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1.
Sci Rep ; 11(1): 452, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432057

RESUMO

Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04-10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29-80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04-4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02-11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02-11.65)], oral atenolol [RR = 0.51 (95% CI 0.20-1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03-25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08-10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma.Trial registration: PROSPERO CRD42020190540.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Progressão da Doença , Ensaios Clínicos Controlados Aleatórios como Assunto , Estado Asmático/induzido quimicamente , Administração Oral , Antagonistas Adrenérgicos beta/administração & dosagem , Atenolol/administração & dosagem , Atenolol/efeitos adversos , Bisoprolol/administração & dosagem , Bisoprolol/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Celiprolol/administração & dosagem , Celiprolol/efeitos adversos , Feminino , Humanos , Incidência , Infusões Intravenosas , Masculino , Practolol/administração & dosagem , Practolol/efeitos adversos , Propranolol/administração & dosagem , Propranolol/efeitos adversos , Risco , Sotalol/administração & dosagem , Sotalol/efeitos adversos , Estado Asmático/epidemiologia , Timolol/administração & dosagem , Timolol/efeitos adversos
2.
Anatol J Cardiol ; 17(5): 367-373, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28100897

RESUMO

OBJECTIVE: Xindening oral liquid (Xin) is a widely used traditional Chinese medicine for the treatment of chronic heart failure (CHF). However, the exact mechanisms related to its therapeutic effects against CHF remain unclear. In the present study, we investigate the effects of Xin on cardiac function in CHF rats and the possible mechanisms involved. METHODS: Transverse aortic constriction (TAC) was conducted to induce a CHF rat model in this study. Sixty male Wistar rats were randomly assigned to six groups 28 days after TAC: sham; CHF model; Xin at concentrations of 5 ml/kg, 10 mL/kg, and 20 mL/kg; and QiLi 0.6 g/kg. After four weeks, the rats were treated with Xin (5, 10, or 20 mL/kg/d) for six weeks consecutively. At the end of the study, the cardiac function, heart weight index (HWI) and left ventricular mass index (LVMI), serum level of LDH, B-type natriuretic peptide (BNP), cTnI and CK-MB, and collagen volume fraction were studied. The expression of transforming growth factor-ß1 (TGF-ß1), drosophila mothers against decapentaplegic protein 3 (Smad3), and p38 mitogen activated protein kinase (p38 MAPK) were detected. RESULTS: The results showed that Xin treatment significantly improved cardiac function but decreased the serum level of LDH, BNP, cTnI, and CKMB of CHF rats. In addition, it reduced the HWI, LVMI, and collagen volume fraction compared with the model group. Xin treatment significantly improved cardiac function and attenuated cardiac fibrosis by suppressing the p38 MAPK and TGF-ß1/Smad3 signaling pathway in CHF rats. CONCLUSION: These results suggested that Xin might be a promising complementary treatment for CHF. More detailed experimental studies will be carried out in our subsequent research.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Practolol/farmacologia , Administração Oral , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Masculino , Practolol/administração & dosagem , Practolol/uso terapêutico , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos
3.
J Nucl Cardiol ; 21(5): 984-92, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24875578

RESUMO

BACKGROUND: The great clinical potential of myocardial ß-AR imaging has been shown by recent studies evaluating the ß-AR-specific, non-selective agent [(11)C]-CGP12177 in the setting of idiopathic-dilated cardiomyopathy, and myocardial infarction. However, the short half-life of (11)C hampers the potential of [(11)C]-CGP12177 for routine clinical use. AMI9 is an analog of the ß-adrenoceptor ligand practolol that can readily be labeled using radioactive isotopes of iodine. The present study was aimed at characterizing the in vitro, ex vivo, and in vivo ß-AR binding properties of [(125)I]-AMI9. METHODS AND RESULTS: Newborn rat cardiomyocytes were used for saturation and kinetic binding assays as well as for displacement and competition experiments. Isolated perfused rat hearts were used to evaluate the pharmacological activity of AMI9. The in vivo kinetics of [(125)I]-AMI9 were studied using biodistribution experiments in mice. [1(25)I]-AMI9 displayed high specific affinity for ß-AR with no ß-AR subtype selectivity (K D, 5.6 ± 0.3 nM; B max, 231 ± 7 fmol·(mg protein)(-1)). AMI9 potently inhibited the inotropic effects of isoproterenol. The early in vivo cardiac and lung activities of [(125)I]-AMI9 compared favorably with those of the clinically validated tracer CGP12177. CONCLUSION: Iodine-labeled AMI9 is a promising agent for the molecular imaging of myocardial ß-AR density.


Assuntos
Imagem Molecular/métodos , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Practolol/análogos & derivados , Practolol/farmacocinética , Receptores Adrenérgicos beta/metabolismo , Antagonistas de Receptores Adrenérgicos beta 1/química , Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Animais , Animais Recém-Nascidos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Coração/diagnóstico por imagem , Radioisótopos do Iodo/química , Radioisótopos do Iodo/farmacocinética , Marcação por Isótopo/métodos , Taxa de Depuração Metabólica , Camundongos , Miócitos Cardíacos/diagnóstico por imagem , Especificidade de Órgãos , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual
4.
J Med Chem ; 57(13): 5509-24, 2014 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-24471412

RESUMO

Sphingosine kinase (SphK) is an oncogenic lipid kinase that regulates the sphingolipid metabolic pathway that has been shown to play a role in numerous hyperproliferative/inflammatory diseases. The SphK isoforms (SphK1 and SphK2) catalyze the conversion of the proapoptotic substrate d-erythrosphingosine to the promitogenic/migratory product sphingosine 1-phosphate (S1P). Accumulation of S1P has been linked to the development/progression of cancer and various other diseases including, but not limited to, asthma, inflammatory bowel disease, rheumatoid arthritis, and diabetic nephropathy. SphK therefore represents a potential new target for developing novel therapeutics for cancer and other diseases. This finding has stimulated the development and evaluation of numerous SphK inhibitors over the past decade or so. In this review, we highlight the recent advancement in the field of SphK inhibitors including SphK1 and SphK2 specific inhibitors. Both sphingolipid based and nolipidic small molecule inhibitors and their importance in treatment of cancer and other diseases are discussed.


Assuntos
Inibidores Enzimáticos/síntese química , Lisofosfolipídeos/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Esfingosina/análogos & derivados , Clofibrato/metabolismo , Combinação de Medicamentos , Humanos , Isoenzimas/metabolismo , Lisofosfolipídeos/agonistas , Neoplasias/tratamento farmacológico , Practolol/metabolismo , Esfingosina/agonistas , Esfingosina/metabolismo , Esfingosina/farmacologia
5.
Int J Cardiol ; 168(6): 5329-35, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23978364

RESUMO

BACKGROUND: Few data exist about the implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: GReek AntiPlatelet rEgistry (GRAPE), initiated on January 2012, is a prospective, observational, multicenter cohort study focusing on contemporary use of P2Y12 inhibitors. In 1434 patients we evaluated appropriateness of P2Y12 selection initially and at discharge by applying an eligibility-assessing algorithm based on P2Y12 inhibitors' contraindications/specific warnings and precautions. RESULTS: Appropriate, less preferable and inappropriate P2Y12 inhibitor selections were made initially in 45.8%, 47.2% and 6.6% and at discharge in 64.1%, 29.2% and 6.6% of patients, respectively. The selection of clopidogrel was most commonly less preferable, both initially (69.7%) and at discharge (75.6%). Appropriate selection of newer agents was high initially (79.2%-82.8%), with further increase as selection at discharge (89.4%-89.8%). Inappropriate selection of the newer agents was 17.2%-20.8% initially, decreasing to 10.2%-10.6% at discharge. Conditions and co-medications related to increased bleeding risk, presentation with ST elevation myocardial infarction and the absence of reperfusion within the first 24h were the most powerful predictors of appropriate P2Y12 selection initially, whereas age ≥75 years, conditions and co-medications related to increased bleeding risk and regional trends mostly affected appropriate P2Y12 selection at discharge. CONCLUSIONS: In GRAPE, adherence with the recently released guidelines on oral antiplatelet therapy was satisfactory. Clopidogrel was most commonly used as a less preferable selection, while prasugrel or ticagrelor selection was mostly appropriate. Certain factors may predict initial and at discharge guideline implementation. Clinical Trial Registration-clinicaltrials.gov Identifier: NCT01774955 http://clinicaltrials.gov/.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/terapia , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Adenosina/análogos & derivados , Administração Oral , Idoso , Clopidogrel , Terapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Practolol , Cloridrato de Prasugrel , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Receptores Purinérgicos P2Y12 , Sistema de Registros , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos
6.
Clin Lab Sci ; 26(2): 89-94, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23772474

RESUMO

The Clinical and Laboratory Standards Institute guidelines require special processing of whole blood specimens with hematocrits greater than 55% due to the possibility of spurious prolongation of routine coagulation studies (PT, aPTT). As samples with hematocrits above 60% are rare at our institution, our study seeks to determine the effect of relative citrate excess on routine coagulation studies in samples with hematocrits of 60% to determine whether special processing is necessary. A calculated volume of 3.2% citrate was added to 1 mL aliquots of 40 whole blood samples in citrated tubes from adult patients to simulate a hematocrit of 60%. A dilutional control was created by adding an equivalent volume of saline to a separate 1 mL aliquot. Routine coagulation studies (PT, aPTT) were run on both samples on the STA Compact Analyzer in accordance with manufacturer instructions. While a paired Student's t-test demonstrated a clinically significant change in both PT and aPTT with the addition of citrate (p = 0.0002 for PT and p = 0.0234 for aPTT), clinical management would not have been altered by any observed change. More interestingly, we observed a shortening of 27/40 PTs and 23/40 aPTTs rather than the expected prolongation. Based on our data, no adjustment of citrate volume appears to be necessary in samples with hematocrits less than or equal to 60%.


Assuntos
Hematócrito/normas , Hematologia/normas , Tempo de Tromboplastina Parcial/normas , Policitemia/sangue , Tempo de Protrombina/normas , Adulto , Citratos , Testes Diagnósticos de Rotina/normas , Humanos , Practolol
7.
AJNR Am J Neuroradiol ; 34(2): 354-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22821922

RESUMO

BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke consists of various mechanical and pharmacologic modalities used for recanalization of arterial occlusions. We performed this study to determine the relationship among procedure time, recanalization, and clinical outcomes in patients with acute ischemic stroke undergoing endovascular treatment. MATERIALS AND METHODS: We analyzed data from consecutive patients with acute ischemic stroke who underwent endovascular treatment during a 6-year period. Demographic characteristics, NIHSS score before and 24 hours after the procedure, and discharge mRS score were ascertained. Procedure time was defined by the time interval between microcatheter placement and recanalization or completion of the procedure. We estimated the procedure time after which favorable clinical outcome was unlikely, even after adjustment for age, time from symptom onset, and admission NIHSS scores. RESULTS: We analyzed 209 patients undergoing endovascular treatment (mean age, 65 ± 16 years; 109 [52%] men; mean admission/preprocedural NIHSS score, 15.3 ± 6.8). Complete or partial recanalization was observed in 176 (84.2%) patients, while unfavorable outcome (mRS 3-6) was observed in 138 (66%) patients at discharge. In univariate analysis, patients with procedure time ≤30 minutes had lower rates of unfavorable outcome at discharge compared with patients with procedure time ≥30 minutes (52.3% versus 72.2%, P = .0049). In our analysis, the rates of favorable outcomes in endovascularly treated patients after 60 minutes were lower than rates observed with placebo treatment in the Prourokinase for Acute Ischemic Stroke Trial. In logistic regression analysis, unfavorable outcome was positively associated with age (P = .0012), admission NIHSS strata (P = .0017), and longer procedure times (P = .0379). CONCLUSIONS: Procedure time in patients with acute ischemic stroke appears to be a critical determinant of outcomes following endovascular treatment. This highlights the need for procedure time guidelines for patients being considered for endovascular treatment in acute ischemic stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Revascularização Cerebral/métodos , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Dispositivos de Acesso Vascular , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/cirurgia , Revascularização Cerebral/estatística & dados numéricos , Bases de Dados Factuais , Procedimentos Endovasculares/estatística & dados numéricos , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Masculino , Trombólise Mecânica/métodos , Trombólise Mecânica/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Practolol , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/cirurgia , Terapia Trombolítica/métodos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento
8.
Pharmacoepidemiol Drug Saf ; 16(11): 1211-6, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17853493

RESUMO

OBJECTIVE: By examination of the original Yellow Card data to determine the duration of the latent period of the sclerosing peritonitis which formed part of the oculomucocutaneous syndrome that was associated with practolol, the beta-adrenergic receptor blocking agent that was withdrawn from clinical usage in the UK in December 1975 in response to reports of the syndrome. METHOD: Relevant drug analysis prints (DAPs) for practolol were obtained from the Medicines and Healthcare Products Regulatory Agency (MHRA) and, by application to the Interim Committee on Yellow Card data, copies were obtained of the anonymised Yellow Card reports for all the 201 cases of sclerosing peritonitis that were reported in patients treated with practolol. These data were used to determine the latent period of this iatrogenic adverse drug reaction. RESULTS: It was shown that no other cause than practolol operated in all or a majority of the cases of sclerosing peritonitis and the suspected adverse reaction could properly be attributed to the drug. The latent period (the time period between the drug start date and the reaction start date) of the sclerosing peritonitis associated with practolol averaged 201 weeks (range 26-606 weeks; standard deviation 130 weeks). CONCLUSION: The latent period of the sclerosing peritonitis that formed part of the practolol oculomucocutaneous syndrome averaged about 4 years and had a range of from 0.5 to over 11.5 years. The Yellow Card Scheme could detect this ultra long-latency adverse reaction.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Peritonite/induzido quimicamente , Practolol/efeitos adversos , Esclerose/induzido quimicamente , Humanos , Vigilância de Produtos Comercializados , Fatores de Tempo , Reino Unido
9.
Soc Hist Med ; 19(1): 127-47, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17153164

RESUMO

This article analyses how practolol, the first British drug disaster of the modern, post-thalidomide regulatory period, related to the pharmaceutical industry, the medical profession and government regulation of patients' health. Drawing on comparison with the USA, it argues that, contrary to public expectation and perception, the aftermath of thalidomide did not give rise to strident British drug control, imposing the highest possible safety standards on the pharmaceutical industry. Rather, there existed a culture of reluctant regulation that was characterised by continued optimism about, and trust in the purported benefits of new drugs among manufacturers and regulators in the United Kingdom, together with commitment to the protection of the industry and its institutional support for the medical profession. In particular, British regulators were willing to allow new drugs on to the market, fully aware of uncertainty about their safety, but unwilling to be pro-active in issuing warning letters about risks and requiring 'certainty' before acting to withdraw a product. Even after the practolol disaster, the British system was unable to reform itself to construct more rigorous and pro-active monitoring of drug risks. This was because of conflicts with industry interests.


Assuntos
Antagonistas Adrenérgicos beta/história , Indústria Farmacêutica/história , Legislação de Medicamentos/história , Practolol/história , Antagonistas Adrenérgicos beta/efeitos adversos , História do Século XX , Humanos , Practolol/efeitos adversos , Reino Unido
10.
Pharmacoepidemiol Drug Saf ; 14(10): 705-10, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16088980

RESUMO

PURPOSE: To display a ranked presentation of the data given in the Drug Analysis Prints (DAPs) provided by the MHRA/CSM so that the monitoring clinician may be readily alerted to the most important findings. The practolol DAP is taken as an example of the presentation. METHOD: The data for the ranked system organ classes, the ranked deaths and the ranked reaction reports within each system organ class are considered separately. RESULTS: It has been found that there are advantages in considering the system-organ classes, the deaths and the reports of the individual reactions separately and then, within these groupings, providing the mathematically ranked data. The results for practolol, withdrawn due to the associated oculomucocutaneous syndrome, are given as a single worked example. CONCLUSIONS: Presentations of the ranked data arising from spontaneous adverse drug reactions reporting may have useful advantages.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Practolol/efeitos adversos , Qualidade de Produtos para o Consumidor , Oftalmopatias/induzido quimicamente , Oftalmopatias/epidemiologia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Gastroenteropatias/mortalidade , Guias de Prática Clínica como Assunto , Dermatopatias/induzido quimicamente , Dermatopatias/epidemiologia , Síndrome , Reino Unido/epidemiologia
11.
J Chromatogr A ; 1072(1): 29-36, 2005 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-15881456

RESUMO

Recently, we demonstrated for the first time liquid-phase microextraction (LPME) of polar drugs based on carrier mediated transport. In this new extraction technique, selected analytes were extracted as ion-pairs from small volumes of biological samples, through a thin layer of a water immiscible organic solvent immobilised in the pores of a porous hollow fibre (liquid membrane), and into a microl volume of an acidic aqueous acceptor solution placed inside the lumen of the hollow fibre. In the current paper, this new extraction technique was combined with liquid chromatography-mass spectrometry (LC-MS) for the first time. Carrier mediated LPME was evaluated for several new model drugs (0.01

Assuntos
Fracionamento Químico/métodos , Cromatografia Líquida/métodos , Microquímica/métodos , Preparações Farmacêuticas/sangue , Anfetamina/sangue , Anfetamina/isolamento & purificação , Atenolol/sangue , Atenolol/isolamento & purificação , Cimetidina/sangue , Cimetidina/isolamento & purificação , Humanos , Morfina/sangue , Morfina/isolamento & purificação , Fenilpropanolamina/sangue , Fenilpropanolamina/isolamento & purificação , Practolol/sangue , Practolol/isolamento & purificação , Sensibilidade e Especificidade , Solventes , Sotalol/sangue , Sotalol/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray/métodos
12.
Farmaco ; 60(3): 255-9, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15784246

RESUMO

Artificial neural networks were used for modeling the mobility of five beta-blockers (i.e., labetalol atenolol, practolol, timolol and propranolol) in running buffer with ternary solvent background electrolyte systems containing 80 mM acetate buffer dissolved in water, methanol, ethanol and their ternary mixtures. The volume fractions of two solvents (f(2), f(3)) and cologarithm of electrophoretic mobilities in pure solvents (i.e., -Lnmu(1), -Lnmu(2) and -Lnmu(3)) were used as inputs and cologarithm of the mobility in mixed solvents was the output of the networks. The number of neurons in hidden layer, learning rate, momentum and the number of epochs were optimized, in which two neurons in hidden layer, 0.2, 0.9 and 20000 were found the optimized values for learning rate, momentum and number of epochs, respectively. Mean percentage deviations (MPD) between calculated and experimental mobilities were computed as an accuracy criterion. To assess the correlative ability of the model, all data points in each set were used as training set and the mobilities were back-calculated by the trained networks, in which the overall MPD (OMPD)+/- standard deviation (SD) for correlative study was 3.1+/- 2.3. To evaluate the prediction capability of the proposed ANN model, the network was trained using 15 data points for each analyte and the remaining data points were predicted. The obtained OMPD (+/-SD) for this analysis was 3.6+/-3.0. To further investigate on the applicability of ANN, a generalized network was trained with 10 data points from each beta-blocker and then the network was employed to predict the mobilities of the analytes in ternary solvent electrolyte systems. The MPDs for predicted mobilities were 3.6%, 3.6%, 3.9%, 3.7% and 2.9% respectively for labetalol, atenolol, practolol, timolol and propranolol.


Assuntos
Antagonistas Adrenérgicos beta/análise , Redes Neurais de Computação , Antagonistas Adrenérgicos beta/química , Atenolol/análise , Eletrólitos , Eletroforese Capilar/métodos , Ensaio de Desvio de Mobilidade Eletroforética , Labetalol/análise , Modelos Químicos , Preparações Farmacêuticas , Practolol/análise , Valor Preditivo dos Testes , Propranolol/análise , Solventes/química , Tecnologia Farmacêutica/métodos , Timolol/análise
13.
Arch Med Sadowej Kryminol ; 53(4): 289-99, 2003.
Artigo em Polonês | MEDLINE | ID: mdl-14971294

RESUMO

The study aimed at finding effective techniques of qualitative and quantitative analysis of selected beta-adrenergic blockers, useful both for monitoring of therapy and for thanatological diagnosis of intoxications. The studies took advantage of gas chromatography (GLC) and high performance liquid chromatography (HPLC). For isolation of studied compounds from biological material, classical and solid phase extraction procedures (SPE) Extrelut-20 (Merck), Abselut Nexus (Varian), STRATA C--18 E (Phenomenex) were used. The program included the analysis of most frequently applied derivatives: Acebutolol, Atenolol, Bunitrolol, Bupranolol, Labetolol, Metipranolol, Metoprolol, Oxprenolol, Practolol, Propranolol.


Assuntos
Antagonistas Adrenérgicos beta/sangue , Antagonistas Adrenérgicos beta/isolamento & purificação , Cromatografia Gasosa/métodos , Cromatografia Líquida de Alta Pressão/métodos , Detecção do Abuso de Substâncias/métodos , Acebutolol/sangue , Atenolol/sangue , Bupranolol/sangue , Estudos de Avaliação como Assunto , Humanos , Labetalol/sangue , Metipranolol/sangue , Metoprolol/sangue , Oxprenolol/sangue , Practolol/sangue , Propanolaminas/sangue , Propranolol/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Eur J Clin Pharmacol ; 58(7): 483-90, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12389072

RESUMO

OBJECTIVE: The aim of this paper is to demonstrate the usefulness of the Bayesian Confidence Propagation Neural Network (BCPNN) in the detection of drug-specific and drug-group effects in the database of adverse drug reactions of the World Health Organization Programme for International Drug Monitoring. METHODS: Examples of drug-adverse reaction combinations highlighted by the BCPNN as quantitative associations were selected. The anatomical therapeutic chemical (ATC) group to which the drug belonged was then identified, and the information component (IC) was calculated for this ATC group and the adverse drug reaction (ADR). The IC of the ATC group with the ADR was then compared with the IC of the drug-ADR by plotting the change in IC and its 95% confidence limit over time for both. RESULTS: The chosen examples show that the BCPNN data-mining approach can identify drug-specific as well as group effects. In the known examples that served as test cases, beta-blocking agents other than practolol are not associated with sclerosing peritonitis, but all angiotensin-converting enzyme inhibitors are associated with coughing, as are antihistamines with heart-rhythm disorders and antipsychotics with myocarditis. The recently identified association between antipsychotics and myocarditis remains even after consideration of concomitant medication. CONCLUSION: The BCPNN can be used to improve the ability of a signal detection system to highlight group and drug-specific effects.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Teorema de Bayes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Armazenamento e Recuperação da Informação , Captopril/efeitos adversos , Clozapina/efeitos adversos , Bases de Dados Factuais , Monitoramento de Medicamentos/métodos , Humanos , Preparações Farmacêuticas/classificação , Practolol/efeitos adversos , Terfenadina/efeitos adversos , Organização Mundial da Saúde
15.
Analyst ; 127(9): 1188-92, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12375841

RESUMO

The electrophoretic mobilities of three beta-blocker drugs, practolol, timolol and propranolol, have been measured in electrolyte systems with mixed binary and ternary water-methanol-ethanol solvents with acetic acid/sodium acetate as buffer using capillary electrophoresis. The highest mobilities for the analytes studied have been observed in pure aqueous, the lowest values in ethanolic buffers. The measured electrophoretic mobilities have been used to evaluate the accuracy of a mathematical model based on a mixture response surface method that expresses the mobility as a function of the solvent composition. Mean percentage error (MPE) has been computed considering experimental and calculated mobilities as an accuracy criterion. The obtained MPE for practolol, timolol and propranolol in the binary mixtures are between 0.9 and 2.6%, in the ternary water-methanol-ethanol solvent system the MPE was about 2.7%. The MPE values resulting from the proposed equation lie within the experimental relative standard deviation values and can be considered as an acceptable error.


Assuntos
Antagonistas Adrenérgicos beta/análise , Eletroforese Capilar/métodos , Modelos Químicos , Practolol/análise , Propranolol/análise , Solventes , Timolol/análise
17.
Cardiovasc Drugs Ther ; 14(3): 271-81, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10935149

RESUMO

Myocardial contractile function after coronary artery bypass graft surgery is often depressed and may require inotropic support, particularly in patients on treatment with beta-adrenergic and Ca2+ blockers. In view of the increase in cytosolic Ca2+ during early reperfusion, use of Ca2+ sensitizing agents may be preferable to adrenergic agonists for enhancement of contractile function after cardioplegic arrest. The aim of this study was to assess the efficacy of the Ca2+ sensitizer, levosimendan, as an inotrope on the mechanical recovery of hearts after normothermic and hypothermic cardioplegic arrest in the absence and presence of Ca2+ and beta-blockers. Isolated perfused working guinea pig hearts were perfused in the absence or presence of propranolol (10(-6) M) and/or nifedipine (10(-8) M), subjected to 45 minutes of normothermic or 180 minutes of hypothermic cardioplegic arrest, reperfused, and exposed to increasing concentrations of levosimendan (10(-9) to 10(-6) M). Levosimendan (10(-7) to 10(-6) M) has positive inotropic, chronotropic, and vasodilatory effects on normoxic perfused control hearts, as well as during reperfusion after 45 minutes of normothermic cardioplegic arrest. Similar effects were elicited in the presence of the blockers. Levosimendan had no stimulatory effect during reperfusion of hearts subjected to prior hypothermic arrest. Except for the increase in heart rate, the effects of levosimendan on functional performance during reperfusion were comparable with those of adrenaline. Levosimendan elicits a positive inotropic and chronotropic response during reperfusion of hearts after normothermic cardioplegic arrest, both in the absence and presence of Ca2+ and beta-adrenergic blockers.


Assuntos
Parada Cardíaca Induzida , Coração/efeitos dos fármacos , Hidrazonas/farmacologia , Contração Miocárdica/efeitos dos fármacos , Piridazinas/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Circulação Coronária/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Cobaias , Hipotermia Induzida , Técnicas In Vitro , Masculino , Practolol/farmacologia , Receptores Adrenérgicos beta/efeitos dos fármacos , Simendana
18.
Xenobiotica ; 30(7): 717-29, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10963062

RESUMO

1. The metabolic fate of 14C/13C-practolol was investigated using on-line HPLC-NMR-MS following oral administration to rat. The major route of elimination for the radiolabel was via the urine with the principal biotransformation products confirmed as the 2-hydroxy- and 2-hydroxyglucronide metabolites. 2. In addition, futile deacetylation, determined by the replacement of 13C-labelled acetyl groups with endogenous 12C-acetyls accounted for approximately 7-10% of the urinary metabolites, corresponding to approximately 5% of the dose undergoing N-deacetylation. 3. Evidence for chiral metabolism was sought via NMR of isolated metabolites using beta-cyclodextrin as a chiral shift agent. Practolol was excreted as a racemate. However, some enantioselective metabolism/excretion had occurred as the hydroxy- and hydroxyglucuronide were not excreted as racemic mixtures. 4. Directly coupled radio-HPLC-NMR-MS is extremely effective for the identification of the metabolites of radiolabelled xenobiotics in urine samples.


Assuntos
Antagonistas Adrenérgicos beta/farmacocinética , Practolol/farmacocinética , Animais , Biotransformação , Cromatografia Líquida de Alta Pressão , Hidrólise , Marcação por Isótopo , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Ratos , Ratos Wistar , Espectrofotometria Ultravioleta
19.
Biomed Chromatogr ; 13(8): 520-4, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10611605

RESUMO

We report a method for the high-performance liquid chromatographic (HPLC) chiral separation of racemic clenbuterol in human plasma. Human plasma was spiked with stock solutions of clenbuterol hydrochloride and practolol as the internal standard. Following a liquid-liquid extraction procedure with 10% (+/-)-2-butanol/isopropyl ether under alkaline conditions, the dried samples were reconstituted in methanol and chromatographed using a macrocyclic antibiotic chiral stationary phase (CSP) known as Chirobiotic T(trade mark) (teicoplanin). The mobile phase composition was methanol:acetonitrile (70:30, v/v), containing 0.3% (v/v) acetic acid and 0.2% (v/v) triethylamine. The resulting chromatogram achieved baseline separation for the clenbuterol enantiomers. Calibration curves (peak area ratio vs plasma concentration, n = 10) were constructed for the (-)-R-and (+)-S-clenbuterol enantiomers with a plasma concentration range of 0. 25-10 microM. The correlation coefficient (r) range was 0.99988-0. 99999 (mean = 0.99999). The lowest concentration measured was 0.25 microM. Inter- and intra-assay variation was determined for the lowest, medium and highest plasma concentration (0.25, 2 and 10 microM) by calculating the analytical recoveries with a range of 96-104%. The percentage recoveries for the clenbuterol enantiomers were 88.4-102% over the concentration range used. Detailed methodology is presented.


Assuntos
Clembuterol/sangue , Teicoplanina , Cromatografia Líquida de Alta Pressão/métodos , Clembuterol/química , Humanos , Indicadores e Reagentes , Practolol/sangue , Análise de Regressão , Sensibilidade e Especificidade , Solventes , Estereoisomerismo
20.
FEBS Lett ; 457(3): 302-6, 1999 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-10471797

RESUMO

We provide the first evidence that point mutations can constitutively activate the beta(1)-adrenergic receptor (AR). Leucine 322 of the beta(1)-AR in the C-terminal portion of its third intracellular loop was replaced with seven amino acids (I, T, E, F, C, A and K) differing in their physico-chemical properties. The beta(1)-AR mutants expressed in HEK-293 cells displayed various levels of constitutive activity which could be partially inhibited by some beta-blockers. The results of this study might have interesting implications for future studies aiming at elucidating the activation process of the beta(1)-AR as well as the mechanism of action of beta-blockers.


Assuntos
Agonistas Adrenérgicos beta/metabolismo , Antagonistas Adrenérgicos beta/metabolismo , Mutação Puntual , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Agonistas de Receptores Adrenérgicos beta 1 , Agonistas de Receptores Adrenérgicos beta 2 , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Substituição de Aminoácidos , Betaxolol/metabolismo , Betaxolol/farmacologia , Carbazóis/metabolismo , Carbazóis/farmacologia , Carvedilol , Linhagem Celular/efeitos dos fármacos , Linhagem Celular/metabolismo , AMP Cíclico/metabolismo , Epinefrina/metabolismo , Epinefrina/farmacologia , Humanos , Imidazóis/metabolismo , Imidazóis/farmacologia , Isoproterenol/metabolismo , Isoproterenol/farmacologia , Labetalol/metabolismo , Labetalol/farmacologia , Practolol/metabolismo , Practolol/farmacologia , Propanolaminas/metabolismo , Propanolaminas/farmacologia , Receptores Adrenérgicos beta 2/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Timolol/metabolismo , Timolol/farmacologia
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