teratogens

Question 1

What is teratogenesis

Answer 1

dysgenesis of fetal organs either structurally or functionally (causing intellectual disability)

Question 2

What is the most famous teratogen

Answer 2

Thiolinamide; originally used to Tx influenza, then used as anti-emetic and sleep aid

Question 3

When is Thiolinamide teratogenic

Answer 3

34th - 50th day after LMP

Question 4

What were the effects of Thiolinamide

Answer 4

Phocomelia (limb defects) 2/2 inhibiting angiogenesis during limb bud formation 
External ear defects 
Visceral anomalies (organ agenesis)

Question 5

When is baby safe from teratogens

Answer 5

Ovum prior to fertilization is resistant

first 2 weeks (conception to implantation), ovum is usually resistant bc/ it is mostly separated from mom’s circulation

Question 6

When does organogenesis occur

Answer 6

days 18-60 gestation; most gross deformities before day 36
GU/craniofacial: later
Palate sensitivity lasts appx 3 weeks
CNS: 2 weeks- near end of gestation

Question 7

What is the “fetal phase”

Answer 7

End of embryonic state (9 weeks) to term

Question 8

What do teratogens usually cause in the fetal phase

Answer 8

CNS dysfunction
IU growth retardation
Organ dysfunction

Question 9

How is dosing related to teratogenesis

Answer 9

Effects occur more frequently at higher doses

Question 10

What are the most accepted theories on the mechanisms of teratogenesis

Answer 10

• Antineoplastic agents are cytotoxic (depressed mitosis, promote cell death) and when the body tries to repair, you get uncoordinated growth (malformation)
• Directly interact with DNA and interfere w/ gene expression
• Affect angiogenesis
• Inhibit enzymes important for organ development
• Nutrient and vitamin deficiencies can be teratogenic (folate)

Question 11

What are the FDA pregnancy categories

Answer 11

A: studies fail to demonstrate risk in first trimester (folic acid, levothyroxine)
B: animal studies fail to demonstrate risk (Amoxicillin, Insulin R and N)
C: animal studies show adverse effects on fetus, only use if benefit>risk (albuterol, fluoxetine, Sertraline)
D: dont use, evidence of human fetal risk (tetracyclines)
X: dont use, positive human fetal risk

Question 12

How are animal studies related to human studies

Answer 12

Not all animal teratogens are harmful in humans BUT relatively all human teratogens are harmful to animals

Question 13

What are the teratogenic drugs in this lecture (most important)

Answer 13

Carbamazepine 
Phenytoin 
Valporate 
Isotretinoin 
Oral anticoagulants (warfarin)

Question 14

What does Carbamazepine cause

Answer 14

Neural tube defects

effects similar to phenytoin embryopathy

Question 15

What does phenytoin cause

Answer 15

short fingers, short nose

Question 16

What does valporate cause

Answer 16

neural tube defects from 1st trimester exposure 
small mouth 
developmental delay 
narrow forehead 
flat philtrum

Question 17

What does isotretinoin cause

Answer 17

external ear defects/absence of ears 
congenital heart defects 
hydrocephalus 
mental retardation 
clefts 
hypertelorism (space between eyes is wide) 
40% miscarriage

Question 18

What does warfarin cause in first trimester exposure (6-9 weeks)

Answer 18

Fetal warfarin syndrome: nasal hypoplasia, calcific stippling of epiphysis, short stubby fingers

Question 19

What does warfarin cause after the first trimester

Answer 19

CNS defects (in utero hemorrhage+scarring) 
Bone defects (dwarfism, scoliosis, skull defects) from inhibited gamma carboxylation of bone proteins

Question 20

What risk factors can cause adverse pregnancy outcomes

Answer 20

Alcohol misuse and obesity

Question 21

What does alcohol in pregnancy cause (fetal alcohol syndrome)

Answer 21

IUGR, microcephaly, mental retardation, facial abnormalities

Question 22

What amount of alcohol is reported safe while pregnant

Answer 22

one drink per day (1 beer, 4 oz wine, 1 shot liquor 40% ethanol)
2-14 drinks per week are said to cause FAS

Question 23

What do FAS babies look like

Answer 23

small head 
epicanthial folds 
short nose 
smooth philtrum 
underdeveloped jaw 
long nasal bridge 
thin upper lip

Question 24

What do ACE and ARB cause

Answer 24

congenital renal failure
skull abnormalities
*Oligohydramnios causing limb contractures, skull and facial deformities

Question 25

Were ACE/ARB always teratogenic?

Answer 25

No, they used to be safe in first trimester until a retrospective study found links to congenital heart disease and CNS abnormalities

Question 26

What HTN meds are safe in pregnancy

Answer 26

Methyldopa

Labetolol

Question 27

What does methotrexate do

Answer 27

Folic acid antagonist, inhibits dihydrofolate reductase
Microcephaly, short limbs, IUGR, Hypoplastic skull w/ wide fontanelles
IF >10mg/week

Question 28

What can tobacco use cause

Answer 28

pre-term birth, low birth weight, spontaneous abortion, increased perinatal mortality

Question 29

What does Diethylstilbesterol cause

Answer 29

clear cell vaginal adenocarcinoma and premature labor in female offspring
hypospadias in male offspring

Question 30

What can radiation cause

Answer 30

Microcephaly and mental retardation

Cancer to the child in the future

Question 31

What do tetracyclines cause

Answer 31

Inhibit protein synthesis= discolored teeth from Abx deposition in calcifying teeth

Question 32

What do tetracyclines do to teeth

Answer 32

Cause discoloration to deciduous teeth after 17 weeks gestation
late use can cause crown staining of permanent teeth

Question 33

What tetracyclines are less likely to produce staining

Answer 33

Oxytetracycline, Doxycycline

Question 34

What is Thiolinamide FDA approved for today

Answer 34

Treating multiple myeloma

treating skin lesions associated with lepracy