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1.
Isr Med Assoc J ; 21(11): 724-727, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31713359

RESUMO

BACKGROUND: The need for postnatal monitoring of infants exposed to intrauterine beta blockers (BBs) has not been clearly defined. OBJECTIVES: To evaluate infants exposed to intrauterine BBs in order to estimate the need for postnatal monitoring. METHODS: This retrospective case-control study comprised 153 term infants born to mothers who had been treated with BBs during pregnancy. Treatment indications included hypertension 76 mothers (49.7%), cardiac arrhythmias 48 (31.4%), rheumatic heart disease 14 (9.1%), cardiomyopathy 11 (7.2%) and migraine 4 (2.6%). The controls were infants of mothers with hypertension not exposed to BBs who were born at the same gestational age and born closest (before or after) to the matched infant in the study group. RESULTS: Compared to the control group, the infants in the study group had a higher prevalence of early asymptomatic hypoglycemia (study 30.7% vs. control 18.3%, P = 0.016), short symptomatic bradycardia events, other cardiac manifestations (P = 0.016), and longer hospitalization (P < 0.001). No life-threatening medical conditions were documented. The birth weight was significantly lower for the high-dose subgroup compared to the low-dose subgroup (P = 0.03), and the high-dose subgroup had a higher incidence of small-for-gestational-age (P = 0.02). CONCLUSIONS: No alarming or life-threatening medical conditions were observed among term infants born to BB treated mothers. These infants can be safely observed for 48 hours after birth close to their mothers in the maternity ward. Glucose follow-up is needed, especially in the first hours of life.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Bradicardia/induzido quimicamente , Hipoglicemia/induzido quimicamente , Doenças do Recém-Nascido/induzido quimicamente , Troca Materno-Fetal , Resultado da Gravidez , Adulto , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Gravidez , Estudos Retrospectivos , Fatores de Risco
2.
Rev Med Suisse ; 15(661): 1566-1571, 2019 Sep 04.
Artigo em Francês | MEDLINE | ID: mdl-31496190

RESUMO

Beta-blockers are very commonly drugs used in clinical practice, but whose mechanisms and clinical impacts are not always well understood, especially in certain specific clinical situations. This article proposes a review of some pharmacology notions over the different generations of ß-blockers, as well as a review of indications and side effects in particular clinical situations, such as COPD, portal hypertension with esophageal varices and erectile dysfunction. Finally, an overview of response variability of these treatments is discussed from a genetic point of view.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/classificação , Disfunção Erétil , Varizes Esofágicas e Gástricas , Humanos , Hipertensão Portal , Masculino , Farmacogenética , Doença Pulmonar Obstrutiva Crônica
3.
Cochrane Database Syst Rev ; 9: CD013435, 2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31544227

RESUMO

BACKGROUND: Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update and assesses the evidence in cardiac surgery only. OBJECTIVES: To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA: We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing cardiac surgery. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 63 studies with 7768 participants; six studies were quasi-randomized and the remaining were RCTs. All participants were undergoing cardiac surgery, and in most studies, at least some of the participants were previously taking beta-blockers. Types of beta-blockers were: propranolol, metoprolol, sotalol, esmolol, landiolol, acebutolol, timolol, carvedilol, nadolol, and atenolol. In twelve studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in nine studies this was before surgery, in 20 studies during surgery, and in the remaining studies beta-blockers were started postoperatively. Overall, we found that most studies did not report sufficient details for us to adequately assess risk of bias. In particular, few studies reported methods used to randomize participants to groups. In some studies, participants in the control group were given beta-blockers as rescue therapy during the study period, and all studies in which the control was standard care were at high risk of performance bias because of the open-label study design. No studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. We judged 68% studies to be at high risk of bias in at least one domain.Study authors reported few deaths (7 per 1000 in both the intervention and control groups), and we found low-certainty evidence that beta-blockers may make little or no difference to all-cause mortality at 30 days (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.47 to 1.90; 29 studies, 4099 participants). For myocardial infarctions, we found no evidence of a difference in events (RR 1.05, 95% CI 0.72 to 1.52; 25 studies, 3946 participants; low-certainty evidence). Few study authors reported cerebrovascular events, and the evidence was uncertain (RR 1.37, 95% CI 0.51 to 3.67; 5 studies, 1471 participants; very low-certainty evidence). Based on a control risk of 54 per 1000, we found low-certainty evidence that beta-blockers may reduce episodes of ventricular arrhythmias by 32 episodes per 1000 (RR 0.40, 95% CI 0.25 to 0.63; 12 studies, 2296 participants). For atrial fibrillation or flutter, there may be 163 fewer incidences with beta-blockers, based on a control risk of 327 incidences per 1000 (RR 0.50, 95% CI 0.42 to 0.59; 40 studies, 5650 participants; low-certainty evidence). However, the evidence for bradycardia and hypotension was less certain. We found that beta-blockers may make little or no difference to bradycardia (RR 1.63, 95% CI 0.92 to 2.91; 12 studies, 1640 participants; low-certainty evidence), or hypotension (RR 1.84, 95% CI 0.89 to 3.80; 10 studies, 1538 participants; low-certainty evidence).We used GRADE to downgrade the certainty of evidence. Owing to studies at high risk of bias in at least one domain, we downgraded each outcome for study limitations. Based on effect size calculations in the previous review, we found an insufficient number of participants in all outcomes (except atrial fibrillation) and, for some outcomes, we noted a wide confidence interval; therefore, we also downgraded outcomes owing to imprecision. The evidence for atrial fibrillation and length of hospital stay had a moderate level of statistical heterogeneity which we could not explain, and we, therefore, downgraded these outcomes for inconsistency. AUTHORS' CONCLUSIONS: We found no evidence of a difference in early all-cause mortality, myocardial infarction, cerebrovascular events, hypotension and bradycardia. However, there may be a reduction in atrial fibrillation and ventricular arrhythmias when beta-blockers are used. A larger sample size is likely to increase the certainty of this evidence. Four studies awaiting classification may alter the conclusions of this review.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Procedimentos Cirúrgicos Cardíacos , Assistência Perioperatória/métodos , Antagonistas Adrenérgicos beta/efeitos adversos , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/prevenção & controle , Bradicardia/induzido quimicamente , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/prevenção & controle , Humanos , Hipotensão/induzido quimicamente , Hipotensão/mortalidade , Hipotensão/prevenção & controle , Morbidade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/prevenção & controle , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Curr Opin Ophthalmol ; 30(5): 319-325, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31394556

RESUMO

PURPOSE OF REVIEW: To evaluate the medical literature on the use of ß-blockers, through different routes, for the treatment of periorbital infantile hemangiomas and to summarize the recommendations available on dosage and monitoring. RECENT FINDINGS: ß-blockers for the treatment of infantile hemangioma are now considered to be first-line treatment. Growing literature on the role of oral propranolol confirmed its efficacy but also presented its multiple side-effects including hypotension, bradycardia, hypoglycemia, and bronchospasm. No universal guidelines exist concerning pretreatment evaluation, dosage, monitoring, and duration of treatment but different protocols have been created.In the aim of minimizing side-effects, other routes of administration and more selective ß-blockers have emerged. Many studies showed promising results for topical timolol especially in the treatment of superficial hemangiomas. Few studies evaluated intralesional propranolol. Limited data exist on the use of more selective ß-blockers promising similar results to propranolol with fewer side-effects. SUMMARY: Oral ß-blockers are now the mainstay of treatment for periorbital hemangiomas but still with no consensus on their administration and monitoring. The topical form or more selective ß-blockers may be the solution to minimize side-effects.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Hemangioma Capilar/tratamento farmacológico , Neoplasias Orbitárias/tratamento farmacológico , Propranolol/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Antagonistas Adrenérgicos beta/efeitos adversos , Feminino , Hemangioma Capilar/patologia , Humanos , Lactente , Masculino , Neoplasias Orbitárias/patologia , Propranolol/efeitos adversos , Neoplasias Cutâneas/patologia , Resultado do Tratamento
5.
Int J Clin Pharmacol Ther ; 57(10): 483-488, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31426904

RESUMO

AIM: The aim of this study was to investigate the potential association between antihypertensive therapy and the incidence of Parkinson's disease (PD) in patients followed in general practices in Germany. MATERIALS AND METHODS: This study included patients aged ≥ 40 who had received initial diagnoses of PD in 1,203 general practices in Germany between January 2013 and December 2017 (index date). After applying similar inclusion criteria, PD cases were matched to non-PD controls using propensity scores based on age, sex, and treating physician. The primary outcome of the study was the incidence of PD as a function of the use of antihypertensive drugs (diuretics, ß-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). Logistic regression models were conducted to study the association between the use of antihypertensive drugs and the incidence of PD after adjusting for codiagnoses and antihypertensive cotherapy. RESULTS: The present study included 9,127 patients with PD and 9,127 patients without PD (mean age: 75.8 years; 48.4% women). The at-least-once use of diuretics (44.8% versus 38.4%; odds ratio (OR) = 1.23 (1.15-1.32)) was associated with an increased incidence of PD. However, this effect was not maintained for a therapy duration of at least 3 years, and no association was observed between the diuretic therapy duration and PD incidence. For all other antihypertensive drug classes, we found no significant associations with PD incidence. CONCLUSION: No association was found between antihypertensive therapy duration and PD incidence. Further epidemiological studies are needed to compare the effects of subclasses of antihypertensives on PD.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Doença de Parkinson/complicações , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Feminino , Medicina Geral , Alemanha , Humanos , Hipertensão/complicações , Incidência , Masculino
6.
Medicine (Baltimore) ; 98(34): e16961, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441899

RESUMO

BACKGROUND: Owing to reports of recurrent cardiac events in some catecholaminergic polymorphic ventricular tachycardia (CPVT) patients using ß-blockers, safer alternatives are being investigated. Flecainide is an alternative adjunctive anti-arrhythmic agent known to provide incomplete protection to CPVT patients. METHODS: To investigate the efficacy and tolerability of flecainide, we searched 4 databases for retrospective cohort studies (RCs) and randomized controlled trials (RCTs) investigating the efficacy and safety of flecainide for CPVT patients. Data were extracted and analyzed (risk ratio [RR] or mean difference [MD]) using RevMan software. Seven RCs and 1 RCT (333 CPVT patients; 152 patients treated with flecainide) were identified. RESULTS: Flecainide monotherapy was superior to standard therapy in alleviating the risk of arrhythmic events (RR = 0.46, confidence interval [CI] = [0.38, 0.56], P < .00001) and exercise-induced arrhythmia scores (MD = -0.39, CI = [-0.74, -0.05], P = .03). Combination therapy of flecainide and ß-blockers was superior to ß-blocker monotherapy in reducing the risk of arrhythmic and symptomatic events (RR = 0.29, CI = [0.13, 0.69], P = .005; RR = 0.36, CI = [0.20, 0.62], P = .0003, respectively), peak heart rate (MD = -16.81, CI = [-28.21, -5.41], P = .004), and exercise-induced arrhythmia scores (MD = -1.87, CI = [-2.71, 1.04], P < .0001). Flecainide did not increase the risk of all side effects (RR = 0.76, CI = [0.42, 1.40], P = .38) compared to that with ß-blockers alone. No deaths were reported among patients treated with flecainide. CONCLUSIONS: Flecainide is an effective and safe anti-arrhythmic agent, and its use as a monotherapy might be a good alternative for CPVT patients with ß-blocker intolerance. Combination therapy was superior to ß-blocker monotherapy. More randomized clinical trials are required to explore the long-term efficacy and safety of flecainide in these patients.


Assuntos
Antiarrítmicos/administração & dosagem , Flecainida/administração & dosagem , Taquicardia Ventricular/tratamento farmacológico , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Antiarrítmicos/efeitos adversos , Feminino , Flecainida/efeitos adversos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
7.
J Dermatol ; 46(9): 770-776, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270853

RESUMO

The efficacy of lauromacrogol injection therapy and intralesional triamcinolone for infantile hemangiomas (IH) has been well documented recently, but with an increase in serious or rare adverse reactions. The aim of this study is to investigate the safety concerns regarding intralesional injection of lauromacrogol combined with triamcinolone for IH and to study its effect on infant growth and development. A total of 1039 IH patients who were subjected to intralesional injection of lauromacrogol combined with triamcinolone in the Plastic Surgery Department of Shandong Provincial Hospital between 1 January 2015 and 31 May 2018 were enrolled in this study. When the dose of lauromacrogol and triamcinolone was less than 3.5 and 2.0 mg/kg respectively, no serious side-effects were observed. The adverse event rate reported was 7.7%. Among the 405 patients not subjected to propranolol before the last injection, the study included three modes of treatment response: regression (82.7%), stabilization (13.8%) and failure (3.5%). By comparing height and weight to the reference standards and also by comparisons between the same-sex groups, our results confirmed that there was no significant effect on children's height and weight, regardless of whether the injection therapy was combined with oral propranolol at the appropriate dose and with more than 4-week intervals. Intralesional injection of lauromacrogol combined with triamcinolone in the treatment of IH was highly safe and effective.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Hemangioma/tratamento farmacológico , Polidocanol/efeitos adversos , Soluções Esclerosantes/efeitos adversos , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lactente , Injeções Intralesionais , Masculino , Polidocanol/administração & dosagem , Propranolol/administração & dosagem , Propranolol/efeitos adversos , Estudos Retrospectivos , Soluções Esclerosantes/administração & dosagem , Resultado do Tratamento , Triancinolona/administração & dosagem , Triancinolona/efeitos adversos
8.
Pan Afr Med J ; 32: 155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303926

RESUMO

Introduction: infantile hemangioma is the most common benign tumor in infancy. Currently, oral propranolol is the treatment of choice for infantile hemangioma, but there is no consensus when it comes to its recommended dosage for this condition. Hence this study was conducted to find out the appropriate dosage of oral propranolol for treatment of infantile hemangioma. Methods: A prospective study was conducted on 25 patients with infantile hemangioma, who were treated with gradually increasing dose of propranolol starting from a lower dose of 1mg/kg/day. Results: 17/22(76%) patients showed regression of the tumor at the dose of 1- 1.5 mg/kg/d. 5/22(24%) patients were unresponsive to the treatment with the lower dose and they did not respond even with the gradually escalated dose of 3-4 mg/kg/day. Conclusion: Propranolol in a lower dose of 1-1.5 mg/kg/day is safe and efficacious in the treatment of infantile hemangioma and the lesions which do not show initial response to the lower dose are unlikely to respond to the higher dose of 3-4 mg/kg/day.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Hemangioma/tratamento farmacológico , Propranolol/administração & dosagem , Administração Oral , Antagonistas Adrenérgicos beta/efeitos adversos , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Hemangioma/patologia , Humanos , Lactente , Masculino , Propranolol/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
9.
Tokai J Exp Clin Med ; 44(2): 29-30, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31250422

RESUMO

The newer generation non selective vasodilating beta adrenergic blocking agent Carvedilol, also has an alpha 1 adrenoceptor antagonistic effect and is widely used in treating various cardiovascular diseases. It is a selective alpha and non-selective beta blocker. It's side effects are vast and not limited to any particular organ system, the neuropsychiatric adverse effects include; somnolence, nervousness, sleep disorder, aggravated depression, vivid dreams, delirium, psychosis, impaired concentration, abnormal thinking, paroniria, and emotional lability. Hallucinations are rarely reported and as far as we know the only reported couple of cases were on metoprolol and propranolol, none has been reported with Carvedilol.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Carvedilol/efeitos adversos , Alucinações/induzido quimicamente , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Carvedilol/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico
10.
Drug Discov Ther ; 13(2): 108-113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080201

RESUMO

Portal hypertension and its complications are the leading causes of morbidity and mortality in patients with liver cirrhosis. Noninvasive assessment of liver stiffness had been an effective tool for assessment of fibrosis progression in chronic liver disease. It was intended to assess liver stiffness measurement (LSM), portal vein diameter (PVD), splenic bipolar diameter (SD), and the platelet count/spleen diameter (PC/SD) ratio in patients who test positive for the hepatitis C virus (HCV) and to study the impact of non-selective beta blockers (NSBB) on the grade of esophageal varices (EVs) and liver elasticity. Subjects were 80 patients with Child-Pugh grade A or B compensated cirrhosis who tested positive for HCV. All of the patients underwent a laboratory workup including AFP, HCV antibodies, HCV RNA, HBsAg, LSM according to real-time elastography, upper gastrointestinal endoscopy (UGIE) to detect and grade EVs, calculation of the PC/SD ratio, and measurement of the PVD and SD according to real-time abdominal ultrasonography. All patients were given the maximum tolerated dose of NSBB for three months, and UGIE, LSM, PC/SD, PVD, and SD were subsequently reassessed and reported. LSM and the PC/SD ratio were exceptional noninvasive tools for prediction of significant EVs (grade ≥ II, p < 0.001) with a sensitivity 82.4% and a specificity 82.6% at a cutoff point 18 kPa for LSM, and a sensitivity 94.1% and specificity 69.6% at a cutoff point 880 for the PC/SD ratio. LSM is highly correlated with PVD, the PC/SD ratio, SD, and the Child-Pugh score. NSBB significantly decreased PVD. The percent change in PVD significantly correlated with LSM, the grade of EVs, and SD. Findings indicated that LSM is a noninvasive, rapid, and reproducible tool with which to detect portal hypertension and EVs. NSBB therapy can effectively decrease PVD and may consequently improve the EV grade with no significant impact on LSM in patients with liver cirrhosis.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Varizes Esofágicas e Gástricas/diagnóstico , Hepatite C/complicações , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Propranolol/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Estudos de Casos e Controles , Progressão da Doença , Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/induzido quimicamente , Feminino , Hepatite C/patologia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Propranolol/efeitos adversos , Estudos Prospectivos , Curva ROC
11.
Br J Anaesth ; 123(2): 118-125, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31101323

RESUMO

BACKGROUND: Recent data suggest that beta blockers are associated with increased perioperative risk in hypertensive patients. We investigated whether beta blockers were associated with an increased risk in elderly patients with raised preoperative arterial blood pressure. METHODS: We conducted a propensity-score-matched cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13), including 84 633 patients aged 65 yr or over. Conditional logistic regression models, including factors that were significantly associated with the outcome, were constructed for 30-day mortality after elective noncardiac surgery. The effects of beta blockers (primary outcome), renin-angiotensin system (RAS) inhibitors, calcium-channel blockers, thiazides, loop diuretics, and statins were investigated at systolic and diastolic arterial pressure thresholds. RESULTS: Beta blockers were associated with increased odds of postoperative 30-day mortality in patients with systolic hypertension (defined as systolic BP >140 mm Hg; adjusted odds ratio [aOR]: 1.92; 95% confidence interval [CI]: 1.05-3.51). After excluding patients for whom prior data suggest benefit from perioperative beta blockade (patients with prior myocardial infarction or heart failure), rather than adjusting for them, the point estimate shifted slightly (aOR: 2.06; 95% CI: 1.09-3.89). Compared with no use, statins (aOR: 0.35; 95% CI: 0.17-0.75) and thiazides (aOR: 0.28; 95% CI: 0.10-0.78) were associated with lower mortality in patients with systolic hypertension. CONCLUSIONS: These data suggest that the safety of perioperative beta blockers may be influenced by preoperative blood pressure thresholds. A randomised controlled trial of beta-blocker withdrawal, in select populations, is required to identify a causal relationship.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Pressão Sanguínea/fisiologia , Hipertensão/tratamento farmacológico , Complicações Pós-Operatórias/mortalidade , Cuidados Pré-Operatórios/métodos , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Masculino , Fatores de Risco , Reino Unido/epidemiologia
12.
Ter Arkh ; 91(1): 101-107, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090380

RESUMO

In conditions of climate warming with an increase in heat waves associated with an increase in cardiovascular morbidity and mortality, the particular interest is the effect of cardiovascular drugs on adaptation to high temperatures. The review reflects the results of European and domestic studies on the safety of therapy during long and short heat waves. Recommendations for the correction of therapy during this period are given. Self-control of blood pressure (SCAD) is a mandatory component of the therapy of arterial hypertension during heat waves. With the development of clinically significant hypotension, a reduction in the dose of antihypertensive drugs is necessary. It is recommended to start with a dose reduction and/or withdrawal of diuretics and nitrates. Not recommended the complete abolition of antihypertensive therapy because of the risk of hypertensive crises, characteristic of abnormal heat, as well as due to the increase in blood pressure when the weather changes and the temperature drops. With increasing blood pressure during heat waves, it is recommended to give preference to calcium channel antagonists, angiotensin converting enzyme inhibitors (ACE inhibitors) and selective beta-blockers. It is necessary to inform patients about the additional protective effect of statins in order to increase adherence to therapy. Patients taking diuretics require individual daily monitoring of fluid intake and body weight. An overview of recommendations on sanogenic behavior during heat waves is given. Details are considered rules for the use of air conditioning, methods of diagnosis of dehydration and drinking mode Keywords: heat waves, cardiovascular complications, preventive measures.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Calor Extremo/efeitos adversos , Hipertensão/tratamento farmacológico , Raios Infravermelhos/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Diuréticos/efeitos adversos , Diuréticos/farmacologia , Humanos , Estações do Ano
13.
BMJ Case Rep ; 12(4)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30948417

RESUMO

Carteolol, a non-selective beta-antagonist with a potential risk of severe bronchial constriction in patients with asthma, is one of the most commonly prescribed medication for managing ocular pressure in glaucoma. We present a case of a 24-year-old woman with a history of atopy but no known asthma who presented an insidious onset of clinical manifestations compatible with drug-induced asthma after the initiation of carteolol for ocular hypertension control. The patient developed progressive chest tightness and dyspnoea for 2 months before the pulmonary function test revealed a positive bronchoprovocation response. She reported significant improvement of respiratory symptoms within 2 weeks after the discontinuation of carteolol, and a negative provocation response was later confirmed by repeat pulmonary function test. In conclusion, eye drops with non-selective beta-antagonising effect can induce asthmatic symptoms in patients without a previous diagnosis of asthma and should be administered with caution in patients with associated risk factors.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Asma/induzido quimicamente , Carteolol/efeitos adversos , Hipertensão Ocular/tratamento farmacológico , Administração Oftálmica , Antagonistas Adrenérgicos beta/farmacologia , Broncoconstrição/efeitos dos fármacos , Carteolol/farmacologia , Humanos , Hipertensão Ocular/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto Jovem
14.
Medicina (Kaunas) ; 55(4)2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31009994

RESUMO

Background and objective: Orthostatic hypotension (OH) is a decrease in systolic blood pressure (BP) of 20 mm Hg and in diastolic BP of 10 mm Hg when changing the position from lying to standing. Arterial hypertension (AH), comorbidities and polypharmacy contribute to its development. The aim was to assess the presence of OH and its predictors in asymptomatic chronic kidney disease (CKD) patients. Material and methods: 45 CKD patients with estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 (CKD+) were examined for signs of OH and its predictors. The results were compared with the control group of 22 patients with eGFR > 60 mL/min/1.73 m2 (CKD-). Asymptomatic patients without ischemic heart disease and previous stroke were qualified. Total blood count, serum creatinine, eGFR, urea, phosphates, calcium, albumins, parathyroid hormone, uric acid, C reactive protein, N-terminal pro b-type natriuretic peptide, lipid profile, and urine protein to creatinine ratio were assessed. Simultaneously, patients underwent echocardiography. To detect OH, a modified Schellong test was performed. Results: OH was diagnosed in 17 out of 45 CKD+ patients (average age 69.12 ± 13.2) and in 8 out of 22 CKD- patients (average age 60.50 ± 14.99). The CKD+ group demonstrated significant differences on average values of systolic and diastolic BP between OH+ and OH- patients, lower when standing. In the eGFR range of 30-60 mL/min/1.73 m2 correlation was revealed between OH and ß-blockers (p = 0.04), in the entire CKD+ group between ß-blockers combined with diuretics (p = 0.007) and ACE-I (p = 0.033). Logistic regression test revealed that chronic heart failure (CHF, OR = 15.31), treatment with ß-blockers (OR = 13.86) were significant factors influencing the presence of OH. Conclusions: Predictors of OH in CKD may include: CHF, treatment with ß-blockers, combined with ACE-I and diuretics.


Assuntos
Doenças Assintomáticas/epidemiologia , Hipotensão Ortostática/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Antagonistas Adrenérgicos beta/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Doença Crônica , Comorbidade , Diuréticos/efeitos adversos , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/complicações , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estatísticas não Paramétricas
15.
Clin Drug Investig ; 39(5): 463-468, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30868473

RESUMO

BACKGROUND: Most patients with Parkinson's disease exhibit intracellular accumulation of the α-synuclein protein encoded by the α-synuclein gene. It was recently shown that ß2-adrenoreceptor agonists downregulate this gene, decreasing the apparent risk of Parkinson's disease by up to 40%. In contrast, exposure to ß-blocking drugs increases production of the α-synuclein protein. OBJECTIVE: The aim of this study was to examine whether chronic exposure to ß-blockers is associated with an increased risk for Parkinson's disease. PATIENTS AND METHODS: From the electronic charts of Maccabi Health Services, we identified all patients receiving their first ß-blocker treatment between 1998 and 2004, and followed them up, for a diagnosis of Parkinson's disease, between 2005 and 2016. We calculated the morbidity hazard of Parkinson's disease diagnosis in users of ß-blockers compared with non-users, as well as users of angiotensin-converting enzyme (ACE) inhibitors for hypertension, after adjusting for sex, age, weight, smoking status, cholesterol levels and use of statins, employing the Cox proportional hazard model. We also conducted a Kaplan-Meier survival analysis. RESULTS: Overall, 145,098 patients received ß-blockers, and 1,187,151 patients did not. The adjusted hazard ratio for Parkinson's disease among ß-blocker users was 1.51 (95% confidence interval 1.28-1.77; p < 0.0001). In contrast, the Parkinson's disease morbidity hazard for patients receiving ACE inhibitors was no different than for the general population. The morbidity risk showed the effect of cumulative dose response with low threshold levels. CONCLUSIONS: Chronic use of ß-blockers confers a time- and dose-dependent increased risk for Parkinson's disease. In view of the available alternatives for ß-blockers, their chronic use should be carefully reconsidered.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/epidemiologia , Adulto , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Registros Eletrônicos de Saúde/tendências , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson Secundária/diagnóstico , Fatores de Risco , Fatores de Tempo
16.
PLoS One ; 14(2): e0212907, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30817783

RESUMO

BACKGROUND: Current heart failure (HF) guidelines recommend titrating angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and beta-blockers (BBs) to target doses used in pivotal placebo-controlled randomized controlled trials (RCTs). Despite a number of RCTs comparing different doses (i.e. higher versus lower doses) of ACEIs, ARBs and BBs, the effects of higher versus lower doses on efficacy and safety remains unclear. For this reason, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of higher versus lower doses of ACEIs, ARBs and BBs in patients with HFrEF. METHODS: We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) via Ovid from inception to April 25th, 2018 and opentrials.net and clinicaltrials.gov for relevant trials that compared different doses of medications in heart failure. We analyzed trials by drug class (ACEIs, ARBs, and BBs) for efficacy outcomes (all-cause mortality, cardiovascular mortality, all-cause hospitalizations, HF hospitalizations, HF worsening). For safety outcomes, we pooled trials within and across drug classes. RESULTS: Our meta-analysis consisted of 14 RCTs. Using GRADE criteria, the quality of evidence for ACEIs and ARBs was assessed as generally moderate for efficacy and high for adverse effects, whereas overall quality for BBs was very low to low. Over ~2-4 years higher versus lower doses of ACEIs, ARBs or BBs did not significantly reduce all-cause mortality [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.87-1.02)], ARBs RR 0.96 (0.87-1.04), BBs RR 0.25 (0.06-1.01)] or all cause hospitalizations [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.86-1.02)], ARBs RR 0.98 (0.93-1.04), BBs RR 0.93 (0.39-2.24)]. However, all point estimates favoured higher doses. Higher doses of ARBs significantly reduced hospitalization for HF [RR 0.89 (0.80-0.99)- 2.8% ARR], and higher doses of ACEIs and ARBs significantly reduced HF worsening [RR 0.85 (0.79-0.92)- 5.1% ARR and 0.91 (0.84-0.99)- 3.2% ARR, respectively] compared to lower doses. None of the differences between higher versus lower doses of BBs were significant; however, precision was low. Higher doses of these medications compared to lower doses increased the risk of discontinuation due to adverse events, hypotension, dizziness, and for ACEIs and ARBs, increased hyperkalemia and elevations in serum creatinine. Absolute increase in harms for adverse effects ranged from ~ 3 to 14%. CONCLUSIONS: Higher doses of ACEIs and ARBs reduce the risk of HF worsening compared to lower doses, and higher doses of ARBs also reduce the risk of HF hospitalization but the evidence is sparse and imprecise. Higher doses increase the chance of adverse effects compared to lower doses. Evidence for BBs is inconclusive. These results support initially always starting at low doses of ACEIs/ARBs and only titrating the dose up if the patient tolerates dose increases.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Volume Sistólico , Resultado do Tratamento
17.
PLoS One ; 14(1): e0210705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682072

RESUMO

The prolonged use of many currently available drugs results in the severe side effect of the disruption of glucose metabolism leading to type 2 diabetes mellitus (T2DM. Gut hormone receptors including glucagon receptor (GCGR) and the incretin hormone receptors: glucagon-like peptide 1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR) are important drug targets for the treatment of T2DM, as they play roles in the regulation of glucose and insulin levels and of food intake. In this study, we hypothesized that we could compensate for the negative influences of specific drugs on glucose metabolism by the positive incretin effect enhanced by the off-target interactions with incretin GPCR receptors. As a test case, we chose to examine beta-blockers because beta-adrenergic receptors and incretin receptors are expressed in a similar location, making off-target interactions possible. The binding affinity of drugs for incretin receptors was approximated by using two docking scoring functions of Autodock VINA (GUT-DOCK) and Glide (Schrodinger) and juxtaposing these values with the medical information on drug-induced T2DM. We observed that beta-blockers with the highest theoretical binding affinities for gut hormone receptors were reported as the least harmful to glucose homeostasis in clinical trials. Notably, a recently discovered beta-blocker compound 15 ([4-((2S)-3-(((S)-3-(3-bromophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-2-(2-cyclohexyl-2-phenylacetamido)-3-oxopropyl)benzamide was among the top-scoring drugs, potentially supporting its use in the treatment of hypertension in diabetic patients. Our recently developed web service GUT-DOCK (gut-dock.miningmembrane.com) allows for the execution of similar studies for any drug-like molecule. Specifically, users can compute the binding affinities for various class B GPCRs, gut hormone receptors, VIPR1 and PAC1R.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Diabetes Mellitus Tipo 2/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Simulação de Dinâmica Molecular , Receptores de Glucagon/metabolismo
18.
Adv Clin Exp Med ; 28(3): 375-384, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30659785

RESUMO

BACKGROUND: Propranolol is an effective method of treatment for infantile hemangiomas (IH). A recent concern is a shift of the therapy into outpatient settings. OBJECTIVES: The aim of the study was to evaluate the safety of initiating and maintaining propranolol therapy for IH. MATERIAL AND METHODS: The study involved 55 consecutive children with IH being treated with propranolol. The patients were assessed in the hospital at the initiation of the therapy and later in outpatient settings during and after the therapy. Each time, the following monitoring methods were used: physical examination, cardiac ultrasound (ECHO), electrocardiography (ECG), blood pressure (BP), heart rate (HR), and biochemical parameters: blood count, blood glucose, aspartate transaminase (AST), alanine transaminase (ALT), and ionogram. The therapeutic dose of propranolol was 2.0 mg/kg/day divided into 2 doses. RESULTS: Four children were excluded during the qualification or the initiation of propranolol; a total of 51 patients were subject to the final analysis. All the children presented clinical improvement. There was a significant reduction in the mean HR values only at the initiation of propranolol. There were no changes in HR during the course of the therapy. Blood pressure values were within normal limits. Both systolic and diastolic values decreased in the first 3 months. Bradycardia and hypotension were observed sporadically, and they were asymptomatic. Electrocardiography did not show significant deviations. The pathological findings of the ECHO scans were not a contraindication to continuing the therapy. There were no changes in biochemical parameters. Apart from 1 symptomatic case of hypoglycemia, other low glucose episodes were asymptomatic and sporadic. The observed adverse effects were mild and the propranolol dose had to be adjusted in only 6 cases. CONCLUSIONS: Propranolol is effective, safe and well-tolerated by children with IH. The positive results of the safety assessment support the strategy of initiating propranolol in outpatient settings. Future studies are needed to assess the benefits of the therapy in ambulatory conditions.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Hemangioma/tratamento farmacológico , Propranolol/administração & dosagem , Neoplasias Cutâneas , Administração Oral , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Criança , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lactente , Propranolol/efeitos adversos , Propranolol/provisão & distribução , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
19.
Am J Clin Dermatol ; 20(2): 289-293, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30618026

RESUMO

BACKGROUND: Concerns have been raised that propranolol treatment of infantile hemangioma (IH) may be associated with increased risks of adverse effects and growth impairment in preterm infants due to their immature development. OBJECTIVE: This study aimed to find out whether treatment of IH with propranolol in preterm infants is associated with higher incidences of long-term adverse effects and growth impairment in comparison with term infants. METHODS: The clinical data of 55 preterm infants and 180 term infants with IH treated with oral propranolol for 6 months were retrospectively collected and analyzed. RESULTS: The preterm and term patients did not differ significantly in terms of the general characteristics and adverse effect incidence (all p > 0.05). Height, weight, and head circumference of the preterm infants at ages 1, 2, and 3 years did not differ significantly from the normal references (all p > 0.05). In the term patients, only 1-year-old female weight and head circumference were significantly higher than the normal references (both p < 0.05). CONCLUSION: Treatment of IH with propranolol for 6 months did not increase the risks for adverse effects or growth impairment up to age 3 years in preterm versus term patients in our study.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Hemangioma/tratamento farmacológico , Propranolol/administração & dosagem , Administração Oral , Antagonistas Adrenérgicos beta/efeitos adversos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Propranolol/efeitos adversos , Estudos Retrospectivos , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
20.
Cardiovasc Drugs Ther ; 33(1): 55-67, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30632033

RESUMO

BACKGROUND/AIMS: Limited comparative data concerning long-term clinical outcomes of combination therapy between beta-blockers (BB) with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) therapy in patients with ST-segment elevation myocardial infarction (STEMI) are available. We thought to compare 2-year major clinical outcomes between BB with ACEI and BB with ARB therapy in patients with STEMI after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: 13,873 STEMI patients who underwent successful PCI with DES were enrolled and divided into two groups as the BB with ACEI group (n = 10,393) and the BB with ARB group (n = 3480). The clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death, cardiac death (CD), recurrent myocardial infarction (re-MI), total coronary revascularization (target lesion revascularization [TLR], target vessel revascularization [TVR], non-TVR) during the 2-year follow-up period. RESULTS: After propensity score-matched (PSM) analysis, two PSM groups (3296 pairs, n = 6592, C-statistic = 0.675) were generated. Although the incidences of re-MI, TLR, and TVR were similar, the incidences of MACE (8.3% vs. 6.8%, log-rank p = 0.038, hazard ratio [HR] 1.210, 95% confidence interval [CI] 1.010-1.451, p = 0.039), all-cause death, CD, total revascularization, and non-TVR of the BB with ARB group were significantly higher than the BB with ACEI group after PSM. In addition, diabetes and multivessel disease were significant predictors for non-TVR. CONCLUSIONS: The combination BB with ACEI may be beneficial for reducing MACE in STEMI patients after successful PCI with DES than the BB with ARB.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Antagonistas Adrenérgicos beta/efeitos adversos , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Angiografia Coronária , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Recidiva , Sistema de Registros , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Fatores de Tempo , Resultado do Tratamento
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