Lecture 25 Adverse Drug Reactions

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22 Apr 2012
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
Minor: unusual morphological traits, no serious medical/cosmetic consequences to
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
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
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
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