Chapter 4: Pharmacotherapy in Pediatrics, Pregnancy & Lactation

Four core concepts guide therapy: understanding how absorption, distribution, metabolism, and excretion (ADME) are altered by maturation in children or physiologic changes in pregnancy; assessing the short- and long-term effects on pediatric growth and development; evaluating the function of the placental-fetal unit; and considering the impact of underlying disease states. In newborns and infants, differences in oral absorption arise from higher gastric pH and delayed gastric emptying time, while distribution is affected by higher total body water and lower plasma protein levels, often necessitating larger milligram-per-kilogram doses for water-soluble agents like aminoglycosides. Drug metabolism (Phase I and II reactions, including CYP enzymes) and renal elimination (glomerular filtration rate and tubular secretion) are immature in early life, requiring age-dependent dosing adjustments to prevent toxic accumulation. During pregnancy, increased cardiac output, tidal volume, and renal blood flow often enhance the clearance and volume of distribution of many medications, while drug transfer to the fetus across the placenta is favored by low molecular weight, lack of protein binding, and high lipophilicity. For pregnant patients, the FDA replaced the old risk categories with the comprehensive Pregnancy and Lactation Labeling Rule (PLLR), which requires detailed clinical and data summaries. Finally, medication use during breastfeeding should be carefully considered based on drug properties (preferring short half-lives and low oral bioavailability), with dose timing immediately after feeding utilized to minimize infant exposure. Practitioners must balance the risks and benefits of therapy, recognizing specific pediatric safety concerns (e.g., suicide risk with antidepressants, long-term growth effects of inhaled steroids) and utilizing standardized procedures, like weight-based dosing and certified drug references, to reduce the high rate of medication errors in this vulnerable population.