Pediatric Pharm Flashcards
Drug administration to a pregnant patient can affect the developing fetus in one of two ways
- Direct fetal effect. Passage into fetal circulation.
2. Indirect fetal effect. Changes in blood flow.
How can drugs in material circulation cross the placenta?
- Passive diffusion (mainly)
- Facilitated diffusion.
- Active transport.
- Pinocytosis/endocytosis
Lipid soluble ions passing the placental barrier
Will readily diffuse across.
Ionized molecules passing the placental barrier
If they are ionized, they will cross slowly resulting in a very low conc of them throughout fetal circulation. However, this is relative. If the concentration of ionized (polar) drugs in material system is high, they may readily diffuse into fetal circulation.
Molecular size and passing the placental barrier
Lower the molecular weight, the more readily the molecule will pass thru placenta. Larger drugs can be transported into fetal circulation.
pH and passing the placental barrier
fetal blood is slightly more acidic (7.3) than material blood (7.4). Ion trapping is possible as basic drug can become ionized in acidic fetal circulation.
Protein bound drugs passing the placental barrier
Highly bound drugs will have more difficulty passing through the placenta. Exception: Highly lipid-soluble drugs can pass thru.
Will maternal or fetal proteins have a higher affinity for drugs?
Maternal proteins have a higher affinity for drugs compared to fetal proteins. This is why dosing adjustments need to be made.
Less protein binding in fetal circulation could result in a greater distribution of the drug since it will be able to travel through capillaries and membranes easier.
Can drug effects differ from pregnant female and same female not pregnant?
Yes, but prob not significantly.
Examples of drugs a pregnant female may need that are not needed otherwise
Insulin, diuretics.
Why might the fetus be a target for therapeutic action?
Ex: Need to mature fetal lungs.
perinatal
Weeks before and after birth
Predictable toxic drug actions perinatal?
Dependence can develop in the fetus.
Can cause organ damage
Teratogenic drug requirements (3)
- Cause the same defect
- Occur at the same stage in development
- Dose-dependent incidence. Specific dose that will cause deformation.
Mechanisms that cause the birth defect are poorly understood. Likely multifactorial.
FDA old risk categories
A: No risk in first trimester or later
B: No risk in animal studies, not done in humans.
OR
Adverse effect in animal studies, no confirmation in humans.
C: Give only if benefits outweigh risks. Adverse effect shown in animal studies with no controlled human studies
OR
Studies in women and animals are not available.
D: Life or death situation. Positive evidence of human fetal risk.
X: Fetal abnormalities. Never give to pregnant patient.
New FDA rulings
Narrative risk summary replaces A-D and X.
Subsections:
1. Pregnancy. Summary of risk.
2. Breast feeding. Summary of risk.
3. Male and female reproductive systems. Summary of risk.
Pharmacodynamic differences are prob not significant in children EXCEPT
Target tissues that mature at birth or shortly after. Ex: lungs.
Pharmacokinetic differences in Children: Absorption (2)
- Blood flow at administration site can be reduced in preterm infants.
- GI secretion, emptying time, and enzyme activity differ. May require dose adjustments or changes to administration.
Pharmacokinetic differences in Children: Distribution (1)
Body water percentage, fat composition, and plasma protein binding are different in infants.
Pharmacokinetic differences in Children: Metabolism (1)
Liver enzyme activity is lower in infants. Individual enzymes take different lengths of time to mature.
Pharmacokinetic differences in Children: Excretion (1)
Lower glomerular filtration rate in newborns. Higher in toddlers.
Percentage of drugs excreted into breast milk?
Concentrations are very small except for antibiotics, sedatives and hypnotics, and opioids
Methadone
Medication to help with heroine withdrawal. Opioid that is complicated during pregnancy/breast feeding.
Pediatric dose=
Adult dose x (child weight in lbs/150)
Not dependent on age.
