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2.
Med J Aust ; 148(1): 31-5, 1988 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-3336297

RESUMO

The efficacy and tolerability of metoprolol (100 mg once a day) were assessed in general practice in 6713 newly-diagnosed or previously-treated hypertensive patients in an open study of eight weeks' duration. In 3534 mildly-hypertensive patients who were eligible for the efficacy analysis, the mean blood pressure level was reduced by 19/10 mmHg; 68% of the patients achieved diastolic blood pressures below 90 mmHg by the end of the assessment period. Of 6557 patients who were eligible for the tolerability analysis, only 5.6% of patients withdrew because of adverse events. The incidence of adverse events diminished considerably from the clinic assessment at four weeks (20%) to that at eight weeks (11%). At the completion of the study, 92% of the mildly-hypertensive patients were to continue with metoprolol, either as monotherapy (including 64% of patients who were receiving 100 mg once a day and 6% of patients who were receiving 50 mg once a day), or as combination therapy. Analysis of the large subgroup of mildly-hypertensive elderly patients (n = 1214) and of moderately-hypertensive patients, whose diastolic pressures exceeded the set upper limits (n = 2505), showed similar efficacy and tolerability results. Sixty-eight per cent of the former and 47% of the latter demonstrated satisfactory control of blood pressure. These results show that the majority of mildly-hypertensive patients can be controlled with 50-100 mg of metoprolol once a day.


Assuntos
Hipertensão/tratamento farmacológico , Metoprolol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Tolerância a Medicamentos , Medicina de Família e Comunidade , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Metoprolol/efeitos adversos , Pessoa de Meia-Idade , Fatores de Tempo
4.
Cell Biochem Funct ; 1(1): 55-63, 1983 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6678618

RESUMO

The effects of promethazine (PM) on different aspects of the hepatotoxic action of CCl4 in the rat were investigated with the objective of finding rapid and reliable indicators of hepatoprotective effects. The study was based on definitive histological assessment of liver damage caused by CCl4 in the presence and absence of PM: PM (78 mumol kg-1, i.p.) protected against CCl4-induced hepatic necrosis 24 h after a low dose of CCl4 (1.3 mmol kg-1) but not against a higher dose (13.0 mmol kg-1). The large increases in plasma activities of GOT, GPT and LDH produced by dosing with CCl4 were partially inhibited by the administration of PM. PM and CCl4 caused a synergistic and long-lasting decrease in body temperature (2-3 degrees C for 8-10 h). Modifying the toxicity with PM, together with a low dose of CCl4, helped to minimize secondary effects of CCl4, to clarify the sequence of toxic events, and to assess the sensitivity of some standard tests of hepatotoxicity. Simultaneous measurement of over 20 commonly used biochemical screening tests in individual animals 3 or 6 h after treatment permitted direct correlation of a wide variety of concentrations, activities and effects. For example, liver CHCl3 concentrations (as a measure of CCl4 metabolism) correlate strongly with increases in diene conjugation of microsomal lipids (as a measure of CCl4-induced lipid peroxidation); malonaldehyde production appears to be less sensitive as a measure of lipid peroxidation in vivo than diene conjugation. The changes induced in each parameter and the correlations between them are discussed with reference to the overall nature of the hepatotoxic reaction and its modification by PM.


Assuntos
Tetracloreto de Carbono/toxicidade , Fígado/efeitos dos fármacos , Prometazina/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Tetracloreto de Carbono/metabolismo , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/patologia , Metabolismo dos Lipídeos , Peróxidos Lipídicos/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Necrose , Proteínas/metabolismo , Ratos , Respiração/efeitos dos fármacos
7.
J Chromatogr ; 192(2): 375-86, 1980 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-7391200

RESUMO

A rapid, sensitive method has been developed to study the kinetics of unchanged promethazine (PM) in biological material using a nitrogen-selective flame ionization detector (N-FID). Unchanged PM is distinguished from its desmethyl metabolite. Sample clean-up of several biological fluids (rat plasma, blood, urine, liver and kidney homogenates) was studied and gas chromatographic (GC) conditions optimized. Usually 50 microliters-1.0 ml samples are extracted into n-heptane by shaking with NaOH, re-extracted into H2SO4 and again extracted into n-heptane by addition of NaOH. Finally, the organic phase is separated, concentrated under N2 and PM determined by N-FID. However, a rapid, single-step method requiring only NaOH extraction into n-heptane may be used whenever GC background permits. Imipramine is used as an internal standard for calibration by peak height ratios in the overall range 5--1500 ng PM per sample. Recovery of both methods is high (97--99%) but precision of the single-step method is lower (relative S.D. 10% versus 3--4%). Use of sample volumes up to 1 ml allows accurate determination of concentrations as low as 10 ng/g. Examples of applications to commonly used animal models employing PM are given and simple adaptation for clinical samples suggested.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Prometazina/sangue , Animais , Estudos de Avaliação como Assunto , Cromatografia Gasosa-Espectrometria de Massas/instrumentação , Fígado/metabolismo , Prometazina/farmacologia , Prometazina/urina , Ratos
8.
J Chromatogr ; 193(1): 71-82, 1980 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-7391206

RESUMO

Two simple gas-liquid chromatographic techniques were developed for the simultaneous determination of CCl4 and CHCl3 in biological material and expired air and principally for use in the well-known CCl4-induced hepatotoxicity model: a non-extractive head-space analysis by flame ionization detection (FID) and a single-step toluene extraction using electron-capture detection (ECD). For head-space analysis, blood or liver homogenate is incubated with buffer in sealed reaction vials and the head-space vapour sampled for FID determination. Absolute signal response to CCl4 and CHCl3 was used for calibration in the range 5-500 microgram per gram of biological material. The method is reasonably accurate, e.g. CCl4 in liver homogenate 98 +/- 21.8 (S.D.) %, in blood 94 +/- 13.3%, but the precision is poor (rel. S.D. 10-20%). Air samples in volumes of up to 2 ml may be determined by direct FID injection. The ECD sensitivity of to CCl4 and CHCl3 permits determination of microsamples (50-500 microliters) of blood and liver homogenate by extraction with buffer into toluene containing an internal standard (propyl iodide). The linear range of the detector allowed calibration by peak area ratio in the concentration range (10-1500 ng of CCl4 or CHCl3 per millilitre of toluene. The accuracy of the method is high, e.g. in blood CHCl3 101 +/- 9.5 (S.D.)%, CCl4 100 +/- 15.2%, as is the precision: rel. S.D. ca 5% for both CCl4 and CHCl3. For elimination studies, CCl4 and CHCl3 in air may be trapped in toluene and determined by ECD. Recovery of known amounts of CCl4 and CHCl3 from air chamber was high: 100 +/- 4.7 (S.D.)% and 111 +/- 10.9%, respectively, and reduction of CCl4 to CHCl3 by the trapping system negligible (less than 0.01%). Cross-checking of the methods and application to the commonly used CCl4 hepatotoxicity model is demonstrated.


Assuntos
Tetracloreto de Carbono/sangue , Clorofórmio/sangue , Ar/análise , Animais , Testes Respiratórios , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Cromatografia Gasosa/métodos , Estudos de Avaliação como Assunto , Microssomos Hepáticos/análise , Ratos
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