Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 10 Drug Therapy in Pediatric Patients

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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.

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pediatric Patients (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

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pharmacokinetics: Neonates and Infants  Absorption  Distribution  Hepatic metabolism  Renal excretion

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Therapy in Pediatric Patients  Pharmacokinetics: neonates and infants  Determining the concentration of a drug at its sites of action  Determining the intensity of duration of response  Elevated drug levels = more intense response  Delayed elimination = prolonged response  Immaturity of organs puts patient at risk for both of these responses.

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig 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.

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Therapy in Neonates and Infants  Increased sensitivity in infants due to:  Immature state of five pharmacokinetic processes: Absorption Absorption Protein binding of drugs Protein binding of drugs Blood-brain barrier Blood-brain barrier Hepatic metabolism Hepatic metabolism Renal drug excretion Renal drug excretion

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pharmacokinetics: Neonates and Infants  Absorption  Oral administration  Intramuscular administration  Percutaneous absorption  Distribution  Protein binding  Blood-brain barrier

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pharmacokinetics: Neonates and Infants  Hepatic metabolism  Renal excretion

12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 Markedly faster until age 2 years; then a gradual decline Sharp decline at puberty Sharp decline at puberty May need to increase dosage or decrease interval between doses May need to increase dosage or decrease interval between doses

14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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) Growth suppression (caused by glucocorticoids) Discoloration of developing teeth (tetracyclines) Discoloration of developing teeth (tetracyclines) Kernicterus (sulfonamides) Kernicterus (sulfonamides)

15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Dosage Determination  Dosing is most commonly based on body surface area (BSA).  Initial pediatric dosing is, at best, an approximation.  Subsequent doses need to be adjusted.  See formula on next slide.

16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Dosage Determination Approximate dosage for a child = Body surface area of the child × adult dose 1.73 m²

17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Promoting Adherence  Provide patient education in writing.  Demonstration techniques should be included as appropriate.

18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Promoting Adherence  Effective education should include  Dosage size and timing  Route and technique of administration  Duration of treatment  Drug storage  The nature and time course of desired responses  The nature and time course of adverse responses