Formulation of Neurological Drugs

Question 1

State the 4 functions of the BBB

Answer 1

1.) Boundary – barrier to environment
2.) Provides protection & support
3.) Regulates what enters and leaves brain
4.) Selectively delivery of nutrients/drugs to the brain parenchyma and maintains homeostasis

Question 2

Explain the BBB

Answer 2

The structural and functional barrier impedes and regulates the influx of most compounds (95%) from blood to the brain. It protects the brain from harmful substances and supplies the brain with the required nutrients for proper function

Question 3

State the 4 pathways to cross the BBB

Answer 3

• Passive diffusion
• Passive transport (facilitated diffusion)
• Active transport
• Transcytosis

Question 4

Explain passive diffusion

Answer 4

The net movement of molecules down a concentration gradient involves moving substances into, through and out of cells that requires no energy input.

Question 5

Explain passive transport

Answer 5

When substances are moved across a membrane using a passive transport protein that allows specific solutes to follow its concentration gradient across a membrane. It allows molecules with low lipid solubility to traverse the BBB.

Question 6

Explain active transport

Answer 6

Active transport moves solutes against their concentration gradient using energy (ATP).

Question 7

Explain transcytosis

Answer 7

The formation and movement of vesicles formed from membranes involving motor proteins and ATP.

Involves endocytosis - the formation of a vesicle from a cell membrane, enclosing materials near the cell surface and bringing them into the cell

And exocytosis - the fusion of a vesicle with a cell membrane, releasing its contents to the surroundings.

Question 8

Name 3 types of receptors involved in receptor-mediated transport in BBB

Answer 8

Transferring receptor - a receptor for BBB targeting and transport in transcytosis

Lactoferrin receptor - two binding sites with absorptive mediated mechanism

Insulin receptor - tyrosine kinase receptors via transcytosis

Question 9

Name 3 targets for BBB regulation

Answer 9

Tight junctions

Active efflux

Transcytosis

Question 10

State the FOUR factors affecting drug delivery across the BBB

Answer 10

Non-ionised

LogP value near 2

Molecular weight <400 Da

Cumulative number of hydrogen bonds between 8-10