RESUMO
According to the high consumption of the mixture of B vitamins and diclofenac in several countries, this combination has constituted a frequently used option in pain therapy from inflammatory origin. Although the evidence obtained from inflammatory pain animal models has shown the existence of analgesic synergy between diclofenac and the B vitamins mixture, the corresponding clinical evidence is scarce. A double-blind, randomized clinical trial study was designed to characterize the analgesic effect and safety of diclofenac and B vitamins against diclofenac alone in patients with severe osteoarthritis. Forty eight patients programmed to total knee arthroplasty with a pain level ≥7 in a 1-10 cm visual analogue scale were allocated to receive a single intramuscular injection of sodium diclofenac (75 mg) alone or combined with thiamine (100 mg), pyridoxine (100 mg) and cyanocobalamin (5 mg), and the pain level was evaluated during 12 h post-injection. Diclofenac+B vitamins mixture showed a superior analgesic effect during the assessed period and also a better assessment of the pain relief perception by patients than diclofenac alone. This study constitutes a clinical support on the improvement of the analgesic effect of diclofenac by B vitamins in patients with osteoarthritis programmed to total knee arthroplasty, as a clinical model of inflammatory pain.
Assuntos
Analgésicos/farmacologia , Diclofenaco/farmacologia , Osteoartrite/tratamento farmacológico , Complexo Vitamínico B/farmacologia , Idoso , Diclofenaco/efeitos adversos , Método Duplo-Cego , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The pharmacokinetics of meloxicam, a potent analgesic and antiinflammatory drug used in several rheumatic diseases, has been studied in rats that received oral doses of 3.2, 5.6 or 10 mg/kg of meloxicam. Blood samples were obtained at selected times during 24 h after administration, and meloxicam concentrations were determined by a validated high-performance liquid chromatography (HPLC) method, using micro-whole-blood samples, developed in our laboratory. After administration of meloxicam, blood concentrations increased reaching a dose-dependent maximal concentration in about 2 h. Then, concentrations decayed with a half-life of 9 h. An increase in C(max) and AUC as a function of the dose was observed, and no statistically significant difference was observed in AUC/dose or C(max)/dose between doses. However, linearity could not be concluded because of the wide variability observed.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Tiazinas/farmacocinética , Tiazóis/farmacocinética , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/sangue , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Meia-Vida , Masculino , Meloxicam , Ratos , Ratos Wistar , Tiazinas/sangue , Tiazóis/sangueAssuntos
Formaldeído , Inflamação/prevenção & controle , Medição da Dor/efeitos dos fármacos , Dor/prevenção & controle , Complexo Vitamínico B/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Feminino , Inflamação/induzido quimicamente , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Dor/induzido quimicamente , Ratos , Ratos WistarAssuntos
Obstrução das Vias Respiratórias/tratamento farmacológico , Asma/tratamento farmacológico , Broncodilatadores/farmacocinética , Broncodilatadores/uso terapêutico , Teofilina/farmacocinética , Teofilina/uso terapêutico , Adulto , Obstrução das Vias Respiratórias/metabolismo , Obstrução das Vias Respiratórias/fisiopatologia , Algoritmos , Asma/metabolismo , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Feminino , Volume Expiratório Forçado , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Teofilina/administração & dosagemAssuntos
Pressão Sanguínea/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Piperazinas/farmacologia , Receptores Adrenérgicos alfa 1/classificação , Animais , Fibras Autônomas Pré-Ganglionares/fisiologia , Estimulação Elétrica , Masculino , Ratos , Ratos Wistar , Vagotomia , Sistema Vasomotor/efeitos dos fármacosRESUMO
The aim of the present study was to assess the role of vascular alpha 1D-adrenoceptors in the sympathetic vasopressor response in vivo. Specifically, we evaluated the effect of a selective alpha 1D-adrenoceptor antagonist, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)dec ane-7,9- dione 2HCl), on the vasopressor response induced by preganglionic (T7-T9) sympathetic stimulation in the pithed rat. The vasopressor response was dose-dependently sensitive to inhibition by intravenous BMY 7378 (0.1, 0.31, 1 and 3.1 mg/kg), doses of 1 and 3.1 mg/kg being equally effective. Like BMY 7378, 5-methylurapidil (0.1, 0.31, 1 and 3.1 mg/kg) antagonized the vasopressor response to spinal stimulation; doses of 1 and 3.1 mg/kg were also equally effective. In combination experiments, BMY 7378 (1 mg/kg, i.v.) and the alpha 1A-adrenoceptor antagonist, 5-methylurapidil (1 mg/kg, i.v.), showed an additive effect. The present results demonstrate that the alpha 1D-adrenoceptor subtype plays an important role in the pressor response to sympathetic nerve stimulation in the pithed rat, and confirm the participation of the alpha 1A-adrenoceptor subtype in the same response.