ADME - Absorption

Question 1

Cmax

Answer 1

Maximum amount of administered drug in plasma at certain time points

Question 2

Tmax

Answer 2

the time it takes for Cmax to be obtained.

Question 3

Half life

Answer 3

50% of the drug left in the body

Question 4

What is drug absorption?

Answer 4

The process by which drugs gain access to the bloodstream from the site of drug administration

Question 5

What effects the rate and extent of drug absorption?

Answer 5

Route of administration

Question 6

What are the most common routes of drug administration?

Answer 6

Enteral
Parenteral

Question 7

Description of enteral drug administration route

Answer 7

Drugs given orally (by mouth)
- Normally swallowed before being absorbed in the stomach of small intestine.
- Then enters the portal venous system and passes through the liver before entering the blood.

Question 8

Why are some drugs introduced in to the GI absorbed directly into the systemic circulation without passing through the liver?

Answer 8

To avoid potential hazards of gastric acid, binding to food and metabolism by gut wall of liver enzymes.

Question 9

What are some routes that enter the systemic circulation without passing through the liver?

Answer 9

Buccal, sublingual or rectal routes

Question 10

Description of parenteral drug administration route

Answer 10

Includes any route that avoids absorption via the GI tract such as administration by injection, inhalation or by application to the skin.

Question 11

What are the two pathways of the mechanism of gastrointestinal drug absorption

Answer 11

Paracellular:
- drugs cross the epithelial lining through space between enterocytes

Transcellular:
- passive diffusion or active transport

Question 12

Enteral administration/expousre

Answer 12

1. Oral drug administration
   2.Disintergration and drug dissolution
2. GI permeation
3. Drug in portal vein
4. Drug in hepatic vein in the liver
5. Drug in systemic circulation

Question 13

When is the need for absorption bypassed entirely?

Answer 13

If drug is administered intravenously (placed directly into the blood stream)

Question 14

What must happen for drug absorption to occur?

Answer 14

must cross a biological barrier

Question 15

How do most drugs cross cellular barriers

Answer 15

Passive transport - high concentration to low concentration

Question 16

Affect of drug ionization and site-specific pH on absorption

Answer 16

Un-ionized drugs are absorbed better than ionized drugs.
- able to diffuse through the lipid cellular membrane and enter the blood stream better than ionized drugs.

Question 17

In what conditions are weakly acidic drugs likely to be absorbed?

Answer 17

More likely to be absorbed in acidic environments where they pick up a proton and become un-ionised.

Less likely to be absorbed in alkaline environments where they remain charged

Question 18

In what conditions are weakly basic drugs likely to be absorbed?

Answer 18

More likely to be absorbed in alkaline environments where they remain un-ionised.

Less likely to be absorbed in acidic environment where they pick up a proton and become charged.

Question 19

Through which mechanism are unionised and ionised drugs absorbed?

Answer 19

unionised drugs can only be absorbed by passive diffusion
Ionised drugs can only be absorbed by active transport via specific transport systems.

Question 20

Describe Ion trapping

Answer 20

If an acidic drug is in an alkaline environment or vice versa, it stays ionised therefore it is not effectively absorbed and can therefore get trapped in that environment

Basically the drug gets stuck - can’t get absorbed

Question 21

Why is ion trapping good in some cases but not in others?

Answer 21

In some cases this is a good thing in others it can lead to toxicity as you get build-up of that drug in a compartment.

Question 22

What is the Henderson Hasselbalch equation

Answer 22

An equation to measure pH

Question 23

Why is it important to know the pH of an environment?

Answer 23

To determine whether that environment will cause un-ionisation

Question 24

Why is the stomach not well suited for drug absorption?

Answer 24

Thick mucus layer
relatively small surface area

Question 25

Why is the small intestine best suited for drug absorption?

Answer 25

Large surface area due to extensive villi and microvilli

Question 26

Where in the small intestine are acidic and basic drugs absorbed?

Answer 26

Acidic drugs -proximal duodenum

Basic drugs - distal ileum

Question 27

Factors influencing absorption

Answer 27

Lipophilic
Bulky/oxygenated
Not too large
Large SA available
If there is a large blood supply for the drug to move down its concentration gradient

Question 28

What is bioavailability?

Answer 28

The fraction of the drug absorbed into the blood when the drug is administered orally.

Question 29

First Pass Metabolism

Answer 29

process in which an orally administered drug is absorbed from the gastrointestinal tract and transported to the liver, where it is metabolised

Question 30

First Pass Effect

Answer 30

The reduction in the total drug delivered to the systemic circulation.

It reflects the loss of drug via its pass through the GI tract and liver before it reaches the systemic circulation

Question 31

What are the causes of low bioavailability?

Answer 31

Water-solubility of drugs (drugs with low solubility will not be absorbed in the gut and eliminated in the faeces without absorption)
Time for absorption. If the drug passes through the GI tract too fast, it has no time to be absorbed at a high rate
Chemical reactions that reduce absorption

Question 32

Examples of chemical reactions that reduce absorption

Answer 32

Healthy gut flora can interfere with the absorption of some drugs
Hydrolysis by gastric acid or digestive enzymes

Question 33

How is bioavailability measured?

Answer 33

By comparing the area under the curve (AUC) - from measurements of plasma concentration following oral admission vs injection (which produces 100% bioavailability)