Drug Absorption

Question 1

Define PharmacoKINETICS

Answer 1

What the body does to the drug once we have taken it

Question 2

Define PharmacoDYNAMICS

Answer 2

What the drug does to our body

Question 3

Give three reasons why ADME is so important?

Answer 3

• Key factors determining the speed of onset of a drug’s effects, the duration of action and the potential problems e.g. toxicity
• For safe and intelligent use of medicines
• Designing dosage regimens
• Monitoring treatment compliance
• Substance of abuse monitoring
• Medicine licensing requirement

Question 4

Define drug absorption

Answer 4

The process by which unchanged drug gets from the site of delivery to the circulation

Question 5

What are things do you have to think about when deciding the route of delivery?

Answer 5

• speed of onset
• convenience (oral or i.v - only at hospitals)
• Bioavailability - proportion of administered drug that reaches the systemic circulation e.g. 100% for i.v
• Side effects

Question 6

What are the main routes of drug delivery?

Answer 6

• Oral tablets
• Inhalers
• Subcutaneous injection
• Intramuscular injection
• Intravenous injection
• Intrathecal
• Rectally
• Sublingual

Question 7

Why does a large amount of oral drug get metabolised before getting around the body?

Answer 7

When you take a tablet, it goes through the gut before going to the liver, then to the rest of the body. Therefore a big chunk can be metabolised in the liver before getting around the baby

Question 8

How can drugs cross biological barriers?

Answer 8

• Most absorption occurs transcellularly (through cells), some goes paracellularly (between cells).

Question 9

How do drugs get through cells?

Answer 9

• Most use passive diffusion

- Some use active transport

Question 10

What are the key principles of Fick’s Law?

Answer 10

• The larger the SA, the quicker the diffusion
• The larger the concentration gradient, the quicker the diffusion
• The more permeable the membrane, the quicker the difusion

Question 11

Can drugs cross membranes easier if they are charged or neutral?

Answer 11

• Neutral
• Drugs that are weak acids will shift between charged and neutral - neutral makes it easier to get through membranes, then can shift back to its more happy ionised state.

Question 12

What is ion trapping?

Answer 12

When a drug turns into its charged form after passing through a membrane so that it is doesn’t get reabsorbed back through

Question 13

What does the H-H equation say about basic and acidic drugs?

Answer 13

For acidic drugs, the more acidic the medium, the more unionised the drug will be
For basic drugs, the more basic the medium, the more unionised the drug will be
For example, Aspirin is a weak acid. In the stomach (acidic) most of it is unionised, whereas when it gets to the circulation (pH 7.4), most is ionised.

Question 14

What are the Lipinski Rules?

Answer 14

A rule-based approach to ADME optimisation
- An oral drug must have no more than one violation of the following:
Mr <500
>5 H bond donors
> 10 H bond acceptors
Log P<5 (partition coefficient)

Question 15

Absorption summary

Answer 15

• Essential for drugs to obtain access to site of action
• most drugs are absorbed by passive diffusion
• unless transported, the drug needs to be uncharged to be absorbed
• slower at thick barriers
• modified by ion trapping where a change in ionisation accompanies the absorption
• the Lipinski Rules determine the optimum approaches for ADME