Pediatric Pharmacology Flashcards
How does the gastric pH of children differ from adults and how does this influence drug absorption?
It is generally higher
Acid labile drugs -> better oral bioavailability
Weak acids -> less absorption (more are in ionized form)
Weak bases -> more absorption (less are in ionized form)
How does dermal absorption of drugs differ in pediatrics?
Dermal absorption is higher due to underdeveloped skin, but riskier due to chance of skin damage
Why are IM injections avoided in neonates?
Low muscle mass and decreased blood flow
What are the relative total body water and body fat in infants? How does this relate to Vd?
Total body water -> higher in infants, due to higher extracellular fluid. Hydrophilic drugs will have higher Vd
Body fat -> Lower in infants, gets higher over first year of life. Lipophilic drugs will have lower Vd
What is the difference in protein binding of infants?
There is not a normal level of albumin until age 1
-> drugs which are generally highly protein bound will have a greater effect by being free in plasma, like sulfa and ampicillin
How do neonatal phase 1 reactions compare to adult levels? Phase 2?
Phase 1: Not at full capacity until 6 months to 1 year of age
Phase 2: Not fully paced until 3 to 4 years of age, can lead to chloramphenicol toxicity
What is the relative activity of CYPs in children?
During childhood, can be up to 2x faster than adults. Normalizes in puberty
What functions of the kidney mature first in infants?
GFR matures first (secretion)
Resorption and excretion matures second (excretion)
-> affects drugs which require extra clearance, like penicillins
How does kidney function between pediatrics and adults differ?
It is generally lower, and full functioning is not reached til age 3.
What is the biggest barrier to finding efficacious drugs in children?
Limited research and development -> only vaccines and childhood diseases are studied, rest of drugs given are adult drugs used off-label for younger children.
What is the newest FDA rule regarding labeling of drugs for safe use?
Need to have 3 subsections for safety of drug.
- Pregnancy
- Lactation
- Males and Females of Reproductive Potential
What are two drugs which are more toxic in newborns due to reduced phase 2 metabolism and why?
- Sulfonamides - displace bilirubin from albumin. Lower levels of glucuronsyl-transferase (UGT) enzyme results in higher plasma concentrations of bilirubin, and resulting kernicterus.
- Chloramphenicol - Lower levels of UGT resulted in accumulation of chloramphenicol which cannot be glucuronated and excreted in urine -> gray baby syndrome
