Pediatrics Part 2 Flashcards
name 2 main factors that affect drug distribution in children
body composition
protein binding
explain how body composition and fluid requirements are a concern in children
they can only hold so much liquid – they need a lot that “space” for nutrition
as they grow, they need less and less nutrition and can hold more and more water
explain the extracellular fluid composition of a neonate/infant and how it changes as they get older
how does this affect the distribution of drugs
when first born, ECF is at highest levels. by 1 y/o, it decreases to 30%
more drug can distribute here and not be effective
IMPACTS DRUG DOSE AND SERUM LEVELS
explain how the body fat composition changes with age
highest in infancy
affects dosing and serum levels of drugs — they can distribute their and not be effectivie
name 2 components of body composition that can affect the drug dose and serum level
ECF and body fat composition
in neonates, there is a ________ Vd than adults
does this mean neonates need a higher or lower dose than adults?
higher
higher dose needed
name 3 drugs that distribute in ECF and thus ALWAYS need a higher dose than an adult
aminoglycosides
vancomycin
linezolid
increase concentration of free, unbound drug = ___________ pharmacologic effect
greater
drugs that are highly protein bound – what can you saw about their therapeutic index?
it is narrow
how do albumin levels differ in an infant/neonate
they have lower levels/reduced binding capacity and affinity
therefore, there will be higher free concentrations of certain medications
name 2 plasma proteins that are lower in neonates/infants
albumin
a-1 acid glycoprotein
when are the adult levels of plasma proteins reached
1 year
lidocaine:
adults % protein bound = 70%
infant %bound = 20%
how should the infant’s dose be altered
dose must be lowered significantly
bilirubin is a byproduct of what?
heme catabolism
explain how bilirubin is a concern in neonates
bilirubin is highly albumin bound
if you give a drug that also is highly albumin bound, the bilirubin may be displaced and enter the brain and cause kernicterus (brain damage, hearing loss)
this is bc bb can’t glucuronidate the bilirubin yet to protect itself - not fully developed phase 2metabolism
DONT USE HIGHLY PROTEIN BOUND DRUG IN A PATIENT WITH A LOT OF BILIRUBIN
Why do neonates have higher bilirubin levels
because of RBC destruction (byproduct of heme catabolism)
and impaired glucuronication
give 3 examples of highly protein bound drugs
(thus, they should not be administered to a pt with a high bilirubin level)
ceftriaxone
phenytoin
trimethoprim-sulfamethoxazole
*** explain metabolism compared to adult:
fetal period
newborn period
early childhood
puberty
fetal period - suppressed metabolism
newborn period - gradual increase in metabolism
early childhood - RAPID METABOLISM — GREATER THAN ADULTS!!! NEED HIGHER DOSE
puberty - metabolism declines to adult levels
***** true or false
a 4 year old has a faster metabolism than an adult
true
explain phase 2 metabolism in neonates/infants
when does it mature?
glucuronidation is definitely undeveloped under 1 year. fully develops after a year
HOWEVER, they do have the sulfation pathway of phase 2 metabolism - well developed in infants
method of acetaminophen metabolism
CYP3A4 metabolizes _____% of all drugs
50%
**** what is the activity of CYP3A4 at birth?
what % of adult activity is it at by 1 month??
12 months??
VERY LOW activity at birth
30-40% of adult activity by 1 month
by 12 months, IT IS MUCH FASTER THAN ADULTS!!!!!!!!
TRUE OR FALSE
for drugs metabolized by CYP3A4, young children need higher doses than adults
TRUE
by 12 months they metabolize through CYP3A4 faster
TRUE OR FALSE
when first born, neonates need higher dosages of drugs that are metabolized by CYP3A4
false - lower doses
very low CYP3A4 activity at birth
most drugs are ________ eliminated
renally
at what age are adult levels of creatinine clearance reached?
at 6-12 months
below 6 months, what is normal creatinine clearance
it will be much lower than adults - this is normal
what is considered the minimal gestational age for a bb to survive outside the womb?
why?
23 weeks
bc that’s when lungs developed and they can breathe
true or false
a less than 6 month old bb with a very low creatinine clearance is most likely in renal failure
FALSE – this is normal for them
a diff eqn must be used for children less than 6 months
by what gestational age is nephrogenesis complete
34-36 weeks