在妊娠哺乳期用药.ppt

* * * The most sensitive period to Teratogenic effects Tetragon= any substance that produces deformity Different in species (animals, humans) Thalidomide Phenytoin 5%, warfarin 25% The most common Teratogenic drugs are: * 2. Organogenesis Drug Effect Danazol Sex hormones Verilization of female fet. Multiple, cardiac Lithium cardiac Phenytoin Craniofacial;limb Carbamazepine Craniofacial;limb Valproate Neural tube warfarin Multiple defects; chondrodysplasia retinoids CNS, craniofacial, heart Predictable toxic drug actions in the fetus Opioids ? dependence of fetus and newborn ACEI ? irreversible renal damage of fetus Diethylstilbosterol? adenocarcinoma of vagina after puberty * Definition: Developmental abnormality drug Animal studies Rate of spontaneous is 1-2% Teratogenic mechanisms: Poorly understood and multi-factorial Direct effect on maternal tissues with 2ry effect on fetal tissues. ▼Oxygen and nutrients through placenta Direct actions on fetal tissues e.g. differentiation of developing tissues. E.g. Vit. A analogues Deficiency of critical substance like folic acid * Teratogenesis Dangerous period: 2nd to 8th weeks of pregnancy (structural abnormalities Later on: dugs affect growth, development, integrity of body structure especially brain But what about the stored drug? Like etritinate? 2 years * Teratogenesis CAUSES OF BIRTH DEFECTS IN HUMANS Schardein JL, 2000. *Evidence: Level B Characters of the teratogen: To be defined as a teratogen, the substance or the process should: Result in a characteristic set of malformation Exert its effect at a particular stage of fetal development Shows dose-dependence incidence E.g. retinoids, warfarin, sex hormones Food and drug administration classification of Drugs in pregnancyFDA Categories : teratogenic risk of drugs DRUG LABELPregnancy “Categories” A Controlled studies in humans no risk e.g Penicillin ???? B animal studies show no risk but no controlled human OR animal studies show adverse effects)