Drug Distribution

Question 1

What is the effect of distribution on concentration vs. time curves?

Answer 1

When drug rapidly distributes into highly perfused tissues and is restricted to these tissues the curve will decline at a constant rate.

When drug distributes into tissues at different rates there will be a slow decline and decrease in parallel.

Question 2

Perfusion rate limited

Answer 2

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.

contains lipophilicity

Question 3

Permeability rate limited

Answer 3

compound that slowly
passes across the endothelial membrane. As a consequence, drug is delivered to the site
of tissues more quickly than drug moves from blood into tissue.

less lipophilicity

Question 4

Transvascular Transport

Answer 4

Movement of drug molecules cross vascular endothelial cells and into tissues interstitial space

Question 5

What is the result of “drug trapping”

Answer 5

significant differences in the drug concentration in tissues compared to blood

the inability of ionized drug to cross membranes can be used to enhance the urinary excretion of drugs by changing urine pH

Question 6

Convection

Answer 6

transvascular transport process that is driven by pressure

Question 7

Redistribution

Answer 7

The initial movement of drug from highly perfused tissues to poorly perfused tissues

Question 8

Differentiate between transvascular movement via convection versus diffusion

Answer 8

pressure serves as the driving force for convection, which is the means the transvascular transport of large molecules such as monoclonal antibodies

most drug molecules undergo transvascular transport via diffusion, for which the concentration gradient is the driving force for drug movement

Question 9

How does plasma protein binding affect the distribution and pharmacologic effect?

Answer 9

limits the distribution of drug into tissues, since only the free drug can cross endothelial membranes

free drug is the pharmacologically active species, thus changes in plasma protein binding will alter the pharmacologic effect

Question 10

How to determine between 2 molecules which would be best for a pregnant women

Answer 10

since polar molecules do not cross the placenta, polar drugs would be the best choice for a pregnant women

Question 11

4 mechanisms by which drugs may gain access to the CNS

Answer 11

1. appropriate physicochemical properties
2. utilize an existing transporter
3. disruption of the BBB
4. direct administration into the CNS