Drug Absorption

Question 1

Pharmaceutical process

Answer 1

get the drug into the patient

Question 2

Pharmacokinetic process

Answer 2

get the drug to the site action

Question 3

Pharmacodynamic process

Answer 3

produce the correct pharmacological effect

Question 4

Therapeutic process

Answer 4

produce the correct therapeutic effect

Question 5

What are the 4 basic factors that determine drug pharmacokinetics?

Answer 5

• absorption
• distribution
• metabolism
• elimination

Question 6

What does ADME enable us to understand?

Answer 6

• dosage
• drug administration
• drug handling
• patient variability
• potential for harm

Question 7

Absorption

Answer 7

• the 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 8

How can drugs be absorbed?

Answer 8

• oral
• IV
• IM
• other GI- sublingual, rectal
• inhalation
• nasal
• transdermal

Question 9

What are important issues to consider with oral absorption?

Answer 9

• amount of drug which enters the systemic circulation

- speed at which this happens

Question 10

What is Tmax?

Answer 10

• the time to peak concentration

- the more rapid the rate of absorption, the earlier the drug concentration peak

Question 11

What is Cmax?

Answer 11

• peak concentration

- increasing dose does not affect the time at which peak concentration is reached but does increase peak concentration

Question 12

What is AUC?

Answer 12

-are under the drug concentration time curve represents the amount of drug which reaches the systemic circulation

Question 13

Therapeutic range

Answer 13

a drug is active over a range of concentrations

Question 14

What happens outwith the therapeutic range?

Answer 14

• below this there will insufficient or no pharmacological action
• above this toxicity occurs

Question 15

Therapeutic index

Answer 15

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

Question 16

Bioavailability

Answer 16

the amount of drug which reaches the circulation and which is available for action

Question 17

What method of administration has 100% bioavailability?

Answer 17

IV

Question 18

Factors affecting bioavailability

Answer 18

• formulation
• ability of the drug to pass physiological barriers
• gastrointestinal effects
• first pass metabolism

Question 19

How can drugs be transported across membranes?

Answer 19

• passive diffusion
• filtration
• bulk flow
• active transport
• facilitated diffusion
• ion-pair transport
• endocytosis

Question 20

What is the degree of ionisation of a drug dependent on?

Answer 20

environment

Question 21

What will happen to the un-ionised form of the drug?

Answer 21

It will cross the membrane and should distribute across the membrane until equilibrium is reached- an equal concentration at each side

Question 22

What is ion trapping?

Answer 22

an acidic drug will be more concentrated in the compartment with high pH

Question 23

What is the Henderson Hasselbalch equation?

Answer 23

the relationship between the local pH and the degree of ionisation

Question 24

What is the result of the Henderson Hasselbalch equation?

Answer 24

small changes in pH may significantly influence the ionisation of a drug and so the rate of absorption or diffusion

Question 25

Aspirin is a weak acid, so should be absorbed more easily from the stomach. Why is it not?

Answer 25

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

Question 26

What must a drug be to pass across a lipid layer?

Answer 26

- in solutions | - lipid soluble

Question 27

How is the ability of a drug to diffuse across a lipid barrier expressed?

Answer 27

lipid-water partition coefficient

Question 28

What is the lipid-water partition coefficient?

Answer 28

the ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact

Question 29

Compare the diffusion of lipid soluble vs not lipid soluble.

Answer 29

- 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 30

What must be true of the drugs fro them to undergo active transport?

Answer 30

they must resemble naturally occurring compounds

Question 31

Where does filtration usually occur?

Answer 31

through channels in the cell membrane

Question 32

What is the driving force for the passage of drugs in filtration?

Answer 32

hydrostatic or the osmotic pressure difference across the membrane