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Chapter 10

Drug Therapy in Pediatric Patients

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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

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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

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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.

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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

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Pharmacokinetics: Neonates and Infants

Absorption Distribution Hepatic metabolism Renal excretion

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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.

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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 thatplasma 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.

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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

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Pharmacokinetics: Neonates and Infants

Absorption Oral administration Intramuscular administration Percutaneous absorption

Distribution Protein binding Blood-brain barrier

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Pharmacokinetics: Neonates and Infants

Hepatic metabolism Renal excretion

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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

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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

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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)

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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.

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Dosage Determination

Approximate dosage for a child =

Body surface area of the child × adult dose1.73 m²

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Promoting Adherence

Provide patient education in writing. Demonstration techniques should be included

as appropriate.

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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