Drugs in Pregnancy/Lactation Flashcards
Changes in maternal physiology
- 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
factors contributing to teratogenicity of medications in pregnancy
- agent used
- timing of exposure
- threshold dose
- species specificity
Old FDA Classification of Medication Use in Pregnancy
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
New FDA Classification of Meds Use in Pregnancy
more complex, and more pt/situation/provider specific
Confounding factors of studies on medication use in pregnancy
- 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
the best time to prevent medication effects on a pregnancy is -
before pregnancy
thalidomide
- 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)
bendectin
antihistamine (doxylamine) and pyrodixine for N/V; withdrawn from mark in 1983 after many lawsuits
no evidence of teratogenicity
lessons from thalidomide use in pregnancy
- placenta is NOT a barrier
- extreme variability in species susceptibility
- precise relationship bw time of exposure and defect
isotretinoin (accutane)
- 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
diethylstilbesterol (DES)
- used bw 1940s-1971 to prevent miscarriage or preterm labor
- Mullerian anomalies (defect in female fetus reproductive organs)
- Vaginal clear cell carcinoma
anti-convulsants/anti-seizure drugs
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)*
Fetal Hydantoin Syndrome
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
alcohol in pregnancy
dose-dependent effect
<1 oz/day: usually no effect
1-2 oz/day: functional and growth disturbances
>3 oz/day: 50% abnormal
effects of warfarin/Coumadin use during each trimester
1st trimester: fetal warfarin syndrome
2nd trimester: mental retardation, blindness
3rd trimester: hemorrhage, stillbirth
warfarin embryopathy
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
effects of ACE inhibitor use in pregnancy
- fetal/neonatal renal failure (renal tubular dysgenesis)
- oligohydramnios
- pulmonary hypoplasia
- intrauterine growth restriction (IUGR)
- stillbirth
effects of misoprostol use in pregnancy
increased risk of miscarriage
use in first trimester associated with Mobius syndrome (CN 6/7 palsy, limb malformations, craniofacial abnormalities)
effects of lithium use in pregnancy
cardiac defects (Ebstein’s anomaly*)
effects of tetracycline use in pregnancy
- readily crosses placenta
- staining of deciduous teeth (>16wks)
- enamel hypoplasia
- inhibition of bone growth
effect of danazol use in pregnancy
- potential teratogen
- weak androgen effect
- virilization of female fetuses exposed <13 wks (clitoromegaly, labial fusion)
effect of metronidazole in pregnancy
-carcinogenic in rodents
-mutagenic in bacteria
- no associated malformaton in humans
- avoid in 1st trimester
effect of aminoglycoside use in pregnancy
potential for ototoxicity (1-2%)
effects of sulfonamide use in pregnancy
- competes with bilirubin-binding sites
- potential for hyperbilirubinemia
