This document discusses drugs and medications in pregnancy. It begins by outlining the objectives of providing an overview of drug metabolism during pregnancy, discussing principles of teratogenicity, and examining the risk to the fetus from some prescription medications, environmental exposures, and illicit drugs. It then covers how maternal physiology changes during pregnancy can impact drug absorption, distribution, metabolism, and elimination. Key principles of teratology and criteria for defining teratogenicity are presented. Finally, several known or suspected teratogens like alcohol, antiepileptics, ACE inhibitors, antineoplastics, and cocaine are examined in more detail.

1. Drugs & Medications In
Pregnancy
Tesfaye A.
( MD, Obstetrician & Gynecologist )
2/13/2023 1

2. Objectives
 Give overview on drug metabolism in pregnancy
 Discuss principles of teratogenicity
 Discuss risk to the fetus from some of prescription
medicines, environmental exposure & illicit drugs
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3. Maternal Physiology During Pregnancy
• Evolves during the course of pregnancy
CVS & Pulmonary-
Renal – increased renal plasma flow & GFR
Hepatic- higher portal venous return
GI - N &V , decreased intestinal motility
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4. Effect Of Physiologic Changes On Drug Metabolism
1) Drug absorption
- the slower intestinal motility and decreased gastric acid secretion
- no confirmatory evidence for increased oral bioavailability
2) Drug distribution
- decreased plasma protein ( albumin & AAG)
- increased free fraction , increased clearance
3) Drug metabolism
- Phase I & Phase II
- Activity of majority of enzymes in cytochrome P450 (CYP) system
increases during pregnancy (impacted by maternal genotype)
4) Drug Elimination
- changes in renal clearance during pregnancy varies widely
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5. Pharmacokinetics Of Drugs Across The
Placenta
• Placental barrier
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6. • Passive diffusion across the villous barrier –predominant
method of the fetus’s exposure
- Small
- lipid soluble, Cross the placenta easily
- unionized, and
- poorly protein
bound
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7. • Placental Transporters
- Specific endogenous substrates
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8. Principles Of Teratology
Teratology - the study of birth defects and their etiology
Teratogen - may be defined as any agent that act
during embryonic or fetal development
to produce a permanent alteration of
form or function.
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10. Wilson’s six general
principles of teratogenesis
1. Genotype interaction with environmental factors
2. Timing of exposure
3. Mechanisms of teratogens
4. Manifestation
5. Agent
6. Dose effect
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12. Fetal risks with maternal pharmacotherapy
 The overall risk of congenital malformations is 2–4%.
 However, only 10% of malformations are linked to
drug exposure
 Administration of drugs early may affect the heart or neural tube;
 Later exposure affects the formation of the ear and palate.
 Before day 31, exposure to a teratogen produces an
all-or-none effect, ( fertilization to implantation)
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13. Criteria To Define Teratogenicity
• Established exposure of the embryo or fetus at a critical
time during development.
• Consistent dysmorphic findings recognized in well conducted
epidemiologic studies.
• Specific defects or syndromes consistently associated with
a specific teratogen
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14. Studies in pregnant women
▪ Case reports or series,
- single case reports which later aggregated
- true risk posed by various drugs and environmental agents.
▪ Case-control studies,
- cases & controls are compared for exposure
▪ Cohort studies
- groups differing in exposure be followed through time,
with outcomes observed.
▪ RCTs- lacking ,unless for evaluating efficiency of prevention or treatment
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15. ▪ Pregnancy Registries
- monitoring potentially harmful agents
- requires knowledge of the baseline prevalence
of that anomaly in the population
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16. Counseling for medication exposure
• Individuals tend to exaggerate potential risks associated with
medication exposure.
• The manner in which information is presented affects perception.
• Negative vs positive information
• Odds ratio vs absolute risk
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17. FDA classification ,
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18. Limitation of letter classification
- Mainly, it is for prescribing physician
- Can lead to overreliance
- higher letter grade did not necessarily mean greater risk
- drugs in the same category often had very different risks
- < 1% category A. while most had no safety data in humans ( category C)
- Does not address inadvertent exposure
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19. Known / Suspected teratogens
1. Alcohol
- No amount of alcohol can be considered safe in pregnancy
- Spectrum of alcohol-related fetal defects known as fetal alcohol syndrome
- CNS abnormalities,
- pre- or postnatal growth impairment, and a
- characteristic pattern of minor facial abnormalities
- In 6% of infants of heavy drinkers
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21. 2. Antiepileptic
• The most frequently reported anomalies are orofacial clefts, cardiac
malformations, and neural-tube defects
• valproic acid confers the greatest risk
• -The risk for fetal malformations is approximately
doubled if multiple agents are required
• Several older anticonvulsants also produce a constellation of
malformations similar to the fetal hydantoin syndrome
• The benefits of AEDs in appropriates doses during pregnancy outweigh
the risks of discontinuation.
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23. •These risks do not appear to hold for the newer
agents levetiracetam and lamotrigine, although
the number of reported pregnancies to date is
smaller
•
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24. 3. ACE inhibitors & Angiotension receptor blockers
- ACE-inhibitor fetopathy
- ACE-inhibitor embryotoxiciy??
4. Antifungals
- Fluconazole - oral clefts, abnormal facies, and cardiac, skull,
long-bone, and joint abnormalities, TOF
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25. 5.NSAIDs
- Indomethacin – Constriction of DA,..
- ASA-
6. Leflunomide
- In several animal species, it results in fetal hydrocephalus,
eye anomalies, skeletal abnormalities, and embryo death
when given at or below human-equivalent doses
- The active metabolite, teriflunomide, is detectable in plasma for
up to 2 years following discontinuation of the medication
- What if a woman becomes pregnant while taking it ?
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26. 7. Antimicrobials –most are safe except;
- aminoglycosides- some preterm neonates developed
ototoxicity &nephrotoxicity
- chloramphenicol - avoided in late pregnancy due to
theoretical concerns.
- Tetracyclines – are associated with yellowish-brown discoloration
of deciduous teeth when used after 25 weeks’ gestation.
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27. 8.Antineoplastic agents
- Cyclophosphamide- high-arched palate, microcephaly, flat nasal bridge,
syndactyly, hypoplasia of the finger, secondary malignancy
- Methotrexate –conotruncal cardiac defect, facial & limb anomalies
,abortion
- Tamoxifen – DES exposure like syndrome in animals
- Trastuzumab - cases of oligohydramnios sequence resulting in pulmonary
hypoplasia, renal failure, skeletal abnormalities, and neonatal deaths have
been reported
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28. 9. Anti virals
▪ For most ,experience in pregnancy is limited
▪ Ribavrin – causes multiple birth defects in different animal species
- skeletal , eye ,palate, GI abnormalities
- women should be on contraceptive for 6 months
after discontinuation of the drug
- contraindicated in men whose partners are pregnant.
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29. Efaverinz - CNS and ocular abnormalities in cynomolgus monkeys
- Antiretroviral Pregnancy Registry has identified
no increased birth defect rates in more than
800 pregnancies with first-trimester exposure
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30. 10. Androgens- cause varying degrees of virilization and may
result in ambiguous genitalia
Danazole- There was a dose-related pattern of clitoromegaly,
fused labia, and urogenital sinus malformation.
( In a review of inadvertent exposure during early
pregnancy when given , 9-12 weeks after conception )
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31. 11. Immunosuppressant Medications
• Corticosteroids – other vs prednisolone
• A meta-analysis of exposure to corticosteroids in the fist trimester
showed an odds ratio of 3.0 for cleft lip and/or cleft palate.
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32. 12. Radioiodine – contraindicated in pregnancy
- Pregnancy testing should be
performed before administration
of radioiodine-131.
- no fetal risk for exposure before 12 weeks of gestation
.
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33. Mercury – environmental spillage
- consumption of certain species of large fish
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34. 13. Psychiatric medications
Lithium
- has been associated with Ebstein anomaly
- These women should be offered appropriate
prenatal diagnosis with ultrasound, including
fetal echocardiography.
- may be withheld for 24 to 48 hours before
delivery to reduce both neonatal complications
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35. • A 1.5- to twofold greater risk for cardiac malformations
following first-trimester paroxetine exposure
• Late pregnancy exposure - neonatal behavioral syndrome , ? PPHN
• Antipsychotic – are not considered teratogenic
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36. 14. Retinoids
- are among the most potent human teratogens
- The prevalence of birth defects after exposure
during embryogenesis is estimated to be as high as 30%
- cause abortion, CNS malformations, cardiac , facial
dysmorphism, etc.
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37. 15.Thalidomide and Lenalidomide
- Possibly the most notorious human teratogen
- causes malformations in 20 percent of fetuses exposed between
34 and 50 days menstrual age.
- The characteristic malformation is phocomelia
- was instructive of several important teratological principles
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38. 16. Warfarin
• Warfarin embryopathy
- nasal hypoplasia, microphthalmia ,hypoplasia of extremities ,IUGR,
cardiac defects ,deafness, mental retardation
- stippled epiphyses
• following exposure during this critical period is estimated to be 6 percent
▪ One embryopathy met analysis , warfarin dosage was ≤5 mg/d identified
in 1 percent of exposed fetuses.
▪ This suggests that risk may be dose dependent
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39. • Abnormalities can also include agenesis of the corpus
callosum; cerebellar vermin agenesis, which is the Dandy-Walker
malformation; microphthalmia; and optic atrophy
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40. 17. Cocaine –
• With this CNS stimulant, most adverse outcomes result from its
vasoconstrictive and hypertensive effects
• Fetal-growth restriction and preterm delivery.
• Children exposed as fetuses have risks for behavioral abnormalities
and cognitive impairments
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41. Thank You
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