RESUMO
A study was made of 134 patients (67 males and 67 females) treated with sodium valproate, with ages from 1.5 to 70 years (50 on monotherapy and 84 on multitherapy), to detect side-effects of this treatment. To meet this goal, a clinical questionnaire was used with special emphasis on biological parameters to detect hepatic and pancreatic toxicity. 71.6% developed side-effects, without differences either between groups of sex or age, or patients on monotherapy and multitherapy, or the duration of the treatment, longer or shorter than six months. The side-effects were mild and transient, and without relationship with doses or plasma levels of the drug. The most noticeable side-effects in the study were the increase in amylase values, mainly in urine (23.9%), eosinophilia (30% in the monotherapy group), increase in gamma-glutamyltranspeptidase (20.2% in the polytherapy group) and weight gain in 25% of adult women on polytherapy. Only a 4.7% developed mild and transient elevation of transaminases, that did not differ from the control population. The relevance of using a clinical questionnaire and biological parameters to evaluate the side-effects of a drug is emphasized.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Pancreatopatias/induzido quimicamente , Ácido Valproico/efeitos adversos , Adolescente , Adulto , Idoso , Amilases/sangue , Peso Corporal/efeitos dos fármacos , Criança , Pré-Escolar , Eosinofilia/induzido quimicamente , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fases do Sono/efeitos dos fármacos , Inquéritos e Questionários , Ácido Valproico/sangue , gama-Glutamiltransferase/sangueRESUMO
The effects of oral administration of valproic acid (VPA) have been studied on the liver of female adult Wistar rats, at doses of 60 and 120 mg/kg/day during 4 and 18 weeks (periods I and II). Other groups received the same doses of VPA with phenobarbital (PB). The animals developed periportal steatosis, more intense at the end of period II and in groups non-induced by PB, and also some degree of mitochondrial swelling. An uncoupling of the oxidative phosphorylation was also evident with both doses in the non-induced groups, and only with the high dose of VPA in the induced group. An in vitro study on isolated liver mitochondria showed uncoupling only with very high concentration of VPA (10 mM). We comment on these findings and propose a chronic model of experimental hepatotoxicity of oral VPA in the rat.
