Which property of the blood-brain barrier explains why lipid-soluble drugs (e.g., thiopental) reach the brain rapidly while water-soluble drugs (e.g., aminoglycosides) do not?

• A Perivascular microglia actively phagocytose hydrophilic drugs before they reach neurons
• B The thick basement membrane of cerebral capillaries physically filters molecules by molecular weight
• C Cerebral capillary endothelium lacks fenestrations and has tight junctions; lipid-soluble drugs diffuse across membranes while polar drugs are excluded ✓
• D Astrocyte foot processes generate an additional hydrophilic layer that repels lipid-soluble compounds

Explanation

Cerebral capillaries differ fundamentally from peripheral capillaries: they lack fenestrations and their endothelial cells are connected by tight junctions (occludin, claudins, ZO-1), forming a continuous barrier. This eliminates paracellular and transcellular aqueous pathways. For a drug to cross the BBB passively, it must dissolve in the lipid bilayer of endothelial membranes — requiring high lipid solubility, low molecular weight, and minimal ionisation at physiological pH. Thiopental is highly lipid-soluble → rapid brain entry; aminoglycosides are polar, poorly lipid-soluble → excluded. Astrocyte foot processes maintain the BBB phenotype but are not a physical filter against lipid-soluble drugs.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.