1. Drug Therapy During Pregnancy and Breast-Feeding

2. Clinical Goal
Provide effective treatment for mother while avoiding harm to fetus or nursing infant

3. Basic Considerations ● Availability of data
● Drug use during pregnancy
● To treat or not treat conditions in the mother
● Avoid drug therapy if at all possible

4. Physiological Changes during Pregnancy
Renal blood flow
Hepatic metabolism
Tone & motility of the bowel

5. Example
Seizure disorder – can the mother go without controlling the condition?
No, unsafe
Which drug to use? Least teratogenic
carbamazepine
What are the pharmacokinetic considerations for achieving therapeutic effects?
Hepatic metabolism increased (enzyme induction)
Increased plasma vol = lower concentrations

6. Placental Drug Transfer
Same pharmacokinetics as before
if lipid soluble, cross easily
If ionized, highly polar, cross with difficulty
Assume that any drug taken during pregnancy will reach the fetus

7. Adverse Reactions during Pregnancy
Examples – if woman is on:
Pain relievers -  resp in neonate
ASA – can suppress contractions in labor;  risk of bleeding
Dependence-producing drugs – infant will go through withdrawal syndrome
Heparin – causes osteoporosis
Greatest concern - teratogenesis

8. Teratogenesis Incidence and causes of congenital anomalies
Gross malformations, behavioral and biochemical anomalies
Teratogenesis and stage of development
Preimplantation/presomite (conception – wk 2)
Embryonic (wk 3 – wk 8)
Fetal period (wk 9 – term)
Identification of teratogens

9. Figure 9-1 Effects of teratogens at various stages of development of the fetus. (From Moore KL: The Developing Human: Clinically Oriented Embryology, 5th ed. Philadelphia: WB Saunders Company, With permission.)

10. Teratogenesis Identification of teratogens Why so difficult? – page 89
Classification of a teratogen

11. FDA pregnancy risk categories
The FDA has established five categories (A, B, C, D, and X) to indicate a drug's potential for causing teratogenicity.
A - Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester, and the possibility of fetal harm appears remote.
B - Animal studies do not indicate a risk to the fetus and there are no controlled human studies, or animal studies do show an adverse effect on the fetus but well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus.
C - Studies have’ shown that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
D - Positive evidence of human fetal risk exists, but benefits in certain situations (e.g., life-threatening situations or serious diseases for which safer drugs cannot be used or are ineffective) may make use of the drug acceptable despite its risks.
X - Studies in animals or humans have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience, or both, and the risk dearly outweighs any possible benefit.

12. Teratogenesis Minimizing the risk of teratogenesis
Responding to teratogen exposure .

13. Case
Sherri - 28 y/o F. At primary care for referral to antepartum care. Positive home pregnancy test, LMP 6 weeks ago.
PMH: seasonal asthma, hypothyroidism, depression.
Medications:
Thyroid hormone, 125 mcg daily, for hypothyroid
Albuterol MDI, 1-2 puffs PRN for asthma
Flovent (fluticasone) MDI, 1 puff/day for asthma
Zoloft (sertraline) 150 mg/d for depression
Ibuprofen, 400 mg, PRN, for headache

14. Drug Therapy During Breast-Feeding
Extent of drug entry into breast milk varies
If drugs need to be used:
Dose immediately after breast-feeding
Avoid drugs that have a long half-life

15. Principles of Therapy During Breastfeeding
Is the drug therapy necessary?
What is the safest option for the infant?
If there’s the possibility of harm, monitor infant blood levels of the drug.
Minimize infant exposure.
American Academy of Pediatrics

16. Examples to consider
Immune suppressants (e.g., cyclosporine. methotrexate)
Amiodarone & antithyroid drugs
Benzodiazepines, anticonvulsants, antihistamine – watch for sedation
Caffeine – high infant exposure = irritability

17. Drug Therapy in Pediatric Patients

18. Pediatric Patients Respond differently to drugs
Drug sensitivity results from organ system immaturity
Why insufficient drug info?

19. Pharmacokinetics: Neonates and Infants
Drug levels differ between infants and adults
Absorption
Distribution
Hepatic metabolism
Renal excretion

20. Pharmacokinetics: Neonates and Infants
Absorption
Oral administration
Gastric emptying time
Gastric acidity
Intramuscular administration
Percutaneous absorption

21. Pharmacokinetics: Neonates and Infants
Distribution
Protein binding
Blood-brain barrier
Hepatic metabolism
Renal excretion

22. Pharmacokinetics: Children Aged 1 Year and Older

23. Adverse Drug Reactions

24. Dosage Determination Approximate dosage for a child =
Body surface area of the child × adult dose
1.73 m²

25. Promoting Adherence
Effective education is critical. The following issues should be addressed:
Administration timing and dose
Administration route and technique
Treatment duration
Drug storage
Nature and time course of desired responses
Nature and time course of adverse responses