Distribution of drugs

Question 1

Determinants of distribution

Answer 1

1. Size of the organ
2. Blood flow
3. Solubility
4. Binding

Question 2

Size of the organ

Answer 2

The size of the organ determines the con

centration gradient between blood and the organ

Question 3

Blood flow

Answer 3

Blood flow to the tissue is an important determinant of the rate of uptake of drug, although blood flow may not affect the amount of drug in the tissue at equilibrium. As a result, well-perfused tissues (eg, brain, heart, kidneys, and splanchnic organs) usually achieve high tissue concentrations sooner than poorly perfused tissues (eg, fat, bone).

Question 4

Solubility

Answer 4

The solubility of a drug in tissue influences the concentration of the drug in the extracellular fluid surrounding the blood vessels. If the drug is very soluble in the cells, the concentration in the perivascular extracellular space will be lower and diffusion from the vessel into the extravascular tissue space will be facilitated. For example, some organs (such as the brain) have a high lipid content and thus dissolve a high concentration of lipid-soluble agents rapidly.

Question 5

Binding

Answer 5

Binding of a drug to macromolecules in the blood or a tissue compartment tends to increase the drug’s concentration in that compartment.