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1. What is teratology?

teratology and teratogenesis will mean the study of (-ology) and induction (-genesis)
of birth defects which are observable at birth (congenital) or at a later time. Birth
defects are usually thought of as structural or anatomical defects but may also include
physiological, functional or behavioral defects as well. Drug induced teratology refer
to birth defects caused by exposure to drugs.
Teratology and teratogenesis both contain the stem, "terat-" which comes from the
Greek word for monstrosity, "teras". A teratogen is a substance that induces a
structural malformation, a metabolic or physiological dysfunction or a behavioral
alteration or deficit in the offspring of an individual who has been challenged with
the teratogen.

2. What are the three basic principles of teratogenesis?


Species susceptibility, stage of fetal development, dosage
3. Why aren't all species equally susceptible to any given drug?
Also within the same species there may be genetic differences that affect the range of
response to a compound. Maternal parity, maternal weight, maternal age, number of
young in litter bearing animals, size of the placenta, extent of the maternal and fetal
production of hormones, the degree of enzymatic activation and differences in nutrient
utilization may all modify the susceptibility to a drug
Different types of placenta meaning differences may be due to the ability of a
teratogen to reach the embryo
4. When is the human embryo most susceptible to drugs?
20-55 or 35-70 days after last menstrual period
5. Why do some drugs cause birth defect while others do not?
Usually, at a given dosage of a drug one will see a range of severity of abnormal young. Some
young will be normal while others will exhibit different degrees of malformation and some
young will be resorbed or be born dead. Again, this variability may be due to genetic differences
between the young or a variety of other causes previously mentioned.

6. What is the impact on fetal development when some of drugs administered late in
gestation?

Table 5. Approximate Timing of Various Defects in Mana

Defect

Time of Induction before

Cyclopia

23 days

Anencephaly

26 days

Cleft lip

36 days

Syndactyly

6 weeks

Cleft Palate

8-9 weeks

Bicornate Uterus

10 weeks

Cryptorchidism

7-9 months

adapted from J.L. Schardein, Chemically Induced Birth Defects, 1985

7. Why should pregnant women always be very careful when they take a drug, even
though all the drugs approved by FDA went through rigorous testing?
It needs to be remembered that the embryo will be more susceptible to deleterious compounds
than will the mother. Thus, a dosage, which has no noticeable effect on the mother, may have
severe effects on the developing fetus. Obviously, at dosages high enough to imperil or have an
effect on the mother the fetus will be at extreme risk.

8. How can different administration routes (intravenous, oral, etc.) of a drug affect the
teratogenicity?
These results may be due to differences in absorption from different sites,
differences in the rate of release from different tissue or differences in the metabolic
fate of the substance with differences in the nature of the metabolites released. The
infamous drug, thalidomide which caused thousands of children in Europe
and Japan to have serious limb deformities, was active when given orally but if it
was injected interperitoneally, no defects were seen.

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