5. PEDIATRIC DOSING
Cards (26)
- Pediatric pharmacology:
- Continuous development from embryo to adolescent
- Pharmacodynamics and pharmacokinetics change with time
- Most profound differences occur in the first weeks through the first year of life
- Descriptive pharmacology in pediatric patients is often lacking
- Dosing based on rules or scaling by body weight or surface area is not always predictable
- Animal studies are not always predictive
- Clinical studies in children face ethical and financial hurdles
- Administration of drugs can be problematic
- Children are not "miniature adults" in terms of drug response
- Only 20-30% of approved drugs have pediatric labeling
- FDA encourages pediatric studies with financial incentives
- Orphan drugs are used to treat rare diseases affecting a small number of people
- Developmental changes in children affect:
- Body composition
- Organ function
- Drug metabolizing enzymes
- Unique metabolic pathways
- Renal function
- Receptor response
- Unique disorders
- Errors in drug administration can be devastating
- Important age-related variations in pharmacokinetics exist depending on the patient's stage of development
- Gastric acid approaches adult values around 3 months in full-term infants
- Gastric emptying time is significantly slower in neonates and infants until about 6 months of age
- Neonates and young infants have a thinner stratum corneum, enhancing transdermal absorption
- Intramuscular drug administration is highly susceptible to variance in absorption due to blood flow and muscle mass
- Differences in drug distribution between infants and adults include proportion of body water, body fat, and protein binding
- The changes in metabolic capacity of different enzymes during the first year of life:
- Enzymes: CYP3A4, CYP1A2, CYP2D6, and UGT2B7
- CYP3A4 shows the greatest increase in activity during the first year of life
- CYP1A2 shows the smallest increase
- CYP2D6 and UGT2B7 show intermediate increases in activity
- Developmental changes in the distribution of body water and fat affect drug distribution between infants and adults
- The acquisition of renal function affects drug elimination:
- Maturation of renal function begins with fetal organogenesis and is complete by early childhood
- Glomerular filtration rate correlates with nephrogenesis and postnatal renal and intrarenal blood flow
- The ontogeny of human hepatic phase I drug metabolizing enzymes (DME):
- Expression of various DME genes during different stages of development, from the first trimester of pregnancy to adulthood
- Symbols in the table indicate whether the gene is expressed (+) or not expressed (-) at each stage of development
- The CYP 450 enzyme system in the liver and small bowel is the most important system for drug metabolism
- Enzyme systems mature at different stages of development and may be absent at birth or exist at reduced levels
- Children may require higher doses on a milligram-per-kilogram basis or more frequent dosing compared to adults due to the greater increase in metabolic rate
- The liver and kidney are the main organs that break down and eliminate drugs from the body
- Drugs in neonates and infants are broken down and eliminated more slowly than in older children and adults due to the maturation of the liver and kidney
- Renal elimination of drugs depends on factors like glomerular filtration rate, renal blood flow, plasma protein binding, and tubular secretion
- In the first 2 years of life, renal function factors are altered, with renal plasma flow and glomerular filtration rate reaching adult levels by specific ages
- Pharmacists play a crucial role in intercepting and preventing medication errors by checking dosing accuracy and providing medication counseling to caregivers
- Pharmacists should obtain patient's age and weight at every visit as drug doses are calculated based on milligram per kilogram
- Expired medications may lose potency and become harmful, so it's important to check expiration dates and encourage proper disposal of unused medications