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1.
Eur J Clin Pharmacol ; 78(10): 1623-1632, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35871665

RESUMO

PURPOSE: To compare the co-prescription of metoprolol and potent CYP2D6-inhibiting antidepressants before and during a 10-year period after implementation of an optimized drug interaction database into clinical decision support systems in Norway. METHODS: The study was a retrospective, cross-sequential nationwide analysis of drug-dispensing data retrieved from the Norwegian Prescription Database over a 1-year period before (2007) and two 1-year periods after (2012 and 2017) implementation of a drug interaction database providing recommendations on non-interacting alternative medications. Primary outcome was changes in co-prescription rates of metoprolol and the potent CYP2D6-inhibiting antidepressants fluoxetine, paroxetine, or bupropion relative to alternative antidepressants with no or limited CYP2D6 inhibitory potential. To control for potential secular trend bias, a comparison group consisting of atenolol/bisoprolol users was included. RESULTS: The co-prescription rate of metoprolol with potent CYP2D6 inhibitors declined following implementation of the optimized database, by 21% (P < 0.001) after 5 years and by 40% (P < 0.001) after 10 years. Compared with atenolol/bisoprolol users, patients treated with metoprolol had significantly reduced likelihood of being prescribed a CYP2D6-inhibiting antidepressant in the two post-implementation periods (OR 0.61 (95% CI 0.54-0.69) and OR 0.45 (95% CI 0.40-0.51), respectively, versus OR 0.84 (95% CI 0.74-0.94) prior to implementation). Small and mostly insignificant differences in average daily metoprolol dosage were found between patients treated with the various antidepressants. CONCLUSION: The present study suggests that implementation of a drug interaction database providing recommendations on non-interacting drug alternatives contributes to reduced co-prescribing of drug combinations associated with potentially serious adverse effects.


Assuntos
Inibidores do Citocromo P-450 CYP2D6 , Citocromo P-450 CYP2D6 , Interações Medicamentosas , Antidepressivos/efeitos adversos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Atenolol , Bisoprolol , Bupropiona/uso terapêutico , Citocromo P-450 CYP2D6/genética , Inibidores do Citocromo P-450 CYP2D6/efeitos adversos , Inibidores do Citocromo P-450 CYP2D6/farmacologia , Inibidores do Citocromo P-450 CYP2D6/uso terapêutico , Prescrições de Medicamentos , Fluoxetina/uso terapêutico , Humanos , Metoprolol/efeitos adversos , Paroxetina/uso terapêutico , Estudos Retrospectivos
3.
Ann Pharmacother ; 56(8): 916-921, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34738470

RESUMO

BACKGROUND: Currently, it remains unclear whether ß-blockers or nondihydropyridine calcium channel blockers are preferred for the acute management of atrial fibrillation (AF). OBJECTIVE: The objective of this study was to compare the efficacy and safety of intravenous (IV) metoprolol and diltiazem for rate control. METHODS: This was a single-center, retrospective cohort study of patients who presented to the emergency department between 2015 and 2019 with AF with rapid ventricular rate (RVR) and received IV metoprolol or diltiazem. The primary outcome was the percentage of patients who achieved rate control (defined as heart rate < 100 beats per minute). Secondary outcomes included time to rate control, percentage of patients requiring additional agents for rate control, and incidence of cardioversion, bradycardia, and hypotension. RESULTS: A total of 200 patients were included in this study. Rate control was achieved in 35% and 41% of the metoprolol and diltiazem groups, respectively (P = 0.38). Mean time to rate control was not significantly different between the metoprolol and diltiazem groups (35 vs 21 minutes, P = 0.23). One patient developed hypotension, no patient developed bradycardia, and 4 patients required electric cardioversion. No adverse events were observed in patients with ejection fraction ≤40%. CONCLUSION AND RELEVANCE: There was no difference in the achievement of rate control between IV metoprolol and diltiazem. This is the largest study to date comparing the two classes of agents for acute rate control in AF. No patient-specific factors were identified that would influence the preferential use of one medication over the other.


Assuntos
Fibrilação Atrial , Hipotensão , Fibrilação Atrial/complicações , Bradicardia/induzido quimicamente , Bloqueadores dos Canais de Cálcio/efeitos adversos , Diltiazem/efeitos adversos , Frequência Cardíaca , Humanos , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Metoprolol/efeitos adversos , Estudos Retrospectivos
5.
Indian J Pharmacol ; 53(4): 264-269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414903

RESUMO

BACKGROUND: Inappropriate sinus tachycardia (IST) is an arrhythmic complication observed after coronary artery bypass graft (CABG) surgery which left untreated, commonly increases chances of postoperative stroke. The primary study objective was comparing effectiveness of beta blocker-metoprolol; a specific If blocker-ivabradine and its combination in patients who develop IST as a complication following CABG. MATERIALS AND METHODS: An open-labeled, investigator initiated, clinical study was conducted on 150 patients who developed IST (heart rate [HR] >100 beats/min) following elective CABG surgery. The patients were randomized into three treatment groups. Group I - received ivabradine (5 mg), Group II - metoprolol (25 mg), and Group III - ivabradine (5 mg) and metoprolol (25 mg). Treatment was given orally, twice a day for 7 days in all the three groups postoperatively. Primary endpoints were comparative effectiveness in HR and blood pressure reduction following treatment. RESULTS: IST was diagnosed by an electrocardiogram (12-lead) considering morphological features of P-wave and with 32% increase from baseline HR in all the three groups. Compared to IST arrthymic rate, HR was reduced in all groups following respective treatment (P = 0.05). Reduction in HR was significant (P < 0.05) in combination group followed by ivabradine which was significantly greater than metoprolol treated group. None of the treatments clinically changed the systolic, diastolic and mean blood pressure till discharge. No surgery/treatment-related complications were observed in any groups. CONCLUSION: Ivabradine stands as a pharmacological option for controlling HR and rhythm without associated side effects in postoperative CABG patients with IST.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Ivabradina/uso terapêutico , Metoprolol/uso terapêutico , Taquicardia Sinusal/tratamento farmacológico , Idoso , Quimioterapia Combinada , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ivabradina/administração & dosagem , Ivabradina/efeitos adversos , Metoprolol/administração & dosagem , Metoprolol/efeitos adversos , Pessoa de Meia-Idade
6.
Pharmacoepidemiol Drug Saf ; 30(10): 1420-1427, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34101945

RESUMO

BACKGROUND: Although prior literature suggests that metoprolol may worsen glucose control compared to carvedilol, whether this has clinical relevance among older adults with diabetes and heart failure (HF) remains an open question. METHODS: This was a US retrospective cohort study utilizing data sourced from a 50% national sample of Medicare fee-for-service claims of patients with part D prescription drug coverage (2007-2017). Among patients with diabetes and HF, we identified initiators of metoprolol or carvedilol, which were 1:1 propensity score matched on >90 variables. The primary outcome was initiation of a new oral or injectable antidiabetic medication (proxy for uncontrolled diabetes); secondary outcomes included initiation of insulin and severe hyperglycemic event (composite of emergency room visits or hospitalizations related to hyperglycemia). RESULTS: Among 24 239 propensity score-matched pairs (mean [SD] age 77.7 [8.0] years; male [39.1%]), there were 8150 (incidence rate per 100 person-years [IR] = 33.5) episodes of antidiabetic medication initiation among metoprolol users (exposure arm) compared to 8576 (IR = 33.4) among carvedilol users (comparator arm) compared to corresponding to an adjusted hazard ratio (aHR) of 0.97 (95% confidence interval [CI]: 0.94, 1.01). Similarly, metoprolol was not associated with a significant increase in the risk of secondary outcomes including insulin initiation: aHR of 0.98 (95% CI: 0.93, 1.04) and severe hyperglycemic events: aHR of 0.98 (95% CI: 0.93, 1.02). CONCLUSIONS: In this large study of older adults with HF and diabetes, initiation of metoprolol compared to carvedilol was not associated with an increase in the risk of clinically relevant hyperglycemia.


Assuntos
Diabetes Mellitus , Insuficiência Cardíaca , Hiperglicemia , Idoso , Carvedilol , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/epidemiologia , Masculino , Medicare , Metoprolol/efeitos adversos , Estudos Retrospectivos , Estados Unidos/epidemiologia
7.
Am J Ther ; 29(1): e34-e42, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33883430

RESUMO

BACKGROUND: Antiarrhythmic drugs remain the first-line therapy for treatment of idiopathic ventricular arrhythmias. STUDY QUESTION: The aim of this study was to assess the therapeutic efficacy of extended-release metoprolol succinate (MetS) and carvedilol for idiopathic, frequent, monomorphic premature ventricular contractions (PVCs). STUDY DESIGN: Study population consisted of 114 consecutive patients: 71 received MetS and 43 received carvedilol. MEASURES AND OUTCOMES: All patients underwent 24-hour Holter monitoring at baseline and during drug therapy. PVC-burden response to drug therapy was categorized as "good" (≥80% reduction), "poor" (either <80% reduction or ≤50% increase), and "proarrhythmic" responses (>50% increase) based on change in PVC burden compared with baseline. RESULTS: Most common presenting symptom was palpitations (65.8%), followed by coincidental discovery (29%). The mean MetS and carvedilol dosages were 65.57 ± 30.67 mg/d and 23.66 ± 4.26 mg/d, respectively. "Good," "poor," and "proarrhythmic" responses were observed in 11.3% and 16.3%, 63.4% and 67.4%, and 25.3% and 16.3% of patients treated with MetS and carvedilol, respectively. In patients with relatively high (≥16%) PVC burden, the sum of "poor"/"proarrhythmic" response was observed in 95.5% and 86.4% of patients treated with MetS and carvedilol, respectively. "Proarrhythmic" response was observed in 21.9% of the patients, particularly in the presence of relatively lower (≤10%) baseline PVC burden. Patients with "good" response during beta-blocker therapy had higher baseline daily average intrinsic total heart beats compared with patients with "poor"/"proarrhythmic" response combined (96,437 ± 26,488 vs. 86,635 ± 15,028, P = 0.047, respectively). Side effects and intolerance were observed in 5.6% and 18.6% of patients treated with MetS and carvedilol, respectively. CONCLUSIONS: MetS and carvedilol for idiopathic, frequent, monomorphic PVCs are frequently inefficient. Therapeutic efficacy decreases further in patients with relatively high (≥16%) PVC burden. Relatively higher baseline daily intrinsic total heart beats may be used to predict "good" response before beta-blocker therapy.


Assuntos
Metoprolol , Complexos Ventriculares Prematuros , Antiarrítmicos/efeitos adversos , Carvedilol , Eletrocardiografia Ambulatorial , Humanos , Metoprolol/efeitos adversos , Complexos Ventriculares Prematuros/tratamento farmacológico
8.
Arq Bras Cardiol ; 116(1): 100-105, 2021 01.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33566972

RESUMO

BACKGROUND: Image quality and radiation dose are optimized with a slow, steady heart rate (HR) when imaging the coronary arteries during cardiac computed tomography angiography (CCTA). The safety, efficacy, and protocol for HR reduction with beta blocker medication is not well described in a pediatric patient population. OBJECTIVE: Provide a safe and efficient metoprolol dose protocol to be used in pediatric outpatients undergoing CCTA. METHODS: We conducted a retrospective review of all pediatric outpatients who received metoprolol during CCTA. Demographic and clinical characteristics were summarized and the average reduction in HR was estimated using a multivariate linear regression model. Images were evaluated on a 1-4 scale (1= optimal). RESULTS: Seventy-eight pediatric outpatients underwent a CCTA scan with the use of metoprolol. The median age was 13 years, median weight of 46 kg, and 36 (46%) were male. The median doses of metoprolol were 1.5 (IQR 1.1, 1.8) mg/kg and 0.4 (IQR 0.2, 0.7) mg/kg for oral and intravenous administrations, respectively. Procedural dose-length product was 57 (IQR 30, 119) mGy*cm. The average reduction in HR was 19 (IQR 12, 26) beats per minute, or 23%. No complications or adverse events were reported. CONCLUSION: Use of metoprolol in a pediatric outpatient setting for HR reduction prior to CCTA is safe and effective. A metoprolol dose protocol can be reproduced when a slower HR is needed, ensuring faster acquisition times, clear images, and associated reduction in radiation exposure in this population. (Arq Bras Cardiol. 2021; 116(1):100-105).


FUNDAMENTO: Qualidade de imagem e dose de radiação são otimizadas com uma frequência cardíaca (FC) lenta e estável na realização de imagens de artérias coronárias durante a angiografia cardíaca por tomografia computadorizada (CCTA, do inglês cardiac computed tomography angiography) A segurança, a eficácia e o protocolo para a redução da FC com medicamento betabloqueador ainda não foi bem descrita em uma população de pacientes pediátricos. OBJETIVO: Oferecer um protocolo de dose de metoprolol eficiente a ser usado em pacientes pediátricos externos durante a CCTA. MÉTODOS: Realizamos uma revisão retrospectiva de todos os pacientes pediátricos externos que receberam o metoprolol durante a CCTA. As características demográficas e clínicas foram resumidas e a redução média em FC foi estimada utilizando-se um modelo de regressão linear multivariada. As imagens foram avaliadas em uma escala de 1 a 4 (1= ideal). RESULTADOS: Um total de 78 pacientes externos passaram a uma CCTA com o uso de metoprolol. A média de idade foi de 13 anos, a média de peso foi de 46 kg, e 36 pacientes (46%) eram do sexo masculino. As doses médias de metoprolol foram 1,5 (IQR 1,1; 1,8) mg/kg, e 0,4 (IQR 0,2; 0,7) mg/kg para administrações orais e intravenosas, respectivamente. O produto dose-comprimento por exame foi de 57 (IQR 30, 119) mGy*cm. A redução média da FC foi 19 (IQR 12, 26) batimentos por minuto, ou 23%. Não foram relatadas complicações ou eventos adversos. CONCLUSÃO: O uso de metoprolol num cenário de pacientes pediátricos externos para redução da FC antes de uma CCTA é seguro e eficiente. Pode-se reproduzir um protocolo de dose de metoprolol quando for necessário atingir uma FC mais lenta, garantindo tempos de aquisição mais rápidos, imagens mais claras e redução na exposição à radiação nessa população. (Arq Bras Cardiol. 2021; 116(1):100-105).


Assuntos
Doença da Artéria Coronariana , Metoprolol , Adolescente , Criança , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Frequência Cardíaca , Humanos , Masculino , Metoprolol/efeitos adversos , Pacientes Ambulatoriais , Doses de Radiação , Estudos Retrospectivos
9.
Arq. bras. cardiol ; 116(1): 100-105, Jan. 2021. tab
Artigo em Inglês, Português | LILACS | ID: biblio-1152972

RESUMO

Resumo Fundamento Qualidade de imagem e dose de radiação são otimizadas com uma frequência cardíaca (FC) lenta e estável na realização de imagens de artérias coronárias durante a angiografia cardíaca por tomografia computadorizada (CCTA, do inglês cardiac computed tomography angiography) A segurança, a eficácia e o protocolo para a redução da FC com medicamento betabloqueador ainda não foi bem descrita em uma população de pacientes pediátricos. Objetivo Oferecer um protocolo de dose de metoprolol eficiente a ser usado em pacientes pediátricos externos durante a CCTA. Métodos Realizamos uma revisão retrospectiva de todos os pacientes pediátricos externos que receberam o metoprolol durante a CCTA. As características demográficas e clínicas foram resumidas e a redução média em FC foi estimada utilizando-se um modelo de regressão linear multivariada. As imagens foram avaliadas em uma escala de 1 a 4 (1= ideal). Resultados Um total de 78 pacientes externos passaram a uma CCTA com o uso de metoprolol. A média de idade foi de 13 anos, a média de peso foi de 46 kg, e 36 pacientes (46%) eram do sexo masculino. As doses médias de metoprolol foram 1,5 (IQR 1,1; 1,8) mg/kg, e 0,4 (IQR 0,2; 0,7) mg/kg para administrações orais e intravenosas, respectivamente. O produto dose-comprimento por exame foi de 57 (IQR 30, 119) mGy*cm. A redução média da FC foi 19 (IQR 12, 26) batimentos por minuto, ou 23%. Não foram relatadas complicações ou eventos adversos. Conclusão O uso de metoprolol num cenário de pacientes pediátricos externos para redução da FC antes de uma CCTA é seguro e eficiente. Pode-se reproduzir um protocolo de dose de metoprolol quando for necessário atingir uma FC mais lenta, garantindo tempos de aquisição mais rápidos, imagens mais claras e redução na exposição à radiação nessa população. (Arq Bras Cardiol. 2021; 116(1):100-105)


Abstract Background Image quality and radiation dose are optimized with a slow, steady heart rate (HR) when imaging the coronary arteries during cardiac computed tomography angiography (CCTA). The safety, efficacy, and protocol for HR reduction with beta blocker medication is not well described in a pediatric patient population. Objective Provide a safe and efficient metoprolol dose protocol to be used in pediatric outpatients undergoing CCTA. Methods We conducted a retrospective review of all pediatric outpatients who received metoprolol during CCTA. Demographic and clinical characteristics were summarized and the average reduction in HR was estimated using a multivariate linear regression model. Images were evaluated on a 1-4 scale (1= optimal). Results Seventy-eight pediatric outpatients underwent a CCTA scan with the use of metoprolol. The median age was 13 years, median weight of 46 kg, and 36 (46%) were male. The median doses of metoprolol were 1.5 (IQR 1.1, 1.8) mg/kg and 0.4 (IQR 0.2, 0.7) mg/kg for oral and intravenous administrations, respectively. Procedural dose-length product was 57 (IQR 30, 119) mGy*cm. The average reduction in HR was 19 (IQR 12, 26) beats per minute, or 23%. No complications or adverse events were reported. Conclusion Use of metoprolol in a pediatric outpatient setting for HR reduction prior to CCTA is safe and effective. A metoprolol dose protocol can be reproduced when a slower HR is needed, ensuring faster acquisition times, clear images, and associated reduction in radiation exposure in this population. (Arq Bras Cardiol. 2021; 116(1):100-105)


Assuntos
Humanos , Masculino , Criança , Adolescente , Doença da Artéria Coronariana , Metoprolol/efeitos adversos , Pacientes Ambulatoriais , Doses de Radiação , Estudos Retrospectivos , Angiografia Coronária , Angiografia por Tomografia Computadorizada , Frequência Cardíaca
10.
J Pharmacol Exp Ther ; 376(1): 127-135, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33100271

RESUMO

The practice of prescribing ß-blockers to lower blood pressure and mitigate perioperative cardiovascular events has been questioned because of reports of an increased risk of stroke. The benefit of ß-blocker therapy primarily relies on preventing activation of cardiac ß1-adrenergic receptors (ARs). However, we reported that ß1ARs also mediate vasodilator responses of rat cerebral arteries (CAs), implying that ß-blockers may impair cerebral blood flow under some conditions. Here, we defined the impact of metoprolol (MET), a widely prescribed ß1AR-selective antagonist, on adrenergic-elicited diameter responses of rat CAs ex vivo and in vivo. MET (1-10 µmol/l) prevented ß1AR-mediated increases in diameter elicited by dobutamine in cannulated rat CAs. The ß1AR-mediated dilation elicited by the endogenous adrenergic agonist norepinephrine (NE) was reversed to a sustained constriction by MET. Acute oral administration of MET (30 mg/kg) to rats in doses that attenuated resting heart rate and dobutamine-induced tachycardia also blunted ß1AR-mediated dilation of CAs. In the same animals, NE-induced dilation of CAs was reversed to sustained constriction. Administration of MET for 2 weeks in drinking water (2 mg/ml) or subcutaneously (15 mg/kg per day) also resulted in NE-induced constriction of CAs in vivo. Thus, doses of MET that protect the heart from adrenergic stimulation also prevent ß1AR-mediated dilation of CAs and favor anomalous adrenergic constriction. Our findings raise the possibility that the increased risk of ischemic stroke in patients on ß-blockers relates in part to adrenergic dysregulation of cerebrovascular tone. SIGNIFICANCE STATEMENT: ß-Blocker therapy using second-generation, cardioselective ß-blockers is associated with an increased risk of stroke, but the responsible mechanisms are unclear. Here, we report that either acute or chronic systemic administration of a cardioselective ß-blocker, metoprolol, mitigates adrenergic stimulation of the heart as an intended beneficial action. However, metoprolol concomitantly eliminates vasodilator responses to adrenergic stimuli of rat cerebral arteries in vivo as a potential cause of dysregulated cerebral blood flow predisposing to ischemic stroke.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Cardiotônicos/farmacologia , Artérias Cerebrais/efeitos dos fármacos , Metoprolol/farmacologia , Receptores Adrenérgicos beta 1/metabolismo , Vasodilatação , Agonistas de Receptores Adrenérgicos beta 1/farmacologia , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Animais , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , Artérias Cerebrais/fisiologia , Dobutamina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Metoprolol/administração & dosagem , Metoprolol/efeitos adversos , Norepinefrina/farmacologia , Ratos , Ratos Sprague-Dawley
11.
Pak J Pharm Sci ; 34(6(Special)): 2473-2478, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35039262

RESUMO

To explore the effect of metoprolol tartrate tablets and recombinant human natriuretic peptide B (NPPB) on sudden cardiac death and malignant arrhythmias in patients with acute myocardial infarction and patients with heart failure (AMI-HF). A total of 105 AMI-HF patients treatedfrom January 2020 and June 2021 were enrolled and divided into Group I (n=53) and Group II (n=52). Both groups received conventional treatment, and Group II was additionally treated with metoprolol tartrate tablets and NPPB. The clinical observation indicators of the two groups of patients were compared. Group II had better left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) (p<0.05). The standard deviation of NN (R-R) interval (SDNN), mean NN (R-R), root mean square of continuous difference (RMSSD) and the percentage of difference between adjacent RR intervals >50ms (pNN50) increased after treatment, with more increase in the Group II (p<0.05). Group II obtained significantly lower levels of B type natriuretic peptide (BNP),N terminal pro B type natriuretic peptide (NT-ProBNP), interleukin (IL)-6 and hs-CRP in contrast to Group I (p<0.05). Markedly higher total response rates were observed in Group II (p<0.05). The combination of metoprolol tartrate tablets and NPPB is effective in treating AMI-HF.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/prevenção & controle , Morte Súbita Cardíaca/prevenção & controle , Insuficiência Cardíaca/tratamento farmacológico , Metoprolol/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Peptídeo Natriurético Encefálico/uso terapêutico , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Idoso , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/sangue , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Interleucina-6/sangue , Masculino , Metoprolol/efeitos adversos , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Peptídeo Natriurético Encefálico/efeitos adversos , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Proteínas Recombinantes/uso terapêutico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
12.
Am Fam Physician ; 102(10): 613-621, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33179891

RESUMO

Drugs are being prescribed with more frequency and in higher quantities. A serious adverse drug event from prescribed medications constitutes 2.4% to 16.2% of all hospital admissions. Many of the adverse drug events present intraorally or periorally in isolation or as a clinical symptom of a systemic effect. Clinical recognition and treatment of adverse drug events are important to increase patient adherence, manage drug therapy, or detect early signs of potentially serious outcomes. Oral manifestations of commonly prescribed medications include gingival enlargement, oral hyperpigmentation, oral hypersensitivity reaction, medication-related osteonecrosis, xerostomia, and other oral or perioral conditions. To prevent dose-dependent adverse drug reactions, physicians should prescribe medications judiciously using the lowest effective dose with minimal duration. Alternatively, for oral hypersensitivity reactions that are not dose dependent, quick recognition of clinical symptoms associated with time-dependent drug onset can allow for immediate discontinuation of the medication without discontinuation of other medications. Physicians can manage oral adverse drug events in the office through oral hygiene instructions for gingival enlargement, medication discontinuation for oral pigmentation, and prescription of higher fluoride toothpastes for xerostomia.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Crescimento Excessivo da Gengiva/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hiperpigmentação/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Xerostomia/induzido quimicamente , Albuterol/efeitos adversos , Anlodipino/efeitos adversos , Anticonvulsivantes/efeitos adversos , Atorvastatina/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Broncodilatadores/efeitos adversos , Desprescrições , Fluoretos/uso terapêutico , Crescimento Excessivo da Gengiva/terapia , Humanos , Hiperpigmentação/terapia , Lisinopril/efeitos adversos , Losartan/efeitos adversos , Metformina/efeitos adversos , Metoprolol/efeitos adversos , Doenças da Boca/induzido quimicamente , Doenças da Boca/terapia , Omeprazol/efeitos adversos , Higiene Bucal , Inibidores da Bomba de Prótons/efeitos adversos , Sinvastatina/efeitos adversos , Tiroxina/efeitos adversos , Cremes Dentais/uso terapêutico , Xerostomia/terapia
13.
J Cardiovasc Magn Reson ; 22(1): 44, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32522198

RESUMO

BACKGROUND: We aimed to evaluate the effect of early intravenous metoprolol treatment, microvascular obstruction (MVO), intramyocardial hemorrhage (IMH) and adverse left ventricular (LV) remodeling on the evolution of infarct and remote zone circumferential strain after acute anterior ST-segment elevation myocardial infarction (STEMI) with feature-tracking cardiovascular magnetic resonance (CMR). METHODS: A total of 191 patients with acute anterior STEMI enrolled in the METOCARD-CNIC randomized clinical trial were evaluated. LV infarct zone and remote zone circumferential strain were measured with feature-tracking CMR at 1 week and 6 months after STEMI. RESULTS: In the overall population, the infarct zone circumferential strain significantly improved from 1 week to 6 months after STEMI (- 8.6 ± 9.0% to - 14.5 ± 8.0%; P < 0.001), while no changes in the remote zone strain were observed (- 19.5 ± 5.9% to - 19.2 ± 3.9%; P = 0.466). Patients who received early intravenous metoprolol had significantly more preserved infarct zone circumferential strain compared to the controls at 1 week (P = 0.038) and at 6 months (P = 0.033) after STEMI, while no differences in remote zone strain were observed. The infarct zone circumferential strain was significantly impaired in patients with MVO and IMH compared to those without (P < 0.001 at 1 week and 6 months), however it improved between both time points regardless of the presence of MVO or IMH (P < 0.001). In patients who developed adverse LV remodeling (defined as ≥ 20% increase in LV end-diastolic volume) remote zone circumferential strain worsened between 1 week and 6 months after STEMI (P = 0.036), while in the absence of adverse LV remodeling no significant changes in remote zone strain were observed. CONCLUSIONS: Regional LV circumferential strain with feature-tracking CMR allowed comprehensive evaluation of the sequelae of an acute STEMI treated with primary percutaneous coronary intervention and demonstrated long-lasting cardioprotective effects of early intravenous metoprolol. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01311700. Registered 8 March 2011 - Retrospectively registered.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Infarto Miocárdico de Parede Anterior/terapia , Metoprolol/administração & dosagem , Miocárdio/patologia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Administração Intravenosa , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Idoso , Infarto Miocárdico de Parede Anterior/diagnóstico por imagem , Infarto Miocárdico de Parede Anterior/patologia , Infarto Miocárdico de Parede Anterior/fisiopatologia , Feminino , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Metoprolol/efeitos adversos , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Recuperação de Função Fisiológica , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
14.
Biomed Res Int ; 2020: 5358467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32351995

RESUMO

BACKGROUND: Chinese herbal medicine Dingji Fumai Decoction (DFD) is widely clinically used for ventricular premature contraction (VPC). This real-word trial was designed to assess the safety and effectiveness of DFD for VPC. METHODS: This was a double-blinded, randomized placebo-controlled trial. Patients with VPC were randomized (1 : 1) to treatment with DFD combined with metoprolol (DFD arm) or metoprolol combined with placebo (MET arm). A primary end point was a composite of clinical symptoms and signs determined by the traditionalChinese medicine syndrome score and the number of VPC determined by the Holter examination. Second outcomes were adverse events, medication compliance, and laboratory examination. RESULTS: 144 patients were randomized to DFD arm (76 patients) or MET arm (68 patients), and 136 cases (71 in DFD arm and 65 in MET arm) finally completed this trial. After a 12-week follow-up, DFD arm significantly decreased traditional Chinese medicine syndrome score and the number of VPC compared with MET arm (P = 0.003 and 0.034, respectively). There was no adverse drug effect and patient medication compliance was good. CONCLUSIONS: Superiority with DFD arm for VPC was demonstrated over MET arm for both the safety and effectiveness end points.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa , Metoprolol/administração & dosagem , Complexos Ventriculares Prematuros/tratamento farmacológico , Idoso , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Metoprolol/efeitos adversos , Pessoa de Meia-Idade
15.
Hypertens Pregnancy ; 39(3): 314-318, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32420783

RESUMO

OBJECTIVE: The aim of the study was to compare the complication of Antihypertensive drug; in pregnant women with chronic hypertension. METHOD: This retrospective cohort study was performed on 300 pregnant women  with chronic hypertension. Results:  a relative risk of preeclampsia among methyldopa group was 3.45 times higher than the metoprolol, the relative risk of preterm labor was not significantly between methyldopa and metoprolol group, LBW, and IUGR in methyldopa and amlodipine groups . CONCLUSION: Methyldopa and amlodipine are associated with the least side effects in pregnant women treated for chronic hypertension.the incidence of preeclampsia was greater in methyldopa group.


Assuntos
Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Metildopa/efeitos adversos , Metoprolol/efeitos adversos , Trabalho de Parto Prematuro/epidemiologia , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Adulto , Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Incidência , Metildopa/administração & dosagem , Metoprolol/administração & dosagem , Trabalho de Parto Prematuro/induzido quimicamente , Gravidez , Prevalência , Estudos Retrospectivos , Risco
16.
J Cardiovasc Pharmacol ; 75(4): 276-283, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032206

RESUMO

Pharmacologic management of atrial fibrillation (AF) is a pressing problem. This arrhythmia afflicts >5 million individuals in the United States and prevalence is estimated to rise to 12 million by 2050. Although the pill-in-the-pocket regimen for self-administered AF cardioversion introduced over a decade ago has proven useful, significant drawbacks exist. Among these are the relatively long latency of effects in the range of hours along with potential for hypotension and other adverse effects. This experience prompted development of a new strategy for increasing plasma concentrations of antiarrhythmic drugs rapidly and for a limited time, namely, pulmonary delivery. In preclinical studies in Yorkshire pigs, intratracheal administration of flecainide was shown to cause a rapid, reproducible increase in plasma drug levels. Moreover, pulmonary delivery of flecainide converted AF to normal sinus rhythm by prolonging atrial depolarization, which slows intra-atrial conduction and seems to be directly correlated with efficacy in converting AF. The rapid rise in plasma flecainide levels optimizes its anti-AF effects while minimizing adverse influences on ventricular depolarization and contractility. A more concentrated and soluble formulation of flecainide using a novel cyclodextrin complex excipient reduced net drug delivery for AF conversion when compared to the acetate formulation. Inhalation of the beta-adrenergic blocking agent metoprolol slows ventricular rate and can also terminate AF. In human subjects, oral inhalation of flecainide acetate with a hand-held, breath-actuated nebulizer results in signature prolongation of the QRS complex without serious adverse events. Thus, pulmonary delivery is a promising advance in pharmacologic approach to management of AF.


Assuntos
Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Flecainida/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Metoprolol/administração & dosagem , Administração por Inalação , Animais , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacocinética , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Modelos Animais de Doenças , Composição de Medicamentos , Flecainida/efeitos adversos , Flecainida/farmacocinética , Humanos , Metoprolol/efeitos adversos , Metoprolol/farmacocinética , Nebulizadores e Vaporizadores , Resultado do Tratamento
17.
Mol Genet Metab ; 129(4): 278-285, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32029355

RESUMO

Eliglustat is an oral substrate reduction therapy indicated for patients with Gaucher disease type 1. Based on in vitro data, clinical trials were conducted to assess the potential for drug-drug interactions between eliglustat and digoxin (P-glycoprotein substrate), metoprolol (sensitive CYP2D6 substrate), a combined oral contraceptive (CYP3A substrate), and acid-reducing agents. Healthy subjects were enrolled in four Phase 1 clinical studies to evaluate the effect of eliglustat on the pharmacokinetics, safety, and tolerability of digoxin (N = 28), metoprolol (N = 14), and a combined oral contraceptive (N = 30) and the effect of acid-reducing agents on eliglustat pharmacokinetics, safety, and tolerability (N = 24). Coadministration resulted in increased exposure to digoxin (1.49-fold) and metoprolol (2-fold) with eliglustat, negligible effects on oral contraceptive pharmacokinetics with eliglustat, and a negligible effect of acid-reducing agents on eliglustat pharmacokinetics. Across all studies, eliglustat was well-tolerated. One serious adverse event (spontaneous abortion) and one discontinuation due to an adverse event (urinary tract infection) were reported, both during the acid-reducing agents study. When eliglustat is coadministered with medications that are P-glycoprotein or CYP2D6 substrates, lower doses of these concomitant medications may be required. Eliglustat may be coadministered with oral contraceptives and acid-reducing agents without dose modifications for either drug.


Assuntos
Anticoncepcionais Orais/farmacocinética , Digoxina/farmacocinética , Metoprolol/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Pirrolidinas/administração & dosagem , Adolescente , Adulto , Anticoncepcionais Orais/administração & dosagem , Anticoncepcionais Orais/efeitos adversos , Estudos Cross-Over , Digoxina/administração & dosagem , Digoxina/efeitos adversos , Interações Medicamentosas , Feminino , Humanos , Masculino , Metoprolol/administração & dosagem , Metoprolol/efeitos adversos , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Adulto Jovem
18.
Br J Clin Pharmacol ; 86(6): 1015-1033, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32090368

RESUMO

AIMS: CYP2D6 genetic polymorphisms are associated with metoprolol pharmacokinetics. Whether the clinical response to metoprolol is also affected remains uncertain. METHODS: We conducted a systematic review on the effects of CYP2D6 polymorphism on the clinical response to metoprolol. Searches were conducted using MEDLINE. Meta-analyses were performed on the impact of CYP2D6-inferred phenotypes on heart rate (HR) reduction, diastolic (DBP) and systolic (SBP) blood pressure reduction, average daily doses, all-type adverse events and bradycardia. RESULTS: Our qualitative assessment indicated inconsistent results in individual studies and endpoints, but CYP2D6 poor metabolizers (PM) generally presented a greater reduction in HR. The meta-analysis of 15 studies, including a total of 1146 individuals, found a reduction in HR of 3 beats/min (P = .017), and of SBP and DBP by 3 mmHg (P = .0048) for PM compared to non-PM individuals using similar metoprolol doses. Bradycardia appeared more frequent by 4-fold for PM, although significant heterogeneity was observed regarding bradycardia, which limits the scope of this finding. CONCLUSION: Patients without any CYP2D6 metabolic capacities appear to have increased reduction in DBP, HR and SBP during metoprolol treatment and may be at a higher risk of bradycardia compared to patients with active CYP2D6 phenotypes. Further prospective data are required to determine whether CYP2D6 is associated with clinical events in patients treated with metoprolol, as well as to demonstrate the clinical utility of an individualized approach of prescribing metoprolol using CYP2D6-inferred phenotypes.


Assuntos
Citocromo P-450 CYP2D6 , Metoprolol , Citocromo P-450 CYP2D6/genética , Genótipo , Humanos , Metoprolol/efeitos adversos , Fenótipo , Polimorfismo Genético
19.
Eur J Clin Pharmacol ; 76(5): 673-683, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31940084

RESUMO

PURPOSE: The ß-1 adrenergic receptor blocker metoprolol is primarily metabolized by the polymorphic enzyme cytochrome P 450 2D6 (CYP2D6), an enzyme with substantial genetic heterogeneity. Our purpose was to investigate the impact of CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction (MI). METHODS: We included 136 patients with MI discharged on treatment with metoprolol with a recommendation to the general practitioner (GP) to increase the metoprolol dose up to 200 mg/day within 2 months if possible. At follow-up, metoprolol dosage after up-titration, metoprolol steady-state trough plasma concentrations, hemodynamic parameters, potential metoprolol-induced adverse drug reactions and number of visits to the GP were measured. CYP2D6 genotyping including the reduced-function variant alleles CYP2D6*9, CYP2D6*10 and CYP2D6*41 was performed after end of follow-up. RESULTS: According to the genotype-defined CYP2D6 phenotypes, 30% of the patients were metoprolol extensive metabolizers (EMs), 55% intermediate metabolizers (IMs) and 13% poor metabolizers (PMs; carriers of non-coding and reduced-function variant included). Dose-adjusted metoprolol trough concentrations were significantly higher in IM (2-fold) and PM (6.2-fold) groups vs. the EM group (p < 0.001). Only 35% of patients in the PM group achieved the primary end point, i.e. reaching at least 85% of the expected maximum heart rate (HR) during exercise, compared with 78% in the EM group (p < 0.01), and maximum observed HR at exercise was significantly lower in the PM group vs. the EM group (129 ± 5 vs. 142 ± 2 bpm, p < 0.007). In contrast, metoprolol maintenance dose, blood pressure, exercise capacity, number of visits at the GP and frequency and severity of self-reported potential metoprolol-related adverse drug reactions were not significantly different between the groups. CONCLUSION: Using a comprehensive CYP2D6 genotyping panel, the present study demonstrates a > 6-fold increase of dose-adjusted plasma metoprolol trough concentration in CYP2D6 PMs vs. EMs with a parallel lower increase in achieved maximum HR during exercise but without association between genotype and frequency or severity of self-reported adverse drug effects. This may indicate that CYP2D6 PMs potentially could benefit of the increased plasma concentration per dose in a naturalistic setting.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Metoprolol/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Antagonistas de Receptores Adrenérgicos beta 1/sangue , Adulto , Idoso , Feminino , Genótipo , Hemodinâmica , Humanos , Masculino , Metoprolol/efeitos adversos , Metoprolol/sangue , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Kardiologiia ; 60(11): 1357, 2020 Dec 15.
Artigo em Russo | MEDLINE | ID: mdl-33487156

RESUMO

This article presents results of a systematic review, which was designed for evaluating the effect of combination treatment with ivabradine and metoprolol on heart rate, frequency of angina attacks, frequency of using short-acting nitrates, and angina severity. The analysis included data from three large observational studies on efficacy of the ivabradine and metoprolol tartrate combination in patients with chronic angina. Results of the analysis supported the efficacy of the metoprolol and ivabradine combination in clinical practice, which provided effective decreases in the heart rate, frequency of angina attacks, requirement for short-acting nitrates, and alleviation of angina severity. The studies demonstrated good tolerability of this treatment.


Assuntos
Angina Estável , Metoprolol , Antagonistas Adrenérgicos beta/uso terapêutico , Angina Estável/tratamento farmacológico , Benzazepinas/efeitos adversos , Quimioterapia Combinada , Frequência Cardíaca , Humanos , Ivabradina/uso terapêutico , Metoprolol/efeitos adversos , Resultado do Tratamento
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