drug absorption

Question 1

Four basic factors determine drug pharmacokinetics:

Answer 1

Absorption
Distribution
Metabolism
Elimination

Question 2

To have biological action most drugs must

Answer 2

enter the blood stream and be distributed to a site of action

Question 3

Absorption =

Answer 3

process of movement of unchanged drug from the site of administration to the systemic circulation.
There is always a correlation between plasma concentration of a drug and the therapeutic response.

Question 4

Oral Absorption considerations

Answer 4

The time to peak concentration (Tmax)
The peak concentration (Cmax)
The area under the drug concentration-time curve (AUC)

Amount of drug which enters the systemic circulation
Speed at which this happens

Question 5

The more rapid the rate of absorption,

Answer 5

the earlier the drug concentration peak.

Tmax

Question 6

Increasing dose does not affect

Answer 6

the time at which peak concentration is reached but does increase the peak concentration.
Cmax

Question 7

The area under the drug concentration-time curve represents

Answer 7

the amount of drug which reaches the systemic circulation: bioavailability.
AUC

Question 8

Therapeutic Range =

Answer 8

A drug is active over a range of concentrations.
Below this there will be insufficient or no pharmacological action.
Above this toxicity occurs

Question 9

therapeutic index

Answer 9

measure of the range at which a drug is safe and active.

Question 10

A drug given intravenously has bioavailability of

Answer 10

100%

Question 11

Factors Affecting Bioavailability (Oral Absorption)

Answer 11

Formulation
    - Slow release preparations
Ability of drug to pass physiological barriers
    - Particle size
    - Lipid solubility
    - pH and ionisation
Gastrointestinal effects
    - Gut motility
    - Food
    - Illness
First pass metabolism

Question 12

Physiological Barriers

Answer 12

Passive diffusion
Filtration
Bulk flow
Active transport

Facilitated diffusion
Ion-pair transport
Endocytosis

Question 13

Diffusion - Ionisation

Answer 13

• Most drugs do not completely ionise in water.
• As most drugs are weak acids or bases the degree of ionisation depends on the pH of the environment.
• Both ionised and un-ionised forms will be present.
• The ionised drug does not cross the membrane.
• The un-ionised form should distribute across the membrane until equilibrium is reached – an equal concentration at each side.
• An acidic drug will be more concentrated in the compartment with high pH (‘ion trapping’)
• The relationship between the local pH and the degree of ionisation is described by Henderson-Hasselbalch equation.
• The result is that small changes in pH may significantly influence the ionisation of a drug and so the rate of absorption or diffusion.
• Proton pump inhibitors and antacids

Question 14

aspirin is a weak acid, so should be absorbed more easily from the

Answer 14

stomach.
However there may be more important factors such as available gut surface area, so in fact aspirin is more absorbed from the small intestine. Even though it is more ionised and less lipid soluble

Question 15

Diffusion – Lipid Solubility

Answer 15

• To pass across a lipid layer a drug must be in solution and be lipid soluble.
• The ability of a drug to diffuse across a lipid barrier is expressed as a lipid-water partition coefficient.
• This is the ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact.
• A drug that is highly lipid soluble will rapidly diffuse across a cell membrane.
• Reach the brain, ovaries, testes and liver
• A drug that is not lipid soluble may not be absorbed at all, for example gentamicin

Question 16

lipid-water partition coefficient =

Answer 16

The ability of a drug to diffuse across a lipid barrier

Question 17

what type of diffusion is most common

Answer 17

passive is more common

active is a bit unusual

Question 18

Active Absorption

Answer 18

Relatively unusual.
Occurs against concentration gradient. 
Requires carrier and energy. 
Specific 
Saturable. 
Iron ,K , Na , Ca 
eg- Uptake of levodopa by brain.

Question 19

To undergo active transport drugs must

Answer 19

resemble naturally occurring compounds.

The drug is reversibly bound to a carrier system.

Question 20

Facilitataed Diffusion

Answer 20

Require carriers
Saturable 
Structure specific
No energy required
Mixed order kinetics
eg- monosaccharides, amino acids, vitamins

Question 21

Passive Diffusion

Answer 21

Non selective 
Not saturable 
Requires no energy 
No carrier is needed 
Depends on lipid solubility and degree of ionsation

Question 22

Filtration / Bulk Flow/ Pore Transport involves

Answer 22

Generally water-soluble drugs e.g. urea, water & sugars, renal excretion, removal of drug from CSF & entry of drug into the liver

Question 23

Filtration normally occurs through

Answer 23

channels in the cell membrane.

Question 24

Filtration / Bulk Flow/ Pore Transport:

The driving force for the passage of the drugs is the

Answer 24

hydrostatic or the osmotic pressure difference across the membrane.

Question 25

Gastrointestinal Factors and Motility

Answer 25

Speed of gastric absorption will affect speed at which drug reaches site of absorption (most drugs are absorbed in small intestine).
Can be affected by other drugs, food/drink and illnesses (esp pain).

Question 26

Gastrointestinal Factors and Food

Answer 26

Can enhance or impair rate of absorption.

Question 27

Gastrointestinal Factors and Illness

Answer 27

Malabsorption (eg Coeliac disease) can increase or decrease rate of absorption
Migraine reduces rate of stomach emptying and therefore rate of absorption of analgesic drugs.

Question 28

First Pass Metabolism

Metabolism of drug prior to reaching systemic circulation can happen in

Answer 28

Gut lumen (acid, enzymes)
Gut wall (metabolic enzymes)
Liver (hepatic enzymes)
These factors can be changed by drugs and disease

Question 29

oral cannot be used for

Answer 29

insulin

Question 30

Subcutaneous / Intra-muscular

Answer 30

Can change the rate of absorption from these sites with different physical properties of formulation.
Depends on blood flow to site.
Needs small volume.
Avoids first pass metabolism.
Some drugs not well absorbed from this route (water soluble better)

Question 31

Sublingual, Buccal

Answer 31

Sublingual absorption from the buccal mucosa bypasses first pass metabolism which will inactivate the drug.
Drugs given this way enter the circulation directly
i.e. GTN for angina

Question 32

Rectal

Answer 32

Drugs given via the rectum bypass first pass metabolism.
Absorption tends to be slow.
The rectum is often used for drugs which cause irritation of the stomach.

Question 33

Inhalation / Nasal

Answer 33

Depends on type of delivery system, particle size, patient technique.
Better for volatile agents.
Can be metabolism in lungs.
Relatively rapid action.
About 5-10% absorbed.

Usually used for topical effect or to avoid problems of oral absorption (eg nausea).

Question 34

Transdermal

Answer 34

Avoids first pass metabolism.
Can provide controlled release.
Few substances well absorbed.
Need to be non-irritant.

Question 35

Considerations for mode of administration

Answer 35

Purpose and site of drug action
     - Local absorption
     - Avoid first pass metabolism
Disease effects
Patients ability to take medicine
Speed of action
Reliability of absorption

Question 36

Drugs generally need to reach

Answer 36

systemic circulation to reach target tissues.

Different methods of absorption in order to ensure this occurs.

Question 37

Chemical properties determine

Answer 37

absorption at different sites – particularly lipid solubility and ionisation.
A number of physiological changes, disease states, drugs and food/drink can influence this.