2- Drugs in Pregnancy Flashcards
At what point in development is the fetus most sensitive to teratogenic agents?
(teratogen = agent that causes birth defect/ congenital malformation, abn development)
1st trimester (most development)
What effect does pregnancy have on drug absorption?
Slows drug absorption
What effect does pregnancy have on drug metabolism?
Increases metabolism (esp if lipid soluble)
What effect does pregnancy have on drug excretion?
Increases excretion (via kidney)
Increase in total blood volume seen during pregnancy has what effect on drugs?
Changes distribution of drug
(and metabolism, absorption, excretion)
What are the sites of drug metabolism between the mother and fetus?
Placenta and fetal circulation/ metabolism
(drug recirculated between fetal liver/ umbilical artery and vein = continuous exposure)
What size molecules easily cross the placenta?
MW < 500 Da
What size molecules do NOT cross the placent easily?
> 1000 Da
What pharmacokinetic properties affect placental drug exchange?
Lipid solubility
Molecular size and pH
Placental transporters
Protein binding
Placental and fetal drug metabolism
What drug has a beneficial effect in fetus to prevent neural tube defects?
Folic acid
(category A)
Drugs with what general mechanisms should NOT be used in pregnancy? (4)
- Damage or inhibit DNA/ RNA synthesis
- Target rapidly proliferating cells (cancer tx)
- Radiation- free radicals damage enzymes
- Hormones that alter development
What drug should be avoided in pregnancy because it is a folic acid antagonist?
Thalidomide
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?
Isotretinoin
What is the leading preventable cause of intellectual disability?
Fetal alcohol syndrome
(no known safe level of alcohol use during pregnancy)
What are the pharmacokinetics of fetal alcohol syndrome?
Alcohol concentration in fetal blood = concentration in mother’s blood
Fetal liver does not have significant ALDH activity = slower alcohol metabolism = acetylaldehyde/ ethanol buildup
Female pt currently taking Warfarin wishing to get pregnant should be switched to what drug?
Heparin- does NOT cross placenta
(Warfarin = risk of vit K antagonist embryofetopathy)
What drug is used as a sedative and to combat nausea in pregnant women but has been found to cause limb deformities?
Thalidomide
Pt of reproductive age with severe acne is beginning treatment with Isotretinoin. What precautions must be taken to avoid drug exposure in pregnancy?
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)
Which anticonvulsants are considered “low risk” for teratogenicity?
(most abundant/ consistent data for low structural and neurodevelopmental teratogenic risk)
Levetiracetam, Lamotrigine
(also Gabapentin, Clonazepam)
Which anticonvulsants are should be avoided in pregnancy?
(substantial risk for major congenital malformations, adverse neurodevelopmental consequences and autism/ autism spectrum disorder)
Valproate
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?
Valproic acid
(fetal Valproate syndrome- AVOID)
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)
Ribavirin
(malformations of skull, palate, eye, jaw, limbs, skeleton, GI tract)
Adenocarcinoma of the vagina/ cervix was a/w offspring of pregnant women taking what drug?
DES
