Pharmacokinetics

Question 1

Define ‘volume of distribution’

Answer 1

the volume of plasma that would contain the total body content of the drug at a concentration equal to that in the plasma

Vd = total amount of drug in body

         conc. drug in plasma

Question 2

What is the Vd for different body compartments?

Answer 2

• plasma - 0.05L/kg
• ECF - 0.2L/kg
• total body water - 0.55L/kg

Question 3

define ‘preferential distribution’

Answer 3

drugs may preferentially distribute to a tissue other than the blood.

Question 4

what can cause preferential distribution?

Answer 4

• ion trapping
• lipid solubility
• irreversible receptor binding
• incorporation into tissue

Question 5

what affects Vd?

Answer 5

• dehydration
• fluid retention
• age
• disease
• species
• obesity
• weight loss

Question 6

Describe phase 1 metabolism

Answer 6

• introduces a functional group to the molecule to make them more functionally reactive to enter phase 2
• occurs in liver, kidney, lungs, skin, plasma, GIT
• products can be: more active, more chemically reactive, more toxic, less lipid soluble, more polar/ionised, more rapidly excreted

Question 7

Describe phase 2 metabolism

Answer 7

• requires a stable functional group susceptible to conjugation
• e.g. glucuronidation, sulphation, methylation, acetylation
• products are: almost always pharmacologically inactive, less lipid soluble, excreted in urine or bile

Question 8

What is presystemic metabolism?

Answer 8

• the liver/gut wall metabolises the drug before it reaches systemic circulation
• consequences: poor bioavailability, larger dose needed, marked inter-individual variation

Question 9

What are the implications of metabolism?

Answer 9

residues in meat, milk, eggs, honey, wool

Question 10

define ‘clearance’

Answer 10

the efficiency of the irreversible elimination of a drug from systemic circulation

Question 11

define ‘zero order kinetics’ and draw a graph

Answer 11

conc. of a drug declines linearly with time and rate of change of conc. over time equals a constant.

Question 12

define ‘first order kinetics’ and draw a graph

Answer 12

conc. of a drug declines exponentially with time. Rate of change of conc. over time equals a constant proportion of conc.

Question 13

define ‘half life of administration’

Answer 13

amount of time taken for a quantity to fall to half its volume as measured at the beginning of the time period