhythmias, Cardiac; Cardiovascular Diseases; Humans; Interleukin-6; Metoprolol; Pacemaker, Artificial; Tumor Necrosis Factor-alpha
PubMed: 35449861
DOI: 10.1155/2022/7340992 -
Pharmacology 2018Bisoprolol and metoprolol are moderately lipophilic, beta(1)-selective betablockers reported to cause adverse effects in the central nervous system (CNS), such as sleep...
BACKGROUND
Bisoprolol and metoprolol are moderately lipophilic, beta(1)-selective betablockers reported to cause adverse effects in the central nervous system (CNS), such as sleep disturbance, suggesting that both drugs may reach relevant concentrations in the brain. CNS beta(2)-receptor blockade has been suspected to be related to such effects. The higher molecular size of bisoprolol (325 Dalton) and the higher beta(1)-selectivity compared to metoprolol (267 Dalton) would suggest a lower rate of CNS effects.
METHODS
To address the pharmacokinetic background of this assumption, we quantified to which extent these beta(1)-blockers are able to enter the cerebrospinal fluid (CSF) in 9 (bisoprolol group) and 10 (metoprolol group) neurological patients who had received one of the drugs orally for therapeutic purposes prior to lumbar puncture. We quantified their total concentrations by liquid chromatography/tandem mass spectrometry in paired serum and CSF samples.
RESULTS
Median (interquartile range) in CSF reached 55% (47-64%) of total serum concentrations for bisoprolol and 43% (27-81%) for metoprolol, corresponding to 78% (67-92%) and 48% (30-91%) of respective unbound serum concentrations.
CONCLUSION
The extent of penetration of bisoprolol and metoprolol into the CSF is similar and compatible with the assumption that both drugs may exert direct effects in the CNS.
Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Aged; Aged, 80 and over; Bisoprolol; Humans; Metoprolol; Middle Aged
PubMed: 28930747
DOI: 10.1159/000480091