Drugs and the BBB

Question 1

Components of BBB and their functions

Answer 1

• Tight junction: creates anchor between two cells which keeps them together and stops flow between them
• Clefts increase rate of absorption: gap between cells that increases rate of flow
• Fenestra: both layers of cell membrane are touching - 4 layer membrane - more rapid transfer of substances

Question 2

Passive diffusion

Answer 2

Down conc grad from one side of the membrane to another

Lipid soluble molecules pass through easily

Question 3

Facilitated diffusion

Answer 3

Energy neutral (passive) - down conc grad through carrier protein across membrane

Question 4

Active transport

Answer 4

AT1: Na+/K+ exchanges one molecule for another
AT2: co-transport - glucose and sodium move to one side of the membrane

Question 5

Pinocytosis

Answer 5

Invagination of membrane moves molecule into vesicle and is released the other side - form of AT

Question 6

factors affecting rate of diffusion

Answer 6

• Molecular size (indirectly proportionate)
• Conc grad (directly proportionate)
• Ionization (indirectly proportionate)
• Lipid solubility (directly proportionate)
• Protein binding (indirectly proportionate)

Question 7

Local anaesthetics

Answer 7

Found in unionised form outside membrane where they diffuse across
Inside the cell they become ionised and gain H+
Because they are ionised they are able to block Na+ channels and stop the propagation of pain

Question 8

Which molecules can pass through tight junctions

Answer 8

Small and water soluble molecules

Question 9

Which molecules can pass through trans cellular pathways

Answer 9

Lipid soluble - small and lipophilic

Question 10

Receptor mediated transcytosis

Answer 10

Pinocytosis moves molecules from outside to inside using vesicles - uses receptors

Question 11

Absorptive transcytosis

Answer 11

Moves albumin and proteins across a membrane, no receptor needed

Question 12

Cell mediated transcytosis

Answer 12

phagocytose molecule using liposomes and move across membrane

Question 13

CNS diseases

Answer 13

• Meningitis
• Brain abscess/tumour
• MS
• Alzheimer’s
• Parkinson’s

Question 14

How does penicillin enter the brain?

Answer 14

When bacteria enters meninges, disrupts integroty of the barrier, allowing benzylpenicillin to pass through into brain

Question 15

Why is levodopa better to administer than dopamine

Answer 15

• Dopamine is too polar to cross BBB and would be metabolised in PNS
• Levodopa is non-polar so it can cross BBB

Question 16

Receptor/vector mediated transport

Answer 16

• Viruses are altered to make them safe but can cause immune response or mutations (cancer)
• Molecule added to virus to pass through barrier

Question 17

Colloidal drug carriers

Answer 17

• Emulsion, liposomes, nanoparticles are lipophilic
• They encase active ingredient so it can pass BBB
• Coated with surfactants like polyoxypropylene etc

Question 18

Invasive delivery to CNS

Answer 18

• Intraventricular

- Sub arachnoid route

Question 19

Ommaya reservoir

Answer 19

• Tube that ends in lateral ventricles of brain that is attached to subcutaneous reservoir underneath skull
• Can deliver drugs directly to ventricles

Question 20

Lumbar puncture

Answer 20

• Access CSF without damaging structures

- Delivers drugs to meninges

Question 21

Intrathecal drug delivery system

Answer 21

• Pocket underneath skin to dispense drugs in lumbar spine

- Used in spasticity

Question 22

Nose-brain pathway

Answer 22

• Close to ethmoidal bone and optic nerve

- pH in nasal epithelium is low - changes ionisation of molecules