Lecture 25 Adverse Drug Reactions – Teratogenesis
Drug use in pregnancy
•Drug effects in pregnancy rarely evaluated befre market release
•Use not recommended unless benefits justify risk
Teratogenic: factor with harmful effect n fetus
Types of malformations
•Major: structural/functional defects, medical/surgical intervention necessary,
incompatible with life, impair individuals’ capability to function normally in
society.
•Minor: unusual morphological traits, no serious medical/cosmetic consequences to
child.
Thalidomide
•Antiemetic during pregnancy
•Limb reduction defect, other abnormalities
•Critical period of exposure 45-50 days after first day of last menstrual period
Critical Periods
•Pregnancy 3 trimesters, ~3 months each
•Also can be divided into: egg/embryo/fetus
•Egg: preimplantation, zygote formation until blastocyst implants in uterine wall
miscarriage
•Embryo: implantation – 8th week of development, rapid growth, differentiation,
organ system development major structural anomalies
•Fetus abnormal organ differentiation, growth, function
Direct effects of drugs on fetus (cellular)
•Receptor-mediated toxicity: relatively predictable/proportional to drug
concentration
•Reactive intermediate mediated toxicity
oProteratogens biotransformed to electrophiles, free radicals target DNA,
proteins, lipids
Indirect effects of drug on fetus (maternal effects)
•Poor nutrition
•Disease states
•Altered blood supply to fetus
Effects on fetus/infant
•Malformation, disruption, deformation
•Fetal loss
•Fetal toxicity/withdrawal