B SYL2017:OBA with shock

Definition

ORAL BIOAVAILABILITY = fraction of dose given orally that reaches systemic circulation

Measurement

  • Plot plasma [ ] of oral dose v IV dose
  • Calculate AVC
OBA
Measurement

Factors Affecting Oral Absorption

  • Rate of diffusion/absorption
  • First pass
  • Patient factors
  • Pharmaceutical prep
  • Physiochemical interactions

Absorption

  • Absorption = ability of drug to cross gut wall
  • Usually passive, governed by diffusion
  • Fick’s law
  • ↑absorption with:
    • ↑SA of gut
    • ↓thickness of diffusion distance
    • ↓MW of drug
    • ↑solubility of drug → pKA
    • ↑[ ] gradient
  • pKa → degree of ionisation affects solubility e. aspirin = unionised in stomach → rapid absorption

First Pass Effect

  • First pass = proportion of drug absorbed, delivered to liver by portal circulation & metabolised before reaching systemic circulation
  • ↑1st pass = ↓OBA e. M is fully absorbed (F = 1) but significant 1st pass (0.67)

∴ OBA = 1 – 0.67 = 53% (v. poor)

  • Pre-systemic elimination can occur
    • Gut wall (oestrogen)
    • Portal circulation (aspirin → salicylic acid)
    • Liver (majority)
  • Hepatic enzyme inducer (phenytoin) = ↑first pass = ↓OBA
  • Hepatic enzyme inhibitor (amiodarone) = ↓first pass = ↑OBA

Patient Factors

  • Malabsorption i.e. Crohn’s
  • Trauma → ↓gastric emptying
  • Blood flow → ischaemic gut ↓rate of diffusion

Pharmaceutical Prep

  • MW = ↑size = ↓absorption
  • PPB = ↑PPB = ↓absorption
  • Lipid formation = disperses quicker = ↑absorption

Physiological Interactions

  • Milk = ↓tetracycline OBA
  • Gut enzymes = inactivate insulin orally

Oba Alteration With Shock

  • Shock = cellular & tissue hypoxia whereby O2 exceeds supply

Absorption

    • ↓SA (dead gut) = ↓absorption
      • ↓thickness/inflammation = ↑absorption
      • ↓blood flow = ↓absorption

First Pass

    • Hepatic enzyme dysfunction = ↓first pass = ↑OBA

Physiochemical Interactions

    • Shocked patients = multiple meds = altered enzyme function → alter hepatic enzyme induction & 1st pass/OBA