Drug Distribution LO

Question 1

Describe the effect of drug distribution on the concentration vs. time curve

Answer 1

When drug rapidly distributes into highly perfused tissues and is restricted to these tissues, it will decrease over time. When drug distributes into tissues at different rates, when distribution rises in the tissue and lowers in the plasma. Meets at a middle time and then is eliminated at the same time.

Question 2

Differentiate between perfusion rate limited and permeability rate limited distribution of drug into tissues

Answer 2

Perfusion rate limited means it can easily cross the blood vessel walls so the rate at which blood delivers the drug to the tissue is what controls how fast the drug reaches the tissue. Permeability rate limited distribution moves slowly across blood vessel walls into tissues. This means the drug reaches the tissues faster in the blood than it actually enters the tissues themselves.

Question 3

Differentiate between transvascular movement via convection vs. diffusion

Answer 3

Convection is a transport process that is driven by pressure. Diffusion is a transport process that is driven by a concentration gradient.

Question 4

Describe how differences in tissue pH may result in the trapping of ionizable drugs.

Answer 4

Drug trapping can cause drug levels to be much higher in tissues than in the blood. When a drug becomes ionized, it can’t easily cross cell membranes, which helps trap it in certain areas. By adjusting urine pH, we can increase the removal of these trapped drugs through urine.

Question 5

Describe how plasma protein binding effects distribution and pharmacologic effect.

Answer 5

When a drug binds to plasma proteins, it becomes “trapped” in the blood, limiting its movement into tissues. High protein-bound drugs have more restricted distribution compared to those that bind less. It limits distribution.
Pharmacological effect: only unbound drug is active, so protein reduces the amount available to act on target cells. As free drug is used or removed, bound drug is gradually released, which can extend the drug’s effects.

Question 6

List 4 mechanisms by which drugs may gain access to the CNS.

Answer 6

Appropriate physicochemical properties (not highly charged, small, lipid soluble), utilize an existing transporter, disruption of the BBB, and direct administration to the CNS

Question 7

Given a choice between 2 drug molecules, indicate which would be the best choice to use in a pregnant woman

Answer 7

Polar drugs do not cross the placenta so it is the best choice for use in a pregnant woman. We don’t want anything to go into the placenta.