RESUMO
Meclizine and caffeine combination is used for the treatment of morning sickness. Both compounds are teratogenic and caffeine is known to possess anti-fertility activity also. The present study was undertaken to evaluate the reproductive toxic effect of meclizine and caffeine combination. Three doses were taken for the study; low dose (LD; meclizine 3.7 mg/kg and caffeine 3 mg/kg) was selected from commercially available formulation, middle dose (MD; meclizine 37 mg/kg and caffeine 30 mg/kg) and high dose (HD; meclizine 370 mg/kg and caffeine 300 mg/kg). The mixture was administered 1-7 days and 8-14 days for fertility and embryotoxic studies respectively. Laparotomy was done on 10th day of gestation period. Number of implants and corpora lutea were counted, pre and post-implantation losses were determined. In embryo toxicity study fetuses were evaluated for external, skeletal and visceral examination. High dose was removed from both fertility and embryotoxicity studies due to its severe toxicity to the dam. Significant anti-fertility activity was observed at middle dose. Embryotoxicity study showed significant reduction in fetal body weight, body length and body mass index, dam body weight gain on gestation day 14. Absolute kidney weight in MD and absolute and relative spleen weight in both LD and MD were significantly reduced. There was no increase in external or internal congenital anomalies at both LD and MD. The, results suggest that prescription of meclizine and caffeine for morning sickness in early pregnancy should be reviewed carefully.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Cafeína/administração & dosagem , Cafeína/toxicidade , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Ingestão de Alimentos/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Peso Fetal/efeitos dos fármacos , Idade Gestacional , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/toxicidade , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Meclizina/efeitos dos fármacos , Meclizina/toxicidade , Tamanho do Órgão/efeitos dos fármacos , Antagonistas de Receptores Purinérgicos P1/administração & dosagem , Antagonistas de Receptores Purinérgicos P1/toxicidade , Ratos Wistar , Baço/efeitos dos fármacos , Baço/patologia , Aumento de Peso/efeitos dos fármacosRESUMO
This paper included 6 cases examined in our Genetics Unit because of their limb malformations. We used a detailed structured questionaire to be sure that the mothers were healthy during the 40 weeks of gestation and have never been exposed to any drug except antihistamine especially in the first trimester. For the 6 patients; careful clinical examination, pedigree analysis, radiological examination, chromosomal study, and metabolic studies were done. The karyotypes and metabolic investigations were normal. Clinical and radiological studies showed a specific defect which is congenital limb- reduction deformity. This indicates a possible teratogenic effect of antihistamines. Thus we recommend to stop using antihistamines during pregnancy especially in the first trimester