Volume of Distribution Flashcards
What is the apparent volume of distribution?
The relationship between concentration and the amount of a drug in the body
What are the units for amount, volume and concentration?
mg L mg/L
How can the loading dose be predicted?
If the target concentration and the drug apparent volume distribution are known
What are the three physical compartments of the body?
Vascular- blood 5L plasma 2.5 L
Extracellular- 18 L
Total body water- 35L
What is the only drug that undergoes tissue binding?
Digoxin (Na/K ATPase)
Why does the measured amount of digoxin lower than if it were evenly distributed throughout the body? (sponge)
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
How does fat affect volume of distribution?
Lipophilic drugs increase apparent volume of distribution
Hydrophilic drugs have no effect
How does bone affect volume of distribution?
Some drugs are absorbed by bone and this will increase their apparent volume of distribution (tetracycline and bisphosphonates)
How does plasma protein binding affect volume of distribution? (red herring)
Leads to a smaller apparent volume
Bind to proteins such as albumin and alpha acid glycoprotein
What is the idea way to measure drug concentration?
Unbound but the loading dose calculated will be the same as long as the target concentration type matches the apparent volume type
Why are plasma proteins insignificant?
Negligible effect on total unbound amount in the body if plasma protein binding is changed
Why does warfarin have a very small apparent volume?
It binds extensively to plasma proteins
Why does gentamicin have a small apparent volume?
It is highly ionised and does not cross cell membranes easily so its apparent volume is close to the physical volume of ECF
What is the apparent volume of distribution of theophylline?
35L-on par with total body fluid as it crosses cell membranes
What is the apparent volume of distribution of digoxin?
500 L due to tissue binding
What are the two pharmokinetic compartments and why do they matter?
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
How does drug concentration change in a single compartment model?
With elimination from the beaker drug concentration drops
How does drug concentration change in a double compartment model?
Concentration remains constant even with elimination
What are the differing distribution half lives between drugs?
Minutes- thiopentone
Hours- digoxin
Days- lithium
