Drug Therapy in Pediatric Patients Chapter 10 Drug Therapy in Pediatric Patients 1

Pediatric Patients All patients younger than16 years Respond differently to drugs than the rest of the population More sensitive to drugs than other patients are Show greater individual variation Sensitivity due mainly to organ system immaturity Increased risk for adverse drug reaction 2

Pediatric Patients Ongoing growth and development Different age groups: different challenges Two-thirds of drugs used in pediatrics have never been tested in pediatrics. Two laws Best Pharmaceuticals for Children Act—2002 Pediatric Research Equity Act of 2003 3

Pediatric Patients 20% of drugs were ineffective in children even though they were effective in adults. 30% of drugs caused unanticipated side effects, some of them potentially lethal. 20% required dosages different from those that had been extrapolated from dosages used in adults. 4

Pediatric Patients Premature infants Full-term infants Neonates (less than 36 weeks’ gestational age) Premature infants (36–40 weeks’ gestational age) Full-term infants (first 4 postnatal weeks) Neonates (weeks 5–52 postnatal) Infants (1–12 years) Children (12–16 years) Adolescents 5

Fig. 10-1. Comparison of plasma drug levels in adults and infants. A, Plasma drug levels following IV injection. Dosage was adjusted for body weight. Note that plasma levels remain above the minimum effective concentration (MEC) much longer in the infant. B, Plasma drug levels following subQ injection. Dosage was adjusted for body weight. Note that both the maximum drug level and the duration of action are greater in the infant. 6

Drug Therapy in Neonates and Infants Increased sensitivity in infants due to: Immature state of five pharmacokinetic processes: Absorption Protein binding of drugs Blood-brain barrier Hepatic metabolism Renal drug excretion 7

Pharmacokinetics: Neonates and Infants Absorption Oral administration (delayed gastric emptying, higher pH in stomach Intramuscular administration (slow and erratic first few days of life) Percutaneous absorption (increased toxicity because of thin skin) Distribution Protein binding- amount of albumin is low and other substrates compete for binding Blood-brain barrier- immature, CNS drugs reach higher concentrations 8

Pharmacokinetics: Neonates and Infants Hepatic metabolism: low at birth, mature by one year Renal excretion: low from birth to a year 9

Pharmacokinetics: Children Age 1 Year and Older Most pharmacokinetic parameters similar to those in adults Drug sensitivity more like that for adults than for children younger than 1 year 10

Pharmacokinetics: Children Age 1 Year and Older One important difference Metabolize drugs faster than adults Markedly faster until age 2 years; then a gradual decline Sharp decline at puberty May need to increase dosage or decrease interval between doses 11

Adverse Drug Reactions Vulnerable to unique adverse effects related to organ immaturity and ongoing growth and development Age-related effects Growth suppression (caused by glucocorticoids) Discoloration of developing teeth (tetracyclines) Kernicterus (sulfonamides) 12

Dosage Determination Dosing is most commonly based on body surface area (BSA). Initial pediatric dosing is, at best, an approximation (even when BSA is used). Subsequent doses need to be adjusted. See formula on next slide. 13

Dosage Determination Approximate dosage for a child = Body surface area of the child × adult dose 1.73 m² 14