V1iii: Factors which influence transfer of drugs across placenta to foetus

Definition  Placenta = organ which is the interface between mother + foetus during pregnancy

Drug Transfer

  • Transfer of drugs influenced by:
    • Fick’s Law
    • Drug Factors
    • Foetal Factors
    • Maternal Factors
    • Placental Factors

Fick’s Law

Rate of Diffusion
  • Large placenta SA 15m2
  • Thin placental distance for diffusion = 3.5µm
  • ↑solubility = ↑diffusion
  • MW = smaller lung = ↑diffusion
  • Drug [ ] influenced by dose, 1st pass, OBA
  • ↑grad = ↑diffusion

Drug Factors

PPB

  • plasma pr] varies with gestational age
  • ↓[albumin] = ↑free drug, but also susceptible to ↑clearance
    • Theoretically ↑drug transfer
  • α1GP → not much ∆

Ionisation

  • Foetal pH is acidotic
  • Traps basic drugs (opioids, LA)
  • Non-ionised drugs transfer more readily

Maternal Factors

  • Uteroplacental BF – affected by:
    • ↓Uterine a. pressure (aorta compression)
    • ↑Uterine v. pressure (cava compression)
    • ↑uterine venous R (pre-eclampsia)
  • ↓drug t/f with compromised uteroplacental flow but also ↓drug removal from foetus
  • No autoregulatory mechanisms to overcome this

Placental Factors

Placental metabolism

  • P450 reaction
  • Phenobarbitol metabolised by placenta

SA placenta

  • Abruption/disease
  • ↓drug transfer

Gestational Age

  • ↑permeability at early stages

Placental Transporters

  • MDR7 & p-glycoprotein remove drugs from foetal circulation