Pharmacotherapy in children

Pharmacokinetics in Children vs. Adults
📌 Pediatric drug handling involves significant variability due to physiological changes across different age stages (newborns, infants, preschoolers, adolescents).
👶 Newborns exhibit immature elimination systems, high gastric pH, prolonged gastric emptying, and immature intestinal mucosa, impacting oral drug absorption.
💧 Total body water content is significantly higher in fetuses (~90%) and newborns (~80%), leading to a larger volume of distribution for water-soluble drugs like penicillins.
🩸 Immature liver function in children under 12 months results in lower plasma protein concentration (albumin), increasing the free fraction of the drug and raising the risk of toxicity, notably with drugs like sulfonamides competing with bilirubin for binding sites.

Absorption and Distribution Specifics
✅ Oral administration is preferred, but in newborns, factors like high pH and mucosal immaturity can necessitate intravenous routes for certain antibiotics.
📈 Preschoolers (2–5 years) may have a larger liver size relative to body weight than adults, potentially leading to a greater first-pass effect, sometimes requiring dose increases.
🧴 Neonates and small infants (<3 months) have increased percutaneous absorption, elevating the risk of systemic adverse effects from topical treatments, such as corticosteroid creams.
🧠 The blood-brain barrier (BBB) is more permeable in newborns, allowing greater passage of lipophilic drugs like opioids and anesthetics, though large molecular weight drugs like aminoglycosides still struggle to cross, even when the BBB is inflamed (e.g., meningitis).

Metabolism and Elimination Maturation
🔄 Phase I metabolism enzymes (Cytochrome P450 system) are subject to genetic polymorphisms and environmental induction (e.g., smoking, grapefruit juice), causing inter- and intra-individual variability.
👶 Neonates have lower metabolic capacity; Phase II reactions like sulfation begin early, but acetylation and glucuronidation mature around three months of age.
🚀 Preschoolers (up to 5 years) can exhibit higher metabolic capacity than adults due to larger liver volume, potentially requiring higher doses for drugs heavily metabolized in the liver, such as some antiepileptics.
🚽 Glomerular filtration matures significantly between 3 and 6 months, while tubular function matures more slowly, influencing the renal excretion of drugs like aminoglycosides, necessitating close monitoring in newborns.

Pharmacodynamics and Safety Considerations
💊 Children often show heightened sensitivity to certain drug effects, such as anticholinergic effects (seen with some antidepressants, antihistamines, and antipsychotics) and the extrapyramidal effects associated with some antihistamines and antipsychotics.
🥴 Paradoxical excitation (nervousness, restlessness) is common with benzodiazepines and phenobarbital in young children (<5 years), thought to be related to an imbalance favoring glutamatergic over GABAergic neurotransmission in the immature CNS.
🛑 Developing children are susceptible to specific adverse drug effects: corticosteroids can affect height, quinolones can damage growth cartilage, and tetracyclines can alter dentition.
⚠️ Adherence failure is high, with 50% of children not receiving treatment adequately, often related to unsuitable pharmaceutical forms (e.g., attempting to fractionate tablets when liquid forms are needed).

Key Points & Insights
➡️ Rational prescribing in pediatrics must follow WHO guidelines: Define the problem, establish the therapeutic objective, and select treatments with proven efficacy and safety in children through clinical trials.
➡️ Monitor response closely, as small variations in dose for narrow therapeutic index drugs (e.g., digoxin, vancomycin, antiepileptics) can quickly lead to toxic levels, especially given immature renal/hepatic clearance.
➡️ Young children, particularly those aged 2 to 5 years, face a high risk of accidental poisoning/intoxication due to their exploratory nature and lack of risk awareness; benzodiazepines are frequently involved.
➡️ When calculating pediatric doses, remember formulas are extrapolated from adult data; dose adjustments are essential based on age-related physiological changes (e.g., CF alters volume of distribution and clearance).

📸 Video summarized with SummaryTube.com on Mar 08, 2026, 00:19 UTC