Drug Distribution

Question 1

Rate of distribution depends on:

Answer 1

• Delivery of drug to tissue by perfusion
• Permeability of tissue membranes
• Physicochemical properties of the drug
• Binding of drug to plasma proteins
• Binding to acidic phospholipids in tissue membranes

Question 2

Perfusion limited distribution:

Answer 2

Occurs when tissue or cell membrane does not represent a barrier to drug distribution.

Question 3

When is perfusion limited distribution likely to occur?

Answer 3

Small and lipophilic molecules distributing across thin permeable membranes

Question 4

Tissue perfusion:

Answer 4

• NOT the same across tissues
• Rapid equilibrium achieved in highly perfused tissues
• Slow equilibrium in poorly perfused tissues (skin, adipose)

Question 5

Examples of highly perfused tissues:

Answer 5

Lungs, kidneys, liver, brain

Equilibrium - Fast

Question 6

Examples of poorly perfused tissues:

Answer 6

Muscle, skin, adipose

Equilibrium - slow

Question 7

Illustration of the rate of tissue distribution:

Answer 7

• Time to reach equilibrium and to eliminate drug is longer in poorly perfused tissues
• Lipophilic drugs typically have a high affinity for adipose (low perfusion tissue

Question 8

Permeability limited distribution likely to occur with:

Answer 8

• Polar molecules and relatively impermeable membranes (e.g., blood brain barrier and cells of some tissues)
• May involve active transporters. Passive diffusion minor component.
• Limiting factor is crossing the membrane, not perfusion

Question 9

ENTRY OF DRUGS IN CEREBROSPINAL FLUID:

Answer 9

• Differences in the rate of distribution linked to lipophilicity and degree of ionization of drugs
• For the same tissue, distribution is slower for more polar drugs

Question 10

How does bounding affect crossing of the membrane:

Answer 10

only unbound molecules cross the membrane (not massively significant)

Question 11

Location of distribution barrier in the brain:

Answer 11

BBB very small pores,

Barrier at capillary

Question 12

Location of distribution barrier in the muscle:

Answer 12

Muscle, kidneys capillaries proud to small molecules. Barrier at cellular level