Drug Distribution

Question 1

What is drug distribution?

Answer 1

movement of a drug to/from blood and tissues of the body

Question 2

What are the factors that affect distribution?

Answer 2

• cardiac output and blood flow
• plasma protein binding
• lipid solubility
• degree of drug ionisation
• pH of compartments
• capillary permeability

Question 3

Describe drug binding to albumin

Answer 3

• lipid-soluble drugs will bind to albumin non-specifically

- weak acids bind to a specific saturable site

Question 4

Hydrophilic drug distribution

Answer 4

• hydrophilic drugs are highly soluble in aqueous polar media
• cannot diffuse through cell membranes
• rate of distribution depends on the diffusion characteristics of the drug

Question 5

Lipophilic drug distribution

Answer 5

• lipophilic drugs are soluble in fats and non-polar solutions
• can diffuse through cell membranes
• rate of diffusion depends on the rate of delivery to tissues

Question 6

Different capillary wall compositions

Answer 6

• continuous
• fenestrated
• discontinuous/sinusoid

Question 7

Continuous capillary

Answer 7

• very fast diffusion of gases and lipophilic molecules
• very slow diffusion of large lipophobic molecules
• tight junctions

Question 8

Fenestrated capillary

Answer 8

allows passage of small lipophobic molecules

Question 9

Discontinuous (sinusoid) capillary

Answer 9

allows passage of large lipophobic molecules and RBC

Question 10

Blood brain barrier

Answer 10

• physical and function barrier with tight junctions between endothelial cells
• only very very lipophilic drugs can pass through
• disease state can alter ability of drugs to pass

Question 11

Placenta barrier

Answer 11

• tight endothelial cell junctions in maternal/fetal capillaries
• protective
• allows passage of lipid soluble/unionised weak acids and base drugs

Question 12

Problem with getting drugs to chronic abscesses

Answer 12

• avascular tissue compartment

- no blood flow makes it difficult to get the drug to the infected area

Question 13

Problem with getting drugs to lung infections

Answer 13

• if a lung infection alters the oxygen/CO2 levels in the lung it can cause vasoconstriction
• decreases blood flow/stops flow making it hard to get the drug to the infection

Question 14

How to calculate the apparent volume of distribution

Answer 14

Vd = total amount of drug in the body/blood plasma concentration of the drug

Question 15

What are the factors that vary Vd?

Answer 15

• height
• weight
• age
• fluid accumulation (ascites, oedema, pleural effusion)
• accumulation of fat

Question 16

What is Vd?

Answer 16

• the theoretical volume of drug required to account for the amount in the body
• not always physiologically possible