Buxton: Pharmacokinetic Considerations in Peds Flashcards
What is unique about pharm in kids?
continuous development from embryo to adolescence
Are children miniature adults?
No, dosing based on a rule or scaling (by body weight or surface area) not always predictable
What is Clark’s rule?
Weight (lbs)/150 x adult dose = approximate child’s dose
What is Young’s rule?
Age (yrs)/Age +12 x adult dose = approximate child’s dose
Only (blank)% of approved drugs have pediatric labeling. In the meantime, the FDA is encouraging pediatric studies.
30%
Young children are “moving targets,” because they undergo many changes over the course of their growth. What are some examples?
Body composition Organ function Drug metabolizing enzymes Unique metabolic pathways Renal function Receptor response Unique disorders
What are some gastric absorption differences in kids vs adults?
Gastric acid - approaches adult values ~ 3 mo in full-term infants.
Digestive enzymes including pancreatic enzymes are low in newborns.
Gastric emptying is delayed and unpredictable in newborns
GI motility is low in newborns; may be increased in children
What are some differences in skin absorption to be aware of in premature infants?
Premature infant has thin skin - a significantly less effective skin barrier to absorption of drugs and toxins
What is one concern with using intramuscular drugs in children?
dispersion driven by muscle contraction is low in neonates
low skeletal muscle blood flow in neonates
these can be very painful, can cause nerve damage, abscess, necrosis, fibrosis
Other sites of administration of drugs for infants?
rectal
pulmonary
unintentional: breast milk & placenta
How does the extracellular and total body water space compare in neonates & young infants vs adults?
Larger extracellular and total-body water spaces in neonate and young infants
How do plasma proteins compare in preemies and neonates? Which is most important to consider?
they are low, so lead to increased free fraction;
most important in displacement of bilirubin from albumin –> kernicterus
How do tissue transporters differ in infants?
reduced expression of P-glycoprotein ATP-binding cassette family of transporters..
What happens to drug metabolizing enzymes in the very young?
they have low activity
**be careful with drugs that have a wider therapeutic index!
What is the major isoform of drug-metabolizing enzymes in the infant?
CYP3A7
**w/i hours after birth, other isoforms appear
Give an example of the differences in half-life of a drug in infants vs 1 wk old full term infant
Phenytoin T1/2 in preemies is 75hrs vs 20hrs in 1 wk old full term infant
What are the phase 1 reactions?
oxidation/reduction/hydrolysis
What are the phase 2 reactions?
conjugation reactions
This conjugation enzyme is decreased in newborns & young children compared to adolescents & adults
glucouronosyl transferase
Clearance of most agents more efficient in (blank) than adults (relative to bodyweight)
prepubescent children
Premature infants have decreases in almost all phase 1 enzymes, except for this one!
CYP3A7
Premature infants have decreased (blank) of phase 2 enzymes
activity
What happens to GFR in children?
progressively increases until about age 6
Estimation of (blank) may be necessary for determining dose regimen for drugs with extensive renal clearance
renal function
This drug can actually alter renal blood flow
indomethacin
What are some things to think about when deciding whether to use a drug in a child or infant?
Has there been documented efficacy for the medication for the disorder in newborn or older infants/children.
Has the safety been established for pediatric population?
Has the pathway of drug clearance been established in children/infants?
Is that pathway established in the child/infant you are treating (based on maturity or physical state)?
Is there reason to believe that pathway may be compromised in the specific child/infant (genetics, disease state, concomitant therapy)?
Have the pharmacokinetics been established in similarly aged children?
The very small doses required in the most immature patients and the immature clearance pathways leave very little (blank)
margin of error
What is retrolental fibroplasia?
retinopathy due to high oxygen (increased blood vessel proliferation on the retina)
This anti-infective can be toxic to infants but was used to eliminate Staph infection in nurseries
Chloramphenicol
This was another anti-infective that went awry in nurseries
novobiocin
This compound was used to disinfect diapers, but was toxic to the children
pentachlorophenate
These caused magnesium toxicity in nurseries
epsom salt enemas
Bottom line: there are many cases of pediatric toxicology
Yes
How often do prescribing errors occur in the pediatric ER?
10% of charts have prescribing errors
Another type of error that occurs often in peds
sedation errors
As few as (blank)% of parents correctly administer proper dose of acetaminophen to their child
Even when parents provided with correct dosing information and child’s weight, correct dose given 40% of the time
30%
Should aspirin be given to children?
NEVER - until about age 15
T/F: Significantly fewer errors associated with simplified color-coded information sheet and color-coded dosing syringe
True
Overdosing & underdosing is very common in pediatrics
Yep
What are the challenges in pediatric prescribing?
- Pediatric prescribing is complex - need to get an accurate weight, convert weight to kg, make calculations, etc
- Off-label medication use is common - increase risk of adverse drug events
- Lack of standardization of recommended doses - they differ depending on your source
- Lack of guidelines regarding use of adult dosing regimens - there’s no standard for when to switch from weight-based dosing to daily dosing
Which children are at the highest risk for prescribing errors?
young children
children who have not been seen in clinic
multiple medications at one time
“prn” medications (analgesics, asthma meds)
What is the major problem with pediatric prescribing?
Not enough is being done by big Pharma to study drug dosing in the pediatric population thought this is slowly improving.
Will computerized physician ordering entries reduce medication dosing erros in children?
Electronic prescribing is a potentially successful strategy but NOT without pediatric decision support
Evidence in inpatient settings that CPOE reduces medication dosing errors
Complexity of pediatric prescribing leads to complexity in designing electronic systems
