The blood-brain barrier (BBB) is formed primarily by cerebral endothelial cells with tight junctions. Which substance is NOT reliably excluded by the intact BBB?

• A Large protein molecules (albumin, immunoglobulins)
• B Highly charged hydrophilic drugs such as gentamicin and penicillin
• C Most circulating catecholamines (dopamine, norepinephrine)
• D Lipid-soluble substances such as CO2, O2, ethanol, and most anesthetic gases ✓

Explanation

Lipid-soluble substances (O2, CO2, ethanol, lipid-soluble anesthetics, most lipophilic drugs) cross the BBB freely by transcellular diffusion. The BBB selectively excludes large molecules (albumin), polar/charged hydrophilic substances (aminoglycosides, penicillin), and most circulating catecholamines (explaining why systemic dopamine does not affect the CNS directly). Glucose and amino acids cross via specific carrier-mediated transporters (GLUT1, large neutral amino acid transporter). This selectivity is why CNS infections are difficult to treat with many antibiotics.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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