Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.486
Filtrar
1.
Cell Physiol Biochem ; 53(4): 587-605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31535830

RESUMO

BACKGROUND/AIMS: To investigate the role of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in renal ischemia/reperfusion-induced (I/R) cardiac inflammatoryprofile. METHODS: Left kidney ischemia was induced in male C57BL/6 mice for 60 min, followed by reperfusion for 12 days, and treatment with or without atenolol, losartan, or enalapril. The expression of vimentin in kidney and atrial natriuretic factor (ANF) in the heart has been investigated by RT-PCR. In cardiac tissue, levels of ß1-adrenoreceptors, adenylyl cyclase, cyclic AMP-dependent protein kinase (PKA), noradrenaline, adrenaline (components of SNS), type 1 angiotensin II receptors (AT1R), angiotensinogen/Ang II and renin (components of RAS) have been measured by Western blotting and HPLC analysis. A panel of cytokines - tumour necrosis factor (TNF-α), interleukin IL-6, and interferon gamma (IFN-γ) - was selected as cardiac inflammatory markers. RESULTS: Renal vimentin mRNA levels increased by >10 times in I/R mice, indicative of kidney injury. ANF, a marker of cardiac lesion, increased after renal I/R, the values being restored to the level of Sham group after atenolol or enalapril treatment. The cardiac inflammatory profile was confirmed by the marked increase in the levels of mRNAs of TNF-α, IL-6, and IFN-γ. Atenolol and losartan reversed the upregulation of TNF-α expression, whereas enalapril restored IL-6 levels to Sham levels; both atenolol and enalapril normalized IFN-γ levels. I/R mice showed upregulation of ß1-adrenoreceptors, adenylyl cyclase, PKA and noradrenaline. Renal I/R increased cardiac levels of AT1R, which decreased after losartan or enalapril treatment. Renin expression also increased, with the upregulation returning to Sham levels after treatment with SNS and RAS blockers. Angiotensinogen/Ang II levels in heart were unaffected by renal I/R, but they were significantly decreased after treatment with losartan and enalapril, whereas increase in renin levels decreased. CONCLUSION: Renal I/R-induced cardiac inflammatory events provoked by the simultaneous upregulation of SNS and RAS in the heart, possibly underpin the mechanism involved in the development of cardiorenal syndrome.


Assuntos
Rim/metabolismo , Miocárdio/metabolismo , Sistema Renina-Angiotensina , Sistema Nervoso Simpático/metabolismo , Animais , Atenolol/farmacologia , Atenolol/uso terapêutico , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Catecolaminas/metabolismo , Enalapril/farmacologia , Enalapril/uso terapêutico , Interleucina-6/metabolismo , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Sistema Nervoso Simpático/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Vimentina/genética , Vimentina/metabolismo
2.
Hypertension ; 74(4): 1033-1040, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476905

RESUMO

Hypertension treatment has been implicated in falls, syncope, and orthostatic hypotension (OH), common events among older adults. Whether the choice of antihypertensive agent influences the risk of falls, syncope, and OH in older adults is unknown. ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) was a randomized clinical trial that compared the effects of hypertension first-step therapy on fatal coronary heart disease or nonfatal myocardial infarction (1994-2002). In a subpopulation of ALLHAT participants, age 65 years and older, we determined the relative risk of falls, syncope, OH, or a composite based on Centers for Medicare and Medicaid Services and Veterans Affairs claims, using Cox regression. We also determined the adjusted association of self-reported atenolol use (ascertained at the 1-month visit for indications other than hypertension) on outcomes in Cox models adjusted for age, sex, and race. Among 23 964 participants (mean age 69.8±6.8 years, 45% women, 31% non-Hispanic black) followed for a mean of 4.9 years, we identified 267 falls, 755 syncopes, 249 OH, and 1157 composite claims. There were no significant differences in the cumulative incidences of events across randomized drug assignments. However, amlodipine increased risk of falls during the first year of follow-up compared with chlorthalidone (hazard ratio [95% CI]: 2.24 [1.06-4.74]; P=0.03) or lisinopril (hazard ratio [95% CI]: 2.61 [1.03-6.72]; P=0.04). Atenolol use (N=928) was not associated with any of the 3 individual or composite claims. In older adults, the choice of antihypertensive agent had no effect on risk of fall, syncope, or OH long-term. However, amlodipine increased risk of falls within 1 year of initiation. These short-term findings require confirmation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipotensão Ortostática/epidemiologia , Síncope/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Anlodipino/uso terapêutico , Atenolol/uso terapêutico , Clortalidona/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Medicare , Resultado do Tratamento , Estados Unidos
3.
Chemosphere ; 236: 124318, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31319310

RESUMO

The present paper deals with the atenolol (ATL) degradation by advanced anodic oxidation using a boron-doped diamond anode supported on niobium (Nb/BDD). Cyclic voltammetry performed on this electrode revealed that it presents a high quality (diamond-sp3/sp2-carbon ratio), high potential for OER and that ATL can be oxidized directly and/or indirectly by the electrogenerated oxidants, such as hydroxyl radicals, persulfate ions and sulfate radicals. Electrolysis experiments demonstrated that ATL degradation and mineralization follow a mixed (first and zero) order kinetics depending on the applied current density. At high applied current densities, the amount of OH radicals is very high and the overall reaction is limited by the transport of ATL (pseudo first-order kinetics) whereas for low applied current densities, the rate of OH radicals generation at the anode is slower than the rate of arrival of ATL molecules (pseudo-zero order kinetics). Estimated values of kzero and kfirst based on the assumption of pseudo-zero or pseudo-first order kinetics were carried oud as a function of the supporting electrolyte concentration, indicating that both parameters increased with its concentration due the higher production of sulfate reactive species that play an important role in degradation. Finally, MCE increased with the decrease of current density, due to the lower amount of OH present in solution, since this species could be rapidly wasted in parasitic reactions; and the increase of sulfate concentration due to the more efficient production of persulfate.


Assuntos
Atenolol/uso terapêutico , Eletrólise/métodos , Nióbio/química , Atenolol/farmacologia , Eletrodos
4.
Pediatr Dermatol ; 36(4): 556-557, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30983047

RESUMO

Infantile hemangiomas are the most common tumors of infancy and are often managed with oral beta-blockers to address or prevent associated complications. However, treatment with propranolol can occasionally be associated with sleep disturbances, which in some cases are severe enough to warrant discontinuation or replacement with another agent. We herein report four cases in which treatment with propranolol resulted in significant sleep disturbances prompting substitution with atenolol, which in some cases resolved these issues.


Assuntos
Atenolol/uso terapêutico , Hemangioma Capilar/tratamento farmacológico , Propranolol/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Transtornos do Sono-Vigília/induzido quimicamente , Administração Oral , Substituição de Medicamentos , Feminino , Hemangioma Capilar/diagnóstico , Humanos , Lactente , Segurança do Paciente , Prognóstico , Propranolol/uso terapêutico , Medição de Risco , Amostragem , Neoplasias Cutâneas/diagnóstico , Transtornos do Sono-Vigília/fisiopatologia , Resultado do Tratamento
6.
Australas J Dermatol ; 60(3): 181-185, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30515761

RESUMO

Recently, several studies have reported their experience in using oral atenolol in patients with infantile haemangioma (IH), especially as an alternative to propranolol, but the efficacy and safety of oral atenolol has not been evaluated. We searched PubMed (Medline), Central, Embase, Web of Science and EBSCOhost (until May 2018) for the eligible studies reporting more than 10 IH patients who were treated with oral atenolol with detailed original data, including outcomes, regimens and adverse events (AEs). The data was standardised and analysed by using R software with meta-package. A total of 9 of 141 identified articles, including 341 infantile haemangioma patients treated with oral atenolol therapy, were included. The pooled response rate of atenolol was 0.90 (95% CI: 0.85-0.93), and the rebound rate was 0.11 (95% CI: 0.08-0.16). Among the 341 patients, 44 patients were switched to atenolol therapy from propranolol due to adverse events. The response rate of subsequent atenolol treatment was 90.9% (40/44). Regarding AEs, 141 patients reported 177 episodes of AEs, and the pooled rate was 0.26 (95% CI: 0.12-0.47). Gastrointestinal symptoms (e.g. constipation, diarrhoea and vomiting) were the most frequent AEs (22.6%). Widely known propranolol-related AEs, including hypoglycaemia, bronchospasm, bradycardia and hypotension, were not recorded. Overall, atenolol appears to be an effective and safe therapy for the treatment of IH and may be a promising alternative to propranolol.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Atenolol/uso terapêutico , Hemangioma/tratamento farmacológico , Administração Oral , Antagonistas Adrenérgicos beta/efeitos adversos , Humanos , Lactente , Propranolol/efeitos adversos
7.
J Pediatr ; 204: 250-255.e1, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30270167

RESUMO

OBJECTIVE: To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial. STUDY DESIGN: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy population norms. The impact of treatment arm (atenolol vs losartan), severity of clinical features, and number of patient-reported symptoms on HRQOL was assessed by general linear models. RESULTS: Mean PedsQL scores in children (5-18 years) with Marfan syndrome were lower than healthy population norms for physical (P ≤ .003) and psychosocial (P < .001) domains; mean psychosocial scores for adults (19-25 years) were greater than healthy norms (P < .001). HRQOL across multiple domains correlated inversely with frequency of patient-reported symptoms (r = 0.30-0.38, P < .0001). Those <18 years of age with neurodevelopmental disorders (mainly learning disability, attention-deficit/hyperactivity disorder) had lower mean PedsQL scores (5.5-7.4 lower, P < .04). A multivariable model found age, sex, patient-reported symptoms, and neurodevelopmental disorder to be independent predictors of HRQOL. There were no differences in HRQOL scores by treatment arm, aortic root z score, number of skeletal features, or presence of ectopia lentis. CONCLUSIONS: Children and adolescents with Marfan syndrome were at high risk for impaired HRQOL. Patient-reported symptoms and neurodevelopmental disorder, but not treatment arm or severity of Marfan syndrome-related physical findings, were associated with lower HRQOL.


Assuntos
Anti-Hipertensivos/uso terapêutico , Atenolol/uso terapêutico , Losartan/uso terapêutico , Síndrome de Marfan/psicologia , Qualidade de Vida , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Adulto Jovem
8.
Drug Res (Stuttg) ; 69(2): 83-92, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29996172

RESUMO

There is a growing global interest in hypertension due to its associated complications including renal dysfunction in patients. The thyroid system reportedly regulates renal function in both animal and human. The present study investigated the therapeutic efficacy of taurine on renal and thyroid dysfunctions in hypertensive rats. Hypertension was induced by oral administration of nitric oxide synthase inhibitor, N-nitro L-arginine-methyl-ester (L-NAME), at 40 mg/kg body weight to the male Wistar rats for 14 consecutive days. The hypertensive rats were subsequently treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for another 14 consecutive days. Hypertensive rats showed renal damage evidenced by elevated plasma creatinine and urea levels when compared with normotensive control rats. Furthermore, L-NAME-induced hypertensive rats showed decreased circulatory concentrations of thyroid stimulating hormone, thyroxine, triiodothyronine and the ratio of triiodothyronine to thyroxine. The marked decrease in the renal antioxidant enzyme activities and nitric oxide level was accompanied by significant increase in myeloperoxidase activity and biomarkers of oxidative stress in hypertensive rats. Histological examination of kidneys from hypertensive rats revealed congestion of blood vessels, hemorrhagic lesion and disorganized glomerular structure. However, treatment with taurine or atenolol significantly reversed the suppression of thyroid function, ameliorated renal oxidative stress and histopathological lesions in L-NAME-induced hypertensive rats. Taurine may be a useful chemotherapeutic supplement in enhancing renal and thyroid functions in hypertensive patients.


Assuntos
Hipertensão/complicações , Insuficiência Renal/prevenção & controle , Taurina/administração & dosagem , Glândula Tireoide/fisiopatologia , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Atenolol/farmacologia , Atenolol/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Humanos , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/patologia , Masculino , NG-Nitroarginina Metil Éster/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/patologia , Glândula Tireoide/efeitos dos fármacos
9.
J Clin Hypertens (Greenwich) ; 20(11): 1603-1609, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30267456

RESUMO

Beta-blockers are one of the most commonly prescribed classes of antihypertensive medications during pregnancy. Previous studies reported an association between beta-blocker exposure and intrauterine growth restriction. Whether some beta-blocker subtypes may be associated with higher risk is not known. This is a retrospective cohort study of pregnant women exposed to beta-blockers in the Kaiser Permanente Southern California Region between 2003 and 2014. Logistic regression models were used to evaluate association between exposure to different beta-blocker agents and risk of low fetal birth weights. In a cohort of 379 238 singleton pregnancies, 4847 (1.3%) were exposed to beta-blockers. The four most commonly prescribed beta-blockers were labetalol (n = 3357), atenolol (n = 638), propranolol (n = 489), and metoprolol (n = 324). Mean birth weight and % low birth weight (<2500 g) were 2926 ± 841 g and 24.4% for labetalol, 3058 ± 748 g and 18.0% for atenolol, 3163 ± 702 g and 13.3% for metoprolol, 3286 ± 651 g and 7.6% for propranolol, and 3353 ± 554 g and 5.2% for non-exposed controls. Exposure to atenolol and labetalol were associated with increased risks of infant born small for gestational age (SGA) (atenolol: adjusted OR 2.4, 95% CI: 1.7-3.3; labetalol: adjusted OR 2.9, 95% CI: 2.6-3.2). Risk of SGA associated with metoprolol or propranolol exposure was not significantly different from the non-exposed group (metoprolol: adjusted OR 1.5, 95% CI: 0.9-2.3; propranolol: adjusted OR 1.3, 95% CI: 0.9-1.9). Association between beta-blocker exposure and SGA does not appear to be a class effect. Variations in pharmacodynamics and confounding by indication may explain these findings.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Hipertensivos/farmacologia , Peso ao Nascer/efeitos dos fármacos , Retardo do Crescimento Fetal/induzido quimicamente , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Atenolol/efeitos adversos , Atenolol/farmacologia , Atenolol/uso terapêutico , California/epidemiologia , Feminino , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/etnologia , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Labetalol/efeitos adversos , Labetalol/farmacologia , Labetalol/uso terapêutico , Masculino , Metoprolol/efeitos adversos , Metoprolol/farmacologia , Metoprolol/uso terapêutico , Gravidez , Prevalência , Propranolol/efeitos adversos , Propranolol/farmacologia , Propranolol/uso terapêutico , Estudos Retrospectivos
10.
J Am Coll Cardiol ; 72(14): 1613-1618, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30261963

RESUMO

BACKGROUND: Beta-blockers are the standard treatment in Marfan syndrome (MFS). Recent clinical trials with limited follow-up yielded conflicting results on losartan's effectiveness in MFS. OBJECTIVES: The present study aimed to evaluate the benefit of losartan compared with atenolol for the prevention of aortic dilation and complications in Marfan patients over a longer observation period (>5 years). METHODS: A total of 128 patients included in the previous LOAT (LOsartan vs ATenolol) clinical trial (64 in the atenolol and 64 in the losartan group) were followed up for an open-label extension of the study, with the initial treatment maintained. RESULTS: Mean clinical follow-up was 6.7 ± 1.5 years. A total of 9 events (14.1%) occurred in the losartan group and 12 (18.8%) in the atenolol group. Survival analysis showed no differences in the combined endpoint of need for aortic surgery, aortic dissection, or death (p = 0.462). Aortic root diameter increased with no differences between groups: 0.4 mm/year (95% confidence interval: 0.2 to 0.5) in the losartan and 0.4 mm/year (95% confidence interval: 0.3 to 0.6) in the atenolol group. In the subgroup analyses, no significant differences were observed considering age, baseline aortic root diameter, or type of dominant negative versus haploinsufficient FBN1 mutation. CONCLUSIONS: Long-term outcome of Marfan syndrome patients randomly assigned to losartan or atenolol showed no differences in aortic dilation rate or presence of clinical events between treatment groups. Therefore, losartan might be a useful, low-risk alternative to beta-blockers in the long-term management of these patients.


Assuntos
Aorta/diagnóstico por imagem , Atenolol/uso terapêutico , Dilatação Patológica/etiologia , Dilatação Patológica/prevenção & controle , Losartan/uso terapêutico , Síndrome de Marfan/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Adulto , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/mortalidade , Aneurisma Dissecante/prevenção & controle , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Aorta/cirurgia , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/prevenção & controle , Dilatação Patológica/diagnóstico por imagem , Progressão da Doença , Feminino , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Síndrome de Marfan/complicações , Síndrome de Marfan/mortalidade , Adulto Jovem
11.
Am J Cardiol ; 122(8): 1429-1436, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30115424

RESUMO

Patients with the Marfan syndrome (MFS) are at risk for sudden death. The contribution of arrhythmias is unclear. This study examines the prevalence of arrhythmias in children with the MFS and their relation to clinical and/or echocardiographic factors. Data from the Pediatric Heart Network randomized trial of atenolol versus losartan in MFS were analyzed (6 months to 25 years old, aortic root diameter z-score > 3.0, no previous aortic surgery and/or dissection). Baseline 24-hour ambulatory electrocardiographic monitoring was performed. Significant ventricular ectopy (VE) and supraventricular ectopy (SVE) were defined as ≥10 VE or SVE/hour, or the presence of high-grade ectopy. Three-year composite clinical outcome of death, aortic dissection, or aortic root replacement was analyzed. There were 274 analyzable monitors on unique patients from 11 centers. Twenty subjects (7%) had significant VE, 13 (5%) significant SVE; of these, 2 (1%) had both. None had sustained ventricular or supraventricular tachycardia. VE was independently associated with increasing number of major Ghent criteria (odds ratio [OR] = 2.13/each additional criterion, p = 0.03) and greater left ventricular end-diastolic dimension z-score (OR = 1.47/each 1 unit increase in z-score, p = 0.01). SVE was independently associated with greater aortic sinotubular junction diameter z-score (OR = 1.56/each 1 unit increase in z-score, p = 0.03). The composite clinical outcome (14 events) was not related to VE or SVE (p ≥ 0.3), but was independently related to heart rate variability (higher triangular index). In conclusion, in this cohort, VE and SVE were rare. VE was related to larger BSA-adjusted left ventricular size. Routine ambulatory electrocardiographic monitoring may be useful for risk stratification in select MFS patients.


Assuntos
Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Síndrome de Marfan/complicações , Síndrome de Marfan/fisiopatologia , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/tratamento farmacológico , Atenolol/uso terapêutico , Criança , Pré-Escolar , Ecocardiografia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Lactente , Losartan/uso terapêutico , Masculino , Estudos Retrospectivos
12.
Lancet ; 392(10153): 1127-1137, 2018 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158072

RESUMO

BACKGROUND: In patients with hypertension, the long-term cardiovascular and all-cause mortality effects of different blood pressure-lowering regimens and lipid-lowering treatment are not well documented, particularly in clinical trial settings. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy Study reports mortality outcomes after 16 years of follow-up of the UK participants in the original ASCOT trial. METHODS: ASCOT was a multicentre randomised trial with a 2 × 2 factorial design. UK-based patients with hypertension were followed up for all-cause and cardiovascular mortality for a median of 15·7 years (IQR 9·7-16·4 years). At baseline, all patients enrolled into the blood pressure-lowering arm (BPLA) of ASCOT were randomly assigned to receive either amlodipine-based or atenolol-based blood pressure-lowering treatment. Of these patients, those who had total cholesterol of 6·5 mmol/L or lower and no previous lipid-lowering treatment underwent further randomisation to receive either atorvastatin or placebo as part of the lipid-lowering arm (LLA) of ASCOT. The remaining patients formed the non-LLA group. A team of two physicians independently adjudicated all causes of death. FINDINGS: Of 8580 UK-based patients in ASCOT, 3282 (38·3%) died, including 1640 (38·4%) of 4275 assigned to atenolol-based treatment and 1642 (38·1%) of 4305 assigned to amlodipine-based treatment. 1768 of the 4605 patients in the LLA died, including 903 (39·5%) of 2288 assigned placebo and 865 (37·3%) of 2317 assigned atorvastatin. Of all deaths, 1210 (36·9%) were from cardiovascular-related causes. Among patients in the BPLA, there was no overall difference in all-cause mortality between treatments (adjusted hazard ratio [HR] 0·90, 95% CI 0·81-1·01, p=0·0776]), although significantly fewer deaths from stroke (adjusted HR 0·71, 0·53-0·97, p=0·0305) occurred in the amlodipine-based treatment group than in the atenolol-based treatment group. There was no interaction between treatment allocation in the BPLA and in the LLA. However, in the 3975 patients in the non-LLA group, there were fewer cardiovascular deaths (adjusted HR 0·79, 0·67-0·93, p=0·0046) among those assigned to amlodipine-based treatment compared with atenolol-based treatment (p=0·022 for the test for interaction between the two blood pressure treatments and allocation to LLA or not). In the LLA, significantly fewer cardiovascular deaths (HR 0·85, 0·72-0·99, p=0·0395) occurred among patients assigned to statin than among those assigned placebo. INTERPRETATION: Our findings show the long-term beneficial effects on mortality of antihypertensive treatment with a calcium channel blocker-based treatment regimen and lipid-lowering with a statin: patients on amlodipine-based treatment had fewer stroke deaths and patients on atorvastatin had fewer cardiovascular deaths more than 10 years after trial closure. Overall, the ASCOT Legacy study supports the notion that interventions for blood pressure and cholesterol are associated with long-term benefits on cardiovascular outcomes. FUNDING: Pfizer.


Assuntos
Anticolesterolemiantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/mortalidade , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Adulto , Idoso , Anlodipino/uso terapêutico , Atenolol/uso terapêutico , Atorvastatina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Reino Unido
13.
J Hum Lact ; 34(3): 592-599, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29870669

RESUMO

BACKGROUND: Atenolol lactation information is limited, and controversy exists over the safety of its use during breastfeeding. In this study, important parameters including milk-to-plasma ratio, ratio of infant plasma to maternal plasma, infant daily dosage, and relative infant dose were investigated. The findings from this study add information to existing data about atenolol transfer in human milk. This may help guide health professionals in decision making regarding the safety of beta blockers used by mothers during breastfeeding. Research aim: The aims of the study were to quantify concentrations of atenolol in human plasma and milk, to evaluate atenolol pharmacokinetics in lactating women, and to investigate subsequent infant exposure to atenolol via mother's milk. METHODS: In this prospective, longitudinal observational study, participants were lactating mothers ( N = 3), 1 to 4 months postpartum, who had been taking atenolol for therapeutic reasons, and one 4-month-old breastfed infant. Eight milk samples were collected over 24 hr at different time points, together with a single blood sample from each lactating mother and the infant, and quantified using a new sensitive liquid chromatography mass spectrometry method developed for this study. RESULTS: Peak milk concentrations of atenolol were observed in the women at 4 hr (Tmax) after oral administration. The dose-normalized maximum concentrations (Cmax) of all patients were similar. The mean milk-to-plasma ratio of the patients who were taking 25 to 100 mg of atenolol was 8.57%. In the mother-infant pair study, the ratio (%) of infant plasma drug concentration to maternal plasma drug concentration observed (18.87%) was similar to the relative infant dose estimated (18.20%). The relative infant dose values (13.96%-18.20%) for all patients were within 10% to 25% of maternal dosage. CONCLUSION: Atenolol use during breastfeeding should be undertaken with some precaution. If clinically indicated, an alternate beta blocker may be preferred.


Assuntos
Atenolol/análise , Lactação/efeitos dos fármacos , Leite Humano/química , Adulto , Atenolol/sangue , Atenolol/uso terapêutico , Aleitamento Materno/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Lactação/sangue , Estudos Longitudinais , Leite Humano/metabolismo , Período Pós-Parto/sangue , Período Pós-Parto/metabolismo , Estudos Prospectivos
14.
Emerg Med J ; 35(9): 559-563, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29921621

RESUMO

OBJECTIVES: Beta blockers (ß-blockers) remain a standard therapy in the early treatment of acute coronary syndromes. However, ß-blocker therapy in patients with cocaine-associated chest pain (CACP) continues to be an area of debate due to the potential risk of unopposed α-adrenergic stimulation and coronary vasospasm. Therefore, we performed a systematic review and meta-analysis of available studies to compare outcomes of ß-blocker versus no ß-blocker use among patients with CACP. METHODS: We searched the MEDLINE and EMBASE databases through September 2016 using the keywords 'beta blocker', 'cocaine' and commonly used ß-blockers ('atenolol', 'bisoprolol', 'carvedilol', 'esmolol', 'metoprolol' and 'propranolol') to identify studies evaluating ß-blocker use among patients with CACP. We specifically focused on studies comparing outcomes between ß-blocker versus no ß-blocker usage in patients with CACP. Studies without a comparison between ß-blocker and no ß-blocker use were excluded. Outcomes of interest included non-fatal myocardial infarction (MI) and all-cause mortality. Quantitative data synthesis was performed using a random-effects model and heterogeneity was assessed using Q and I2statistics. RESULTS: A total of five studies evaluating 1794 subjects were included. Overall, there was no significant difference on MI in patients with CACP on ß-blocker versus no ß-blocker (OR 1.36, 95% CI 0.68 to 2.75; p=0.39). Similarly, there was no significant difference in all-cause mortality in patients on ß-blocker versus no ß-blocker (OR 0.68, 95% CI 0.26 to 1.79; p=0.43). CONCLUSIONS: In patients presenting with acute chest pain and underlying cocaine, ß-blocker use does not appear to be associated with an increased risk of MI or all-cause mortality.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Cocaína/efeitos adversos , Síndrome Coronariana Aguda/etiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Atenolol/farmacologia , Atenolol/uso terapêutico , Bisoprolol/farmacologia , Bisoprolol/uso terapêutico , Carvedilol/farmacologia , Carvedilol/uso terapêutico , Humanos , Metoprolol/farmacologia , Metoprolol/uso terapêutico , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Propranolol/farmacologia , Propranolol/uso terapêutico
15.
Pediatr Cardiol ; 39(7): 1453-1461, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29948025

RESUMO

Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36 months read in the core laboratory of 608 trial subjects, aged 6 months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz) > 3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year > 90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R2 = 0.01) or by change in AoR diameter (AoRd)/year > 90th percentile with higher sinotubular junction z-score and non-white race (R2 = 0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R2 = 0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34 cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364.


Assuntos
Aorta/patologia , Doenças da Aorta/etiologia , Síndrome de Marfan/complicações , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos , Adolescente , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Anti-Hipertensivos/uso terapêutico , Aorta/cirurgia , Doenças da Aorta/epidemiologia , Doenças da Aorta/cirurgia , Atenolol/uso terapêutico , Criança , Pré-Escolar , Dilatação , Ecocardiografia/métodos , Feminino , Humanos , Lactente , Losartan/uso terapêutico , Masculino , Síndrome de Marfan/tratamento farmacológico , Síndrome de Marfan/cirurgia , Curva ROC , Encaminhamento e Consulta/estatística & dados numéricos , Medição de Risco/métodos , Fatores de Risco , Adulto Jovem
16.
Chemosphere ; 207: 174-182, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29793029

RESUMO

Atenolol (ATL) has been widely detected in wastewater and aquatic environment. Although satisfactory removal of ATL from wastewater could be achieved, the mineralization ratio is usually low, which may result in the accumulation of its transformation products in the effluent and cause additional ecological risk to the environment. The aim of this study is to explore the effectiveness of heat activated persulfate (PS) in the removal of ATL from wastewater. Influencing factors including temperature, PS dosage, solution pH, existence of NO3-, Cl-, HCO3- and Suwannee river fulvic acid (SRFA) were examined. Complete removal of ATL was achieved within 40 min at pH 7.0 and 70 °C by using 0.5 mM PS. Inhibitive effects of HCO3- and FA had been observed on ATL oxidation, which was increased with the increase of their concentration. Sulfate radical (SO4-) was determined as the main reactive species by quenching experiment. Eight intermediates produced in ATL degradation were identified, and four degradation pathways were proposed based on the analysis of mass spectrum and frontier electron densities. The distribution of major intermediates was influenced by reaction temperature. Hydroxylation intermediates and deamidation intermediate were the most prominent at 50 °C and 60 °C, respectively. All intermediates were completely degraded in 40 min except P134 at 70 °C. Effective removal of TOC (74.12%) was achieved with 0.5 mM PS, pH 7.0 and 70 °C after 240 min. The results proved that heat activation of PS is a promising method to remove organic pollutants in wastewater.


Assuntos
Atenolol/uso terapêutico , Sulfetos/química , Poluentes Químicos da Água/química , Atenolol/farmacologia , Temperatura Alta , Cinética , Oxirredução , Poluentes Químicos da Água/análise
17.
A A Pract ; 11(3): 63-67, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29634558

RESUMO

We describe a case of refractory pulseless polymorphic ventricular tachycardia successfully treated with a bolus of propranolol intravenously, followed by an esmolol infusion and extracorporeal life support for 4 days in a 12-year-old boy later diagnosed with catecholaminergic polymorphic ventricular tachycardia. He had an excellent neurological outcome. Genetic testing for mutations associated with cardiac arrhythmias yielded a mutation of the syntrophin α-1 gene. The pathogenicity of this specific variant is uncertain. A mutation of this gene at a different locus is implicated in rare cases of long-QT syndrome. The patient subsequently underwent left cardiac sympathetic denervation followed by implantable cardiac defibrillator insertion. He remains symptom and arrhythmia free on atenolol.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Proteínas de Ligação ao Cálcio , Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca/terapia , Proteínas de Membrana , Proteínas Musculares , Propranolol/uso terapêutico , Taquicardia Ventricular/terapia , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Antiarrítmicos/uso terapêutico , Atenolol/uso terapêutico , Proteínas de Ligação ao Cálcio/genética , Criança , Terapia Combinada , Desfibriladores Implantáveis , Eletrocardiografia , Parada Cardíaca/genética , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas Musculares/genética , Mutação , Propanolaminas/administração & dosagem , Propanolaminas/uso terapêutico , Propranolol/administração & dosagem , Simpatectomia , Taquicardia Ventricular/genética
18.
Circ Genom Precis Med ; 11(4): e001854, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29650764

RESUMO

BACKGROUND: Plasma renin is an important regulator of blood pressure (BP). Plasma renin activity (PRA) has been shown to correlate with variability in BP response to antihypertensive agents. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with baseline PRA using data from the PEAR study (Pharmacogenomic Evaluation of Antihypertensive Responses). METHODS: Multiple linear regression analysis was performed in 461 whites and 297 blacks using an additive model, adjusting for age, sex, and ancestry-specific principal components. Top SNPs were prioritized by testing the expected direction of association for BP response to atenolol and hydrochlorothiazide. Top regions from the BP response prioritization were tested for functional evidence through differences in gene expression by genotype using RNA sequencing data. Regions with functional evidence were assessed for replication with baseline PRA in an independent study (PEAR-2). RESULTS: Our top SNP rs3784921 was in the SNN-TXNDC11 gene region. The G allele of rs3784921 was associated with higher baseline PRA (ß=0.47; P=2.09×10-6) and smaller systolic BP reduction in response to hydrochlorothiazide (ß=2.97; 1-sided P=0.006). In addition, TXNDC11 expression differed by rs3784921 genotype (P=0.007), and rs1802409, a proxy SNP for rs3784921 (r2=0.98-1.00), replicated in PEAR-2 (ß=0.15; 1-sided P=0.038). Additional SNPs associated with baseline PRA that passed BP response prioritization were in/near the genes CHD9, XIRP2, and GHR. CONCLUSIONS: We identified multiple regions associated with baseline PRA that were prioritized through BP response signals to 2 mechanistically different antihypertensive drugs. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00246519.


Assuntos
Anti-Hipertensivos/uso terapêutico , Atenolol/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Renina/sangue , Adolescente , Adulto , Idoso , Pressão Sanguínea/genética , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/sangue , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Renina/genética , Resultado do Tratamento , Estados Unidos , Adulto Jovem
19.
J Am Heart Assoc ; 7(5)2018 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-29478026

RESUMO

BACKGROUND: For many indications, the negative chronotropic effect of ß-blockers is important to their efficacy, yet the heart rate (HR) response to ß-blockers varies. Herein, we sought to use a genome-wide association approach to identify novel single nucleotide polymorphisms (SNPs) associated with HR response to ß-blockers. METHODS AND RESULTS: We first performed 4 genome-wide association analyses for HR response to atenolol (a ß1-adrenergic receptor blocker) as: (1) monotherapy or (2) add-on therapy, in 426 whites and 273 blacks separately from the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) study. A meta-analysis was then performed between the genome-wide association analysis performed in PEAR atenolol monotherapy and add-on therapy, in each race separately, using the inverse variance method assuming fixed effects. From this analysis, SNPs associated with HR response to atenolol at a P<1E-05 were tested for replication in whites (n=200) and blacks (n=168) treated with metoprolol (a ß1-adrenergic receptor blocker). From the genome-wide association meta-analyses, SNP rs17117817 near olfactory receptor family10 subfamily-p-member1 (OR10P1), and SNP rs2364349 in sorting nexin-9 (SNX9) replicated in blacks. The combined studies meta-analysis P values for the rs17117817 and rs2364349 reached genome-wide significance (rs17117817G-allele; Meta-ß=5.53 beats per minute, Meta-P=2E-09 and rs2364349 A-allele; Meta-ß=3.5 beats per minute, Meta-P=1E-08). Additionally, SNPs in the OR10P1 and SNX9 gene regions were also associated with HR response in whites. CONCLUSIONS: This study highlights OR10P1 and SNX9 as novel genes associated with changes in HR in response to ß-blockers. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00246519.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Atenolol/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Receptores Odorantes/genética , Nexinas de Classificação/genética , Adulto , Afro-Americanos/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Fenótipo , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Am J Physiol Endocrinol Metab ; 315(2): E240-E249, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29486140

RESUMO

We previously demonstrated that insulin-induced severe hypoglycemia-associated sudden death is largely mediated by fatal cardiac arrhythmias. In the current study, a pharmacological approach was taken to explore the potential contribution of hypoglycemic seizures and the sympathoadrenergic system in mediating severe hypoglycemia-associated sudden death. Adult Sprague-Dawley rats were randomized into one of four treatment groups: 1) saline (SAL), 2) anti-arrhythmic (ß1 blocker atenolol), 3) antiseizure (levetiracetam), and 4) combination antiarrhythmic and antiseizure (ß1 Blocker+Levetiracetam). All rats underwent hyperinsulinemic severe hypoglycemic clamps for 3.5 h. When administered individually during severe hypoglycemia, ß1 blocker reduced 2nd and 3rd degree heart block by 7.7- and 1.6-fold, respectively, and levetiracetam reduced seizures 2.7-fold, but mortality in these groups did not decrease. However, it was combined treatment with both ß1 blocker and levetiracetam that remarkably reduced seizures and completely prevented respiratory arrest, while also eliminating 2nd and 3rd degree heart block, leading to 100% survival. These novel findings demonstrate that, in mediating sudden death, hypoglycemia elicits two distinct pathways (seizure-associated respiratory arrest and arrhythmia-associated cardiac arrest), and therefore, prevention of both seizures and cardiac arrhythmias is necessary to prevent severe hypoglycemia-induced mortality.


Assuntos
Arritmias Cardíacas/etiologia , Morte Súbita Cardíaca/etiologia , Hipoglicemia/complicações , Convulsões/etiologia , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Animais , Antiarrítmicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Arritmias Cardíacas/fisiopatologia , Atenolol/uso terapêutico , Quimioterapia Combinada , Eletrocardiografia , Levetiracetam/uso terapêutico , Masculino , Ratos , Ratos Sprague-Dawley , Convulsões/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA