Blood-brain barrier

Question 1

What is the name of the supportive cells that help maintain homeostasis of the brain?

Answer 1

Astrocytes

Question 2

Which ways/methods can drugs move across the transmembrane?

Answer 2

Active transport
Facilitated transport
Transcytosis
Passive diffusion

Question 3

How do the anaesthetic agents (barbiturates, propofol) move across the blood brain barrier?
What is an important property of these drugs?

Answer 3

Passive diffusion

They are highly lipophilic

Question 4

How does L-DOPA move across the blood brain barrier?

What is an important property of this drug?

Answer 4

Active transport

Substrate for LAT (amino acid) transport system

Question 5

How does insulin move across the blood brain barrier?

Answer 5

Receptor mediated endocytosis

Question 6

List PK properties of propofol

Answer 6

Weak acid
Highly protein bound, small molecule
Rapidly distributes to fatty tissue
Rapid clearance

Moves across the BBB by simple diffusion

Question 7

What is pKa?

Answer 7

pKa is the pH at which ionised and unionised concentrations are equal

Question 8

Can dopamine pass the BBB?

Give an explanation

Answer 8

Dopamine is a polar molecule and cannot cross the BBB

L-dopa is the precursor of domaine (a substrate of an amino acid transporter)

Within the CNS L-dopa is metabolised to dopamine by dopa-decarboxylase and exerts its physiological effects.

Question 9

Give examples of drugs that are excluded from the brain by the actions of p-glycoprotein

Answer 9

opioid loperamide, Ivermectin, digoxin, domperidone

Question 10

Give an example of an efflux transporter

Answer 10

p-glycoprotein

Question 11

what is the role of p-glycoproteins?

Answer 11

P-glycoprotein functions as a transmembrane efflux pump, pumping its substrates from inside to outside the cell.

Drugs which induce or inhibit P-glycoprotein can interact with other drugs handled by the pump.

Question 12

What is loperamide?

Answer 12

An opioid that acts on mu-opioid receptors
It is a substrate for p-glycoprotein
so it can cross the endothelial cells from the blood but it pumped back out again

Question 13

Therapeutic uses of loperamide and why?

Answer 13

Anti-diarrheal medicine

Although it is an opioid because there are no unwanted adverse CNS effects due to the actions of p-glycoprotein

Question 14

What is CSF?

Answer 14

Cerebrospinal fluid is a clear and colourless fluid that provides protection and homeostatic function of the brain.
CSF is produced in the choroid plexus of the brain

Around 100-200-ml of CSF around the CNS

Question 15

What is the difference between the blood-CSF and CSF-brain barrier?
Therapeutic effects of this difference…

Answer 15

The blood-CSF barrier is more porous than the CSF-brain barrier.

Due to blood-CSF being more porous many more drugs can penetrate into the CSF than into the brain tissue

Question 16

What is bupivacaine?

What is heavy bupivacaine?

What is this used for?

Answer 16

A local anaesthetic agent used for spinal anaesthesia

heavy bupivacaine is chemically alterted to make it more dense than CSF (it has an added glucose molecule)
This is used at the level of a spinal injection and doesn’t travel up.

Question 17

Properties of gabapentin and how does it cross the BBB?

Answer 17

Hydrophilic drug

Crosses the BBB via the LAT-1 transport system