Developmental Pharma Flashcards
What are the factors that affect drug absorption in children?
Blood flow at the site of administration
GIT function: Gastric acid secretion, Peristalsis, GI enzymes
Age after birth
What organs are vessel-rich therefore drugs can easily reach their receptors?
Brain
Kidney
Liver
What are the diff physiological conditions that reduce blood flow to the brain, liver, and kidneys?
CV shock
Vasoconstriction due to sympathomimetic agents
HF
What are the diff drugs that are affected by diminished peripheral perfusion at the IM route?
Cardiac glycosides
Aminoglycosides
Anticonvulsants
What route of admin has a greater skin to BSA ratio, approx 3x in adults?
Transdermal route
What drug agents when administred to children transdermally can cause dangerous AEs? What are these AEs?
- Hexachlorphene - bathing of infants -> neurotoxicity
- Povidone-iodine topical disinfectant -> neonatal thyroid dysf
- Hydrocortisone cream for diaper rash -> HPA axis suppression
- 4% Lidocaine -> Arrhythmias
What is the most useful and well-absorbed route of admin in children? Why?
Rectal route -> strong retal contractility in infants
What are the 4 important developmental alterations in pediatric clinical pharma?
- Diff in extravascular absorption rate & extent
- Altered body composition influences distribution
- Marked ontogeny of drug metabolizing enzymes
- Dynamic influence of devt on renal function
What are the 4 GIT factors that affect oral absorption?
GAstric pH
Gastric emptying time
Peristalsis
GI Enzymes
What are the 8 factors that affect extraoral absorption?
Barrier thickness
Regional blood flow
Temperature
Diffusional surface area
Hydration
Tissue binding sites
Local pH
Drug vehicle interaction
What oral drugs have a decreased oral absorption effect on neonates?
Acetaminophen
Phenobarbital
Phenytoin
What oral drugs have an increased oral absorption in neonates?
Ampicillin
Penicllin G
What oral drugs have a normal oral absorption in neonates?
Diazepam
Digoxin
Sulfonamides
What are the 5 factors that affect drug distribution in neonates/infants?
TBW
% fat content
Protein binding
Membrane permeability
Larger potential compartment
Larger potential compartment
What is the % TBW in neonates/infants?
% TBW
Neonates: 70-75%
Preterm: 85%
1 y/o: 6-65%
ECW: 40% body weight
WHat happens when neonates/infants have a larger TBW/ECW space?
There’s lower plasma concentration of the drug
What drugs have a greater distribution rate in neonates/infants?
Aminoglycosides (Amikacin)
Linezolid
Paracetamol
What drugs have a reducd capacity to accumulate in neonates/infants bcos they are lipid-soluble drugs?
Amphoteriicn
Benzodiazepines (Diazepam)
Digoxin
Amiodarone
What is the total body fat in preterm, full term, and 1 y/o?
Preterm: 1%
Full term: 10-15%
1 Y/o: 20-25%
At what age of infants can lipid-soluble drugs accumulate in small amts?
Premature infants (DEC fat content)
T/F Neonates & young infant have higher concentrations of most relevant plasma binding protein?
False
They have lower concentrations
What factors affect or influences the amount & type of circulating plasma proteins?
Drug disposition & drug action
T/F Protein binding is generally reduced in neonates?
True
THis leads to INC free/unbound levels of the drug
How come drug distribution in the CNS is hard for children?
Drug distribution to deep compartments is delayed & limited
How come infants are more susceptible to drug-induced neurotoxicity?
At this age, the brain is 10-12% of total body weight
what are the diff diseases that alter drug distribution in the brain?
Obesity
Protein malnutrition
PDA and Sepsis
Hypoalbuminemia
Environmental aspects
Binding characteristics
Meningitis
ECMO (Extracellular corporeal membrane oxygenation)
What are the diff altered body composition influences distribution?
- Neonates w/ iNC TBW & ECW
- Neonates w/ DEC fat
- DEC protein-binding
- Competitive binding of bilirubin
- INC brain to body proportion
- Membrane permeability
Why don’t we give Ceftriaxone to neonates?
Bcos this will displace binding of Bilirubin to Albumin —> INC level of free bilirubin —> goes to the brain —> Kernicterus
What are maturational changes in hepatic biotranformation in the CYP system?
- CYP system is immature at birth
- CYP450 system
- HYP3A7
- CYP3A4/5
- Age from birth (not AOG)
Are CYP2D6 poor metabolizers?
Yes
What are the diff drug metab in neonates from adults?
- slow clearance rates
- prolonged elimination half-lives
- DEC renal function —> DEC rate of elimination
What drug can indice matureation of fetal hepatic enzymes when taken by a pregnantmother?
Phenobarbital
At 12-36 mons (todderls), metab rate of drugs and elimination half-lives are?
Metab rate: exceed adult values
SHorter elimination half-lives than older children & adults
What is the potentially lethal AE of a child’s exposure to Chloremphenicol?
Gray baby syndrome
What is a dangerous AE of children if they take Valproate?
Hepatotoxicity
What is a dangerous AE of Ifosfamide in children?
Renal tubular toxicity
What happens if diseases/inflammation take effect on drug metab in children?
INC drug exposure, proinflam cytokines
Adverse drug rxns
DEC drug metab, CYP450
Whta are the 3 processes responsible for elimination of drugs by the kidneys?
GFR
Tubular excretion
Tubular reabsorption
At what age can GFR increase to 50% and 90% of adult value?
3rd wks AOG = INC to ~50% of adult
1 y/o = INC to ~90% of adult
When does tubular secretion & tubular reabsorption mature in children?
Tubular reabsorption = 2yo
Tubular secretion = 15 mons
What are the diff PK changes in puberty?
Hormonal fluctuations
Sexual maturation
INC in body fat
INC serum proteins
GFR -> exceeds ave adult values
Metabolic changes -> DEC drug clearance
What drug can boys at the age of 12yo have a 37% greater clearance than girls?
Lopinavir
Girls/Boys. Which one can have Caffeine metabolism DEC earlier during puberty?
Girls
Are neonates more sensitive to the central depressant efefcts of opioids than older chldren & adults?
Yes
T/F Infants are susceptible to the effects of B-adrenergic agonists like Dopamine?
False
what topical agent has the potential to cause toxic epidermal necrolysis?
Lamotrigine
What drug group can cause weight gain in adolescents?
Atypiacl antipsychotic agents
What form of soln are evenly distributed with and without shaking?
Elixir: w/o shaking
Suspension: w/ shaking
Drug dosage in pedia px depend on what ff factors?
Age, weight, & surface area
What is the formula for pediatric dose if u only have the age of the px? WHat is this formula called?
Young’s Rule:
Dose = Adult dose x [(Age in yrs)/(Age +12)]
What is the formula for pediatric dose if u only hgave the wt (kg & lbs) of the px? What is this formula called?
Clark’s rule:
Dose = Adult dose x [(weight in kg)/(70)]
Dose = Adult dose x [(Weight in lbs)/(150)]
For breastfeeding mothers, at what time should drugs be taken?
30-60 minutes after nursing
3-4hrs before next feeding
What is the side effect of Chloral hdyrate in breastfeeding mothers?
Drowsiness if infant is fed at peak conc of milk
What is the side effect of Chloramphenicol in breastfeeding mothers?
BM suppression
What is the side effect of Codeine in breastfeeding mothers?
Neonatal toxicity
What is the side effect of large amts of consumed alcohol in breastfeeding mothers?
ALcohol effects in infants
What is the side effect of Heroine in breastfeeding mothers?
Neonatal opioid dependence
What is the side effect of Radioactive iodine in breastfeeding mothers?
Thyroid suppression in infants
What is the side effect of Isoniazide in breastfeeding mothers?
Pyridozine def
What is the side effect of oral contraceptives in breastfeeding mothers?
Suppress lactation in high doses
What is the side effect of Phenobarbital in breastfeeding mothers?
Sedation in infants
What is the side effect of Prednisone in breastfeeding mothers?
If dose is 2x the physiological amt (>15mg/day) —> IMmunosuppressant effect
What is the side effect of Tetracycline in breastfeeding mothers?
Permanent staiing of the developing teeth of an infant
