Fetal Pharmacology

Question 1

important teratogens to know

Answer 1

isotretinoin, ACE inhibitors, tetracycline, coumadin (warfarin), anti-seizure meds (phenytoin, valproate, carbamazepine), lithium, thalidomide, DES, cocaine

Question 2

isotretinoin effects on fetus

Answer 2

spontanous abortion

craniofacial, cardiac, and CNS defects

Question 3

ACE inhibitors effects on the fetus

Answer 3

first trimester: CV and CNS defects
2nd and 3rd trimester: oligohydramnios
mechanism: decreased placental bloodflow, ACEis cross the placenta and decrease vascularization on the retina and kidney

Question 4

fetal alcohol syndrome

Answer 4

mental retardation, structural abnormalities, withdrawal in newborn period

Question 5

signs of withdrawal from abused prescription agents

Answer 5

autonomic hyperactivity, irritability, excessive cryine, poor feeding, and abnormal reflexes

Question 6

thalidomide effects on the fetus

Answer 6

phocomelia: limb reduction

Question 7

opiate receptor location

Answer 7

concentrated in the CNS and GI

Question 8

opiate withdrawal symptoms

Answer 8

CNS hyperactivity with associated autonomic hyperactivity, vomiting, diarrhea, dehydration, poor weight gain, and poor feeding.

Question 9

determinants of trans-placental drug passage

Answer 9

lipid solubility, degree of ionization at physiologic pH, molecular weight < 600, maternal plasma drug binding, placental blood flow, and energy dependent drug transporter proteins (Pgp, MRP, etc.)

Question 10

most important factors in determining drug effect on fetus

Answer 10

timing and duration of exposure

Question 11

effects of warfarin on fetus

Answer 11

fetal warfarin syndrome: hypoplasia of the nose and extremities and developmental retardation.

Question 12

DES effects on fetus

Answer 12

cervical/uterine developmental defects

Question 13

cocaine effects on fetus

Answer 13

placental abruption and pre-term contractions

Question 14

teratogenic mechanisms

Answer 14

folate antagonism, neural crest disruption, endocrine disruption, oxidative stress, vascular disruption, and specific receptor or enzyme mediated events

Question 15

effect of early SSRI exposure

Answer 15

congenital malformations: anencephaly, omphalocele, septal defects, and cardiac abnormalities, neurological defects (decreased pain sensation and increased risk of autism)
persistant PAH
decreased serotonin, norepinephrine, and metabolites

Question 16

pregnancy category A

Answer 16

adequate studies have demonstrated no risk

Question 17

pregnancy cat. B

Answer 17

animal studies have not demonstrated risk but there are no adequate studies in pregnant women or animal studies have shown risk but adequate studies in pregnant women have not shown risk

Question 18

pregnancy cat. C

Answer 18

animal studies have shown risk, but there are no adequate studies in humans or there are no animal reproduction studies or human studies

Question 19

pregnancy cat. D

Answer 19

there is evidence of human fetal risk, but the potential benefits from the use of the drug in pregnant women may be acceptable

Question 20

pregnancy category x

Answer 20

studies in animals or humans demonstrate fetal abnormalities or adverse reaction; reports indicate evidence of risk, risk of use in a pregnant woman clearly outweighs any possible benefit.

Question 21

neonatal pharmacology

Answer 21

slower GI, but faster IM absorption
more body water than lipid in early life
limited protein binding 
larger liver/body weight ratio
immature enzymes
larger brain/body weight ratio
higher BBB permeability
immature renal function
longer drug half lives

Question 22

pediatric dosing

Answer 22

adult dose x (body weigh (kg) / 70)

Question 23

drugs in breast milk pharmacokinetics

Answer 23

milk will concentrate bases and lipid soluble drugs due to its low pH and high fat content
dosing after feeding allows for levels to decline