Pregnancy Flashcards
Embryocidal
leading to fetal death
Teratogenic
leading to irreversible changes in structure or function.
• Includes structural abnormalities, developmental impairment, or late carcinogenesis (i.e. thalidomide)
Fetotoxic
Altering growth or development in the 2nd or 3rd trimesters (i.e. nicotine-cause intrauterine growth restriction)
Medication properties to consider
- Molecule Size
- Lipid Solubility
- Protein Binding
Pregnancy properties to consider
- Placental Transporters
- Placental & Fetal Drug Metabolism
Molecule size/molecular weight
[Med properties to consider]
• The lower the molecular weight (smaller molecules), the more readily the drug will cross the placenta
<500g/mole (tylenol, cocaine, morphine, penicillin) – readily crosses placenta
500-1k g/mole (dig) – crosses placenta slowly
>1000 g/mole (heparin, insulin) – transfer across placenta severely impeded [usually safe]
Lipid Solubility
[Med properties to consider]
• Lipophilic (lipid-soluble) drugs will cross the placenta more freely than hydrophilic (water-soluble) drugs
(ex: many CNS medications)
• Many antibiotics will cross
Protein Binding
[Med properties to consider]
- Unbound drugs readily cross the placenta
- Highly lipid soluble are less likely to be bound to protein
- Also varies on degree of binding
Placental Transporters
[Pregnancy properties to consider]
• Located in the placenta and pumps drugs back into maternal circulation away from the fetus
Placental & Fetal Drug Metabolism
[Pregnancy properties to consider]
Placenta
- Provides semipermeable barrier and site of metabolism
- Metabolize drugs before reaching fetus, but may create toxic metabolites
Umbilical Vein
• 40-60% umbilical blood flow directed toward fetal liver (adds additional metabolism)
Stages of development
1st trimester: 1-12 week
- CNS, Heart - major morph. abnormalities
2nd trimester: 12-28
- physiologic defects, minor morph. abnormalities
3rd trimester: 29-40
FDA Pregnancy Categories/Pregnancy Risk Factors (outdated)
A: Controlled studies in pregnant women failed to demo risk in 1st trimester (or later)
B: Controlled animal repro studies failed to demo risk to fetus
- and* no well-controlled studies in pregnant women
- or* animal repro studies show neg effect but well-controlled studies in women failed to demo risk in 1st trimester (+ no evidence of harm in later trimesters)
C: Animal repro studies show adverse fx, no well-controlled studies in humans
- and* benefits may outweigh risks for pregnant women
- OR* animal repro studies have not been conducted
D: Positive evidence of human fetal risk based on adverse rxn data from investigational or marketing experience or studies in humans
but benefits may outweigh risks for pregnant women
X: studies in animals or humans demo fetal abnormalities
- and/or* evidence of human fetal risk
- and risk of the use of the drug clearly outweighs any potential benefits*
Pregnancy and Lactation labeling rule (PLLR)
Added category re: risk for females and males of reproduction potential (sect 8.3)
Other categories:
- 8.1 Pregnancy, combined with L&D
- 8.2 Lactation
+ Added more detailed study information so prescribers can weigh decision to prescribe
Lactation - properties to consider
Medication Properties that readily transfer into breastmilk:
- Lower molecular weight (smaller molecules)
- Lipophilic (lipid-soluble) (medications with CNS activity)
- Less protein bound, free drugs
- Drugs pass by simple diffusion
Breastfed infants (risk levels)
Lowest risk: older infants (6-12mo); can metabolize medications
Moderate risk: younger infants (<4mo); infants with metabolic/GI abnormalities, complications from birth, apnea
Highest risk: preemies or neonates, unstable infants, poor renal output
