RESUMO
The antinociceptive effect of tramal and its combinations with nonsteroidal anti-inflammatory drugs (ortophen, indomethacin, naproxen, acetylsalicylic acid, and ibuprofen) was studied in 110 male albino rats on models of electric and thermal stimulation. Possessing their own antinociceptive activity, nonsteroidal anti-inflammatory drugs potentiated the analogous effect of tramal. In vitro tramal was intensively demethylated by the rat liver microsomal fraction. In therapeutic concentrations ortophen and naproxen suppressed the rate of tramal demethylation by the rat microsomes. The potentiating effect of nonsteroidal anti-inflammatory drugs in relation to tramal is apparently connected with the delay in its biotransformation and conversion to inactive metabolites.
Assuntos
Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Tramadol/uso terapêutico , Analgésicos Opioides/farmacocinética , Animais , Biotransformação , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Masculino , Microssomos Hepáticos/metabolismo , Dor/tratamento farmacológico , Dor/etiologia , Dor/metabolismo , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Fatores de Tempo , Tramadol/farmacocinéticaRESUMO
Phenobarbital in a dose of 70 mg/kg (one-time daily intraperitoneal administration for 5 days) promotes naproxen elimination from rat blood and reduces its analgesic activity. Cymetidine (intragastric one-time daily administration in a dose of 100 mg/kg for a week) inhibits naproxen elimination from blood and increases it analgesic effect. Thiamine diphosphate administered intraperitoneally in a dose of 10 mg/kg (one time a day for a week) does not change pharmacokinetic and analgesic effect of naproxene.
Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/uso terapêutico , Antiulcerosos/farmacologia , Cimetidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Naproxeno/farmacocinética , Naproxeno/uso terapêutico , Fenobarbital/farmacologia , Tiamina Pirofosfato/farmacologia , Animais , Anti-Inflamatórios não Esteroides/sangue , Artrite Experimental/sangue , Artrite Experimental/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Masculino , Naproxeno/sangue , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The influence of retinol, alpha-tocopherol, and cimetidine on ulceration induced by ortophen, indomethacin, naproxen was studied on rats. It was shown that alfa-tocopherol, retinol, and cimetidine reduce the damaging effect of these drugs on the gastroduodenal mucosa of rats thus normalizing the phospholipid content. The influence of alpha-tocopherol and retinol on the side-effects of ortophen was studied in children with rheumatoid arthritis. Ortophen was found to cause gastroduodenal side-effects in more than 30% of patients and decrease the levels of vitamin A and E in children. The use of retinol and alpha-tocopherol in cotherapy decreases the frequency and severity of side-effects and reduces the vitamin deficiency.