lecture 2 - volume of distribution

Question 1

define the volume of distribution

Answer 1

the apparent volume of distribution describes the relationship between concentration and the amount of drug in the body
Amount (loading dose) = V x Conc

Question 2

name physiological determinants of volume of distribution

Answer 2

vascular

extracellular

total body water

Question 3

describe why apparent volume of distribution may not necessarily correspond to any physical compartment

Answer 3

because of binding to tissues, binding to plasma proteins, prefential partitioning into fat or adsorption onto bone

Question 4

give an example of a drug that carries out the action of tissue binding and how this effects apparent volume

Answer 4

digoxin
- binds extensively to Na+/K+/ATPase (found in many excitable cells)
apparent volume of distribution will be large when there is extensive binding to tissue proteins

Question 5

why might an obese person have a large apparent volume

Answer 5

due to partitioning - drugs can bind to fat

Question 6

why might the apparent volume of distribution not correspond to a physical volume, but instead be smaller

Answer 6

plasma protein binding e.g. warfarin & aspirin
- drugs bind to plasma proteins like albumin and are extracted from plasma. Therefore they’re included in drug concentration measurements. Referred to as ‘red herring’

Question 7

define the ‘red herring’ effect

Answer 7

caused by drugs binding to plasma proteins
- conc of drug will be higher in the sample than compared to the rest due to the high conc of drug bound to the ‘red herring’
higher conc in the sample leads to lower apparent volume of distribution

Question 8

describe warfarin and how it is referred to as having a ‘red herring’ effect

Answer 8

about 99% of warfarin is bound to plasma proteins
about 1% is unbound
apparent volume = 10L
unbound concentration = 1000L
(depends on whether bound or unbound is used for calculations)

Question 9

describe gentamicins apparent volume of distribution

Answer 9

doesnt bind to plasma proteins
highly ionised and doesnt cross cell membranes easily

apparent volume of distribution is quite close to the physical volume of ECF
indicating that is doesnt bind extensively to tissues

Question 10

describe the relationship with apparent volume and time

Answer 10

apparent volume changes with time until steady state is reached
initially drug is distributed in the plasma volume then diffuses into the extracellular space then into cells. Diffusion takes time