Blood brain barrier

Question 1

What is the CNS comprised of?

Answer 1

• brain
• cerebellum
• brainstem
• spinal cord

Question 2

What are the name of the arteries that supply blood to the brain from the aorta?

Answer 2

Carotid arteries

Question 3

Due to tight junctions along the capillary endothelium - for a molecule to move across to the brain name 4 ways it can do this

Answer 3

1. Active transport
2. facilitated diffusion
3. Pinocytosis
4. Passive diffusion

Question 4

Give 3 drug examples that cross the BBB readily

Answer 4

1. anaesthetic agents (barbiturates, propofol
2. L-DOPA
3. Insulin

Question 5

What is meant by pKa

Answer 5

pH at which ionised and unionised concentration of drugs are equal

Weak acid - pKa>pH then more of the drug will exist in its unionised state (lipophilic)

Weak base - pKa

Question 6

Name one efflux transporter that drugs need to avoid in order to cross the BBB successfully

Answer 6

p-glycoprotein

Question 7

Name one drug that is a effluxed back out of the cell by p-glycoprotein and what it is used for

Answer 7

Loperamide (an opioid) used for diarrhea

Question 8

List 5 features of cerebrospinal fluid

Answer 8

1. protects the brain
2. flows in ventricles in the brain
3. provides some homeostatic processes
4. produced in choroid plexus
5. travels to the subarachnoid space of the brain + spinal cord where valves are located allowing it to move back into the blood vessels

Question 9

By what method are drugs more likely to reach the brain tissue

Answer 9

diffusion across capillaries

Question 10

Name two other barriers to the brain tissue

Answer 10

1. blood-CSF barrier
2. CSF-brain barrier

Question 11

List 4 features of blood-CSF/CSF-brain barrier

Answer 11

1. more porous than BBB so more drugs get into CSF
2. smaller surface area than capillaries
3. Allows specific molecules in such as immune cells
4. the ependymal cells lining the brain that is in contact with CSF don’t have tight junctions

Question 12

Why is administering drugs directly into CSF not preferred over capillaries

Answer 12

CSF doesn’t penetrate deep into the brain tissue and diffusion is challenging and slow whereas capillaries travel deep into brain tissue

Question 13

Give an example of a drug that is injected directly into the CSF

Answer 13

epidural

Question 14

Name 3 aspects of PK that could be used to optimise drugs for CNS effects

Answer 14

1. choosing the right drug
2. Altering the molecule
3. using endogenous carrier/receptor-mediated transporters