Unit 2 - Pharmacokinetics - distribution

Question 1

What is drug distribution? (Definition)

Answer 1

Movement of a drug from the bloodstream into:

1) various tissues of the body
2) The site of target cells/tissues

Question 2

Drug distribution is the combination of two factors, these are?

Answer 2

Perfusion

Permeability

Question 3

Perfusion can also be referred to as?

Answer 3

Blood flow

Question 4

Permeability can also be referred to as?

Answer 4

The nature of the biological membrane

Question 5

An organ with high ______ ________ will have more exposure to the drug.

Answer 5

Blood perfusion

Question 6

An organ whose capillaries’ membranes are ________ will have _____ concentration of the drug than the organ with high membrane _________ capillaries

Answer 6

restricted
less
permeability

Question 7

Provide, in order, from highest to lowest, amount of blood flow to organs. (no need to give an actual value)

Answer 7

Kidneys, liver, heart, brain, skin, muscle, fat

Question 8

Blood perfusion to each organ is ______.

Answer 8

varied

Question 9

What are commonly mentioned proteins in the bloodstream?

Answer 9

Albumins, immunoglobulins, fibrinogens

Question 10

What is the main buffering system of the blood?

Answer 10

bicarbonate buffer system

Question 11

When thinking about distribution, one must also consider drug interactions with blood-borne ________.

Answer 11

proteins

Question 12

Drugs may be bound to plasma proteins such as albumin in the blood.
Why is this important?

Answer 12

Only free (unbound) drug can cross membranes, bind to receptors and be excreted by the kidney.

Question 13

Interactions of drugs with plasma proteins are of what type?

Answer 13

Low affinity, high capacity

Question 14

Give an example of a drug that binds strongly to plasma proteins.

Answer 14

Heparin and warfarin (both anticoagulants)

Question 15

What does warfarin do?

Answer 15

inhibits fibrinogen conversion to fibrin, decrease coagulation potential

Question 16

What is an issue related to warfarin and bound/free drugs?

Answer 16

Toxic dose and effective dose of warfarin are very close.
If a person takes warfarin but then suffers an infection and needs to take another drug, this drug might displace it off of serum proteins, increasing serum concentration.
This can lead to toxicity.

Question 17

Only the _______ ______ form can penetrate into the target site.
The ______ form cannot.

Answer 17

free drug

bound

Question 18

Drugs that bind tightly to blood proteins are limited in what way?

Answer 18

Permeability limited, rather than perfusion limited.

They are limited in their ability to cross a membrane and bind to their targets.

Question 19

Describe the binding of drugs to macromolecules (plasma proteins).

Answer 19

• Consists of inter-molecular forces (ionic, vdw, hydrogen)
• Reversible
• Non-specific

Question 20

What does the non-specific nature of binding of drugs with macromolecules mean?

Answer 20

One drug can replace another (in binding the macromolecule)

Question 21

What would happen if warfarin and sulphonamides are administered together?

Answer 21

The plasma level of warfarin might be toxic, leading to fatal haemorrhage.

Question 22

The interaction of a drug with a plasma protein tends to be on the ______ of the protein.

Answer 22

surface

Question 23

What are human (body) factors that affect drug distribution?

Answer 23

Blood flow - perfusion
Capillary permeability
Biomolecules

Question 24

How does blood flow/perfusion affect drug distribution?

Answer 24

The amount of dedicated blood flow to a certain organ will affect how much of the drug is delivered there.

Question 25

Describe how capillary permeability affects drug distribution

Answer 25

Differences in capillary structure will affect how the drug can travel to the target site.

Question 26

Describe how biomolecules affect drug distribution.

Answer 26

Biomolecules in the blood or in the target tissue can have proteins that will bind to the drug.

Question 27

Describe compartmentalization.

Answer 27

Each organ/tissue contains different biomolecules and cell types that could effect the distribution (retention) of a drug.

Question 28

Once in the tissue, there are three things that can affect drug retention. What are they?

Answer 28

1 - Tissue protein binding
2 - intracellular/tissue fluid pH
3 - lipids of fat cells can bind to the drug

Question 29

What are drug properties that will affect drug distribution?

Answer 29

• Pka (ionization, charged or uncharged
• Water and lipid solubility (P-value)
• Binding to serum proteins and/or tissue-specific biomolecules

Question 30

What are the different factors that affect drug distribution?

Answer 30

Human Body

• blood flow
• capillary permeability
• biomolecules

Drug properties

• pKa
• P-value
• binding to serum proteins and/or tissue specific biomolecules