1. Medication use during pregnancy
Uzoma Samuel Ikonne Ph.D.

2. COPYRIGHT WARNING
THE COPYRIGHTED MATERIALS AVAILABLE IN THIS PRESENTATION ARE FOR EDUCATIONAL USE ONLY. ONE COPY PER STUDENT IS PERMITTED FOR EDUCATIONAL PURPOSES. REDISTRIBUTION IS NOT PERMITTED

3. Learning Objectives
1. Discuss pharmacokinetic factors that affect drug transfer during pregnancy: Lipid solubility, Molecular size and pH, Placental Transporters, Protein Binding, and Placental and Fetal Drug Metabolism 2. Discuss changes to pregnancy categories 3. Describe Therapeutic Drug Action 4. Describe Toxic drug action on Fetus: ACE inhibitors and Opioids 5. Discuss Teratogen and Teratogenic mechanisms: Folic Acid, Thalidomide, Tobacco Smoking/Nicotine, Fetal Alcohol Distress Syndrome

4. Recommended Reading
Koren G (2015). Special Aspects of Perinatal & Pediatric Pharmacology. InKatzung B.G., Trevor A.J. (Eds), Basic & Clinical Pharmacology, 13e. 

5. Lipid Solubility Drugs in Cesarean section
Lipophilic drugs tend to cross placenta easier i.e. Thiopental
Highly ionized i.e Succinylcholine moves slowly
Staud, F., Cerveny, L., & Ceckova, M. (2012). Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure. Journal of drug targeting, 20(9),

6. Molecular size and pH Molecular weight 250-500 easier
more difficult
>1000 very difficult
Heparin vs Warfarin pH
Maternal blood pH 7.4
Placenta blood pH 7.3

7. Placental Transporters
Staud, F., Cerveny, L., & Ceckova, M. (2012). Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure. Journal of drug targeting, 20(9),

8. Protein Binding
Highly-Lipid Soluble – not affected as much by protein binding
Lower-Lipid Soluble affected more
Differences in maternal and fetal protein binding affinities

9. Placental and Fetal Drug Metabolism
Monticone, S., Auchus, R. J., & Rainey, W. E. (2012). Adrenal disorders in pregnancy. Nature Reviews Endocrinology, 8(11),

11. Therapeutic Drug Action: Respiratory Distress Syndrome

12. Toxic Drug Action: Angiotensin-Converting Enzyme (ACE) Inhibitors “–prils-”
Contraindicated in Pregnancy: significant renal failure in infants

13. Toxic Drug Action on Fetus: Opioids
Neonatal Abstinence Syndrome (NAS)
Tremors (trembling)
Irritability (excessive crying)
High-pitched crying
Seizures
Vomiting
(not exhaustive)

14. https://www. drugabuse

15. A B C D

16. Teratogen Characteristics Effects
Result in characteristic set of malformations
Selectivity for target organs
Exerts its effects at a particular stage of fetal development
Dose-dependent incidence
Major malformations
Thalidomide
Growth restriction
Cigarette smoking
Miscarriage
Alcohol
Stillbirth
Cigarette smoke
Neurocognitive delay
Courtesy Dr. Thompson

17. Human Development

18. FDA Teratogenic Risk Categories (OLD)

19. New Pregnancy Labels

20. Examples: Old vs New
Versus

21. Teratogenic Mechanisms
Direct effects on maternal tissue affecting the fetus
Interference with passage of oxygen/ nutrients through the placenta
Direct effects on differentiation of tissues
Vitamin A
Deficiency of critical substances
Folic acid
Multifactroial
Courtesy Dr. Thompson

22. Thalidomide: Malformations
Phocomelia – malformation of limbs
Risk: 4-7 weeks gestation

23. Tobacco Smoking/Nicotine: Growth Restriction
Symptoms:
Intrauterine growth restriction
Stillbirth
Neurobehavioral deficiency
Risk Factor for SIDS
Wickstrom, R. (2007). Effects of nicotine during pregnancy: human and experimental evidence.Current neuropharmacology, 5(3),

24. Fetal Alcohol Spectrum Disorder
Symptoms:
Poor Growth
Decreased muscle tone and poor coordination
Delayed development: thinking, speech, movement, or social skills (3 of 4)
Heart Defects (heart murmur)
Alcohol Use Increases risk of Miscarriage

26. Vitamin A (retinoic acid): Differentiation
Cunningham, T. J., & Duester, G. (2015). Mechanisms of retinoic acid signalling and its roles in organ and limb development. Nature reviews Molecular cell biology, 16(2),

27. Folic Acid: Deficiency
Neural Tube Defects i.e. Spina bifida

29. References