Drug Distribution Flashcards
What is the effect of drug distribution on the concentration versus time curve?
When a drug is only distributed to rapidly perfused tissues, you get a linear decline at a constant rate because the highest concentration is achieved immediately after dose is administered.
When drug distributes to different tissues at different rates, you have a curve linear period where it declines quickly then levels out to a slower more even decline. This is because the drug enters the highly perfused tissues first and then distributes into other tissues. Although the concentration of drug will not be the same in all tissues, the decline will be the same.
What is the difference between perfusion rate limited and permeability rate limited distribution of drug into tissues?
Perfusion rate limited distribution is a compound that readily penetrates endothelial membranes so that the delivery rate of the drug to the tissue by perfusing blood is what determines how quickly drug appears in tissue.
Permeability rate limited distribution is a compound that slowly passes across the endothelial membrane. AS a consequence, the drug delivered to the site of tissues more quickly than drug moves from blood into tissue.
What is the difference between transvascular movement via convection versus diffusion?
Transvascular diffusion is driven by concentration while transvascular convection is driven by pressure. Pressure will be used for larger molecules such as MAB’s.
How do differences in tissue pH result in the trapping of ionizable drugs?
The concentration of drug within a tissue due to pH differences that lead to ionization of the drug in the tissue environment and “trapping” the drug on one side of the membrane.
How does plasma protein binding, effect distribution and pharmacologic effect?
Drugs reversibly bind to the plasma proteins allowing for an equilibrium and determines if the drug gets into tissue or not. Free drug is going to be able to diffuse through the tissue membrane and once across, some will bind to tissue proteins (receptors). Most of the drug that makes it to the tissue will nonspecifically bind.
What are the 4 mechanisms by which drugs may gain access to the CNS?
1) Appropriate physicochemical properties
2) Utilize an existing transporter
3) Direct administration into the CNS
4) Disruption of the blood brain barrier (BBB)
If given the choice between 2 drug molecules, which one would be the best choice for a pregnant women and why?
The molecule should be polar and large since polar drugs do not usually cross the placenta.
What is distribution?
The movement of a drug molecule across biological membranes into various tissues in the body.
What is transvascular protein?
The movement of drug molecules across vascular endothelial cells and into tissue or interstitial space.
Do you know what redistribution is?
The initial movement of drug from highly perfused tissues to poorly perfused tissues.
