Drug absorption

Question 1

Define ADME

Answer 1

Absorption - Process by which unchanged drug enters the circulation

Distribution: Reversible transfer of drug from one location in the body to another

Metabolism: Transformation of a drug into daughter compound

Excretion: Removal of drugs/metabolites from the body

Question 2

What is the importance of ADME

Answer 2

Giving insight into the time course of the different stages of the drug as it is handled by the body

Question 3

Give some examples of drugs being acids/bases

Answer 3

R-COOH and R-NH2 are both unionised and more likely to go into lipids. The unionised drug moves into the membrane easier.

At acidic pH< R-COOH drug can move into the membrane.

Question 4

What 3 mechanisms are involved in drug absorption from site of administration to the site of action

Answer 4

1. Passive transcellular diffusion
2. Facilitated/carrier-mediated diffusion through cells
3. Active transport through cells

Question 5

Describe passive transcellular diffusion in drug absorption

Answer 5

Drug is orally administered, travels to the stomach and the small intestine where very thin highly vascularised moist villi help in the absorption of the drug.

Question 6

Describe facilitated-carrier mediated diffusion in drug absorption

Answer 6

e.g. Sodium-dependent glucose

Amino acid transporter transports beta-lactam, ACE inhibitors (Cardiovascular disease), zidovudine (HIV)

Question 7

What factors affect the rate of diffusion of a drug

Answer 7

Size of the drug molecule and its configuration
Chemical structure (lipid solubility, ionisation) of the molecule
Surface area of absorption site
Cell membrane is lipid - diffusion occurs more readily if the drug is lipid-soluble (lipophilic); propine (lipophilic prodrug) -> Adrenaline

Question 8

What is Fick’s Law

Answer 8

Rate of diffusion = SA x Concentration difference x permeability

Question 9

Describe choline uptake as an example of active transport in drug absorption

Answer 9

All cells have low affinity for choline, cholinergic nerves have a high affinity uptake system for choline. They synthesise ACh

Question 10

What does hemicholinium do

Answer 10

Blocks high affinity active transport system that gets choline into nerves.

This gradually depletes ACh levels, and nerve function is impaired - decreased release of ACh

Question 11

What happens with the sodium pump (Na+/K+ atpase)

Answer 11

Action potentials pass through excitable cells