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](https://jennysjamjar.com.au/wp-content/uploads/2020/02/Rate-of-Diffusion.png)
- 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