Introduction to Pharmacokinetics

Question 1

What does ADME stand for? What is its significance?

Answer 1

Absorption
Distribution
Metabolism
Excretion

This is the path of an orally administered drug.

Question 2

What is the therapeutic window of a drug?

Answer 2

The difference between the effectrive concentration and toxic concentration.

Question 3

What is the difference between pharmacokinetics and pharmacodynamics?

Answer 3

Pharmacodynamics is how a drug affects the body.

Pharmacokinetics is how the body affects a drug.

Question 4

What is the apparent volume of distribution?

What is its equation?

Answer 4

The volume of fluid required to dilute the absorbed dose to the concentration found in plasma.

AVD (volume) = dose (mass) / plasma concentration (mass/volume)

Question 5

If a drug is heavily tissue bound, will the AVD be greater or lower than if a drug is heavily plasma bound?

Answer 5

Greater, as the plasma concentration of a heavily tissue bound drug will be lower, so a greater dilution will be required to make the sample concentration equal to the plasma concentration.

Question 6

What are enteral routes of administration?

Answer 6

Oral or rectal routes.

Question 7

What are parenteral routes of administration?

Answer 7

Subcutaneous, intramuscular or intravenous routes.

Question 8

What are percutaneous routes of administration?

Answer 8

Inhalation, sublingual, or topical routes.

Question 9

List 5 factors that affect rate of absorption of drugs.

Answer 9

1 - Route of administration.

2 - Blood flow at site of administration; surface area.

3 - Dose of drug.

4 - Active vs passive diffusion through the membrane.

5 - Drug solubility in water and in lipids.

Question 10

List 3 factors that affect distribution of drugs.

Answer 10

1 - Lipid solubility and diffusion barriers.

2 - Tissue binding.

3 - Plasma protein binding.

Question 11

What is the most common plasma protein that drugs bind to?

Answer 11

Albumin.

Question 12

Where is first pass metabolism done?

Answer 12

In the liver.

Question 13

What are biotransformation phases I and II?

Answer 13

Phase I - Oxidative, reductive and hydrolytic reactions

Phase II - Conjugation reactions, e.g. sulfation.

Question 14

Where can biotransformation phases I and II be carried out?

Answer 14

• In the liver.
• In the skin.
• In the lungs.

Question 15

Where can conjugation reactions, e.g. sulfation pathways, be carried out?

Answer 15

Basically anywhere in the body.

Question 16

Where can oxidation by cytochrome p450 enzymes be carried out?

Answer 16

Mostly in the liver but also in microbiomes of the body.

Question 17

What is a prodrug?

Answer 17

A drug that is inactive until metabolised.

Question 18

List 3 examples of prodrug.

Answer 18

1 - L-DOPA

2 - Diazepam
-> desmethyldiazepam

3 - Tamoxifen
-> 4-hydroxy-tamoxifen

Question 19

What are the two phases of first pass metabolism?

Answer 19

Phase I - Oxidation via cytochrome p450 enzymes.

• Addition of hydroxyl groups.
• Compounds become more hydrophilic.

Phase II - Conjugation reactions.

• Charged groups linked to compounds.
• Compounds EVEN MORE hydrophilic.

Question 20

List 2 examples of groups that are linked in phase II conjugation reactions.

Answer 20

• Sulfates

- Glucuronidates

Question 21

What is the name of the enzymes that conjugate sulfates to substrates?

Answer 21

Sulfotransferases.

Question 22

What are the 7 points at which the available concentration of a drug changes, from administration to site of action?

Answer 22

1 - Total oral dose.

2 - Dissolved in GIT.

3 - Absorbed.

4 - In liver.

5 - General circulation.

6 - In tissues.

7 - At site of action.

Question 23

List 4 pre-clinical outcomes from doing pharmacokinetics.

Answer 23

1 - Select compounds that have the maximum potential of reaching the site of action.

2 - Select the appropriate route of administration.

3 - Understand how the plasma concentration relates to efficacy and toxicity.
- Used to select safe dosage.

4 - Decide on the frequency and duration of dosing.
- Used to sustain drug at target.

Question 24

What are the 4 steps of a pharmacokinetics study?

Answer 24

1 - Administer dose.

2 - Collect samples from blood, urine, bile and faeces at various times.

3 - Analyse for drug (spectroscopy or chromatography).

4 - Data analysis.

Question 25

What is plasma half life?

Answer 25

The time taken for the drug plasma concentration to half.