Block 3 Lecture 1 -- Drugs and Pregnancy Flashcards
What factors influence the variance of outcomes of drug exposure on the fetus?
1) type of exposure
2) timing of exposure
3) dose/route/frequency
4) co-exposure
5) genetics
drugs can turn good bad
Thalidomide’s currently approved uses:
multiple myeloma
pulmonary fibrosis
leprosy
Preconception folate requirement
400 mcg
When does organogenesis and cell differentiation occur?
GD20 - GD56
What is spina bifida?
failure to zipper the neural tube
Why is folic acid required?
bi-directional zippering of neural tube, which is derived from ectoderm
FDA reproductive toxicity tests must be in:
rabbits + rats/mice at 3 doses
Cat A
adequate controlled studies in pregnant women
– safe, no increased risk for fetal abnormalities
Cat B
no evidence of harm in animal studies, or
ADRs in animals, but no evidence in controlled studies of pregnant women
Cat C
ADRs in animal studies but no human studies, or
no studies in either
Cat D
controlled or simple observational human studies show fetal harm
Cat C
studies in animals or pregnant women demonstrate fetal abnormality
– may induce labor
Cat C drugs
ASA (except for 3rd trimester)
NRT gum
Zyban
Chantix
Cat D drugs
ACE-I, Li, phenytoin, carbamazepine, valproate, BZDs
nicotine patch
Cat B drugs
APAP
Problem with old pregnancy categories
give incorrect impression that all drugs in category are of similar risk
What are the new pregnancy categorization?
3 sections of narrative form
- Clinical Management Statement
- Summary Risk Assessment
- Discussion of Animal and Human Data
What are the required components of the adverse developmental outcomes statemetn?
1) structural abnormalities
2) embryo
3) functional impairment
4) alterations to growth
What is the new rule on risk statements?
1) human data
2) animal data
3) pharmacological considerations
in that order
What are the old labeling categoreis
pregnancy
labor and delivery
nursing mothers
What are the new labeling categories?
pregnancy
lactation
females and males of reproductive potential
Why is nicotine patch in Cat D?
associated with premature labor and delivery
What were the effects of prenatal oral nicotine administration in mice?
1) upregulation of nAChRs in SN and VTA
- - long-term development changes
- - tolerance in striatum
- - sensitaization in hippocampus
2) more likely to use nicotine
3) PNE-induced hyperactivity present in males (late) and females (early)
- - passed to offspring via female
Describe nicotine’s distribution affecting the baby.
Readily crosses placenta
accumulates in amniotic fluid
