Volume of Distribution

Question 1

What is the apparent volume of distribution?

Answer 1

The relationship between concentration and the amount of a drug in the body

Question 2

What are the units for amount, volume and concentration?

Answer 2

mg L mg/L

Question 3

How can the loading dose be predicted?

Answer 3

If the target concentration and the drug apparent volume distribution are known

Question 4

What are the three physical compartments of the body?

Answer 4

Vascular- blood 5L plasma 2.5 L
Extracellular- 18 L
Total body water- 35L

Question 5

What is the only drug that undergoes tissue binding?

Answer 5

Digoxin (Na/K ATPase)

Question 6

Why does the measured amount of digoxin lower than if it were evenly distributed throughout the body? (sponge)

Answer 6

The apparent volume must be larger than the physical volume. The apparent volume of distribution will be large when there is extensive binding to tissue proteins

Question 7

How does fat affect volume of distribution?

Answer 7

Lipophilic drugs increase apparent volume of distribution

Hydrophilic drugs have no effect

Question 8

How does bone affect volume of distribution?

Answer 8

Some drugs are absorbed by bone and this will increase their apparent volume of distribution (tetracycline and bisphosphonates)

Question 9

How does plasma protein binding affect volume of distribution? (red herring)

Answer 9

Leads to a smaller apparent volume

Bind to proteins such as albumin and alpha acid glycoprotein

Question 10

What is the idea way to measure drug concentration?

Answer 10

Unbound but the loading dose calculated will be the same as long as the target concentration type matches the apparent volume type

Question 11

Why are plasma proteins insignificant?

Answer 11

Negligible effect on total unbound amount in the body if plasma protein binding is changed

Question 12

Why does warfarin have a very small apparent volume?

Answer 12

It binds extensively to plasma proteins

Question 13

Why does gentamicin have a small apparent volume?

Answer 13

It is highly ionised and does not cross cell membranes easily so its apparent volume is close to the physical volume of ECF

Question 14

What is the apparent volume of distribution of theophylline?

Answer 14

35L-on par with total body fluid as it crosses cell membranes

Question 15

What is the apparent volume of distribution of digoxin?

Answer 15

500 L due to tissue binding

Question 16

What are the two pharmokinetic compartments and why do they matter?

Answer 16

Drugs travel from plasma to extracellular space and finally to tissues so is in different places at different times. Apparent central compartment volume (ECF volume) and apparent tissue compartment volume

Question 17

How does drug concentration change in a single compartment model?

Answer 17

With elimination from the beaker drug concentration drops

Question 18

How does drug concentration change in a double compartment model?

Answer 18

Concentration remains constant even with elimination

Question 19

What are the differing distribution half lives between drugs?

Answer 19

Minutes- thiopentone
Hours- digoxin
Days- lithium