Metoprolol scientific update |
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Int J Cardiovasc Imaging. 2010 Jun 23. [Epub ahead of print]
Khan M, Cummings KW, Gutierrez FR, Bhalla S, Woodard PK, Saeed IM.
Washington University School of Medicine, 4323D Laclede Ave, St. Louis, MO, 63108, USA, mtkhan@gmail.com.
Contraindications and side effects of commonly used medications in coronary CT angiography.
For certain clinical applications, coronary CT angiography (CCTA) has become a useful tool for the noninvasive evaluation of coronary artery atherosclerosis. To optimize image quality in CCTA, medications are often given prior to scanning to slow the heart rate or distend the arteries. These medications have side effects and are contraindicated in certain patient populations. Metoprolol is the ss-blocker of choice in CCTA, and it has been shown to be effective in achieving the goal heart rate of less than 65 beats per minute for CCTA and in minimizing variability of heart rate. It is contraindicated in patients with hypotension or high degree AV block, and it must be used with caution in patients with asthma or obstructive pulmonary disease, patients with decompensated heart failure, and those with vasospastic or vasoocclusive disease. Diltiazem, the calcium channel blocker of choice in CCTA, is a reasonable alternative for heart control, particularly in patients with asthma or bronchospastic disease, and patients with orthotopic heart transplants that have been sympathetically denervated. Sublingual nitroglycerin is especially useful in order to dilate distal arteries to improve stenosis visibility. However, it is contraindicated in patients on erectile dysfunction medications and those with severe anemia. It must be used cautiously in patients with aortic stenosis or other preload-dependant cardiac pathologies.
Arq Bras Cardiol. 2010 Jun 11. pii: S0066-782X2010005000062. [Epub ahead of print]
Marques F, Castro RB, Nobre F, Pintya AO, Gallo Júnior L, Maciel BC, Simões MV.
Hospital das Clínicas, Faculdade de Medicina de Ribeirão, USP, Ribeirão Preto, SP, Brasil.
[Replacement of carvedilol for propranolol in patients with heart failure.] [Article in Portuguese]
BACKGROUND: Large clinical trials using the betablockers carvedilol, metoprolol, bisoprolol and nebivolol have demonstrated improvement of survival and symptoms in patients with heart failure. Despite the lack of scientific evidence, it is plausible that their beneficial effects are extensible to other betablockers. OBJECTIVE: To evaluate the impact of the replacement of carvedilol for propranolol on left ventricular function, functional capacity, quality of life, pressure levels, and cardiac autonomic control in patients with heart failure. METHODS: Twenty nine patients receiving optimized drug therapy including maximum tolerated doses of carvedilol were divided into two groups: replacement of carvedilol for propranolol (n = 15) and continued carvedilol (n = 14). At baseline and 6 months later, clinical and laboratorial assessments were carried out with radionuclide ventriculography, echocardiography, Minnesota questionnaire, walk test, APBM and Holter monitoring. RESULTS: The clinical and demographic characteristics were similar in the two groups at baseline. Individualized propranolol dose adjustment ensured a similar degree of beta-blockade, as assessed by resting heart rate and chronotropic reserve. The mean propranolol dose used was 109 +/- 43 mg/day. Only one patient presented with intolerance to propranolol, thus carvedilol was reintroduced. One death was recorded in group propranolol. Ejection fraction significantly increased in the propranolol group. No significant change was observed in the other cardiovascular variables after betablocker replacement. CONCLUSION: Our results indicate that replacement of carvedilol for propranolol in patients with heart failure is not associated with deterioration of the ejection fraction, functional capacity, quality of life, and other cardiovascular variables related to autonomic and blood pressure control., PP.0-0).
Circ J. 2010 Jun 16. [Epub ahead of print]
Ito H, Nagatomo Y, Kohno T, Anzai T, Meguro T, Ogawa S, Yoshikawa T.
Cardiology Division, Department of Medicine, Keio University School of Medicine.
Differential Effects of Carvedilol and Metoprolol on Renal Function in Patients With Heart Failure.
Background: The aim of the present study was to verify the effects of beta-blockers on renal function in patients with heart failure (HF). Methods and Results: A total of 40 patients with HF (New York Heart Association class, II-III) were enrolled, who had beta-blocker therapy initiated with carvedilol (n=23) or metoprolol (n=17). The changes in renal and cardiac function were retrospectively analyzed over 16 weeks. The study population was divided into 2 groups according to the median baseline (65.9 ml/min) of estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease formula. eGFR significantly decreased in the higher eGFR group (P=0.04), but did not in the lower eGFR group. Left ventricular ejection fraction significantly increased in both groups with lower eGFR (P=0.01) and higher eGFR (P<0.01). There was an interaction between plasma norepinephrine concentration and eGFR in terms of beta-blocker treatment (P=0.02, ANOVA). eGFR significantly decreased in patients who received metoprolol (from 75.7+/-33.5 to 59.5+/-20.0 ml.min(-1).1.73 m(-2), P<0.01), but did not change in those who received carvedilol (from 67.1+/-27.7 ml.min(-1).1.73 m(-2) to 65.6+/-23.2 ml.min(-1).1.73 m(-2)). Conclusions: beta-Blockers preserved renal function in HF patients with lower baseline eGFR, but not in those with higher baseline eGFR. Carvedilol may be preferable to metoprolol to prevent the development of chronic kidney disease during beta-blocker therapy for HF.
Mol Pharm. 2010 Jun 28. [Epub ahead of print]
Tsume Y, Amidon GL.
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065.
The Biowaiver Extension for BCS Class III Drugs: The Effect of Dissolution Rate on the Bioequivalence of BCS Class III Immediate-Release Drugs Predicted by Computer Simulation.
The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaivers. The World Health Organization (WHO) has shortened the requisite dissolution time of BCS class III drugs on their Essential Medicine List (EML) from 30 to 15 min for extended biowaivers; however, the impact of the shorter dissolution time on AUC(0-inf) and C(max) is unknown. The objectives of this investigation were to assess the ability of gastrointestinal simulation software to predict the oral absorption of the BCS class I drugs propranolol and metoprolol and the BCS class III drugs cimetidine, atenolol, and amoxicillin, and to perform in silico bioequivalence studies to assess the feasibility of extending biowaivers to BCS class III drugs. The drug absorption from the gastrointestinal tract was predicted using physicochemical and pharmacokinetic properties of test drugs provided by GastroPlus (version 6.0). Virtual trials with a 200 mL dose volume at different drug release rates (T(85%) = 15 to 180 min) were performed to predict the oral absorption (C(max) and AUC(0-inf)) of the above drugs. Both BCS class I drugs satisfied bioequivalence with regard to the release rates up to 120 min. The results with BCS class III drugs demonstrated bioequivalence using the prolonged release rate, T(85%) = 45 or 60 min, indicating that the dissolution standard for bioequivalence is dependent on the intestinal membrane permeability and permeability profile throughout the gastrointestinal tract. The results of GastroPlus simulations indicate that the dissolution rate of BCS class III drugs could be prolonged to the point where dissolution, rather than permeability, would control the overall absorption. For BCS class III drugs with intestinal absorption patterns similar to those of cimetidine, atenolol or amoxicillin, the dissolution criteria for extension of biowaivers to BCS class III drugs warrants further investigation.
Clin Transl Sci. 2009 Dec;2(6):422-30.
Serpi R, Tolonen AM, Tenhunen O, Pieviläinen O, Kubin AM, Vaskivuo T, Soini Y, Kerkelä R, Leskinen H, Ruskoaho H.
Institute of Biomedicine, Department of Pharmacology and Toxicology, Biocenter, Oulu, Finland.
Divergent effects of losartan and metoprolol on cardiac remodeling, C-kit+ cells, proliferation and apoptosis in the left ventricle after myocardial infarction.
There is strong evidence for the use of angiotensin converting enzyme inhibitors and beta-blockers to reduce morbidity and mortality in patients with myocardial infarction (MI), whereas the effect of angiotensin receptor blockers is less clear. We evaluated the effects of an angiotensin receptor blocker losartan and a beta-blocker metoprolol on left ventricular (LV) remodeling, c-kit+ cells, proliferation, fibrosis, apoptosis, and angiogenesis using a model of coronary ligation in rats. Metoprolol treatment for 2 weeks improved LV systolic function. In contrast, losartan triggered deleterious structural remodeling and functional deterioration of LV systolic function, ejection fraction being 41% and fractional shortening 47% lower in losartan group than in controls 2 weeks after MI. The number of c-kit+ cells as well as expression of Ki-67 was increased by metoprolol. Losartan-induced thinning of the anterior wall and ventricular dilation were associated with increased apoptosis and fibrosis, while losartan had no effect on the expression of c-kit or Ki-67. Metoprolol or losartan had no effect on microvessel density. These results demonstrate that beta-blocker treatment attenuated adverse remodeling via c-kit+ cells and proliferation, whereas angiotensin receptor blocker-induced worsening of LV systolic function was associated with increased apoptosis and fibrosis in the peri-infarct region.
J Am Soc Hypertens. 2009 May-Jun;3(3):210-20. Epub 2009 Mar 29.
Fonarow GC, Deedwania P, Fonseca V, Nesto RW, Watson K, Tarka E, Lukas MA, Madan A, Shabbout M.
Division of Cardiology, University of California, Los Angeles School of Medicine, Los Angeles, California, USA.
Differential effects of extended-release carvedilol and extended-release metoprolol on lipid profiles in patients with hypertension: results of the Extended-Release Carvedilol Lipid Trial.
Some beta-blockers, although they are effective antihypertensive agents, may adversely effect dyslipidemia and decrease insulin sensitivity. beta-blockers without adverse metabolic effects may provide an improvement in long-term hypertension therapy. Hypertensive patients (n = 568) without diabetes, not requiring lipid-lowering therapy, were randomized to once-daily extended-release carvedilol or extended-release metoprolol and titrated to target blood pressure (BP). Co-primary endpoints were comparison between groups in high-density lipoprotein (HDL) or triglycerides at 24 weeks. Extended-release carvedilol was superior to extended-release metoprolol in meeting the primary endpoint of a difference in triglycerides; the median % change in triglycerides being -8.026% (P = .0141; 97.5% confidence interval [CI], -15.35, -0.67)] from baseline to 24 weeks. Triglycerides were unchanged with carvedilol and increased with metoprolol. There was no significant difference in effect on HDL. BP was similar between treatment groups. There was a significant decrease with extended-release carvedilol vs. extended-release metoprolol in insulin (-2.56 muU/mL [P = .0213; 95% CI, -4.74 to -0.38]) and c-peptide [(-0.43 ng/mL [P = .0007; 95% CI, -0.68 to -0.18]). In hypertension, extended-release carvedilol resulted in lower triglycerides, insulin, and C-peptide levels compared with extended-release metoprolol. Similar effects were observed in high-risk subgroups. Both treatments were well tolerated. This differential metabolic profile could be useful in determining antihypertensive treatment options.
Med Pregl. 2009 Sep-Oct;62(9-10):450-5.
Radović VV.
Institut Hemofarm", Hemofarm A.D., Beograd.
[Studies of the outcome of the treatment with beta-blockers in secondary prevention of the ischemic heart disease] [Article in Serbian]
Convincing evidence of the decline of mortality has been achieved with beta-blockers in patients with an acute myocardial infarction and in post-infarction follow-up. The beta-blockers are also the most efficient antianginal medications for the decrease of ischemia in outpatients. They are highly efficient as a monotherapy for angina and are also a medication of choice for angina after the coronary. The objective of this work was an estimate of the use of beta-blockers in secondary prevention of the ischemic heart disease and eliminating doubts concerning their prescription. The method of the analysis sums up the results of a twenty-five-year study on of the outcome of the treatment with beta-blockers in secondary prevention of the ischemic heart disease. The method of the work implies an examination of the professional literature and the data-bases, such as MEDLINE, Pub-Med and KOBSON. The first studies concerned non-selective beta-blockers, used orally. The following studies concerned cardioselective beta-blockers, metoprolol and atenolol. Several studies followed also the effect of beta-blockers and heparin, or beta-blockers and antagonists of calcium towards placebo, in patients with an unstable angina pectoris. Beta-blockers are an essential drug in secondary prevention of the myocardial infarction and in chronic heart failure. The necessary condition for the efficiency of beta-blockers is an early use. Beta-blockers should be given within 12 hours after the appearance of pain. The continuation of the therapy with beta-blockers after the acute phase is considered to be important in the decrease of the infarction zone expansion. Prophylactic use of beta-blockers after the coronary has an excellent effect, above all in patients with a minor, uncomplicated coronary. Though certain groups of beta-blockers have some special characteristics, when it comes to the treatment of angina pectoris, all beta-blockers are efficient. Generally, patients react well to them. Preference is given to cardioselective remedies, in patients with diabetes or lung disease. Exhaustive controlled clinical studies affirm beta-blockers as drugs that reduce mortality in secondary prevention of the ischemic heart disease.
Clin Ther. 2009 Dec;31(12):2894-9.
Kelesidis T, Kelesidis I.
Department of Medicine, Caritas Saint Elizabeth's Medical Center, Tufts University School of Medicine Boston, Massachusetts 02135, USA. tkelesid@gmail.com
Unexplained high fever in an elderly patient treated with clonidine, duloxetine, and atorvastatin.
BACKGROUND: Drug-induced fever is a clinical diagnosis and should always be considered when the fever is constant and high without a clear source of infection. Although drug-induced fever has been reported with other centrally acting antihypertensive drugs such as methyldopa, published reports of this adverse effect with clonidine in humans were not identified in a search of the literature. CASE SUMMARY: A 66-year-old institutionalized white female with a history of morbid obesity (body mass index, 40 kg/m2), Alzheimer's dementia, hypertension, and depression presented to a hospital in Boston, Massachusetts (Caritas Saint Elizabeth's Medical Center) with generalized weakness and shortness of breath and was found to have a non-ST segment elevation myocardial infarction. Before hospitalization, the patient was taking memantine 10 mg PO BID, donepezil 10 mg PO once daily, duloxetine 60 mg PO once daily, clonidine 0.1 mg PO TID, metoprolol 50 mg PO BID, and amlodipine 10 mg PO once daily. On admission, the patient was initiated on aspirin 325 mg, atorvastatin 80 mg, and clopidogrel 75 mg PO daily. Her dose of clonidine was increased to 0.2 mg PO TID to optimize blood pressure control, and metoprolol and amlodipine were continued at the same doses. The patient developed fever on the third day after the cardiac catheterization. The fever ranged from 99.0 degrees F to 102.7 degrees F. The physical examination, laboratory data analysis, multiple blood cultures, urinalysis, chest radiograph, and a computed tomography of the head, chest, abdomen, and pelvis did not reveal any source of infection. On the sixth day after admission, clonidine was reduced to the baseline dose of 0.1 mg PO TID and on the ninth day it was stopped. The patient was afebrile on the twelfth day and remained so for the duration of her hospitalization. Naranjo scores for her newly initiated concomitant medications were as follows: aspirin, 1; atorvastatin, 3; clonidine, 6; and clopidogrel, 1. The rating of 6 for clonidine suggests that it was probably associated with the fever in this patient. CONCLUSION: We describe a case of drug-induced fever probably associated with clonidine administration. The higher dose of clonidine alone or in interaction with duloxetine and atorvastatin may have contributed to the development of drug-induced fever.
Kathmandu Univ Med J (KUMJ). 2008 Oct-Dec;6(24):514-5.
Dronacahrya L, Poudel R.
Manipal Teaching Hospital, Pokhara, Nepal. dreamysu@hotmail.com
Lightning induced atrial fibrillation.
Atrial fibrillation (AF) is a common arrhythmia that occurs in paroxysmal and persistent forms. It occurs in varied situations but lightning induced AF is extremely rare. Here is a case which reverted to sinus rhythm spontaneously. This 37-year-old man without any underlying heart disease had new onset AF after being struck by a lightning. Oral Metoprolol alone was given to control ventricular rate. Spontaneous reversion to sinus rhythm within 36 hours is in favor of new onset lightning induced AF.
J Physiol Pharmacol. 2008 Dec;59(4):661-72.
Suleyman H, Halici Z, Cadirci E, Hacimuftuoglu A, Bilen H.
Department of Pharmacology, Erzurum, Ataturk University, Faculty of Medicine, Turkey. suleyman@atauni.edu.tr
Indirect role of beta2-adrenergic receptors in the mechanism of anti-inflammatory action of NSAIDS.
In this study we investigated both intact and adrenalectomized rats to determine whether or not the anti-inflammatory effects of indomethacin, diclofenac sodium, ibuprofen, nimesulide, tenoxicam and aspirin (IDINTA) are related to adrenal gland hormones in carrageenan-induced inflammation model of rats. Also, we investigated the anti-inflammatory action mechanism of hormones (adrenalin, cortisol) which perform a role in the anti-inflammatory effect of IDINTAon the adrenergic receptors. he results show that IDINTA produces significant anti-inflammatory effects in intact rats (ID(50): 9.82, 10.81, 95.21, 75.23, 8.21 and 61.84 mg/kg), but insignificant effects in adrenalectomized rats (ID(50): 152.97, 188.17, 1275.0, 433.67, 188.16 and 1028.17 mg/kg). In addition, adrenalin and prednisolone caused anti-inflammatory effect rates of 78.3% and 95.7% respectively in adrenalectomized rats. The anti-inflammatory effects of adrenalin and prednisolone did not change when prazosin (alpha(1)-receptor blocker), yohimbine (alpha(2)a2-receptor blocker) and phenoxybenzamine (alpha(2)- and alpha(2)-receptor blocker) were given to rat groups; however, in adrenalectomized rats administered with propranolol (a non-selective blocker of beta(1) and beta(2)-receptors) the anti-inflammatory effect of adrenalin was lost, and that of prednisolone decreased to 36.2%. It was also found that metoprolol (a selective blocker of beta(1)-receptors) did not alter the anti-inflammatory effects of the drugs. As a result, it was shown that anti-inflammatory effects of IDINTA are related to adrenalin and cortisol (corticosterone in rats). It was also determined for the first time that adrenalin (totally) and prednisolone (partially) triggered anti-inflammatory effects via the beta(2)-receptors but not via the alpha(1), alpha(2) and beta(1)-receptors.
Gac Med Mex. 2008 Nov-Dec;144(6):503-7.
Márquez MF, Urias-Medina K, Gómez-Flores J, Sobrino A, Sotomayor-González A, González-Hermosillo A, Cárdenas M.
Departamento de Electrocardiología, Instituto Nacional de Cardiología Ignacio Chávez, SSA, Tlalpan, México DF, México. manliomarquez@yahoo.com
[Comparison of metoprolol vs clonazepam as a first treatment choice among patients with neurocardiogenic syncope] [Article in Spanish]
OBJECTIVE: We compared the effects of a metoprolol and clonazepam in patients with neurocardiogenic syncope. METHODS: We compared the effects of a metoprolol and clonazepam in a prospective, randomised trial in 54 patients. Patients were randomly assigned to metoprolol (starting dose 50 mg bid) or clonazepam (starting dose 0.5 mg qd). We assessed a primary combined endpoint of syncope and pre-syncope on a follow-up of 12 months. RESULTS: The primary combined endpoint of syncope and presyncope occurred in the metoprolol group in 3, 4, and 10% of patients at 3, 6, and 12 months respectively. In the clonazepam group it was no recurrence in the first 6 months, and 5% recurrence at 12 months follow-up (nonsignificant differences between groups). Clinical symptoms commonly associated with neurally mediated syncope were decreased similarly in both treatment groups, in the metoprolol group from 5.2+/-2.5 to 1.9+/-2.1 (p < 0.001) and in the clonazepam group from 5.5+/-2.5 to 1.5+/-2.2 (p<0.001). CONCLUSIONS: Pharmacological treatment of neurocardiogenic syncope with metoprolol or clonazepam resulted in similar prevention of syncope and presyncope. Both treatments decreased clinical symptoms but complete symptomatic resolution was rarely observed.
Ned Tijdschr Geneeskd. 2008 Nov 29;152(48):2603-5.
Koelemay MJ, Legemate DA.
Academisch Medisch Centrum, Universiteit van Amsterdam, Afd. Chirurgie, G5-153, Postbus 22.600, 1100 DD Amsterdam. m.j.koelemaij@amc.uva.nl
[Perioperative beta-blockade for reduction of cardiovascular complications in non-cardiac surgery: advantages and disadvantages] [Article in Dutch]
The results of the recently published PeriOperative ISchemic Evaluation (POISE) trial show that perioperative use of metoprolol in patients with atherosclerosis undergoing major non-cardiac surgery reduces the risk of cardiovascular complications. This effect was primarily produced by a 1.5% reduction in non-fatal myocardial infarction (MI), but this advantage was outweighed by a 0.8% increase in total mortality and a 0.5% increase in nonfatal stroke. These results, combined with previous meta-analyses, confirm that non-fatal MI is reduced at the cost of a statistically significant increase in stroke rate and a near significant increase in mortality. It is likely that the increase in complications is due to a high dose of metoprolol being given too shortly before the operation. These findings call for judicious perioperative use of adrenergic beta-antagonists in cardiac-high-risk patients undergoing high risk non-cardiac surgery. Dosage should be lower and administration should be implemented longer before the operation.
Ther Clin Risk Manag. 2007 Aug;3(4):569-78.
Metra M, Nodari S, Bordonali T, Milani P, Lombardi C, Bugatti S, Fontanella B, Verzura G, Danesi R, Dei Cas L.
Section of Cardiovascular Diseases, Department of Experimental and Applied Medicine, University of Brescia Italy.
Bisoprolol in the treatment of chronic heart failure: from pathophysiology to clinical pharmacology and trial results.
Clinical trials have consistently shown the benefits of beta-blocker treatment in patients with chronic heart failure (HF). As a result, bisoprolol, carvedilol, and metoprolol succinate are now indicated for the treatment of all patients with chronic HF who do not have major contraindications. Bisoprolol is the first beta-blocker shown to improve survival in an outcome trial. In the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), all-cause mortality and sudden death were reduced in patients treated with bisoprolol compared with those on placebo (11.8% vs 17.3%; p < 0.0001 and 3.6% vs 6.3%, p < 0.002; respectively) regardless of age, NYHA functional class, and co-morbidities. Further studies have shown both the efficacy of bisoprolol on secondary endpoints and patients subgroups as well its high cost effectiveness. More recently, CIBIS-III has shown similar efficacy and safety of the initiation of HF treatment with either bisoprolol or enalapril, with a tendency to a survival advantage with bisoprolol. Nowadays, the role of bisoprolol, as well as that of carvedilol and metoprolol succinate, in HF treatment is firmly established and research is mainly focused on implementation of treatment and better dosing. This article will summarize evidence for the efficacy of bisoprolol in the treatment of HF.
Zhonghua Er Ke Za Zhi. 2007 Dec;45(12):885-8.
Chen L, DU JB, Zhang QY, Wang C, DU ZD, Wang HW, Tian H, Chen JJ, Wang YL, Hu XF, Li WZ, Han L.
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
[A multicenter study on treatment of autonomous nerve-mediated syncope in children with beta-receptor blocker] [Article in Chinese]
OBJECTIVE: Syncope is a common pediatric emergency. Based on an epidemiologic survey in the USA, around 15% of children experienced syncopal attack, which strongly influenced the life, study and hurt the children mentally and physiologically. Therefore, exploring the therapeutic regimen has become a hot topic in the field of pediatric cardiology. The aim of this study was to examine the effect of beta receptor blocker in the treatment of children with autonomous nerve mediated syncope. METHODS: Totally 103 children (43 males, 60 females, age 5 - 19 yrs, median 12.0 +/- 2.6 yrs) with autonomous nerve mediated syncope from Beijing, Hunan, Hubei and Shanghai, were included in this study. Forty-nine of them suffered from vasovagal syncope (VVS) and 54 suffered from postural tachycardia syndrome (POTS). They were randomally devided into treatment group accepting oral metoprolol treatment and control group accepting oral rehydration salt treatment. The frequency of syncopal episodes and the outcome of head-up tilt (HUT) test were observed. SPSS 10.0 software was used for the statistical analysis of these data. RESULTS: The cure rate of children who suffered from VVS and POTS and took oral metoprolol was 60.61% and 68.75%, respectively, but in the control group, the cure rate was only 18.75% and 0.00%, respectively. The rate of improvement of children who suffered from VVS and POTS and were treated with oral metoprolol was 15.15% and 15.63%, respectively, and in the control group, it was 6.25% and 40.91%, respectively. The effective rates for cases of VVS and POTS treated with oral metoprolol were higher than those of cases received oral rehydration salt treatment (P < 0.01). The percentage of the change from positive HUT to negative for children with VVS and POTS who took oral metoprolol therapy was 60.61% and 68.75%, respectively, but in control group, it was only 18.75% and 9.09%, respectively (P < 0.01). There was a significant difference in the percentage of the change from positive HUT to negative between children with VVS treated with oral metoprolol and with oral rehydration salt (P < 0.01). Also, a significant difference was found in the percentage of the change from positive HUT to negative between children with POTS treated with oral metoprolol and with oral rehydration salt (P < 0.01). CONCLUSION: beta receptor blocker is effective in the treatment of children with VVS or POTS.
Yao Xue Xue Bao. 2007 Nov;42(11):1206-14.
Wang WG, Yun LH, Wang R, Fu GY, Liu ZY.
Department of Pharmacy, Affiliated Hospital, Academy of Military Medical Sciences, Beijing 100071, China. Jason_wwg@hotmail.com
[Preparation of transdermal drug delivery system of felodipine-metoprolol and its bioavailability in rabbits] [Article in Chinese]
To prepare transdermal drug delivery system (TDDS) of felodipine and metoprolol and to study its pharmaceutical characteristics, pharmacokinetics and bioavailability in rabbits, an HPLC assay was established for the simultaneous determination of felodipine and metoprolol in the permeation receptor and patch. The permeation rate and permeation mechanism of felodipine-metoprolol-TDDS through rabbit skin in vitro was examined. The determination of drug content, the examination of content uniformity and stability of the TDDS were carried out. GC-ECD assays were established for the determination of felodipine and metoprolol in plasma separately and then employed to study the pharmacokinetics and bioavailability of felodipine and metoprolol after a single dose of oral or transdermal administration in rabbits. The results indicated that the permeation of flodipine and metoprolol from the patch through excised rabbit skin exhibited zero-order kinetic characteristics. The determination of drug content and the quality control of content uniformity of the patch accorded with Pharmacopoeia of the People's Republic of China of 2005 edition and the pharmaceutical characterization showed good stability. In contrast to oral delivery, relatively constant, sustained blood concentration with minimal fluctuation and prolonged peak time were observed over a long period after transdermal administration. The relative bioavailability of felodipine and metoprolol were 275.37% and 189.76% versus oral administration respectively. It was evident that the felodipine-metoprolol-TDDS exhibited good controlled release properties that satisfied the demands of original design that enhancing bioavailability and maintaining appropriate blood levels for a prolonged time without adverse effects associated with frequent oral administration.
Kidney Int. 2006 Oct 4;
Bakris GL, Hart P, Ritz E.
Department of Medicine, Hypertension Center, Endocrine Division, University of Chicago School of Medicine, Chicago, Illinois, USA.
Beta blockers in the management of chronic kidney disease.
The sympathetic nervous system modulates renal function through its receptors namely beta(1) (cardiac output and renin release), alpha(1) (systemic and renovascular constriction), and beta(2) renovascular dilation. Sympathetic overactivity is commonly seen in chronic kidney disease (CKD) and is an important contributor to increasing the risk of cardiovascular events as well as increasing renal disease progression. Recent evaluations of drug use in people with CKD shows a remarkably low percentage of patients receiving beta-blockers, especially in more advanced stage CKD when cardiovascular risk is higher. This is in large part due to tolerability of these agents. Moreover, water-soluble beta-blockers such as atenolol and metoprolol are dialyzable and require supplementation to avoid exacerbation of arrhythmias following dialysis. Newer vasodilating beta-blockers have better tolerability and different effects on renal hemodynamics as well as metabolic variables. These effects are related to the relative alpha(1)-blocking effect of agents such as carvedilol and labetolol, with carvedilol having relatively greater alpha-blocking effects. Few studies evaluate beta-blockers on cardiovascular risk in CKD patients. Studies with carvedilol demonstrate attenuated increases in albuminuria as well as reduction in cardiovascular events in CKD patients with hypertension. This paper reviews the animal and clinical trial data that evaluate beta-blockers in CKD highlighting the vasodilating beta-blockers. It is apparent that greater use of this drug class for blood pressure control would further enhance reduction of risk of heart failure, the most common cause of death in the first year of starting dialysis.Kidney International advance online publication, 4 October 2006; doi:10.1038/sj.ki.5001835.
Clin Pharmacol Ther. 2005 Mar;77(3):189-201.
Tu W, Morris AB, Li J, Wu J, Young J, Brater DC, Murray MD.
Association between adherence measurements of metoprolol and health care utilization in older patients with heart failure.
Objective Data from electronic dosing monitors and published pharmacokinetic parameters were used to derive medication adherence measures for immediate-release metoprolol and examine their association with health care utilization of outpatients aged 50 years or older with heart failure. Methods We used a 1-compartment model and published population pharmacokinetic parameters to estimate mean plasma metoprolol concentrations for patients treated for 6 to 12 months. In the absence of directly measured plasma concentrations, we calculated the intended mean plasma concentration (Cp' ave ) under the assumption of perfect adherence to the prescribed dose and frequency of administration. Projected mean plasma concentrations (Cp ave ) were estimated by use of data from recorded dosing times. In addition to taking adherence (percentage of dose taken) and scheduling adherence (percentage of doses taken on schedule), we calculated the deviation from the intended exposure (DeltaCp ave = Cp' ave - Cp ave ) and the proportion of intended exposure achieved by the patient (Cp ave /Cp' ave ). We assessed the association between the adherence measures and the numbers of emergency department visits and hospital admissions experienced by the patients. Results Patients (N = 80) were aged 62 +/- 8 years. Mean DeltaCp ave and Cp ave /Cp' ave were 7.9 ng/mL (SD, 10.7) and 0.6 (SD, 0.3), respectively. Log-linear models adjusted for patient functional status indicated that greater deviation from the intended metoprolol exposure (DeltaCp ave ) was associated with increased numbers of emergency department visits ( P < .0001) and hospital admissions ( P < .0001). A higher proportion of intended exposure (Cp ave /Cp' ave ) corresponded to a reduced number of emergency department visits ( P = .0204) and hospital admissions ( P = .0093). Taking adherence was univariately associated with both emergency department visits and hospital visits ( P < .0001 and P = .0010, respectively). Scheduling adherence was associated with the number of emergency department visits ( P = .0181) but not with the number of hospital admissions ( P = .1602). Model selection procedures consistently chose the proposed measures over taking adherence and scheduling adherence. Conclusion Deviation from the intended exposure and proportion of intended exposure achieved by the patient are valid adherence measures for immediate-release metoprolol and are associated with health care utilization. The potential utility of these measures for other beta-adrenergic antagonists and perhaps other cardiovascular drugs should be investigated.
Am Heart J. 2005 Jan;149(1):159-67.
Jeedwania PC, Giles TD, Klibaner M, Ghali JK, Herlitz J, Hildebrandt P, Kjekshus J, Spinar J, Vitovec J, Stanbrook H, Wikstrand J;
Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF.
BACKGROUND: The objective of the current study was to examine the efficacy and tolerability of the beta-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF). METHODS: The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI). RESULTS: The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%). Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37% in the diabetic group (95% CI 53% to 15%), and by 35% in the non-diabetic group (95% CI 48% to 19%). Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II), MERIT-HF, and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed similar survival benefits in patients with diabetes (25%; 95% CI 40% to 4%) and without diabetes (36%; 95% CI 44% to 27%); test of diabetes by treatment interaction was non-significant. Adverse events were reported more often on placebo than on metoprolol CR/XL. CONCLUSIONS: Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes. Regardless of diabetic status, a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy, which was very well tolerated also by patients with diabetes. Furthermore, the pooled data showed a statistically significant survival benefit in patients with diabetes.
Am Heart J. 2005 Feb;149(2):370-6.
Torp-Pedersen C, Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lutiger B, Metra M, Remme WJ, Scherhag A,
Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark.
Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET.
BACKGROUND: Beta-blockers with different receptor bindings reduce mortality in patients with chronic heart failure. We compared the effects of the beta1-blocker metoprolol tartrate and the beta1-, beta2-, and alpha1-blocker carvedilol. METHODS: In a randomized double-blind design, 3029 patients with chronic congestive heart failure requiring diuretic therapy and with left ventricular dysfunction were randomized to treatment with carvedilol (n = 1511) or metoprolol tartrate (n = 1518) and titrated to target doses of 25 mg of carvedilol twice daily or 50 mg of metoprolol tartrate twice daily. The main outcome measures were total mortality and the combination of mortality or hospitalization for any cause. Secondary end points were cardiovascular death, combinations of morbidity and mortality, New York Heart Association class, worsening of heart failure, hospitalizations, and discontinuation of study therapy. RESULTS: A total of 512 and 600 patients in the carvedilol group and metoprolol group, respectively, died (hazard ratio [HR] 0.83, 95% CI 0.74-0.93, P = .0017). Cardiovascular death was reduced by carvedilol (HR 0.80, 95% CI 0.70-0.90, P = .0004). There were fewer sudden deaths and deaths caused by circulatory failure or by stroke in the carvedilol group. There was no difference in all-cause hospitalizations or in worsening heart failure between treatment groups. The incidence of fatal or nonfatal acute myocardial infarction was significantly lower in the carvedilol group (HR 0.71, 95% CI 0.52-0.97, P = .03). Discontinuations of study therapy were similar in the 2 groups. CONCLUSION: Compared with metoprolol tartrate, carvedilol reduced cardiovascular mortality, sudden death, death caused by circulatory failure, death caused by stroke, as well as fatal and nonfatal myocardial infarctions.
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Drug category:Hypotensive agents
 Metoprolol scientific update
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