Which of the following substances is actively excluded by the blood-brain barrier (BBB) via efflux transport, and deficiency of this transporter is implicated in increased CNS drug toxicity?

• A Glucose — excluded by GLUT-1 downregulation
• B Albumin — excluded by lack of transcytosis in tight junction-expressing endothelium
• C Dopamine — excluded because it is metabolized by MAO in endothelial cells before crossing
• D P-glycoprotein (ABCB1) substrates — P-gp on luminal side of brain endothelium actively pumps lipophilic drugs back into blood ✓

Explanation

P-glycoprotein (P-gp, encoded by ABCB1/MDR1) is a luminal efflux transporter in brain capillary endothelial cells that actively pumps many lipophilic substrates (anti-epileptics, chemotherapy, HIV drugs) back into the bloodstream, limiting CNS penetration. Genetic or pharmacological P-gp deficiency leads to dramatically increased brain concentrations of P-gp substrates and CNS toxicity (e.g., ivermectin toxicity in collies with MDR1 mutation). Glucose enters via GLUT-1 (facilitated diffusion), it is not excluded. Albumin exclusion is due to restricted paracellular flux and minimal transcytosis (structural BBB property). Dopamine is excluded because it does not cross the BBB (levodopa is used as a precursor), but the mechanism for dopamine is lack of specific transporter and enzymatic degradation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.