Lecture 17

Question 1

Bioavailability?

Answer 1

Amount of drug that enters the systemic circulation and is accessible at the site of action.

Question 2

Factors affecting the concentration of drugs in solution in GI fluids?

Answer 2

Complexation, adsorption, chemical stability, micellar solubilisation

Question 3

Complexation?

Answer 3

Mucin which is present in the GI fluids forms complexes with some drugs and reduces absorption & bioavailability.

Question 4

Adsorption?

Answer 4

(sticking to surface of something): co-administration of drugs/medicines containing solids adsorbents may resultin absorbents interfering with absorption of drug

Question 5

Chemical stability?

Answer 5

Drugs that breakdown in GI tract will have reduced absorption/bioavailability, instability caused by stomach pH/enzyme degradation

Question 6

Micellar solubilisation?

Answer 6

Can increase solubility of drugs, ability of bile salts to solubilise drugs depends mainly on lipophilicity of drug

Question 7

Surfactant structure?

Answer 7

Hydrophobic tail, hydrophilic head (e.g. bile salts)

Question 8

Formation of micelles?

Answer 8

When interface full surfactant must enter bulk phase resulting in hydrophobic tail being in contact with aqueous phase -> at certain concentration (critical micellar concentration - CMC), surfactant molecules aggregate into structure which avoids hydrophobic tail being in contact with water

Question 9

Drug absorption from GI tract process?

Answer 9

Step 1 = partitioning of molecules between the GIT fluid (aqueous) and the GIT membrane (non-aqueous)
Step 2 = Diffusion occurs across the membrane from high to low concentration. C in systemic circulation is low due to constant removal of drug into the bloodstream
Step 3 = partitioning of molecules between the GIT membrane (non-aqueous) and extracellular fluid (aqueous), prior to entering the bloodstream

Question 10

What part of drug partitions into membrane?

Answer 10

Non-ionised (non-polar) form, the amount of non-ionised drug thus influences the extent of absorption, as only this portion of the drug is available to diffuse across the membrane

Question 11

Ka value?

Answer 11

Measure of how strong/weak acid/base is relative to water

Question 12

pKa value?

Answer 12

pH at which exactly half of acid/base is dissociated (50% ionised, 50% unionised), larger pKa = weaker the acid

Question 13

Rule of 2?

Answer 13

2 pH units above/below pKa gives 100% ionised or 100% unionised

Question 14

Log D?

Answer 14

Measure of lipophilicity, like log P, but takes into account both ionised and unionised form of drug (always less than log P)