Lecture 2: Volume of distibution Flashcards
Apparent volume of distribution?
describes the relationship between concentration and the amount of drug in the body
Loading dose requires what to be known?
Volume of distribution and target conc. Volume = amount/conc
Total body water?
0.5L/kg for the average person
Tissue binding?
When a drug binds to a tissue so the apparent volume of distribution doesn’t correspond to any particular compartment. (eg. Digoxin binds to Na/K ATPase)
Sponge model (tissue binding) of volume distribution?
describes how if we measure the conc of the bath water it appears as though the apparent volume of distribution is massive
Partition
rather than binding to tissues some drugs become partitioned into fat (lipophilic or hydrophilic) or bone (tetracycline - stains teeth or bisphosphonates - decreases bone breakdown in osteoporosis) etc.
Plasma protein binding?
to albumin or alpha1-acid-glycoproteins gives a smaller apparent volume RED HERRING phenomenon
EG of plasma bound?
Warfarin is 99% bound to albumin and the 1% unbound is hard and expensive to measure so if we assume that this ratio is constant then we don’t have to measure it.
Binding displacement?
NSAID can displace warfarin from albumin, as much as 10%of the bound drug. This however, has negligible effect. Because only 25% of the drug is bound to plasma proteins this equates to an increase of 2.5% which does not much at all.
Apparent volume size from different binding sites?
tiny = plasma proteins = 10L small = ECF = 18L medium = total body water = 35L large = muscle, nervous tissue etc. = 500L
Two compartment model?
The idea that the initial compartment is the plasma volume but over time this diffuses onto extracellular space and cells and so over time the volume of distribution increases and so the conc decreases.
Distribution rate?
A so called distribution half life can be calculated and ranges from minutes to days dependent upon the drug.
examples of distribution half life?
Thiopentone - minutes
digoxin - hours
lithium - days
