4)Drug Distribution/Pharmacokinetics

Question 1

Drug Distribution

Answer 1

When a drug reversibly leaves the bloodstream + enters extracellular fluids/cells of tissues

Factors of distribution include:

• Blood flow
• Capillary permeability
• Binding of drugs to plasma proteins
• Volume of distribution/apparent volume of distribution

Question 2

Blood Flow

Answer 2

• Rate of blood flow varies widely
• eg blood flow to brain/kidneys > blood flow to skeletal muscles

Question 3

Capillary Permeability

Answer 3

CP is determined by: Capillary structure + chemical nature of drug

Capillary structure:

• Varies widely in terms of: Fraction of basement membranes that’s exposed by slit junctions between endothelial cells
• In the brain - No slit junction

Blood Brain Barrier

• To enter brain - drugs must pass through endothelial cells of CNS capillaries
• Lipid-soluble drugs - Readily penetrate fail to enter
• ionised/Polar drugs - Fail to enter

Drug Structure

• Hydrophobic (no net charge) drugs - readily move across most membranes
• Hydrophilic (+/- charge) - Need to go through slit junctions as they don’t readily penetrate membranes

Question 4

Binding of drugs to plasma proteins

Answer 4

Plasma albumin = Major drug binding protein + can act as a drug resovoir

• Binding to plasma proteins = Reversible + slows transfer out of the vascular component
• Bound Drug = No effect - Only unbound drugs can act ⇢ This enables plasma proteins to act as Resovoirs + decreases toxicity of drug

Factors that influence binding include:

• Free drug/protein concentrations
• Affinity of binding sites

Question 5

Volume of distribution/Apparent Volume of distribution

Answer 5

Volume of Distribution = Vol of liquid into which the drug is dispersed

• Includes water components such as: Plasma compartments, EC fluid + total body water

Apparent vol of which a drug distributes (Vd) calculated by:

Vd = D/C C=Plasma conc of drug D=total drug in body

• Drugs w/small Vd = largely stay in plasma compartment + therefore small doses only
• Drugs w/high Vd = distribute throughout vascular + Ec fluid requiring higher dose