Teratogens B&B

Question 1

when is the “all or none” period of teratogen exposure and what does this mean?

Answer 1

embryonic period (1st trimester) is most dangerous for teratogen exposure

first 2 weeks is “all or none” period - teratogen will cause spontaneous abortion or have no effect

Question 2

which category of drugs is absolutely contraindicated in pregnancy?

Answer 2

category X - risk clearly outweighs benefits, drug is known teratogen in animals and humans

Question 3

why are ACE inhibitors and ARBs teratogens? what drug class are they?

Answer 3

pregnancy class D

2nd/3rd trimester cause oligohydramnios which can lead to Potter’s syndrome (pulmonary hypoplasia, limb/skeletal deformities)

this makes sense because ACEI/ARBs will decrease fetal kidney function by disrupting RAAS and may cause fetal renal failure

Question 4

why are anti-seizure drugs teratogenic and which drug in particular poses a large risk?

Answer 4

associated with neural tube defects due to folate depletion, especially valproic acid

recall pregnant women take folate supplements to prevent neural tube defects, so pregnant women on seizure drugs taken high dose folic acid supplements

Question 5

which 4 anti-seizure drugs are considered particularly high risk for neural tube defects in fetuses? what is done to prevent this effect in pregnant women with epilepsy?

Answer 5

1. valproic acid - very high risk
2. phenytoin
3. phenobarbital
4. carbamazepine

[Very Powerful Pills Control epilepsy]

cause a decrease in folic acid, so pregnant women taking these drugs take high dose folic acid supplements (recall all pregnant women taken folic acid supplements to prevent neural tube defect)

Question 6

what precautionary step should be taken in pregnant women with medically-treated epilepsy?

Answer 6

seizure drugs (esp. valproic acid) are teratogenic due to decrease in folic acid, which is associated with risk of neural tube defect

therefore, pregnant women should take extra high doses of folic acid

Question 7

what causes Fetal Hydantoin Syndrome?

Answer 7

associated with phenytoin (seizure drug, form of hydantoin) use during pregnancy

—> growth deficiency, microcephaly, cleft lip/palate, broad/short nose + wide-spaced eyes

Question 8

what fetal abnormalities are associated with phenytoin use during pregnancy?

Answer 8

Fetal Hydantoin Syndrome: associated with phenytoin (seizure drug, form of hydantoin) use during pregnancy

—> growth deficiency, microcephaly, cleft lip/palate, broad/short nose + wide-spaced eyes

Question 9

what are the highest risk chemotherapy agents for fetal abnormalities?

Answer 9

alkylating agents and antimetabolites

—> spontaneous abortion, missing digits, etc

Question 10

Patient is a 17yo F beginning isotretinoin therapy for severe acne. What must be prescribed concurrently?

Answer 10

birth control is mandatory in females of child-bearing age taking isotretinoin (derivative of vitamin A), because it is a Class X teratogen

frequently causes spontaneous abortions or embryopathy (abnormalities)

Question 11

This acne drug is considered Class X, mandating concurrent use of birth control in female patients of child-bearing age. What is?

Answer 11

isotretinoin: derivative of vitamin A, frequently causes spontaneous abortions or embryopathy if used by a pregnant woman

Question 12

why is methotrexate a Class X drug? be specific

Answer 12

methotrexate: anti-inflammatory drug that inhibits folate metabolism

recall low folate is associated with neural tube defects in pregnant women

methotrexate is used to induce abortion in ectopic pregnancy

Question 13

what are the classic findings of Warfarin Embryopathy?

Answer 13

warfarin - pregnancy class D

warfarin embryopathy causes bone and cartilage abnormalities - stippled epiphyses (small, round densities on X-ray), nasal or limb hypoplasia

Question 14

what teratogenic drug is associated with causing stippled epiphyses seen on X-ray of the baby?

Answer 14

warfarin - pregnancy class D

warfarin embryopathy causes bone and cartilage abnormalities

Question 15

what is the classic effect of methimazole use during pregnancy?

Answer 15

methimazole: drug for hyperthyroidism, pregnancy class D - may cause fetal/neonatal hypothyroidism

classically causes aplasia cutis - patch of missing epidermis on scalp (missing skin/hair)

recall PTU (propylthiouracil) is used during 1st trimester (embryonic period)

Question 16

A woman gives birth to a baby with a missing patch of skin on its head. What teratogenic drug was likely used during pregnancy?

Answer 16

methimazole: drug for hyperthyroidism, pregnancy class D - may cause fetal/neonatal hypothyroidism

classically causes aplasia cutis - patch of missing epidermis on scalp (missing skin/hair)

recall PTU (propylthiouracil) is used during 1st trimester (embryonic period)

Question 17

the teratogenic effects of lithium primarily involve ______

Answer 17

the heart - most commonly causes Ebstein’s anomaly (displaced tricuspid valve, atrialization of the RV)

Question 18

this teratogenic drug is known for causing Ebstein’s anomaly in the fetus - what is?

Answer 18

lithium (psychiatric drug) - teratogenic effects on the heart, most commonly Ebstein’s anomaly (displaced tricuspid valve, atrialization of the RV)

Question 19

what are the teratogenic effects of the following antibiotic classes?
a. aminoglycosides
b. tetracyclines
c. fluoroquinolones
d. sulfonamides

Answer 19

a. aminoglycosides - permanent deafness

b. tetracyclines - permanent discoloration of fetal teeth

c. fluoroquinolones - fetal cartilage damage

d. sulfonamides - kernicterus (brain damage due to high bilirubin)

Question 20

methotrexate and trimethoprim are similar in that they both have this teratogenic effect…

Answer 20

methotrexate - induces abortion in ectopic pregnancy
trimethoprim - antibiotic

both disrupt folate metabolism, which is associated with neural tube defects!

Question 21

why is thalidomide pregnancy class X?

Answer 21

thalidomide: used in 1950s as sedative during pregnancy, caused limb deformities

—> amelia (limb absence), micromelia (short limbs), phocomelia (abnormal limbs)

Question 22

what reproductive tract abnormalities are common in female babies born from mothers who used DES (diethylstilbestrol) during pregnancy?

Answer 22

hypoplastic uterus, cervical hypoplasia —> infertility

vaginal adenosis (metaplasia of cervical/endometrial epithelium in vagina due to persistent Mullerian tissue) —> vaginal clear cell adenocarcinoma

Question 23

What are the clinical features of fetal alcohol syndrome?

Answer 23

intellectual disability + congenital heart defects + skeletal anomalies (small) + characteristic facial features —>

smooth philtrum (grove above lip), short palpebral fissures (small eye opening), thin upper lip

highest risk in first trimester!

Question 24

what components of smoking make it teratogenic to babies? (2)

Answer 24

1. nicotine - induces vasoconstriction, reducing placental blood flow
2. carbon monoxide - competes with O2 binding on hemoglobin, reducing oxyhemoglobin

both of these impair O2 delivery to fetus! —> low birthweight, placental abnormalities

Question 25

What are the consequences of smoking during pregnancy?

Answer 25

low birthweight, placental abnormalities (abruption, previa, rupture), preterm labor, SIDS

[recall nicotine + CO reduce O2 flow to fetus]

Question 26

what are the effects of cocaine on pregnancy?

Answer 26

causes vasoconstriction, reducing blood flow to placenta

—> low birthweight, placental abruption, preterm birth, miscarriage

Question 27

why does neonatal hypoglycemia occur?

Answer 27

babies born to diabetic mothers make excess insulin (hyperinsulinemic state)

when blood glucose falls after birth, excess insulin production can cause hypoglycemia

transient state, usually first 24 hours

Question 28

what is the classic congenital heart defect associated with maternal diabetes?

Answer 28

transposition of the great arteries! [STEP clue]

Question 29

what is the risk associated with pregnant women with PKU (phenylketonuria)?

Answer 29

women with PKU cannot metabolize phenylalanine, which if consumed at high levels can act as a teratogen —> low birthweight, microcephaly, intellectual disability, congenital heart defects (coarctation of the aorta, hypoplastic left heart)

dietary restriction/ serum monitoring essential