Pregnancy & Lactation (KEY POINTS) Flashcards
Overall PK changes seen in pregnancy
Various factors work to increase Vd, increase clearance, decrease protein binding, & shorten or lengthen 1/2 life
If major PK changes occur in pregnancy, what usually happens?
Increased clearance wins
Lower maternal drug levels
What type of drugs more easily cross the placental membranes to enter into the fetal circulation?
Highly lipophilic
What type of drugs have a lower free fraction that is available to diffuse into the fetal circulation?
Highly protein-bound
therefore these drugs do not reach the fetus in high concentrations
Which type of drugs reach higher concentrations in the fetus?
the least maternal protein-bound drugs (digoxin, ampicillin)
What happens if there is more fetal than maternal protein binding?
Tends to concentrate drug on fetal side
During pregnancy - what happens to albumin in the fetus vs the mother?
Gradual lowering in mom
Gradual rise in fetus
What molecular weight of drugs can readily cross the placenta?
< 500 Da (daltons)
Which drugs do NOT cross the placenta in significant amounts?
MW > 1000
Ex. insulin & heparin
Is maternal or fetal pH lower?
Fetal!
Does placental CYP450 have a major role in drug metabolism?
It is not clear
The placenta converts prednisolone to…
inactive prednisone
Therefore, it can be used in pregnancy!
What type of drugs cross the placenta well & produce fetal effects that are recognized at delivery?
Drugs used for anesthesia & analgesia
Ex. Respiratory distress from narcotics given to mom
What happens to CYP450 throughout pregnancy?
Appears at 14wks & increases throughout
When does glucuronidation mature?
Near or after birth
However, conjugating systems in the fetus are found
What abx are avoided during pregnancy due to displacement of bilirubin from albumin & enhancement of kernicterus?
Sulfonamides
What type of antiemetic is used for “refractory & serious cases” during pregnancy?
Ondansetron (Zofran)
What is MOA of bromocriptine (a previously used drug for lactation)?
Ergot derivative
Activates D2 receptors & inhibits PRL release –> suppression of lactation
Why is bromocriptine no longer used for suppression of lactation?
Stroke, MI, seizures, HTN
How do you drugs move into breast milk?
By passive diffusion & carrier-mediated transporters
What is a safe exposure index value for infants?
No more than 10% of a dose
What drugs should you avoid in breast feeding women?
- Oxycodone & meperidine (in large doses)
- Methotrexate
- Lithium
- Phenobarbital
- Primidone, ethosuximide
- Chemo drugs
- Amiodarone, atenolol, nadolol
What drugs are considered safe for breast feeding women?
Low dose morphine & even intermittent low doses of oxycodone
Methadone
Which 2 BBs are safe for breast feeding women?
Propranolol & labetalol
