Volume of distribution

Question 1

Define volume of distribution

Answer 1

How much drug needs to be in the body (amount) to achieve a certain plasma concentration

Question 2

Formula describing Vd

Answer 2

Amount= VD*Concentration

Or Vd= Amount/Concentration

Question 3

Describe loading dose

Answer 3

The dose required to achieve target concentration

Question 4

How can loading dose be calculated

Answer 4

Using Vd and target concentration

Amount (loading dose) = Vd*concentration

Question 5

Why is the volume of distribution different to the physical volume?

Answer 5

Because it is based on how the drug binds to cells/proteins. Vd is calculated based on amount (dose)/plasma concentration. If the drug binds to cells outside of the plasma the Vd will be larger than physical volume or where drug binds to plasma proteins and Vd will be smaller than physical volume.

Question 6

If a drug binds readily to plasma proteins will its Vd be smaller or larger relative to physical volume?

Answer 6

Smaller (drug concentration in plasma higher)

Question 7

If a drug binds readily to cells outside of the plasma will its Vd be smaller or larger relative to physical volume?

Answer 7

Larger (drug concentration in plasma smaller)

Question 8

Does warfarin have a have a large or small volume of distribution?

Answer 8

Small (99% bound to plasma proteins)

Question 9

Does digoxin have a large or small volume of distribution?

Answer 9

Large (extensively bound to Na+/K+/ATPase pumps outside of plasma)

Question 10

What is digoxin?

Answer 10

Drug used to treat congestive heart failure. It acts to increase myocardial contractions though increasing Ca2+ availability for excitation-contraction coupling.

Question 11

What are the applications of understanding volume of distribution?

Answer 11

For calculating loading dose and half life

Question 12

What are other body tissues that may change the apparent Vd

Answer 12

Fat, bone. Drugs that are lipophilic have increased Vd

Question 13

What is the difference between bound and unbound plasma concentrations

Answer 13

Bound includes all the free drug in the plasma as well as that which is bound to albumin.
Unbound is only the plasma concentration which is free. This is the concentration which is able to be used by the body.

Question 14

What is the concern with plasma binding in relation to drug interactions. Level of concern?

Answer 14

One drug may displace another from plasma proteins increasing its unbound plasma concentration. Usually does not produce important pharmacological effects as unbound drug clearance is unchanged and the body just gets rid of more.

Question 15

Why does volume of distribution of digoxin decrease in old sick people and what is the relevance to treatment?

Answer 15

Because digoxin binds to muscle cells and kidney tissue (among others) and old sick people have lower muscle mass/ renal disease. This means that plasma concentration in these people will be higher and thus a lower Vd therefore loading dose needs to be smaller