Pediatric and Geriatric Pharmacology

Pediatric Pharmacokinetics & Dynamics - Tiny Patients, Big Challenges

• Absorption (A):
  • Neonates: ↑ Gastric pH, delayed emptying.
  • Skin: ↑ Percutaneous absorption (thin, ↑ Surface Area to Body Weight ratio).
  • IM: Erratic (↓ muscle mass & flow).
• Distribution (D):
  • Body Composition: Neonates ↑ Total Body Water (TBW, ~75-80%), ↓ Fat.
  • Vd: ↑ for water-soluble drugs, ↓ for lipid-soluble drugs.
  • Protein Binding: ↓ plasma protein binding → ↑ free drug fraction.
• Metabolism (M):
  • Liver: Immature enzymes (Phase I CYP450 & Phase II glucuronidation ↓).
  • Risk: Chloramphenicol toxicity (Gray Baby Syndrome) due to ↓ glucuronidation.
• Excretion (E):
  • Kidneys: ↓ Glomerular Filtration Rate (GFR) & tubular function in neonates.
  • Maturation: Renal function matures by 6-12 months; prolonged drug $t_{1/2}$ until then.
• Pharmacodynamics (PD):
  • Receptors: Altered number, affinity, or post-receptor responses.
  • Reactions: Paradoxical drug effects possible (e.g., benzodiazepines → agitation).

⭐ Neonates have ↑ Total Body Water & ↓ body fat, significantly altering drug Volume of Distribution (Vd).

Pediatric Dosing & ADRs - Measure Twice, Dose Once

• Dosing Methods:
  • Weight-based (mg/kg): Most common & reliable.
  • Body Surface Area (BSA): $Dose = \frac{BSA (m^2)}{1.73 m^2} \times AdultDose$. For chemotherapy, nephrotoxic drugs.
  • Age-based (Young’s, Clark’s rules): Less accurate, historical.
• Flowchart: Choosing Dosing Method

• Key Age-Specific ADRs: 📌 Remember CAST for major risks:
  • Chloramphenicol: Grey baby syndrome (neonates).
  • Aspirin: Reye's syndrome (children with viral illness).
  • Sulfonamides: Kernicterus (neonates, esp. premature).
  • Tetracyclines: Teeth staining & ↓bone growth (< 8 yrs).

⭐ Aspirin is contraindicated in children with viral fever due to risk of Reye's syndrome.

Geriatric Pharmacokinetics & Dynamics - Golden Years, Altered Drugs

• Pharmacokinetics (ADME Changes):
  • Absorption: Variable; ↓ gastric acid & motility.
  • Distribution: ↓ Total body water, ↑ body fat (affects Vd); ↓ albumin (↑ free drug).
  • Metabolism: ↓ Hepatic blood flow & Phase I (CYP450) activity; Phase II often preserved.
  • Excretion: Crucial! ↓ Renal clearance (GFR). Use Cockcroft-Gault: $CrCl = \frac{(140-age) \times IBW (kg)}{72 \times SCr (mg/dL)} (\times 0.85 \text{ if female})$.
• Pharmacodynamics:
  • Altered receptor sensitivity (e.g., ↑ to sedatives, ↓ to β-agonists/antagonists).
  • Impaired homeostatic mechanisms (e.g., postural hypotension).

⭐ Renal function (eGFR or CrCl) is the most significant factor affecting drug dosing in the elderly.

Geriatric Prescribing & Polypharmacy - Pill Puzzles, Safe Solutions

Polypharmacy (use of ≥5 drugs) ↑risks: ADRs, drug interactions, non-adherence, falls, cognitive decline. Prescribing mantra: 'Start low, go slow,' individualize therapy, and conduct regular medication reviews.

• Risk Mitigation Tools:

  • Beers Criteria: Identifies Potentially Inappropriate Medications (PIMs) to ↓ADRs. Key classes:
    • Strong Anticholinergics (e.g., diphenhydramine)
    • Benzodiazepines & Z-drugs
    • Chronic systemic NSAIDs
    • Certain Antipsychotics (e.g., haloperidol)
    • Sliding-scale Insulin (without basal)
  • STOPP/START Criteria: Tools to identify PIMs & prescribing omissions.

• Common Drug-Related Problems & Culprits:

  • Falls: Benzodiazepines, antipsychotics, antihypertensives.
  • Cognitive Impairment: Anticholinergics (📌 "Can't see, can't pee, can't spit, can't shit"), sedatives.
  • Bleeding: Anticoagulants, NSAIDs, antiplatelets.

⭐ Anticholinergic drugs are a major cause of cognitive impairment and delirium in the elderly.

High‑Yield Points - ⚡ Biggest Takeaways

• Pediatrics: ↑ Total body water affects Vd of hydrophilic drugs; immature liver/kidney function slows drug elimination.
• Key pediatric ADRs: Gray baby syndrome (chloramphenicol), Reye's syndrome (aspirin), kernicterus (sulfonamides).
• Geriatrics: ↓ Renal clearance is the most significant PK alteration; ↑ body fat affects Vd of lipophilic drugs.
• Polypharmacy and ↑ sensitivity to CNS drugs (e.g., benzodiazepines) are prevalent in elderly.
• Beers criteria helps avoid potentially inappropriate medications in older adults.