Drug Response Variability — Obesity PK

Pharmacodynamics

• Receptor resistance
  • Insulin resistance secondary to obesity

Pharmacokinetics

Absorption

• Increased cardiac output
  → Delayed onset of action of inhalational agents (volatile anaesthetic agents)
• Decreased subcutaneous absorption due to tissue binding (heparin)
• Failure of IM administration due to increased depth (adrenaline is anaphylaxis)

Distribution

• Increased total body fat
  • Increased volume of distribution of lipophillic drugs
    • Barbiturates, benzodiazepines → should be administered according to actual weight
    • Lipid insoluble drugs should be dosed according to ideal weight
• Decreased fractional proportion of total body water
• Increased blood volume and cardiac output
  • May require increased loading dose for therapeutic effect (thiopentone)
• Displacement of protein bound drug due by fatty acids (propofol)

Metabolism

• Decreased hepatic function due to non-alcoholic steatohepatitis
  • Increased T_1/2b of drugs metabolized by liver
• Increased plasma and tissue esterases
  • Increased metabolism of suxamethonium, remifentanyl

Excretion

• Increased cardiac output
  → Increased renal blood flow
  → Increased GFR
  → Increased tubular secretion
  → Increased renal clearance
• Increased T_1/2b  due to accumulation of lipid soluble drugs in fat, and slow redristribution into central component
  • Propofol, volatile anaesthetics

Sakurai 2016

Answer by Sakurai