Getting Medicine into the CNS- 11 Flashcards
What is the Blood Brain Barrier
A permeability barrier that separates the circulating blood from the brain’s extracellular fluid.
What are the three lines of defense at the BBB.
1) An anatomic barrier of endothelial cells with tight junctions, the basement membrane and surrounding astrocytes.
2) An enzymatic barrier of degrading enzymes localised in endothelial cells.
3) Transport systems actively transporting substances from the brain back to blood.
What molecules can pass the BBB.
Lipid soluble and <400Da of MW
What is the paracellular aqueous pathway
Water soluble agents pass through tight junctions.
What is the transcellular lipophilic pathway
When lipid soluble agents under 400 dalton pass through the membrane.
What are transporter proteins function in the BBB.
Transporter proteins for glucose, amino acids, nucleosides and other substances.
Some transporters are energy-dependent and act as efflux transporters.
What is the function of receptor-mediated transcytosis.
Specific receptor-mediated endocytosis and transcytosis for some proteins ie insulin and transferrin.
What is the role of absorptive transcytosis.
Uptake by absorptive-mediated endocytosis and transcytosis increased by cationization of poorly transported proteins (albumin and other plasma proteins)
What are ways of chemically modifying a drug to pass the BBB.
Increasing the lipophilicity of a drug so that it can pass the transcellular lipophilic pathway.
Use of the trojan horse strategy to conjugate the drug to a molecule to cross the BBB via encapsulation of the drug in a delivery system. (Liposome, Micelle, Nanoparticle).
This allows protection of the drug against degredation.
How can the BBB be disrupted?
Opening of the BBB by administration of pharmacological agents or osmotic opening.
Using agents such as vasoactive agents, and angiotensin II.
Intercarotid injection of hypertonic solutions of mannitol or urea. Meaning shrinkage of the size of endothelial cells and opening of tight junction network.
Why is the nose a good place for drug delivery to the brain?
Nasal drug delivery bypasses the BBB for direct nose-to-brain drug delivery.
