Volume Distribution

Question 1

What is the volume distribution?

Answer 1

The relationship between concentration and the amount of drug on the body

Amount (loading dose)= V x concentration in L

A higher V will mean more of the drug is distributed around

Question 2

What can be said about the sponge model of volume distribution using the example of digoxin? (Tissue binding)

Answer 2

Digoxin binds to Na+/K+ ATPase which is very abundant in the body. Thus the concentration in the serum is low as it binds to all tissues. This gives an unusually large volume distribution

Question 3

What is drug partition?

Answer 3

Fat: a lipophilic drug will have an increased V with people who have more fat (thiopentone). A hydrophilic drug won’t change the V.

Bone: drug adsorption, like tetracycline and bisphosphonates

Question 4

What can be said about plasma protein binding and the red herring model?

Answer 4

Albumin: warfarin will bind to it, causing a smaller than apparent V. (weak acids)
Alpha-acid-glycoprotein: lignocaine. (weak bases)

Red herring: due to binding to plasma proteins, and serum contains these, the volume distribution appear lower that it actually is. Have to consider the unbound concentration

Question 5

What can be said about drugs bound to plasma proteins, and other drugs displacing them?

Answer 5

As plasma proteins are a small part of the bound amount in the body, if you give a drug that displaces it (eg ibuprofen with warfarin), the amount that is displaced will cause a negligible effect. No acute affect

Question 6

What are some examples of different drugs and the size of their volume distributions?

Answer 6

TINY: warfarin, 10L due to plasma protein binding
SMALL: gentamicin, 18L
MEDIUM: theophylline at 35 L
LARGE: digoxin, 500L due to tissue binding

Question 7

What are the two pharmokinetic compartments?

Answer 7

Apparent central compartment volume (approx the ECF volume), and this reflects the initial rapid distribution

Apparent tissue compartment volume, this reflects the space after time has passed to reach steady state

Question 8

What is the one compartment model?

Answer 8

A one compartment system, there is a beaker with no elimination occurring so following drug administration conc increases and stays the same.

In the other beaker, the rate in matches the rate put and this is drug elimination occurring, so drug conc will increase then slowly decrease

Question 9

What is the two compartment model?

Answer 9

Two beakers connected, no elimination occurring however drug conc will increase in serum, then decrease and plateau as it diffuses into the ECF

Two beakers with elimination, the drug conc will increase, then gradually decrease as it distributes to the ECF and is eliminated

Question 10

What are the distribution rates of some drugs?

Answer 10

Minutes: thiopentone (short acting anaesthetic)
Hours: digoxin
Days: lithium (bipolar disorder)