Drug Movement in the Body

Question 1

Absorption

Answer 1

drug is absorbed from the site of administration - entry into plasma

Question 2

Distribution

Answer 2

drug reversibly leaves the bloodstream and is distributed into interstitial and intracellular fluids

Question 3

Metabolism

Answer 3

drug transformation by metabolism by the liver and other tissues

Question 4

Excretion

Answer 4

drug and/or drug metabolites excreted in urine, faeces or bile

Question 5

Drug movement around the body

Answer 5

Bulk flow via circulatory system (blood stream); diffusion of drug molecules over short distances; solubility - lipid soluble drugs are more likely to diffuse across lipid bilayer membranes; large drug molecules move more slowly than smaller ones.

Question 6

Barriers

Answer 6

Cell membranes are barriers between the aqueous compartments of the body.
Plasma membrane separates the extracellular ‘compartment’ from the intracellular ‘compartment’

Question 7

Passive Diffusion (small molecules)

Answer 7

directly through lipid or aqueous pores formed by aquaporins that transverse the piped bilayer.

Question 8

Facilitated Diffusion (small molecules)

Answer 8

via specialised carrier proteins that bind the drug on one side of the bind molecule on one side of the membrane then change conformation and release on the other side. No energy required, but does need a concentration gradient.

Question 9

Active Transport (small molecules)

Answer 9

via specialised carrier proteins. Requires energy. Can move drug molecules against the concentration gradient.

Question 10

Endocytosis (pinocytosis) (small molecules)

Answer 10

invagination of a part of the membrane. Drug is encased in a small vesicle then released inside the cell.

Question 11

pH and Ionisation

Answer 11

many drugs are weak acids/bases. Exist in both ionised and un-ionised forms. Proportion of ionisation of a drug depends on the pKa and the local pH. Many drugs can permeate the membrane in their non-ionised form.

Question 12

pKa =

Answer 12

pH at which 50% of drug is ionised, and 50% is un-ionised

Question 13

Apparent Volume of Distribution (Vd)

Answer 13

extent to which a drug partitions between the plasma and tissue compartments.
Not a physical volume - some drugs have a Vd greater than the body’s total volume of water (41l)

Question 14

Plasma Protein Binding

Answer 14

albumin is most abundant plasma protein. Many drugs bind with low affinity to albumin via electrostatic and hydrophobic forces. Binding reduces the availability of the drug for diffusion to the drug target organ, may also reduce the transport of the drug to non-vascular compartments.