Drug Response Variability: Responses

Master answer

Pharmacokinetic:

• Absorption
  • Skin: Faster absorption of transdermal drugs such as Fentanyl
  • GIT:
    • Less gut motility may delay absorption
    • Laxatives and prokinetics increase gastric emptying and reduce absorption of oral agents
• Distribution
  • Less total body water and lean body mass
    • water soluble drugs (digoxin) have smaller Vd
    • higher central compartment concentration
  • Increased fat content %
    • fat soluble drugs (diazepam) have higher Vd
  • Reduced albumin
    • the free fraction of protein bound drugs (warfarin) is increased
  • Reduced cardiac output
    • reduced organ ­flow
    • altered redistribution phase
    • important in drug termination (thiopentone)
• Metabolism
  • ↓ Hepatic blood flow – high Extraction drugs (CCB) have ↓ clearance
  • ↓ Enzymatic activity
    Phase I > Phase II.
• Elimination
  • Loss of nephron number with age reduces renal clearance
  • Reduced GFR / nephrons / renal blood ­ow
    • renal drug excretion slowed
    • un-metabolised drugs (aminoglycosides) or active metabolites have prolonged activity

Pharmacodynamic:

• Increased sensitivity to sedatives, opioids, and hypnotics
• Decreased sensitivity to β-agonists and antagonists
• Decreased MAC
• Polypharmacy increases potential for drug interactions

JC 2019

Answer by JC