Age-Related Changes in Pharmacodynamics

Intro to Age & PD - Not Mini Adults

Pharmacodynamics (PD): What the drug does to the body; its mechanism of action. Both pediatric and geriatric populations exhibit significant age-related variations in PD.

• Pediatrics: Not "mini-adults." Organ immaturity & developing receptor systems lead to unique drug effects and sensitivities.
• Geriatrics: Degenerative changes, altered receptor sensitivity (↑ or ↓), and reduced homeostatic control significantly modify drug responses. Polypharmacy is a common confounder.

⭐ Paradoxical drug reactions (e.g., benzodiazepine-induced agitation in elderly, or diphenhydramine-induced hyperactivity in children) are more common in pediatric and geriatric patients due to altered receptor responses or neurotransmitter systems a

Pediatric PD Changes - Little Patients, Unique Responses

• Receptor System Variations:
  • Benzodiazepines (e.g., diazepam): ↑ sensitivity, risk of paradoxical excitement.
  • Opioids (e.g., morphine): ↑ respiratory depression risk (immature centers, altered receptors).
  • β-agonists (e.g., salbutamol): ↓ responsiveness in neonates/infants (↓ receptor density/coupling).
• Immature Blood-Brain Barrier (BBB):
  • ↑ CNS drug penetration & exaggerated effects.
• Paradoxical Drug Reactions:
  • Antihistamines (e.g., diphenhydramine): CNS excitation.
  • Barbiturates, Benzodiazepines: Hyperactivity/agitation.
• Key Drug-Specific PD Alterations:
  • Digoxin: Variable sensitivity; requires careful dose titration.
  • Valproic acid: ↑ risk of fatal hepatotoxicity in children < 2 years.
  • Aspirin: Reye's syndrome risk with viral illness.

⭐ Paradoxical reactions to drugs like benzodiazepines (excitation instead of sedation) are more common in children due to developmental differences in neurotransmitter systems.

Geriatric PD Changes - Seniors & Sensitivity Shifts

• Receptor Alterations & Sensitivity Shifts:

  • ↓ Beta-adrenergic receptor responsiveness:
    • ↓ Response to agonists (e.g., isoproterenol).
    • ↑ Sensitivity to antagonists (beta-blockers).
  • ↑ Sensitivity to CNS depressants:
    • Benzodiazepines, opioids, antipsychotics (↑ sedation, confusion, falls).
  • Other key sensitivities:
    • ↑ Anticholinergic effects (confusion, dry mouth, retention).
    • ↑ Warfarin effects (↑ bleeding risk).
    • ↓ Dopamine (D2) receptors (affects antipsychotics).

• Impaired Homeostatic Mechanisms:

  • ↓ Baroreceptor reflex → ↑ orthostatic hypotension risk (esp. with antihypertensives, vasodilators).
  • Impaired thermoregulation → ↑ risk of hypothermia/hyperthermia.
  • ↓ Postural stability → ↑ fall risk (psychoactive drugs).

• Polypharmacy & PD Interactions:

  • Common in seniors, significantly ↑ risk of PD interactions.
  • Additive/synergistic adverse effects common.
  • One drug can unpredictably alter sensitivity to another.

⭐ > Elderly patients often exhibit heightened sensitivity to benzodiazepines, leading to increased risks of sedation, cognitive impairment, and falls even at standard adult doses.

Clinical Applications - Age-Adapted Dosing

• Pediatrics:
  • Dosing often weight-based (mg/kg) or using Body Surface Area (BSA) for precision.
  • Neonates/infants: immature organ (liver/kidney) function necessitates cautious dose titration and monitoring.
  • Children: may exhibit faster drug metabolism for certain drugs, requiring dose adjustments.
• Geriatrics:
  • 📌 Guiding principle: "Start low, go slow."
  • Physiological changes: ↓ renal/hepatic clearance, ↑ body fat, ↓ body water, altered receptor sensitivity.
  • Increased risk of polypharmacy, drug-drug interactions, and ADRs.
  • Utilize clinical tools:
    • Beers Criteria: Identifies Potentially Inappropriate Medications (PIMs).
    • STOPP/START criteria: Optimize prescribing.
• Monitoring (Both Groups):
  • Crucial: Regular assessment for therapeutic efficacy and adverse drug reactions (ADRs).
  • Consider Therapeutic Drug Monitoring (TDM) for drugs with a narrow therapeutic index.

⭐ In geriatrics, drugs with significant anticholinergic properties (e.g., first-generation antihistamines, TCAs) are frequently associated with adverse effects like confusion, falls, and urinary retention, making them key targets in Beers Criteria.

High‑Yield Points - ⚡ Biggest Takeaways

• Pediatrics: Receptor immaturity (e.g., β-receptors) & permeable BBB alter drug responses.
• Pediatrics: Higher risk of paradoxical reactions (e.g., benzodiazepine-induced agitation).
• Geriatrics: Reduced receptor density/affinity (e.g., β-adrenergic, cholinergic) is typical.
• Geriatrics: Increased sensitivity to CNS depressants (benzodiazepines, opioids) and anticholinergics.
• Geriatrics: Impaired homeostatic counter-regulation (e.g., baroreflex) predisposes to ADRs.
• Overall: Both age extremes exhibit greater pharmacodynamic variability and narrower therapeutic windows.