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2.
Braz J Med Biol Res ; 52(10): e8491, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618368

RESUMO

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for ß-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.


Assuntos
Tecido Adiposo Marrom/metabolismo , Antagonistas Adrenérgicos beta/administração & dosagem , Iodeto Peroxidase/metabolismo , Infarto do Miocárdio/metabolismo , Propranolol/administração & dosagem , Tiroxina/sangue , Tri-Iodotironina/sangue , Tecido Adiposo Marrom/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Iodeto Peroxidase/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Tiroxina/efeitos dos fármacos , Tri-Iodotironina/efeitos dos fármacos
3.
Expert Opin Ther Pat ; 29(10): 805-815, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31486689

RESUMO

Introduction: Glaucoma is a neurodegenerative disease of the eye characterized by selective retinal ganglion cell loss that provokes progressive defects in the visual field. Elevated intraocular pressure (IOP) is an important contributor for the progression of glaucoma. The current therapeutic arsenal for reducing IOP includes prostaglandin analogs, ß-blockers, carbonic anhydrase inhibitors, α-adrenergic agonist, miotics, rho-kinase inhibitors and combinations thereof, generally administered as eye drops. Areas covered: This manuscript reviews the state of art on adrenergic modulators for treating glaucoma. Both monotherapy and fixed-drugs combinations including α2-adrenergic agonists and ß-blockers are discussed as well as drug delivery systems where these classes of drugs are used. The review then covers the patent literature involving adrenoceptors modulators over the period 2013-2019. Expert opinion: While the scientific community is moving forward novel targets and related modulators for treating glaucoma and ocular hypertension, adrenergic modulators held a prominent position in the therapy of glaucoma and related disorders. Indeed, though not embodying anymore the first-choice monotherapy, they are widely marketed worldwide ordinarily in combination with other drugs, are subjects of many studies for identifying new drug compositions and have been assessed as active ingredients in several innovative ocular drug delivery systems.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Glaucoma/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Animais , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Desenho de Drogas , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Patentes como Assunto
4.
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
5.
Lancet ; 394(10205): 1254-1263, 2019 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-31447116

RESUMO

BACKGROUND: Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and ß blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and ß blockers in patients with HFrEF. METHODS: We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and ß blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF. FINDINGS: Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and ß blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and ß blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and ß blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels. INTERPRETATION: This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and ß blockers than men, and brings into question what the true optimal medical therapy is for women versus men. FUNDING: European Commission.


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/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Estudos Prospectivos , Fatores Sexuais , Volume Sistólico/efeitos dos fármacos
6.
Rom J Ophthalmol ; 63(2): 142-145, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334392

RESUMO

Purpose: To quantitatively evaluate the cardiopulmonary effects of various topical antiglaucoma drugs. Material & method: In this study, forty consecutive cases of newly diagnosed primary open angle glaucoma were recruited. After taking a detailed history, an ophthalmological examination and a systemic examination including resting pulse rate, blood pressure, ECG, auscultation of the chest and spirometry were performed. Then the patients were randomly divided into four groups and one of the four topical anti glaucoma medication (Timolol, Latanoprost, Brimonidine, and Dorzolamide) prescribed. Patients were reviewed 4 weeks later and the same ocular and systemic examinations were performed. Result: Timolol therapy reduced all the spirometry parameters that are statistically significant difference with the P value of less than 0.1. Timolol therapy resulted in the mean reduction of pulse rate by 3.2 beats/ minute and a mean reduction of systolic and diastolic blood pressure by 5.8 mmHg and 5.6 mmHg, respectively all the spirometry & cardiovascular parameters remained unchanged in the other three groups after 4 weeks of treatment. Conclusion: Timolol significantly affects the cardiopulmonary status. Therefore, we could advice the assessment of cardiopulmonary status mandatory in patients receiving topical beta-blockers. Bronchospasm may be of clinical significance in the elderly, who commonly have undiagnosed reversible airway obstruction.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Respiração/efeitos dos fármacos , Timolol/administração & dosagem , Administração Tópica , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos , Espirometria
7.
Gynecol Oncol ; 154(3): 524-530, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31353053

RESUMO

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. CONCLUSION: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Propranolol/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Citocinas/sangue , Citocinas/genética , Citocinas/imunologia , Estudos de Viabilidade , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Estudos Longitudinais , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida
8.
J Cardiothorac Surg ; 14(1): 145, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345252

RESUMO

BACKGROUND: Sinus tachycardia coupled with high-dose catecholamine is common after cardiopulmonary bypass (CPB). The present study assessed the hemodynamic efficacy and safety of combination therapy using low-dose ß1-selective adrenergic blocker (landiolol) and inotropes. METHODS: This was a retrospective, single center, self-comparison study at post-anesthesia care unit within a tertiary care center. The study included adults who underwent cardiac surgery with CPB and received landiolol between April 2007 and November 2011. We assessed hemodynamic data prior to and 1 h after initiation of landiolol therapy. RESULTS: We evaluated 11 patients who were administered 2.6 ± 1.3 µg/kg/min (mean ± SD) landiolol with sinus tachycardia and received catecholamine therapy after on-pump cardiovascular surgery. Landiolol administration led to a significant reduction in heart rate (HR; 112.4 ± 5.8 vs 126.0 ± 7.6 beats/min, p < 0.001), and a significant increase in stroke volume index (SVI) assessed by pulmonary artery catheterization (22.4 ± 5.4 vs. 18.9 ± 4.2 mL/m2, p = 0.04). Only one patient showed no HR reduction, whereas seven patients showed decreased HR and increased SVI (64, 95% confidence interval: 30-98%). Moreover, all five patients who received high-dose catecholamine support showed improved hemodynamics. In terms of safety, no patients required cessation of landiolol therapy. CONCLUSIONS: Low-dose landiolol therapy may safely decrease HR and improve hemodynamics among patients with sinus tachycardia receiving catecholamine treatment after cardiovascular surgery. TRIAL REGISTRATION: This study is retrospective. Registration number: 11. Duration of registration: April 2007~November 2011.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Procedimentos Cirúrgicos Cardíacos , Catecolaminas/uso terapêutico , Morfolinas/uso terapêutico , Taquicardia Sinusal/tratamento farmacológico , Ureia/análogos & derivados , Antagonistas Adrenérgicos beta/administração & dosagem , Adulto , Idoso , Feminino , Frequência Cardíaca , Hemodinâmica , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Centros de Atenção Terciária , Ureia/administração & dosagem , Ureia/uso terapêutico , Adulto Jovem
9.
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
10.
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
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.
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
14.
Trop Doct ; 49(3): 246-248, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31014195

RESUMO

Infantile haemangioma is a relatively common benign tumour which often does not require treatment. We present a case of a segmental infantile haemangioma with periocular involvement impacting on early visual development which was successfully treated with topical timolol maleate 0.5% drops in the developing world.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Neoplasias Palpebrais/tratamento farmacológico , Hemangioma Capilar/tratamento farmacológico , Timolol/administração & dosagem , Administração Tópica , Humanos , Lactente , Masculino , Resultado do Tratamento
15.
JAAPA ; 32(5): 37-39, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31033713

RESUMO

This article describes a patient who presented to the ED after multiple episodes of syncope. His physical examination was unremarkable and an initial workup was negative. Transthoracic echocardiography and chest CT confirmed the diagnosis of congenital complete absence of the pericardium, a rare developmental abnormality most common in men.


Assuntos
Cardiopatias Congênitas/diagnóstico por imagem , Pericárdio/anormalidades , Pericárdio/diagnóstico por imagem , Antagonistas Adrenérgicos beta/administração & dosagem , Tratamento Conservador , Diagnóstico Diferencial , Ecocardiografia , Cardiopatias Congênitas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Síncope/etiologia , Tomografia Computadorizada por Raios X
16.
J Cancer Res Clin Oncol ; 145(7): 1835-1843, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31006846

RESUMO

INTRODUCTION: Based on the observation of beneficial effects on cancer metabolism, microenvironment, or VEGF-signaling, several non-anticancer drugs have been discussed as useful in renal cell carcinoma (RCC). In the present study, we investigated the prognostic impact of concomitant medication in RCC and correlated comedication with cell-cycle and proliferation activity in corresponding surgical specimen. METHODS: A total of 388 patients who underwent surgery for localized RCC were included. The individual medication was evaluated according to substance classes. Tissue microarrays from corresponding tumor specimen were immunohistochemically (IHC) stained for Cyclin D1 and Ki67 and semi-quantitatively evaluated. Uni- and multivariate analyses were used to compare survival outcomes. For the comparison of IHC expression according to medication subgroups, Kruskal-Wallis analysis was performed. RESULTS: Median follow-up was 57.93 months (95% CI 53.27-69.43) and median OS accounted for 181.12 months (129.72-237.17). Univariate analysis identified pathological standard variables (T-stage > T2, Grading > G2, L1, N1, M1, sarcomatoid subtype, necrosis) as significant determinants of OS. Moreover, statin use (p = 0.009) and sartan use (p = 0.032) were significantly associated with improved OS. Multivariate analysis identified M1-stage (p < 0.001), statin and sartan use (p = 0.003 and p = 0.033, respectively) as independent prognosticators of survival. Expression of Ki67 was significantly reduced in patients with statin use (p = 0.013), while Cyclin D1 expression showed no correlation with comedication. CONCLUSIONS: Concomitant intake of statins and sartans identifies as an independent predictor of OS in RCC, and reduced Ki67 expression was significantly associated with statin use. Further evaluation of drug repurposing approaches with these substances in RCC appear warranted.


Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Preparações Farmacêuticas/administração & dosagem , Adolescente , Antagonistas Adrenérgicos beta/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diuréticos/administração & dosagem , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
17.
Lancet ; 393(10181): 1597-1608, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30910320

RESUMO

BACKGROUND: Clinical decompensation of cirrhosis is associated with poor prognosis. Clinically significant portal hypertension (CSPH), defined by a hepatic venous pressure gradient (HVPG) ≥10 mm Hg, is the strongest predictor of decompensation. This study aimed at assessing whether lowering HVPG with ß blockers could decrease the risk of decompensation or death in compensated cirrhosis with CSPH. METHODS: This study on ß blockers to prevent decompensation of cirrhosis with portal hypertension (PREDESCI) was an investigator-initiated, double-blind, randomised controlled trial done in eight hospitals in Spain. We enrolled patients with compensated cirrhosis and CSPH without high-risk varices. All participants had HVPG measurements with assessment of acute HVPG-response to intravenous propranolol. Responders (HVPG-decrease ≥10%) were randomly assigned to propranolol (up to 160 mg twice a day) versus placebo and non-responders to carvedilol (≤25 mg/day) versus placebo. Doses were individually determined during an open-label titration period after which randomisation was done with 1:1 allocation by a centralised web-based system. The primary endpoint was incidence of cirrhosis decompensation (defined as development of ascites, bleeding, or overt encephalopathy) or death. Since death in compensated cirrhosis is usually unrelated to the liver, an intention-to-treat analysis considering deaths unrelated to the liver as competing events was done. This study is registered with ClinicalTrials.gov, number NCT01059396. The trial is now completed. FINDINGS: Between Jan 18, 2010, and July 31, 2013, 631 patients were evaluated and 201 were randomly assigned. 101 patients received placebo and 100 received active treatment (67 propranolol and 33 carvedilol). The primary endpoint occurred in 16 (16%) of 100 patients in the ß blockers group versus 27 (27%) of 101 in the placebo group (hazard ratio [HR] 0·51, 95% CI 0·26-0·97, p=0·041). The difference was due to a reduced incidence of ascites (HR=0·44, 95%CI=0·20-0·97, p=0·0297). The overall incidence of adverse events was similar in both groups. Six patients (four in the ß blockers group) had severe adverse events. INTERPRETATION: Long-term treatment with ß blockers could increase decompensation-free survival in patients with compensated cirrhosis and CSPH, mainly by reducing the incidence of ascites. FUNDING: Spanish Ministries of Health and Economy.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Carvedilol/administração & dosagem , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Propranolol/administração & dosagem , Administração Oral , Adulto , Idoso , Ascite/prevenção & controle , Método Duplo-Cego , Feminino , Hemorragia Gastrointestinal/prevenção & controle , Encefalopatia Hepática/prevenção & controle , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/mortalidade , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença
18.
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
19.
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
20.
Life Sci ; 221: 362-376, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30797820

RESUMO

The human eye being a complex and a very sensitive organ makes the drug delivery task challenging. An increase in the intra-ocular pressure at the aqueous humour leads to glaucoma which is not only indecipherable but can also be the reason of blindness for many. The presently available marketed formulations using anti-glaucoma drugs have issues of either difficulty in crossing the blood- retinal barrier or lower systemic bioavailability. Hence, the drugs having lower therapeutic index would need to be administered frequently, which eventually lead to deposition of concentrated solutions at ocular site, producing toxic effects and cellular damage to the eye. To overcome these drawbacks the novel drug delivery systems like In-situ gels, liposomes, niosomes, hydrogel, dendrimers, nanoparticles, solid lipid nanoparticles, Microneedles or ocular inserts play an important role to enhance the therapeutic efficacy of the anti-glaucomic drugs. The present review briefs the current treatments in terms of drugs used and in detail the impact of utilizing the above mentioned novel drug delivery systems in the treatment of glaucoma.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Glaucoma/tratamento farmacológico , Glaucoma/terapia , Agonistas Adrenérgicos/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Disponibilidade Biológica , Inibidores da Anidrase Carbônica/administração & dosagem , Dendrímeros , Composição de Medicamentos , Olho , Humanos , Pressão Intraocular , Lipossomos , Prostaglandinas Sintéticas/administração & dosagem
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