When is the best time to prevent medication effects on the fetus?
Prior to conception
How do medications generally affect the fetus as the pregnancy continues on?
Embryo = death. Fetus = major malformations -> retarded growth as the pregnancy goes on
GI changes in pregnancy
Decreased gastric acid and higher pH
CV changes in pregnancy
Plasma volume expanded, increased CO
Changes in blood during pregnancy
Plasma albumin levels decrease
Changes in kidney during pregnancy
Increased renal blood flow, increased GFR (increased clearance) but tubular absorption rates stay the same
Hepatic changes during pregnancy
CYP3A4 increased (methadone), CYP2D6 decreased, increased glucuronidation (increased clearance of lamotrigine and betamethasone)
Definition of a congenital defect
Minor (does not need surgery) or major (needs surgery) deviation from normal morphology or function that happens during embryonic or fetal development.
What factors are considered when determining if a medication is teratogenic? What is a common confounder?
Proven exposure at critical time, consistent findings by > 2 epi studies, rare exposure = rare defect, teratogenic in animals and biologically plausible. A common confounder are drugs administered for conditions which are teratogenic in themselves (e.g. diabetes + insulin = caudal regression or SGA baby due to diabetes).
Limb reduction, ear, renal and cardiac defects happen in babies exposed to what drug?
Thalidomide (critical period of 27-40 days post-conception)
Possible defect in using topamax or lamotrigine, which are class C drugs
Cleft lip and palate. Note that lamotrigine is still the safest drug for seizures.
Pregnancy class of ACE inhibitors
C & D. Class C for minor cardiovascular abnormalities in 1st trimester exposure. Class D for fetal kidney dysgenesis, oligiohydramnios, pulmonary hypoplasia, growth restriction and still birth (Potter’s sequence)
Pregnancy class of valproic acid and gentamycin
Class D. Valproic acid = neural tube defects, increase prevention with folic acid supplementation.
Pregnancy class of prenatal vitamins and levothyroxine
Pregnancy class of penicillin and tylenol
Pregnancy class of nifedipine, sumatriptan and lamotrigine
Pregnancy class of isotretinoin (acetone), misoprostol and warfarin
Class X. Isotretinoin can cause spontaneous abortion in 40%, 25% of pregnancies show CNS, CV and craniofacial malformations (small eyes, retinoid regression).
Warfarin use in 1st trimester? 2nd? 3rd?
1st = 25% have embryopathy (microcephaly, nasal hypoplasia, stippled vertebrae) if exposed in 6-9 week period. 2nd = mental retardation and blindness 3rd = maternal hemorrhage and still birth.
Category for drugs that have not yet been classified
What drug used to treat bacterial vaginosis is a possible teratogen?
Metronidazole (flagyl): carcinogenic in rodents but no associated malformations. Avoid in 1st trimester.
What drug used to treat bacterial infections can cause ototoxicity in 1-2% of babies?
What drugs used for UTIs can cause hyperbilirubinemia but have no associated malformations?
Sulfonamides. They compete with bilirubin-binding sites and may result in kernicterus.
What drugs used to treat bacterial infections can cause arthropathy in children?
Quinolones, they have a high affinity for bone and cartilage.
Most common preventable cause of mental retardation in babies
Alcohol (especially binge drinking) can cause the distinct phenotype of fetal alcohol syndrome.
Absent philtrum, midface hypoplasia, low nasal bridge, low set ears, microcephaly and shorted palpebral fissures.
Fetal alcohol syndrome
Illicit drug that can cause fetal vascular disruptions? Dose-related IUGR? IUGR, cardiac defects, facial clefts? Neonatal withdraw and psychiatric effects?
Cocaine = vascular. Marijuana = IUGR does-related. Amphetamine = IUGR, cardiac defects and facial clefts. Heroin/Methadone = withdraw + psych.
Drugs that can cause gastroschisis
Illicit drugs. This can also be found in people that are very young and very old.
Drugs used to stop preterm labor (tocolytics)?
17-OH-progesterone for more long term. Acutely used: MgSO4, beta-mimetics, indomethacin (can cause pre-mature closure of PDA = polyhydramnios), Ca-channel blockers (IUGR)
Medications that help you deliver the baby
Oxytocin, cervical ripening agents (PGE1 and dinoprostone)
Drug used to dilate the cervix. Associated with Mobius syndrome (CN palsy, limb malformation, craniofacial abnormalities) when used in 1st trimester.
Misoprostol. Note that this drug is category X due to risk of uterine contractions and miscarriage.
Drugs used post-delivery to treat maternal hemorrhage
Oxytocin, methyl ergonovine and PGE1 and PGF2 alpha
Drugs used for fetal benefit
Beta-methasone for pulmonary immaturity (may cause cleft palate/lip) and penicillin for neonatal GBS.
Things to consider w/lactation
Consider dose, portion excreted in milk and amount absorbed by infant.It is also important to assess how they respond to drugs like codeine that have varied metabolism.
Drugs absolutely contraindicated in lactation
MTX and Li (may also cause Ebstein’s anomaly in pregnancy)