CPTP 2.1

Question 1

The mechanisms of drug movement across physiological barriers

Answer 1

• Main site of absorption of oral drugs is the small intestine
• Passive diffusion through lipid
• Diffusion through aqueous channel
• Carrier mediated transport

Question 2

How does the pKa of drug affect its absorption?

Answer 2

• Lipid solubility is an important determinant of rate of absorption
• Non-polar/ un-ionised substances dissolve in lipid
• Ionised species have low lipid solubility
• Many drugs are weak acids or bases and therefore exist in both ionised and un-ionised forms

Question 3

What is drug distribution?

Answer 3

Drug distribution is the reversible transfer of drug from one location to another within the body

For most drugs this occurs as passive diffusion of the un-ionised from across cell membranes until equilibrium is reached.

Question 4

Factors affecting rate of distribution?

Answer 4

Membrane permeability
; Drugs perfuse faster through the highly permeable capillaries

Blood perfusion
; Drugs reaches highly vascularised tissues more rapidly

Question 5

Explain how the lipid solubility of drug affects its extent of distribution

Answer 5

Ionised lipid insoluble drugs cannot easily enter cells

Question 6

Define volume of distribution (Vd)

Answer 6

Vd = amount of drug in body/ [drug]plasma

If drugs accumulate outside the plasma e.g. by being stroed in fat, the Vd will be large

Question 7

Explain how plasma protein bound drug affects the extent of distribution

Answer 7

The unbound drug is pharmacologically active

The binding is reversible and competitive

A highly plasma protein bound drug will show slower acting and prolonged therapeutic effects

Question 8

How does tissue binding drug affect the extent of distribution

Answer 8

Drugs which accumulate in tissues have a large volume of distribution

Tissue can bind drugs due to their composition/ cellular components
E.g. Lipid soluble drugs will accumulate in fat