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
____ is the most commonly used marker for renal assessment in adults and children
serum creatinine
as mentioned, serum creatinine is the most commonly used marker for renal assessment in adults and children
name 2 issues with this
kids will have lower serum creatine levels bc of decreased muscle mass and variable glomerular filatration rates
not a lot of valid formulas to estimate creatine clearants in infants less than 1 year and neonates
when calculating creatinine clearance for less than 1 year of age, the “L” (length) must be in what units?
cms
when calculating creatinine clearance for less than 1 yr, serum creatinine must be in what units
mg/dL
true or false
GFR and creatinine clearance increases as the neonate gets older
true
an adult patient with lower than normal creatinine clearance will get a higher or lower dose?
lower
___________ can change the Vd and clearance
DISEASE STATES!!
at what pediatric weight should be start using adult dosing instead of pediatric
40kg (88 pounds)
true or false
growth is linear
FALSE - this is why dosing is challenging
birth weight doubles by 6 months and triples by a year, and then slows down
as the child gains weight, the dose has to be ___________
increased
true or false
it is never acceptable to round doses
false - may be safe for some medications and age groups, but NOT for others
TRUE OR FALSE
growth slows during early childhood and increases during puberty
true
true or false
if the child has only increased by 1kg since last dispensed a prescription, dose adjustment is not necessary
FALSE - it absolutely is
just 1kg can make a huge dosing difference for peds
_____ is used in dosing certain medications, rather than body weight
BSA (body surface area)
what is IBW and what formula is used to calculate
ideal body weight
there is no ideal formula, but can use 50 percentile for age
greater than or equal to what percentile is considered obese?
greater than or equal to what percentile is considered overweight?
overweight - greater than or equal to 85th %Ile
obese - greater than or equal to 95th %ile
how does obesity affect clearance
larger kidney - may increase GFR and greater frequency of dosing needed – getting rid of it so quick
in obesity, will there be a higher or lower vd for lipophilic drugs?
what about hydrophilic?
higher VD for lipophilic drugs
can be higher or lower Vd for hydrophilic drugs
what %ile range is considered “healthy weight” according to the CDC
5-85th percentile
how is metabolism affected by obesity
possible decrease in HEPATIC clearance bc fatty infiltrates
increase in phase 1 and 2 reactions
what org gave 40kg as the cut off for stopping pediatroic dosing
the pediatric pharmacy group
in children less than 18 but weigh greater than or equal to 40kg, would you use weight based or adult dosing?
weight based, UNLESS adult dosing will be exceeded
is it acceptable to exceed adult dosing in a pediatric, based on their weight?
NO
if exceeds, use adult dosingq
when dosing children, a ___ analysis should be performed whenever possible to provide a more accurate dosing assessment
pharmacokinetic
why is it that there are more med errors in pediatrics than adults
have to calculate dosing, lot of measurement units (lbs->kg) mcg vs mg
trailing zeros and leading zeros
trailing zeros should be AVOIDED
leading zeroes should be used — ie: 0.5 insteas of .5
which should be used – mL or tsp/tbsp
mL
if a child less than 6 can’t swallow sollid dosage forms, what should they be given
liquids
at ______- age, there are AGAIN altered pharmacokinetics
adolescent – puberty
at what age range is parental and child adherence the best
less than 5
give 2 scenarios in which extemporaneous preparations of PO drugs may be needed in pediatrics
kid can’t swallow solids
the exact dose isn’t available in solid dosage form
true or false
capsules and tablets cannot be crushed if they are sustained release or long acting
true
give 4 challenges of IV administration in pediatrics
-may not be done in time - gravity not working to drive into vein
-collapsable veins - peds veins easily collapse
-limited sites for IV
-cooperation from child
what may be needed when giving IV to pediatric patient to ensure the dose is delivered on time
a pump
if a drug is not soluble in water or alcohol and you need a liquid dosage form to give to the child, what should you do?
what must the parent be counseled on?
prepare a suspension with suspending agent
must be counseled to SHAKE WELL BEFORE USE
Name 5 stability concerns with compounding suspension
physical
chemical
microbiological
therapeutic
toxicologic
name an alternative to preparing suspensions for drugs that are insoluble in water and alcohol
crush with powder paper and lactose and have parent administer in jello/apple sauce/ice cream
what is an issue with opening capsules for PO administration
possible uneven drug distribution, lack of stability data
by the age of ______, children can provide and receive info
by the age of _______, children tend to be more interested in their healthcare when given the chance
3,7
caregivers who aren’t educated about drug administration give liquid medication dose correctly around what % of time
only 50% — very important to educate
just 1-3 mins increases correct dose administration to 95%
true or false
as a pharmacist, you should speak to the child in a light and airy tone of voice
false - just talk normally and at or below their eye level
when communicating with a parent, information should be written at what level
6 grade level
what act was made as a result of the sulfanilamide elixir tragedy
1938 FDCA
new drugs must be proven SAFE and have adequate directions for use
chloramphenicol in children
does not get converted to the base
no glucuronidation pathway – gray baby syndrome
what is the concern with sulfonamide antibiotics?
at what age is this relevant?
less than 2 months - should be used with caution
can displace bilirubin from albumin – bilirubin can cross BBB and cause kernicterus (irreversible brain damage)
TRUE OR FALSE
tetracyclines ARE CONTRAINDICATED in less than 8 years of age
true
bc calcium chelates with tetracyclines and deposits in kids’ bones and teeth
causes permanent teeth staining and possible growth retardation from deposition in bone (not permanent - when therapy discontinued it gradually reverses)
