Assuntos
Anlodipino/toxicidade , Overdose de Drogas/terapia , Hemodinâmica/efeitos dos fármacos , Labetalol/toxicidade , Fosfolipídeos/uso terapêutico , Ressuscitação/métodos , Óleo de Soja/uso terapêutico , Overdose de Drogas/etiologia , Emulsões/farmacologia , Emulsões/uso terapêutico , Glucagon/uso terapêutico , Glucose/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Fosfolipídeos/farmacologia , Óleo de Soja/farmacologia , Resultado do TratamentoRESUMO
Dilevalol (SCH 19927) is an antihypertensive agent with direct vasodilating properties due to beta 2-adrenergic receptor agonist activity and nonselective beta-receptor blocking activity. In acute (single dose) oral and parenteral studies a low order of toxicity was observed. Clinical signs observed at the higher doses included salivation, prostration, tremors, and convulsions. In multidose oral studies dilevalol produced an increase in mean absolute and/or relative heart weights observed as early as 1 month in the high-dose (300 mg/kg) rats and at all dose levels (35, 90, 220 mg/kg) in rats treated for 1 year. There were no microscopic changes that could be associated with the change in heart weight. Intraalveolar macrophages were observed in the lung tissue of rats treated for 3 months or 1 year with an increase in relative lung weights noted in the high-dose (220 mg/kg) group treated for 1 year. In a 2-year rat study, no evidence of oncogenicity was observed. On the basis of these studies, dilevalol has a low order of toxicity and lacks oncogenic potential in the rat.
Assuntos
Anti-Hipertensivos/toxicidade , Labetalol/toxicidade , Animais , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
1 The toxicity of labetalol has been studied in mice, rats, rabbits, and dogs, and reproductive studies have been carried out in rats and rabbits. Nothing was observed in any of these species to suggest that patients taking labetalol might be exposed to any toxic hazard. 2 During the reproductive studies 14C-labetalol was used to study placental transfer. Radioactivity was present in the uveal tract of the foetal eye. 3 Radioactive labetalol but not its metabolites was bound to the melanin pigment of the eye. This binding was reversible. It was not possible to saturate the melanin of the cat and dog eye even with prolonged dosing with labetalol. 4 Chloroquine, given orally at doses of 1.5-6 mg/kg/d for 4-7 weeks, produced changes in the cat retina. When oral doses of 20 mg labetalol/d were given to cats for 7 months, no oculotoxic effects were observed. 5 Detailed ophthalmological and histological examinations were carried out on the rats, rabbits, cats and dogs used in these studies. No changes indicative of oculotoxicity were observed. In the reproductive studies no effects were observed in the developing rat or rabbit eye, which could be consequent on the placental transfer of labetalol or its metabolites.