Drug absorption

Question 1

Absorption

Answer 1

Process by which unchanged drug enter the circulation

Question 2

Distribution

Answer 2

Dispersion of a drug among fluids and tissues of the body

Question 3

Metabolism

Answer 3

Transformation of a drug into daughter components

Question 4

Excretion

Answer 4

Is the removal of drugs from the body

Question 5

What is the importance of ADME?

Answer 5

• Essential for safe and intelligent use of medicines by all doctors
• Designing dosing regimens
• Monitoring treatment compliance
• Substance of abuse monitoring
• Medicine licensing requirement

Question 6

What do different routes of administration result in?

Answer 6

Result in bio-availability and onset

Question 7

Reasons as to why choice of delivery is a compromise

Answer 7

○ Speed of onset
○ Convenience: Oral or i.v
○ Bioavailability: proportion of administered drug reaching the systemic circulation
○ Side effects/specificity of action

Question 8

What do drugs have to do in order to reach there target?

Answer 8

Requires drugs to cross biological barriers like lipophilic membranes

Question 9

Where does most absorption occur but where some can occur?

Answer 9

• Most absorption occurs through cells, however some occurs between cells

Question 10

How can absorption occur?

Answer 10

○ Active transport
○ Facilitated diffusion through cells
○ Passive diffustion

Question 11

What is the equation of ficks law?

Answer 11

§ Rate of diffusion=surface area x Concentration difference x permeability

Question 12

What are key determinants of Ficks law?

Answer 12

§ Lipid solubility/ionization are key determinants of permeability

Question 13

What are most drugs and hence what are they?

Answer 13

• Most drugs are weak acids or bases and are thus ionisable

Question 14

What are weak acidic drugs?

Answer 14

Proton donors

Question 15

what are basic drugs?

Answer 15

Proton acceptors

Question 16

What does the extent of ionisation depend on ?

Answer 16

§ pH of environment

Acid-base dissociation constant of the drug

Question 17

What state must drugs be in order to diffuse across cell membranes?

Answer 17

Uncharged

Question 18

What type of drugs least effectively absorbed

Answer 18

Ionised drugs

Question 19

What type of drugs most effectively absorbed?

Answer 19

○ Non-ionisable, lipophilic drugs absorbed most effectively

Question 20

Henderson-Hasselbalch equation for acid

Answer 20

§ pH=pKa-log[non-ionised]/[ionised]

Question 21

Henderson-Hasselbalch equation for base

Answer 21

§ pH=pKa+log[non-ionised]/[ionised]

Question 22

When does pH=pKa?

Answer 22

When drug is 50% ionised

Question 23

What happens to an acidic drug as as pH becomes more acidic?

Answer 23

More of the drug stays unionised

Question 24

What happens to a basic drug as pH becomes more alkaline?

Answer 24

More of the drug stays ionized

Question 25

Absorption of aspirin the gastric mucosa

Answer 25

Aspirin is a weak acid | pKa=3.5

Question 26

Ion trapping vs site of absorption

Answer 26

• Acidic drugs absorbed efficiently from stomach • Basic drugs absorbed less efficiently in stomach but better absorbed in intestine ○ pH more ideal in intestine than stomach

Question 27

Where are many drugs absorbed?

Answer 27

Many drugs absorbed in the intestine

Question 28

What are the lipinski rules that orally active drugs have no more than violation to?

Answer 28

○ Molecular weight<500 ○ No more than 5 H-bond donors ○ No more than 10 H-bond donors ○ Log P<5

Question 29

What don't the lipinski rules do?

Answer 29

don't predict pharmacological activities

Question 30

What might ADME optimization result in?

Answer 30

§ ADME optimisation might minimize desirable properties like receptor binding