2- Drugs in Pregnancy

Question 1

At what point in development is the fetus most sensitive to teratogenic agents?

(teratogen = agent that causes birth defect/ congenital malformation, abn development)

Answer 1

1st trimester (most development)

Question 2

What effect does pregnancy have on drug absorption?

Answer 2

Slows drug absorption

Question 3

What effect does pregnancy have on drug metabolism?

Answer 3

Increases metabolism (esp if lipid soluble)

Question 4

What effect does pregnancy have on drug excretion?

Answer 4

Increases excretion (via kidney)

Question 5

Increase in total blood volume seen during pregnancy has what effect on drugs?

Answer 5

Changes distribution of drug

(and metabolism, absorption, excretion)

Question 6

What are the sites of drug metabolism between the mother and fetus?

Answer 6

Placenta and fetal circulation/ metabolism

(drug recirculated between fetal liver/ umbilical artery and vein = continuous exposure)

Question 7

What size molecules easily cross the placenta?

Answer 7

MW < 500 Da

Question 8

What size molecules do NOT cross the placent easily?

Answer 8

> 1000 Da

Question 9

What pharmacokinetic properties affect placental drug exchange?

Answer 9

Lipid solubility

Molecular size and pH

Placental transporters

Protein binding

Placental and fetal drug metabolism

Question 10

What drug has a beneficial effect in fetus to prevent neural tube defects?

Answer 10

Folic acid

(category A)

Question 11

Drugs with what general mechanisms should NOT be used in pregnancy? (4)

Answer 11

• Damage or inhibit DNA/ RNA synthesis
• Target rapidly proliferating cells (cancer tx)
• Radiation- free radicals damage enzymes
• Hormones that alter development

Question 12

What drug should be avoided in pregnancy because it is a folic acid antagonist?

Answer 12

Thalidomide

Question 13

What drug should be avoided in pregnancy because it affects cell differentiation/ proliferation, can lead to birth defects, and increases risk of miscarriage, premature delivery, and infant deaths?

Answer 13

Isotretinoin

Question 14

What is the leading preventable cause of intellectual disability?

Answer 14

Fetal alcohol syndrome

(no known safe level of alcohol use during pregnancy)

Question 15

What are the pharmacokinetics of fetal alcohol syndrome?

Answer 15

Alcohol concentration in fetal blood = concentration in mother’s blood

Fetal liver does not have significant ALDH activity = slower alcohol metabolism = acetylaldehyde/ ethanol buildup

Question 16

Female pt currently taking Warfarin wishing to get pregnant should be switched to what drug?

Answer 16

Heparin- does NOT cross placenta

(Warfarin = risk of vit K antagonist embryofetopathy)

Question 17

What drug is used as a sedative and to combat nausea in pregnant women but has been found to cause limb deformities?

Answer 17

Thalidomide

Question 18

Pt of reproductive age with severe acne is beginning treatment with Isotretinoin. What precautions must be taken to avoid drug exposure in pregnancy?

Answer 18

iPledge program

(-) pregnancy test + 2 forms of BC (1 of which is surgical/ hormonal starting 1 month prior and continuing 1 months after drug therapy)

Question 19

Which anticonvulsants are considered “low risk” for teratogenicity?

(most abundant/ consistent data for low structural and neurodevelopmental teratogenic risk)

Answer 19

Levetiracetam, Lamotrigine

(also Gabapentin, Clonazepam)

Question 20

Which anticonvulsants are should be avoided in pregnancy?

(substantial risk for major congenital malformations, adverse neurodevelopmental consequences and autism/ autism spectrum disorder)

Answer 20

Valproate

Question 21

Baby presents with neural tube defects, trigonocephaly, broad forehead, thin arched eyebrows, flat nasal bridge, and thin upper lip. What drug was the mother likely taking during pregnancy?

Answer 21

Valproic acid

(fetal Valproate syndrome- AVOID)

Question 22

What drug used to treat HCV or RSV can lead to male and female-mediated teratogenicity therefore requiring pregnancy testing prior/ throughout therapy, and contraception requirements for males and females?

(2 forms of contraception during tx and for 6 months after tx discontinuation)

Answer 22

Ribavirin

(malformations of skull, palate, eye, jaw, limbs, skeleton, GI tract)

Question 23

Adenocarcinoma of the vagina/ cervix was a/w offspring of pregnant women taking what drug?

Answer 23

DES