lactation/pregnancy Flashcards
what 5 aspects must be considered in regards to pregnancy/lactation and medications?
- Drug safety during pregnancy and lactation
- Drug toxicity during pregnancy
- Physiological changes during pregnancy that may affect drug action and kinetics
- Cross-placental transfer of drug molecules and their metabolites
- Excretion in breast milk
__% of pregnant women are exposed to teratogenic medications with __% of children born with physical or mental birth defects. why is this important?
6%, 3%
risk of exposure to these meds is small but IMPACTFUL when there is exposure
FDA published the _____________to address the limitation of prescription drug labeling
Pregnancy and Lactation Labeling Rule (PLLR)
what was the previous FDA labeling for drugs with regards to pregnancy risk?
A–>X
this was misleading, those assumed A was safer than X but this wasn’t ENTIRELY true…
what are the old FDA labels for drugs? A-X? (weeds maybe)
A: studies have failed to demonstrate a risk to the fetus in the first trimester
B: animal studies FAILED to demonstrate risk to fetus. no adequate and well-controlled studies in pregnant women
C. animal studies showed adverse effect to fetus, no adequate and well-controlled studies in humans
D. positive evidence of HUMAN fetal risk, benefits MAY warrant use
X: positive evidence HUMAN fetal risk, risks outweigh benefits
what changed in the new FDA labeling?
more options with more information from pt taken into account… “ risk categories replaced with narrative sections”
best resource for information on drugs in pregnancy?
Briggs
when is the most dangerous exposure time for a teratogen?
first 8 weeks
teratogen effect in the first 2 weeks of fetal development?
“all or none”: if a drug is a teratogen will either terminate pregnancy or have no effect
teratogen effect in wks 3-8 wks of fetal development?
most devastating defects. this is the most critical time of development
weeks 9-40 of fetal development, what is happening?
growth and developmental function
what defect can aminoglycosides (GNATS) cause?
8th cranial nerve tox- vestibular dysfunction
what defect can Alkylating Agents (Cyclophosphamide) (chemo agents) cause?
Absence of digits, multiple anomalies
Antiepileptic Drugs (Valproate, carbamazepine, phenytoin, phenobarbital) defects?
neural tube defects and others
Isotretinoin (for acne) defects ?
multiple severe birth defects
warfarin defects?
Bone deformities, fetal hemorrhage
statin defects?
spina bifida
alcohol abuse defects?
fetal alc syndrome, microcephaly
cocaine and nicotine defects?
low birth weight, pre-term birth
what about the gut in pregnancy causes altered drug absorption?
INCREASED PH ( absorption of weak acids and bases altered) & N/V and DELAYED GASTRIC EMPTYING (general drug abs altered)
how can drug distribution change b.c of pregnancy?
Increased body fat increases volume of distribution of fat soluble medications
Fat soluble medications have a decrease in elimination due to the greater volume of distribution
how can metabolism of drugs change b/c of pregnancy?
Mixed effects with increases and decreases in CYP450 enzymes and changes in transport proteins
how can excretion of drugs change b/c of pregnancy?
Increases in maternal plasma volume, cardiac output, and GFR increase – subsequently decreases plasma concentrations of renally eliminated medications
5 PK properties that influence placental drug transfer?
- lipid solubility
- molecular size
- placental transporters
- protein binding
- placental & fetal drug metabolism
