Special Populations (Pediatric, Geriatric, Pregnancy)

Pediatric Pharmacology - Small Doses, Big Impact

• Unique Pharmacokinetics (ADME):
  • Absorption: Variable. Gastric pH ↑ (neonate). Percutaneous absorption ↑.
  • Distribution: ↑ Total Body Water (TBW) → ↑ Volume of Distribution (Vd) for water-soluble drugs. ↓ Plasma protein binding → ↑ free drug concentration.
  • Metabolism: Immature hepatic enzymes (e.g., CYP450, UGT glucuronidation).

    ⭐ Neonates have reduced glucuronidation capacity, increasing risk of toxicity with drugs like chloramphenicol (Grey Baby Syndrome).

  • Excretion: ↓ Glomerular Filtration Rate (GFR) & tubular function in neonates/infants; matures by 6-12 months.
• Dosing Strategies:
  • Primarily weight-based (mg/kg) or Body Surface Area (BSA)-based.
  • BSA often preferred for drugs with narrow therapeutic index (e.g., chemotherapy).
• Adverse Drug Reactions (ADRs) & Precautions:
  • Higher susceptibility due to developmental factors.
  • ⚠️ Avoid: Tetracyclines (<8 yrs - dental staining, bone growth inhibition), Aspirin (Reye's syndrome risk with viral illness), Fluoroquinolones (arthropathy/cartilage damage concerns).
• Key Considerations:
  • Off-label drug use is common; requires careful risk-benefit assessment.
  • Therapeutic Drug Monitoring (TDM) crucial for many drugs.

Geriatric Pharmacology - Navigating Golden Maze

Age-related physiological changes significantly impact drug therapy in older adults (typically >65 years).

• Pharmacokinetics (PK) - "ADME" Changes:
  • Absorption: Variable; ↓ GI motility, ↑ gastric pH.
  • Distribution: ↑ body fat (↑ Vd lipophilic drugs, e.g., diazepam); ↓ total body water (↓ Vd hydrophilic drugs, e.g., lithium); ↓ albumin (↑ free drug for highly protein-bound drugs, e.g., warfarin, phenytoin).
  • Metabolism: ↓ Phase I (CYP450) hepatic metabolism; Phase II (conjugation) relatively preserved. ↓ first-pass effect.
  • Excretion: ↓ Renal clearance due to ↓ GFR. Estimate CrCl (e.g., Cockcroft-Gault: $CrCl = \frac{((140 - Age_{years}) \times Weight_{kg})}{(72 \times SCr_{mg/dL})} \times (0.85 \text{ if female})$).
• Pharmacodynamics (PD) Changes:
  • ↑ sensitivity to drugs (e.g., benzodiazepines, opioids, anticholinergics).
  • Altered receptor affinity/density.
  • Impaired homeostasis (e.g., ↓ baroreceptor reflex → orthostatic hypotension).
• Prescribing Principles:
  • "Start low, go slow, but go."
  • Regular medication review.
  • Avoid anticholinergic burden.

⭐ Polypharmacy (≥5 drugs) is common in geriatrics, significantly increasing the risk of adverse drug events and interactions; Beers criteria helps guide safer prescribing.

Pregnancy & Lactation Rx - Two Patients, One Plan

• Core Principle: Always weigh maternal benefit vs. fetal/neonatal risk. Use lowest effective dose, shortest duration.
• Physiological Changes (Pregnancy): ↑ Plasma volume, ↑ GFR, ↑ hepatic metabolism (e.g., lamotrigine, levothyroxine clearance ↑), altered drug protein binding.
• Teratogenicity: Highest risk during organogenesis (1st trimester, 3-8 weeks post-conception).
  • ⚠️ Key Teratogens: Thalidomide (phocomelia), Valproate (NTDs), Isotretinoin, Warfarin, Methotrexate, Lithium (Ebstein's).

  ⭐ ACE inhibitors are contraindicated in the 2nd and 3rd trimesters of pregnancy due to risks of fetal renal damage and oligohydramnios.

• Labeling: Prefer PLLR (Pregnancy and Lactation Labeling Rule) over old FDA categories (A,B,C,D,X).
• Lactation: Most drugs enter breast milk.
  • Consider: Drug properties (MW, lipid solubility, pKa), infant's age, milk-to-plasma ratio.
  • Resources: LactMed database.
  • Generally safe: Paracetamol, penicillins, cephalosporins, LMWH, labetalol.
  • ⚠️ Avoid: Codeine/tramadol (CYP2D6 UM risk), amiodarone, chemotherapy, radioactive iodine.

High‑Yield Points - ⚡ Biggest Takeaways

• Pediatrics: Weight-based dosing crucial. Immature hepatic/renal function alters PK. Avoid aspirin (Reye's), tetracyclines.
• Geriatrics: Polypharmacy major risk. Reduced renal clearance key. Increased sensitivity to CNS drugs. Start low, go slow.
• Pregnancy: Most drugs cross placenta. Key teratogens: ACEIs, valproate, warfarin, isotretinoin. Folic acid essential.
• PK Changes: Pediatrics: ↑Vd water-soluble drugs. Geriatrics: ↓renal excretion, ↑body fat. Pregnancy: ↑plasma volume, ↑GFR.
• Beers Criteria: Guides safe prescribing in elderly; identify potentially inappropriate medications.
• Breastfeeding: Consider drug properties (lipid solubility, half-life) and infant risk; choose safer alternatives if possible.