bbb Flashcards
What is the blood-brain barrier (BBB)?
A highly selective permeability barrier that separates the circulating blood from the brain extracellular fluid in the central nervous system.
Who discovered the blood-brain barrier?
Edwin Goldmann in 1913.
What is the primary function of the blood-brain barrier?
To protect the brain from harmful substances and common bacterial infections.
What are the factors affecting drug delivery to the brain?
- Blood-brain barrier (BBB)
- Cerebrospinal fluid
- Physico-chemical factors
What types of cells are involved in the structure of the BBB?
- Endothelial cells
- Astrocytes
- Pericytes
- Neurons
What is the role of astrocytes in the BBB?
They cover 99% of the brain side of capillaries and have an inductive effect on the maturation of the BBB.
What is cerebrospinal fluid (CSF)?
A fluid in the brain that counteracts the slow diffusion of drugs from CSF into brain tissue.
What is P-glycoprotein (P-gp)?
A transmembrane protein that functions as an energy-dependent efflux pump, expelling various substances out of cells.
What is the impact of P-glycoprotein on drug absorption?
Restricts the entry of foreign toxic substances into the brain and has a high impact on brain uptake.
What are the physico-chemical factors affecting drug delivery to the brain?
- Molecular Weight < 600
- < 6 H-bond donors
- log Po/w close to 3
- Polar surface < 70 Ų
What are invasive techniques for CNS drug delivery?
- Intracerebral injection/implant
- Intra-cerebroventricular (ICV) infusion
- Disruption of the BBB
What are non-invasive techniques for CNS drug delivery?
- Pharmacological approach
- Receptor-Mediated Transport
- Chemical Techniques
- Colloidal Techniques
- Miscellaneous approaches
Fill in the blank: The BBB can be transiently disrupted by techniques such as _______.
Osmotic disruption technique, MRI guided focused ultrasound, application of vasoactive compounds.
True or False: The BBB is present in all vertebrate brains.
True.
What is the consequence of the slow diffusion of drugs from CSF into brain tissue?
It limits the effectiveness of drug delivery to the brain.
How does P-glycoprotein influence drug efficacy and toxicity?
Variations in P-gp expression and function can lead to differences in drug ADMET.
What types of molecules utilize transporters to cross the BBB?
- Small hydrophilic molecules (e.g., amino acids, glucose)
- Larger or hydrophilic essential molecules (e.g., hormones, transferrin)
What is the production rate of cerebrospinal fluid (CSF)?
20 ml/h.
What is a significant challenge in drug delivery to the brain?
Overcoming the restrictions imposed by the blood-brain barrier while ensuring drug efficacy.
Fill in the blank: The absence of _______ and no fenestration are characteristics of the BBB.
Pinocytosis.
What are examples of antineoplastic drugs mentioned?
- Hydroxyurea
- Cytosine arabinoside
- Thiotepa
- Carmustine (BCNU)
