Drugs in Pregnancy/Lactation

Question 1

Changes in maternal physiology

Answer 1

• altered absorption, distribution, elimination
• decreased gastric emptying
• increased intestinal transit time
• increased pulmonary blood flow and hyperventilation
• increased tidal volume, which increases absorption of inhalation agents
• increased GFR until about 28wks

Question 2

factors contributing to teratogenicity of medications in pregnancy

Answer 2

• agent used
• timing of exposure
• threshold dose
• species specificity

Question 3

Old FDA Classification of Medication Use in Pregnancy

Answer 3

Category A = no risk in human studies

Category B = no risk in animal studies but no human studies done; or, no risk in human studies but increased risk in animal studies

Category C = increased risk in animal studies but no human studies done; or, no animal and no human studies

Category D = proven risk in humans; benefits must outweigh risks

Category X = proven risk in all studies done; RISK OUTWEIGHS benefit

Question 4

New FDA Classification of Meds Use in Pregnancy

Answer 4

more complex, and more pt/situation/provider specific

Question 5

Confounding factors of studies on medication use in pregnancy

Answer 5

• drug given for a condition may itself be teratogenic
• malformation causes sx which then prompt trx with a drug
• drug inhibits abortion of an already malformed fetus
• drug frequently used with a second drug that is teratogenic
• common risk factors for drug use and anomalies

Question 6

the best time to prevent medication effects on a pregnancy is -

Answer 6

before pregnancy

Question 7

thalidomide

Answer 7

• used in 1950s-1960s for morning sickness
• causes severe limb reduction defects
• ear, renal, cardiac abnormalities
• affected 20-30% of fetuses exposed between 27-40th day after conception

(27-30th day = arms only)
(30-33rd day = legs only)

Question 8

bendectin

Answer 8

antihistamine (doxylamine) and pyrodixine for N/V; withdrawn from mark in 1983 after many lawsuits

no evidence of teratogenicity

Question 9

lessons from thalidomide use in pregnancy

Answer 9

• placenta is NOT a barrier
• extreme variability in species susceptibility
• precise relationship bw time of exposure and defect

Question 10

isotretinoin (accutane)

Answer 10

• spontaneous abortion (40%)
• major malformations (>25%) - CNS, cardio, craniofacial
• known to be teratogenic before used clinically
• explicit warning labels utilized
• many cases of retinoid embryopathy reported di

Question 11

diethylstilbesterol (DES)

Answer 11

• used bw 1940s-1971 to prevent miscarriage or preterm labor
• Mullerian anomalies (defect in female fetus reproductive organs)
• Vaginal clear cell carcinoma

Question 12

anti-convulsants/anti-seizure drugs

Answer 12

increased risk for neural tube defects. impaired folic acid metabolism.

Pregnant pts on these drugs are given 4mg of folic acid to help prevent this.

(phenytoin and carbamazepine also increase risk for hydantoin syndrome)*

Question 13

Fetal Hydantoin Syndrome

Answer 13

after fetal exposure to phenytoin or carbamazepine.

mnemonic - PHEN
P - cleft Palate
H - small Head, Hypoplastic face, Hirsutism
E - Embryopathy, anti-Epileptic drug use
N - hypoplastic Nails/digits, Neurologic defects

Question 14

alcohol in pregnancy

Answer 14

dose-dependent effect
<1 oz/day: usually no effect
1-2 oz/day: functional and growth disturbances
>3 oz/day: 50% abnormal

Question 15

effects of warfarin/Coumadin use during each trimester

Answer 15

1st trimester: fetal warfarin syndrome
2nd trimester: mental retardation, blindness
3rd trimester: hemorrhage, stillbirth

Question 16

warfarin embryopathy

Answer 16

features: microcephaly; nasal hypoplasia; stippled vertebrae and femoral epiphyses

15-25% affected with 1st trimester exposure

critical period is 6-9 wks

likely results from tissue microhemorrhages

Question 17

effects of ACE inhibitor use in pregnancy

Answer 17

• fetal/neonatal renal failure (renal tubular dysgenesis)
• oligohydramnios
• pulmonary hypoplasia
• intrauterine growth restriction (IUGR)
• stillbirth

Question 18

effects of misoprostol use in pregnancy

Answer 18

increased risk of miscarriage

use in first trimester associated with Mobius syndrome (CN 6/7 palsy, limb malformations, craniofacial abnormalities)

Question 19

effects of lithium use in pregnancy

Answer 19

cardiac defects (Ebstein’s anomaly*)

Question 20

effects of tetracycline use in pregnancy

Answer 20

• readily crosses placenta
• staining of deciduous teeth (>16wks)
• enamel hypoplasia
• inhibition of bone growth

Question 21

effect of danazol use in pregnancy

Answer 21

• potential teratogen
• weak androgen effect
• virilization of female fetuses exposed <13 wks (clitoromegaly, labial fusion)

Question 22

effect of metronidazole in pregnancy

Answer 22

-carcinogenic in rodents
-mutagenic in bacteria
- no associated malformaton in humans
- avoid in 1st trimester

Question 23

effect of aminoglycoside use in pregnancy

Answer 23

potential for ototoxicity (1-2%)

Question 24

effects of sulfonamide use in pregnancy

Answer 24

• competes with bilirubin-binding sites
• potential for hyperbilirubinemia

Question 25

effects of quinolone use in pregnancy

Answer 25

• high affinity for bone/cartilage
• arthropathy in children