Exam 2

Question 1

What are determinants of drug distribution?

Answer 1

1. Physiochemical properties of the drug (Size, charge, log p, membrane crossing, capillaries, lipid bilayer)
2. Affinity for components of tissue (Binding even, lipids, proteins, organelles)
3. Affinity for components of the blood (Plasma proteins, RBCs)
4. Presence of transporter proteins and/ or anatomical barriers
5. Blood flow

Question 2

Digoxin has what R value and what does this mean?

Answer 2

R=100

Meaning its concentration is 100 x higher in the tissue over blood

Question 3

Flutamides R value is?

Answer 3

R=2 meaning its concentration is much higher in the blood

Question 4

Big tissue —>?

Adrenals and Kidneys —>

Answer 4

Harder distribution

Faster ditribution

Question 5

In a perfusion limited permeation If there is a change in Blood flow there is a change in?

What if there is a change in membrane?

What about diffusion limited?

Answer 5

Change in blood flow change in uptake rate determining step is Blood Flow

Change in membrane= no change in output

Diffusion limited the opposite is true : Rate determining step is the membrane itself

Question 6

What effects diffusion limited permeation?

Answer 6

• Physiochemical properties
• Transporter proteins
• Anatomical barriers

Question 7

Drugs that are extensively accumulated within the tissues have large?

Answer 7

Vds

Fats, Lysosomes

Question 8

Weakly basic drugs have high concentrations in lysosomes, explain ion trapping and why this isnt a very good name. (Also called pH partitioning)

Answer 8

• Drugs passively diffuse into the cytosol there the pH is about 7.4 in physiological pH weakly basic drugs are 50% ionized and 50% unionized
• The unionized form is able to diffuse into the lysosome and follow there gradient where the pH is 4.5 at this point now 99.999% of the drug is ionized and unable to traverse out of the lysosome
• Once the concentration of unionized drug is less in the cytosol than the lysosome reverse diffusion can take place
• This is why ion trapping is not a good name because they arent really trapped

Question 9

What happens to the Vapp when the unbound fractions in the tissue and plasma compartments are changed?

If Fu and Fut=0?

If very high Fut?

Answer 9

Plasma concentration = Vd

Vapp = infinity there will be no detection in the plasma because Fut is very small and the Vd will be very large

Question 10

What factors increase drug activity?

Answer 10

1. Directly increasing the free unbound drug concentrations as a result of reduced binding in the blood
2. Increase the free drug concentration that reaches the receptor sites directly, causeing a more intense pharmacodynamic, or toxic response

Question 11

What factors decrease drug activity?

Answer 11

1. Increase in the free drug concentration causing a transient increase in Vd and decreasing partly some of the increase in free plasma drug concentration
2. Increase the free drug concentration, resulting in more drug diffusion into the tissues of eliminating organs, particularly the liver and kidney, resulting in a transient increase in drug elimination

Question 12

High protein binding long half life =

Answer 12

Low renal clearance the opposite is true with low protein binding

Question 13

Liver disease, renal disease, trauma, surgery and burns all?

Answer 13

Factors that decrease plasma protein concentrations

Question 14

When a highly protein boun drug is displaced from binding by a second drug or agent what occurs?

Answer 14

This causes a very sharp increase in the amount of free drug in the plasma and may lead to toxicity

When a drug is not as highly protein bound it is much less significant when it gets displaced