Pediatrics: Introduction

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Remarkable progress has been made in the clinical management of disease in pediatric patients. This chapter highlights important principles of pediatric pharmacotherapy that must be considered when the diseases discussed in other chapters of this book occur in pediatric patients, defined as those younger than 18 years. Newborn infants born before 37 weeks of gestational age are termed premature; those between 1 day and 1 month of age are neonates; 1 month to 1 year are infants; 1 to 11 years are children; and 12 to 16 years are adolescents. This chapter covers notable examples of problems in pediatrics, pharmacokinetic differences in pediatric patients, drug efficacy and toxicity in this patient group, and various factors affecting pediatric pharmacotherapy. Specific examples of problems and special considerations in pediatric patients are cited to enhance understanding.

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Image not available.Infant mortality up to 1 year of age has declined from 200 per 1,000 births in the 19th century to 75 per 1,000 births in 1925 and to 6.7 per 1,000 births in 2006.1 This success has resulted largely from improvements in identification, prevention, and treatment of diseases once common during delivery and the infancy period. Although most marketed drugs are used in pediatric patients, only one fourth of the drugs approved by the U.S. Food and Drug Administration (FDA) have indications specific for use in the pediatric population. Data on the pharmacokinetics, pharmacodynamics, efficacy, and safety of drugs in infants and children are scarce. Lack of this type of information led to disasters such as gray baby syndrome from chloramphenicol, phocomelia from thalidomide, and kernicterus from sulfonamide therapy. Gray baby syndrome was first reported in two neonates who died after excessive doses of chloramphenicol (100–300 mg/kg/day); the serum concentrations of chloramphenicol immediately before death were 75 and 100 mcg/mL (75 and 100 mg/L; 232 and 309 μmol/L). Patients with gray baby syndrome usually have abdominal distension, vomiting, diarrhea, a characteristic gray color, respiratory distress, hypotension, and progressive shock.

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Thalidomide is well known for its teratogenic effects. Clearly implicated as the cause of multiple congenital fetal abnormalities (particularly limb deformities), thalidomide also can cause polyneuritis, nerve damage, and mental retardation. Isotretinoin (Accutane) is another teratogen. Because it is used to treat severe acnevulgaris, which is common in teenage patients who may be sexually active but not willing to acknowledge that activity to healthcare professionals, isotretinoin has presented a difficult problem in patient education since its marketing in the 1980s.

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Kernicterus was reported in neonates receiving sulfonamides, which displaced bilirubin from protein-binding sites in the blood to cause hyperbilirubinemia. This results in deposition of bilirubin in the brain and induces encephalopathy in infants.

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Another area of concern in pediatrics is identifying an optimal dosage. Dosage regimens cannot be based simply on body weight or surface area of a pediatric patient extrapolated from adult data. Bioavailability, pharmacokinetics, pharmacodynamics, efficacy, and safety information can differ markedly between pediatric and adult patients, as well as among pediatric patients, because of differences in age, organ function, and disease state. Significant progress has been made in the area of pediatric pharmacokinetics during the past 2 decades, but few such studies have correlated pharmacokinetics with the outcomes of efficacy, adverse effects, or quality of life.

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Several additional factors should be considered in optimizing pediatric drug therapy. Many drugs prescribed widely for infants and children are not available in suitable dosage forms. For example, extemporaneous liquid dosage forms of amiodarone, captopril, omeprazole, and spironolactone are prepared for infants and children who cannot swallow tablets or capsules, and injectable dosage forms of aminophylline, methylprednisolone, morphine, and phenobarbital are diluted to accurately measure small doses for infants. Alteration (dilution or reformulation) of dosage forms intended for adult patients raises questions about the bioavailability, stability, and compatibility of these drugs. Because of low fluid volume requirements and limited access to intravenous sites, special methods must be used for delivery of intravenous drugs to infants and children. As simple as it may seem, administration of oral drugs to young patients continues to be a difficult task for nurses and parents. Similarly, ensuring adherence to pharmacotherapy in pediatric patients poses a special challenge.

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Finally, the need for additional pharmacologic or therapeutic research brings up the issue of ethical justification for conducting research. Investigators proposing studies and institutional review committees approving human studies must assess the risk-to-benefit ratio of each study to be fair to children who are not in a position to accept or reject the opportunity to participate in the research project.

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Enormous progress in pharmacokinetics has been made in pediatric patients. Two factors have contributed to this progress: (a) the availability of sensitive and specific analytic methods to measure drugs and their metabolites in small volumes of biologic fluids and (b) awareness of the importance of clinical pharmacokinetics in optimization of drug therapy. Absorption, distribution, metabolism, and elimination of many drugs are different in premature infants, full-term infants, and older children, and this topic is discussed in detail in the next few sections.

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