Pharmacokinetics: Absorption and Distribution

Question 1

What is Pharmacokinetics?

Answer 1

The science and study of the factors which determine the amount of chemical agents at their sites of biological action after the application of an agent or drug.

Question 2

What are the 4 main topics that are studied in pharmacokinetics?

Answer 2

1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 3

Describe the “perfect drug”

Answer 3

1. Stable form to introduce to the body
2. Pass into the body
3. Reach it’s biological target
4. Remain long enough in the body to achieve a therapeutic effect (blood stream)
5. Not produce harm in the body
6. Exit the body when the job is done

Question 4

Describe the absorption phase?

Answer 4

When the drug must cross the lipid bilayer membrane and pass the polar and fatty acid regions (lipophillic) to get to it’s desired target

Question 5

What properties of the drug determine the absorption phase?

Answer 5

The chemical properties of how lipophilic and hydrophilic they are

Question 6

What may happen if a drug is too lipophilic?

Answer 6

1. Be insoluble in aqueous media
2. Bind too strongly in plasma proteins
3. Distribute into lipid bilayers

Question 7

What may happen if a drug is too hydrophilic?

Answer 7

Cannot cross the plasma membrane

Question 8

What does amphiphilic mean?

Answer 8

Can be hydrophilic or lipophillic

Question 9

How does molecule size affect absorption in relation to the way it goes from extracellular to intracellular?

Answer 9

1. Smaller= diffusion= going down concentration gradient
2. Medium = Aqueous channels = aqua porin allows water to pass through
3. Larger= carrier proteins (ATP needed)

Question 10

What environment is the extracellular, the membrane and intracellular in?

Answer 10

1. Extracellular- hydrophillic
2. Membrane- Hydrophobic
3. Intracellular- hydrophillic

Question 11

What is ionisation?

Answer 11

Protonation or deprotonation resulting in a charged molecule

Question 12

How can you tell if a drug is in an unionised form and why is it important to have this form?

Answer 12

1. When the pKa and pH value are equal values and there are equal amounts of ionised and unionised form
2. Unionised form means it can pass through if it’s in an acidic environment

Question 13

Describe the concept of pH trapping?

Answer 13

1. A weakly acidic drug crosses the membrane to the side with higher pH (urine pH 6 to plasma pH 7.2)
2. A basic drug crosses the membrane to the side with the lower pH (plasma pH 7.2 to urine pH 6)
3. The drug becomes trapped in the plasma or urine

Question 14

What are the four groups of enteral treatment?

Answer 14

1. Oral
2. Sublingual- beneath tongue
3. Rectal
4. Inhalation

Question 15

What is topical treatment?

Answer 15

Application to the epithelial surfaces- example: skin, cornea, vagina, nasal mucosa

Question 16

What are the four groups of injection parenteral treatment?

Answer 16

1. Subcutaneous
2. Intramuscular
3. Intravenous
4. Intrathecal- spinal fluid

Question 17

Why do we need to consider the different ways of drug administration?

Answer 17

1. Different administration methods have different speeds of delivery
2. Metabolism of compound- sublingual administration of isosorbide dinitrate passes through the liver to metabolise first
3. Targeting- intrathecal injection targets spinal cord directly

Question 18

What is bioavailability?

Answer 18

The fraction of administered dose that reaches the systemic circulation.

Question 19

What are the 4 factors that affect the absorption of a drug?

Answer 19

1. GI motility
2. Splanchnic blood flow
3. Formulation of medicine
4. Physiochemical properties of drugs.

Question 20

How can incomplete metabolism occur?

Answer 20

1. Incomplete absorption and loss in faeces

2. 1st pass metabolism- starts metabolising the drug before it reaches the blood stream

Question 21

Where abouts is the drug distributed to in the body and to what proportions?

Answer 21

1. Intracellular 2/3 and extracellular 1/3

2. Extracellular contains interstitial fluid that has plasma

Question 22

What is the volume of distribution?

Answer 22

The volume of fluid thats required to contain the total amount of drug in the body at the same concentration as present in the plasma

Question 23

How do you work out volume of distribution and what is it measured in?

Answer 23

1. Total amount of drug in the body/blood concentration

2. Measured in litres, cannot be smaller than the volume of intravascular plasma which is 3 Litres

Question 24

What are the physiochemical properties of a drug?

Answer 24

1. Size of drug (larger molecules don’t cross membranes well)
2. pKa of a drug (pH different between plasma and tissue can lead to accumulation)

Example: hydrophobic substances tend to become enriched in fat tissue

Question 25

What are the pharmacological properties of the drug?

Answer 25

1. Binding of molecule to particular plasma or tissue proteins that might allow specific uptake into tissue

Question 26

What are the four factors that affect distribution of drugs into tissue?

Answer 26

1. Physiochemical factors
2. Pharmacological properties
3. Blood flow in the organ and tissue
4. Barriers of organ and tissue

Question 27

How does blood flow effect distribution of drug to various organs?

Answer 27

1. The rate at which a drug is distributed to various organs depends on the proportion of cardiac output the organ receives
2. Brain, heart, liver and kidney receive more compared to skin bone and fat

Question 28

What are the two major barriers that exist and the challenges behind them?

Answer 28

1. Blood brain barrier- difficult to get drugs across to the brain
2. Placenta- lipid soluble drugs can pass readily from mother to foetus, want to allow mother to take drugs without harming the baby

Challenges: Access to site of action, toxic side effects, formulation