Pharmacological Considerations in Pediatrics

Pharmacological Considerations in Pediatrics

Pharmacological Considerations in Pediatrics

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Pediatric PK/PD - Tiny Bodies, Big Changes

  • Absorption (A):
    • Neonates: Gastric pH ↑, GI transit variable, IM absorption erratic, skin permeability ↑.
  • Distribution (D):
    • Total Body Water (TBW) ↑ (70-80% vs. 60% adult) & Extracellular Fluid (ECF) ↑ → ↑ Volume of Distribution (Vd) for water-soluble drugs.
    • Fat content ↓ → ↓ Vd for lipid-soluble drugs.
    • Protein binding ↓ (e.g., albumin) → ↑ free drug fraction.
  • Metabolism (M):
    • CYP450 enzyme system immature; Phase I reactions (e.g., oxidation) slower.
    • Phase II glucuronidation ↓ significantly in neonates. 📌 Neonates Generally Lack UDPGT (UDP-glucuronosyltransferase).
  • Excretion (E):
    • Glomerular Filtration Rate (GFR) ↓ in neonates/infants (reaches adult values by 6-12 months).
  • Pharmacodynamics (PD):
    • Receptor density & affinity may differ.
    • Paradoxical drug responses (e.g., benzodiazepines causing agitation).

⭐ Minimum Alveolar Concentration (MAC) values for volatile anesthetics are highest in infants (peak at 1-6 months), often ~1.5x adult values (e.g., Sevoflurane).

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Inhalational Agents - Sweet Dreams, Safe Air

  • MAC (Minimum Alveolar Concentration): Peaks at ~6 months (Sevoflurane/Isoflurane); lower in neonates & older children vs. infants.
  • Kinetics: Faster induction/emergence (↑ $V_A$/FRC, ↑ CO to VRG, ↓ blood:gas solubility effect).
  • Agents:
    • Sevoflurane: Choice for induction; non-pungent.
    • Desflurane: Airway irritant; rapid recovery. Not for induction.
    • Halothane: Historical; halothane hepatitis risk.
    • Nitrous Oxide ($N_2O$): Diffusion hypoxia risk (administer 100% O₂ post-use).

⭐ Sevoflurane is preferred for pediatric inhalational induction due to low pungency and rapid onset.

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IV Anesthetics & Opioids - Vein Voyage, Pain Vanquishers

  • Propofol:
    • Induction/maintenance. Neonates: ↑ Vd, ↑ dose (2.5-3.5 mg/kg).
    • ⚠️ Risk: Propofol Infusion Syndrome (PRIS).
  • Ketamine:
    • Dissociative anesthesia, potent analgesia, bronchodilation.
    • Dose (IV): Induction 1-2 mg/kg; Analgesia 0.25-0.5 mg/kg.
    • ⚠️ Emergence delirium; ↓ with benzodiazepines.
  • Opioids:
    • Morphine: Neonates: ↓ clearance, prolonged effect. Dose: 0.05-0.1 mg/kg.
    • Fentanyl: Neonates: ↑ sensitivity. Dose: 1-2 mcg/kg. ⚠️ Chest wall rigidity with high doses/rapid injection.
    • Remifentanil: Ultra-short acting; plasma esterase metabolism. Ideal for TIVA.
  • Dexmedetomidine:
    • α2-agonist: sedative, analgesic. Minimal respiratory depression.
    • Loading dose: 0.5-1 mcg/kg over 10 min; Maintenance: 0.2-0.7 mcg/kg/hr.

Pediatric IV Anesthetics & Opioids

⭐ Fentanyl is approximately 100 times more potent than morphine.

Muscle Relaxants & Reversal - Still Muscles, Swift Wake-up

  • Succinylcholine (SCh): 1-2 mg/kg IV. Risks: MH, hyperkalemia, masseter spasm; atropine for bradycardia.
  • Non-depolarizers (NDMRs):
    • Rocuronium: 0.6-1.2 mg/kg. Reversal: Sugammadex.
    • Atracurium/Cisatracurium: Hoffman/ester hydrolysis.
  • Pediatric Considerations:
    • Neonates: ↑ sensitivity to NDMRs, ↓ plasma cholinesterase.
  • Reversal:
    • Neostigmine (0.05-0.07 mg/kg) + Glycopyrrolate (0.01-0.02 mg/kg).
    • Sugammadex (for Rocuronium). Pediatric Muscle Relaxant Comparison

⭐ Neonates: ↑ NDMR sensitivity, ↓ plasma cholinesterase (prolongs SCh).

Local Anesthetics & Dosing - Numb & Numbered Right

  • Max Doses (mg/kg):
    • Lidocaine: Plain 3-5; With Epi 5-7
    • Bupivacaine: Plain ~2
    • Ropivacaine: Plain ~2-3 Max local anesthetic doses for pediatric patients
  • Neonates: ↓ protein binding (↑ free fraction), ↓ metabolism.
  • LAST (Local Anesthetic Systemic Toxicity):
    • Signs: CNS (tinnitus, seizures) → CVS (arrhythmias, collapse).
    • Management: Intralipid 20%.
  • Common Applications: Caudal blocks, EMLA cream.

⭐ For LAST, Intralipid 20% initial bolus is 1.5 mL/kg (ideal body weight) over 1 min; may repeat bolus 1-2 times for persistent asystole/CV collapse.

High‑Yield Points - ⚡ Biggest Takeaways

  • Neonates/Infants: ↑ Vd for water-soluble drugs (e.g., succinylcholine) means higher mg/kg doses.
  • Immature hepatic metabolism (glucuronidation) prolongs effects of opioids (morphine) & benzodiazepines.
  • Reduced GFR in neonates slows renal drug excretion (e.g., aminoglycosides).
  • MAC values are higher in infants (peak ~6 months); sevoflurane highest in neonates.
  • Marked sensitivity to respiratory depression from opioids and sedatives.
  • Rapid inhalational induction/emergence due to ↑ alveolar ventilation/FRC ratio.
  • Propofol: Higher induction doses (mg/kg) due to larger Vd & faster clearance.

Practice Questions: Pharmacological Considerations in Pediatrics

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What is the correct dose of i.v. adrenaline in term infants during neonatal resuscitation?

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Flashcards: Pharmacological Considerations in Pediatrics

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Minimum alveolar concentration is highest at the age of _____

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Minimum alveolar concentration is highest at the age of _____

6 months

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