Pediatric Flashcards
Pediatric Research Equity Act
Requires pediatric studies of drug applications for:
- New active ingredients
- New indications
- New dosage forms
- New dosing regimens
- New routes of administration
Peds: GI Absorption
Gastric pH does not reach adult values until age 20-30 months
- Oral bioavailability of acid-labile compounds is increased
— Beta-lactams
- Oral bioavailability of weak organic acids is decreased
— Phenobarbital and phenytoin
- Basic drugs have increased absorption
— Diazepam and theophylline
Most orally administered drugs are absorbed in small intestine
Infants have proportionately larger small intestinal surface area
- Unpredictable absorption compared with adults
Infants have increased intestinal motility
- Alters the absorption of drugs with limited water solubility
— Phenytoin and carbamazepine
Peds: Distribution
- Newborns and Infants have higher percentage of water
- Blood-brain barrier is incomplete and permeable in newborn
- Infants younger than 6 months of age have decreased plasma proteins available for drug binding
- Total body fat decreases in adolescence
- Lean body mass increases more in males
- Fat distribution: decreases in males; increases in females
- It is difficult to predict the pharmacokinetics of some drugs in adolescents
Peds: Metabolism
Drugs are metabolized by both metabolic and enzymatic reactions
- Phase I and phase II enzymes
- Enzyme maturation occurs at varying rates
Peds: Phase I Enzymes
Cytochrome (CYP) 450
- Family of drug-metabolizing enzymes
- Account for majority of drug metabolism in humans
- Enzymes may be slowed (inhibited) or increased (induced)
- Concurrent therapy with an inhibitor or inducer may alter the metabolism of a medication
Peds: CYP1A2
- Developmental variation
- – Reaches adult levels at 4 months
- – Exceeds adult levels at 1-2 years
- – Reaches adult levels at puberty
- Diseases, such as cystic fibrosis (CF), can affect CYP1A2
- Medications: many
- – Theophylline, erythromycin, cimetadine, phenobarbitol, phenytoin, carbamazepine, clarithromycin, etc.
- Food: grapefruit juice, cruciferous vegetables, charbroiled foods
- Cigarette Smoke
Peds: CYP1A2- Implications for Practice
Drug dosages adjusted as child goes through phases of CYP1A2
- Higher dosages may be needed from age 1 year until puberty
- Monitor levels as child goes through puberty
CF patients do not metabolize some drugs predictably
Foods may interact with drug metabolism
Peds: CYP3A4
Developmental variations
- low activity at birth
- 30% to 40% of adult level by age 1 month
- Full adult level at age 6 months
- Exceeds adult level at 1-4 years of age
- Decreases to adult level after puberty
Used to metabolize more than 20 commonly used pediatric medications
- Carbamazepine, prednisone, oral contraceptives, macrolides, NSAIDs, antihistamines, etc.
Implications for practice
- Monitor when more than one drug metabolized by CYP3A4 enzyme
- Monitor during developmental changes
Peds: Phase II Enzymes
- Responsible for synthesis of water-soluble compounds
- Most reach adult activity by age 3-4 years
- Less information available on phase II activity in children
- Ethnic variations: adult activity levels of thiopurine methyltransferase (TPMT) not reached until 7-9 years in Koreans
- Common medications: acetaminophen, morphine, propofol, caffeine
- Implications for practice:
- – Monitor therapeutic effectiveness according to developmental age
- – Be aware that ethnic variations in metabolism may be present
- Patients with low levels of TPMT activity are at greater risk of hepatic toxicity from some chemotherapy drugs (thiopurines)
- Patients with low or undetectable levels of TPMT activity experience severe myelosuppression when treated w/ “standard” doses of thiopurines
- Patients with high levels of TPMT activity are likely to have reduced clinical responses
Peds: Excretion
Renal blood flow and glomerular filtration rate reach adult levels at age 9 months
- Adjust dosages of medications to account for decreased renal function
- Avoid ibuprofen before 6 months of age
Breastfed Infants
Excretion of drugs in breast milk Factors that influence infant exposure to maternal drugs - Maternal phenylketonuria - Time of feeding in relation to dosing - Infant phenylketonuria - Susceptibility to drugs effects - Milk-to-plasma (M:P) ratio
LactMed database
Pediatric Medication Administration
Infants
- Teach parents about medications
- Teach how to administer medications
Toddlers and preschoolers
- Toddlers are independent
- Use higher concentrations and therefore lower volumes
School-age children
- Industrious
- Liquid vs. pills
Improving Adherence
- Medication concentration
- Written and oral instructions
- Calendars
- – Sticker charts
- Telephone reminders
- Administering medications at school (asthma controllers)
- Contracts
