Physiological Barriers

Drugs cross different physiological barriers to move into intracellular compartments. These barriers, such as vascular endothelium, cell membrane, blood-brain, and blood-placental barriers, are semi-permeable and restrict drug distribution in tissues.

Of these, the vascular endothelium is freely permeable to most drugs, including ionized, un-ionized or lipophilic drugs smaller than 600 Daltons.

After diffusing from capillary walls into the extracellular fluid, drugs must cross the cell membrane to enter cells. While lipophilic drugs and small molecules can easily permeate the cell membrane, others require active transport via carrier proteins.

Unlike other capillaries, the capillaries in the brain are made of endothelial cells held together by continuous tight junctions forming the blood-brain barrier.

It is impervious to all non-lipophilic drugs but allows some drugs to be actively transported into the brain.

Lastly, the blood-placental barrier allows lipophilic molecules smaller than 1000 Daltons to pass into fetal circulation by passive diffusion. This barrier is less effective than the blood-brain barrier. So to avoid teratogenicity, drug usage is restricted during pregnancy.