Distribution

Question 1

What happens once a drug has entered the blood stream?

Answer 1

Once in the blood stream, drugs will distribute to the body’s tissues.

Question 2

How is a drug distributed and why?

Answer 2

Distribution is generally uneven because of differences in blood perfusion, protein binding (e.g. due to lipid content), regional pH and permeability of cell membranes.

Question 3

How does blood perfusion affect distribution? Give an example.

Answer 3

Well-perfused tissues such as lungs and kidney show highest concentration of drugs.

Poorly-perfused tissue such as fat show a lower concentration.

If intravenously administered it enters directly into the blood stream. For example, thiopentone, an quick short-acting IV anaesthetic, has rapid onset due to rich blood supply to brain and rapid penetration of blood-brain barrier. Slower action due to redistribution to muscle and fat.

Question 4

What is protein binding?

Answer 4

In blood plasma, most drugs bind to plasma or tissue protein to some extent.

In most instances, the binding is non-covalent and readily available.

Question 5

Which proteins bind which drugs?

Answer 5

Albumin is a major plasma protein responsible for binding many drugs - acidic.

Alpha-glycoprotein is important for the binding of many basic drugs.

Question 6

How does protein binding affect distribution and therefore action of a drug?

Answer 6

Only unbound drug is available for diffusion to sites where pharmacological effects occur.

Question 7

What are the consequences of protein binding?

Answer 7

• Activity - inactive when bound
• Absorption - keeps free concentration low maintaining conc grad important for absorption
• Distribution
• Storage
• Elimination - bound drug not filtered so increase half life
• Interactions - low specificity of binding so competition for binding sites frequently occur

Question 8

How does the blood-brain barrier affect drug distribution?

Answer 8

Drugs reach the CNS via the brain capillaries and cerbrospinal fluid (CSF). Drug penetration is restricted by the blood brain barrier.

Question 9

What is the blood brain barrier?

Answer 9

The blood–brain barrier is formed by brain endothelial cells, which are connected by tight junctions.

Question 10

What is the effect of age on the blood brain barrier?

Answer 10

As age increases, the blood brain barrier is less effective so increase passage of compounds into the brain.

Question 11

What are the individual variations that affect distribution?

Answer 11

• Body size/obesity
• Oedema (fluid retention)
• Change in protein conc in disease
• Drug interaction