What drug properties affect placental transfer? (i.e. make a drug more likely to cross the placenta)
Small molecules, lipophilic, unbound drugs
lipophilic drugs are less likely to be bound to a protein
What are ways the placenta protects to fetus from drug transfer?
- Placental transporters (pump drug back into maternal circulation)
- Placenta acts as a semipermeable barrier and a site of metabolism. (this however, can cause toxic metabolites to get through)
- Umbilical vein - 40-60% of blood is directed to fetal liver for additional metabolism
Define teratogenic
- Results in a characteristic set of malformations
- Exerts its effects at a particular stage of development
- Show a dose-dependent incidence
During pregnancy when are most drugs CI?
the first trimester d/t early development
Name a few known teratogenic drugs
Thalidomide - seal limbs, babies born w/o limbs, nerve damage
Carbamzepine - 1st trimester, neural tube defects
Pheytoin - All - fetal hydrantoin syndrome
Valporic acid - All - neural tube defects, cardiac and limb manifestations
FDA Label A
No s/e to pregnancy
FDA Label B
EITHER Animal studies showed no risk & no well controlled women studies
OR
animal studies show some adverse effect, but there are well controlled women studies that show no risk (fail to so risk)
FDA Label C
Benefits outweight risks
OR
no animal studies
FDA Label D
Fetal risk but potential benefit outweight risk
ex: epilepsy, bipolar.
FDA Label X
Risks outweigh benefits -> known abnormalitis
FDA labels 8.1-8.3
- 1 - Pregnancy, L & D
- 2 - Nursing mother’s, lactation
- 3 - Females and males of reproductive potential
Laws for accutane? IPLEDGE, IREMS
If used by females who are of reproductive potential they must be on 2 forms of BC and have monthly pregnancy tests.
What’s a NO NO during lactation?
tetrocyclines (doxy) - permanent tooth staining
barbiturates - lethargy, sedation, poor suck reflex
lithium - could cause baby to go into renal failure
What classifies a neonate?
<28 days
What classifies a preme?
36 weeks and under
What classifies a full term?
37 weeks or later
What classifies a Term pregnancy?
37-42 weeks of gestation
What pharmacokinetic/pharmacodynamic effects are different in babies and children?
- GI Absorption - increased for weak bases
- Skin absorption - absorbs readily always limit topical meds/ use smallest corticosteroid conc
- Distribution - babies are all water - water soluble drugs require higher conc
- Protein Binding - decreased protein binding = increased unbound drug
- Metabolism - slower at birth and matures rapidly and peaks around 1-9 yrs (exceeding adult values), slowly decreased to adult levels about 9-12 yrs. Requires higher dose of hepatic metabolized drugs.
- Glucoronidation Metabolism - immature, adult values at 3-4 yrs, Chloramphenicol toxicity in neonate - grey baby syndrome
- Renal Elim - Reduced in neonate and slowest in preme, inc to adult values by 7-12 moth. Peaks at 3-12 yrs and gradually declines. -> longer frequencies in children, shorter freq in babies
What is the significant of the BBB in neonates?
It has not been formed yet, therefore all drugs can reach the CNS, and increase CNS effects and increase permeability of drugs (aminoglycosides)
What is the significance of Bilirubin in neonates?
Drugs can displace bilirubin from albumin, increased unbound bilirubin, increased risk of kernicterus.
Neonate have increased production and decreased clearance of bilirubin.
When is the Schwart’z equation most ideal?
ideal for peds patients, considers serum creatinine, height, gender and age
When is the Schwart’s equation not ideal?
PICU
infants younger than 1 week
Pts w obesity, malnutrition or muscle wasting
What drugs are not CI, but benefits may outweigh risks in infants, children?
Quinolones (floxacins)
Tetracyclines (esp < 4 yrs)
Dose of APAP in children?
10-15 mg/kg/dose Q4-6 hours
Max of 5 doses/day
COMES IN 80mg, 160mg, 325mg (suppositories)
Oral soln 160mg/5ml
