Drugs and the BBB Flashcards
Components of BBB and their functions
- 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
Passive diffusion
Down conc grad from one side of the membrane to another
Lipid soluble molecules pass through easily
Facilitated diffusion
Energy neutral (passive) - down conc grad through carrier protein across membrane
Active transport
AT1: Na+/K+ exchanges one molecule for another
AT2: co-transport - glucose and sodium move to one side of the membrane
Pinocytosis
Invagination of membrane moves molecule into vesicle and is released the other side - form of AT
factors affecting rate of diffusion
- Molecular size (indirectly proportionate)
- Conc grad (directly proportionate)
- Ionization (indirectly proportionate)
- Lipid solubility (directly proportionate)
- Protein binding (indirectly proportionate)
Local anaesthetics
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
Which molecules can pass through tight junctions
Small and water soluble molecules
Which molecules can pass through trans cellular pathways
Lipid soluble - small and lipophilic
Receptor mediated transcytosis
Pinocytosis moves molecules from outside to inside using vesicles - uses receptors
Absorptive transcytosis
Moves albumin and proteins across a membrane, no receptor needed
Cell mediated transcytosis
phagocytose molecule using liposomes and move across membrane
CNS diseases
- Meningitis
- Brain abscess/tumour
- MS
- Alzheimer’s
- Parkinson’s
How does penicillin enter the brain?
When bacteria enters meninges, disrupts integroty of the barrier, allowing benzylpenicillin to pass through into brain
Why is levodopa better to administer than dopamine
- Dopamine is too polar to cross BBB and would be metabolised in PNS
- Levodopa is non-polar so it can cross BBB
Receptor/vector mediated transport
- Viruses are altered to make them safe but can cause immune response or mutations (cancer)
- Molecule added to virus to pass through barrier
Colloidal drug carriers
- Emulsion, liposomes, nanoparticles are lipophilic
- They encase active ingredient so it can pass BBB
- Coated with surfactants like polyoxypropylene etc
Invasive delivery to CNS
- Intraventricular
- Sub arachnoid route
Ommaya reservoir
- Tube that ends in lateral ventricles of brain that is attached to subcutaneous reservoir underneath skull
- Can deliver drugs directly to ventricles
Lumbar puncture
- Access CSF without damaging structures
- Delivers drugs to meninges
Intrathecal drug delivery system
- Pocket underneath skin to dispense drugs in lumbar spine
- Used in spasticity
Nose-brain pathway
- Close to ethmoidal bone and optic nerve
- pH in nasal epithelium is low - changes ionisation of molecules
