Drug Movement In The Body

Question 1

Mechanisms that allow drugs cross cell barriers:

Answer 1

Simple passive diffusion:
- Through lipid/aquaporins

Facilitated diffusion:
- no energy required
- transports water soluble drugs via specialised carrier proteins

Active transport:
- energy required
- transports water soluble drugs via specialised carrier proteins
- can show saturation kinetics

Endocytosis:
- Transports large drugs
- Invagination of membrane

Question 2

How do the particular physiochemical properties of drugs favour particular routes across cell barriers.

Answer 2

Non-ionised drugs can permeate the membrane

pH trapping across plasma membranes:
- Traps drug based on physiochemical property
- Facilitates absorption at target

Absorption of weak acids is done by stomach lumen whereas bases are not absorbed until small intestine

Question 3

Define the term “apparent volume of distribution” and what is the equation?

Answer 3

The apparent volume of distribution (Vd) describes the extent to which a drug partitions between the plasma and tissue compartments

Vd = Dose/(Drug)plasma

Question 4

How can plasma protein binding and tissue protein binding determine the volume of distribution?

Answer 4

Reduces the availability of the drug for diffusion to target organ

Reduces transport of the drug to non-vascular compartments

Reduces penetration into the CNS by preventing transport across the blood brain barrier

High protein binding slows drug elimination by preventing metabolism in the liver and glomerular filtration

Question 5

Drug distribution in different body compartments:

Answer 5

Total body water- small water-soluble molecules

Extracellular water- larger water-soluble molecules

Blood plasma- highly plasma protein-bound molecules, large molecules, highly charged molecules

Adipose tissue- highly lipid soluble molecules

Bone and teeth- certain ions

Question 6

ADME

Answer 6

Absorption - Drug absorbed from administration site into plasma

Distribution - Drug leaves bloodstream and is distributed into interstitial and intracellular fluids

Metabolism - Drug transformation by metabolism by the liver and other tissues

Excretion- Drug and/or drug metabolites excreted in urine, faeces or bile

Question 7

Henderson-Hasselbalch equation

Answer 7

Determines proportions of ionised and unionised drugs in a given pH environment

pKa:
- pH + log(AH/A-)
- pH where 50% of drug is ionised and 50% is ionised

Lower pKa (higher Ka) = strong acid