THE PLACENTAL BARRIER

The placenta forms a barrier to the transfer of drugs between the mother and the fetus, but increasing lipid-solubility, decreasing maternal protein binding, decreasing molecular weight, increased materno-fetal concentration gradient and placental blood flow etc will increase the placental transfer of drugs

The relative distribution of the drug across the placenta is represented by Feto-Maternal (F/M) concentration ratio

Pethidine and diamorphine are both metabolised in the fetus to less lipid-soluble products like norpethidine and morphine respectively, which remain on the fetal side of the placenta. The elimination half-lives of these drugs are also longer in the fetus because of immature hepatic metabolism. This again prolongs its existence in the fetal side.

Lipid solubility of drugs like thiopentone sodium are high; so they cross the placenta easily, and can accumulate as the pH is lower in the fetus

Diazepam is metabolised to less lipid-soluble products. So it can have an F/ M ratio of 2 even one hour after maternal administration.

Local anaesthetic agents are weak bases which are largely UN-IONISED at physiological pH, and cross the placenta readily. Foetal ‘trapping’ occurs only in severe acidosis, when the molecules become IONIZED in the fetal side.

Leave a comment