Delivering Drugs to the CNS Flashcards
What does Kp indicate?
the ratio between drug in the blood and drug in the brain
What does a Kp > 1 indicate?
A higher concentration in the brain than the blood
How can drugs move between body compartments?
transcellular
paracellular
How can the rate that a compound crosses the membrane be measured?
Passive permeability using artificial membranes PAMPA
Or MDCK
What is the free-drug hypothesis?
Pharmacological activity is dependent on free drug availability
What affects the free drug?
the amount bound to protein and the amount unbound from protein
What is fractional binding affected by?
protein - NOT drug
How is fractional binding calculated?
protein/protein+affinity
What is Kp u,u?
the ratio of unbound drug concentrations in the brain and the blood
What is occurring if Kp is something other than =1?
more than passive diffusion
What is the blood brain barrier made up of?
endothelial cells, astrocytes, pericytes
What is the function of the blood brain barrier?
allows distribution of v. small molecules
prevents ionic flux that might affect neuronal function
provides selective uptake mechanism for required molecules
provide protected environment for CNS
What is P-gp?
transporter that actively pumps molecules back out to prevent transcellular permeation
Where is P-gp found?
only on the apical side of the cell
