lecture 19

Question 1

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

Answer 1

When drug rapidly distributes into highly perfused tissues and is restricted to these tissues, the concentration vs time curve is linear with a downward slope.

When drug distributes into tissues at different rates, plasma concentration decreases with a downward “linear” trend, while tissue concentration is parabolic, increasing then decreasing

Question 2

Differentiate between perfusion rate limited and permeability rate limited distribution of drug into a tissue.

Answer 2

Perfusion rate limited distribution is

Permeability rate limited distribution is

Question 3

Differentiate between trans-vascular movement via convection vs distribution.

Answer 3

convection: due to the pressure gradient, pressure pushes molecules out and in-between the cells

diffusion:

Question 4

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

Answer 4

equilibrium between different compartments can be shifted by drug trapping due to differences in protonation states in different pH environment

Question 5

Describe how plasma protein binding effects distribution and pharmacologic effect

Answer 5

only free drug can cross biological membranes
the more free drug available, the more pharmacologic effect
the more protein-bound drug, the less pharmacologic effect

Question 6

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

Answer 6

1. physiochemical properties- unionized and lipophilic
2. utilize existing transporters- ex glucose, amino acid transporters
3. disruption of the BBB- microwaves, radiation, trauma, HTN, infection, focused ultrasounds
4. direct administration into the CNS- ex injection into the spine or catheter put right into the brain, some antibiotics and anti-fungal drugs

Question 7

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

Answer 7

the pH of maternal tissues is 7.4, while the pH of fetal tissues is 7.0. this means there is a potential for ion trapping in the fetal tissue.
polar metabolites may form in the fetal tissues and not go back into maternal tissues
free drug is able to get across the placental membrane and into the fetal tissues
ask- is the drug metabolized by fetal tissue, is it lipophilic and able to cross into the fetal tissue