Placental Drug Transfer: Determinants

Advanced, Clinical Subspecialties

All drugs cross the placenta to some degree but several factors determine the degree of placental transfer. Major determinants include lipid/water solubility, molecular weight, degree of ionization, and protein binding. Drugs that are lipid soluble, smaller (<500Da), have a low ionized fraction, and non-protein bound tend to cross the placenta to a greater degree. Classes of drugs that are known to cross the placenta include opiates, benzodiazepines, ephedrine, local anesthetics, beta blockers, barbiturates, and propofol. Drugs that are known to cross the placenta but are generally considered safe include propofol, ketamine, and fentanyl. 

Some drugs in the same class may differ in their propensity to cross the placenta. For example, glycopyrrolate is a quaternary ammonium structure and does not cross the placenta readily as a result. Atropine on the other hand is a tertiary amine and crosses to a much greater degree. 

One easy pneumonic to remember drugs that do NOT cross the placenta and are also considered safe is: He Is Going Nowhere Soon (Heparin, Insulin, Glycopyrrolate, NDNMB, Succinylcholine). 

Heparin, Insulin and NDNMB are large molecules, glycopyrrolate as previously noted is a quaternary amine, and succinylcholine is highly ionized.  Local anesthetic drugs can be particularly dangerous as they are weak bases and once across the placenta into the more acidic fetal circulation, become trapped and lead to fetal toxicity in a process known as ion trapping.


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Elliot Winters, MD