Developmental Pharmacology

Dev Pharma Basics - Age & Stages

Developmental pharmacology: Studies drug effects across human development, focusing on how age-related physiological changes impact pharmacokinetics (PK) and pharmacodynamics (PD).

• Pediatric Age Groups:

  • Neonate: Birth - 28 days
    • Preterm: < 37 weeks gestation
    • Term: 37-42 weeks gestation
  • Infant: 29 days - 1 year
  • Child: 1 year - 12 years
  • Adolescent: 12 years - 18 years

• Scope Comparison:

  • Pediatric: Focuses on growth, organ system maturation, and unique drug responses in developing individuals.
  • Geriatric: Addresses age-related organ function decline, polypharmacy, and altered drug responses in elderly.

⭐ 'Off-label' drug use (unapproved indication, age, dose, or route) is prevalent in pediatrics due to limited specific drug trials for children; estimates suggest over 50% of drugs prescribed to children are off-label in some settings.

Pediatric PK - Tiny Bodies, Big Changes

⭐ Chloramphenicol toxicity ("Grey Baby Syndrome") in neonates is due to deficient glucuronidation (immature UGT enzyme), leading to drug accumulation.

Pediatric PD & Dosing - Kid Doses, Big Impact

• PD Differences: Variable receptor density & affinity. Paradoxical drug effects (e.g., benzodiazepines causing agitation).
• Pediatric Dosing:
  • Weight-based (mg/kg) is common.
  • Body Surface Area (BSA)-based for cytotoxic drugs: Mosteller formula $BSA (m^2) = \sqrt{\frac{Ht(cm) \times Wt(kg)}{3600}}$.
• Common Pediatric ADRs:

  Drug	Adverse Drug Reaction	Age Restriction/Concern
  Aspirin	Reye's Syndrome	<12-15 yrs (viral illness)
  Tetracyclines	Teeth discoloration, bone issues	<8 yrs
  Fluoroquinolones	Arthropathy, tendon damage	<18 yrs
  Sulfonamides	Kernicterus	Neonates (<2 months)
  Valproate	Fatal hepatotoxicity	<2 yrs (esp. polytherapy)

• Off-label drug use is prevalent; requires careful monitoring for efficacy and safety.

⭐ Aspirin is contraindicated in children (typically <12-15 years) with suspected viral illness due to the risk of Reye's syndrome.

Geriatric Pharmacology - Golden Years, Gentle Doses

• Pharmacokinetic (PK) Changes & Implications:

  Parameter	Change in Elderly	Clinical Implication
  Absorption	↓Gastric acid, ↓Motility	Variable absorption
  Distribution	↓TBW, ↓Lean mass, ↑Fat, ↓Albumin	Altered Vd, ↑free drug
  Metabolism	↓Hepatic flow, ↓Phase I	↓Clearance, ↑t½
  Excretion	↓GFR (Est. CrCl: $CrCl = \frac{(140-age) \times Wt(kg)}{72 \times SCr(mg/dL)} (\times 0.85 \text{ if female})$)	↓Elimination, ↑toxicity risk

• PD Changes: Altered receptor sensitivity, impaired homeostasis (e.g., baroreceptors).
• Key Issues: Polypharmacy, prescribing cascade, Beers Criteria (e.g., benzodiazepines, anticholinergics), adherence.

⭐ Benzodiazepines: High risk of falls, fractures, confusion in elderly; key Beers criteria PIM (Potentially Inappropriate Medication).

High‑Yield Points - ⚡ Biggest Takeaways

• Neonates: Immature hepatic enzymes (e.g., Gray Baby Syndrome) & decreased GFR affect drug handling.
• Pediatric Vd: Affected by higher total body water, lower body fat, and lower plasma protein binding.
• Key pediatric contraindications: Sulfonamides (kernicterus), tetracyclines (dental/bone), aspirin (Reye's).
• Geriatric PK: Reduced renal excretion (GFR ↓) is most consistent; body fat ↑, total body water ↓.
• Geriatric PD: Increased sensitivity to many drugs; polypharmacy elevates ADR risk (Beers criteria).
• Elderly hepatic metabolism: Phase I (CYP450) declines more than Phase II (conjugation).