pharmacokinetics 2

Question 1

what are the characteristics of phase 1 of metabolism which occurs in the liver?

Answer 1

• usually some sort of breaking down reaction (e.g. oxidation, reduction or hydrolysis)
• often introduces/reveals a reactive functional group

Question 2

what are the characteristics of phase 2 of metabolism which occurs in the liver?

Answer 2

• synthetic conjugate reactions (involves the addition of a large conjugate group)
• usually the drug is transformed into a hydrophilic compound so it can be excreted in the urine more easily

Question 3

what process can be disrupted in drug metabolism by taking antibiotics?

Answer 3

bacteria in the gut can break off the conjugate group of the drug and allow its reuptake into the liver (some drugs rely on this property e.g. oral contraceptive)

Question 4

what enzymes which breakdown drugs and are often involved in phase 1 metabolism are found extensively throughout the body, especially in the liver?

Answer 4

cytochrome P450 enzymes

also involved in biosynthesis of fatty acids, and bile acids

Question 5

what happens to a small proportion of parcetemol in the liver which generates a toxic metabolite?

Answer 5

it is acted on by cytochrome P450 enzymes in a phase 1 metabolism step

Question 6

how is this toxic metabolite generated by paracetemol detoxified?

Answer 6

by combining it with glutathione which stimulates conjugation and excretion

Question 7

what happens when there are depleted glutathione levels i the liver?

Answer 7

the toxic metabolite (produced by paracetamol) is combined with hepatic proteins and becomes toxic

Question 8

what does phenobarbital increase the expression of?

Answer 8

cytochrome P450 enzymes which metabolise warfarin

Question 9

what is the relationship between statin plasma levels and grapefruit juice

Answer 9

there is a cytochrome p450 enzyme in the wall of the enzymes which begins metabolism of statins before they even reach the liver, however grapefruit juice blocks this enzyme and therefore hugely increases plasma concentration of statins

Question 10

what type of drugs are eliminated more easily - hydrophilic or lipophilic?

Answer 10

hydrophilic

Question 11

which organ is the most important in terms of exertion?

Answer 11

the kidneys

Question 12

what is the therapeutic window?

Answer 12

the plasma concentration of drug between being ineffective and producing side effects and toxicity

Question 13

what is the onset of action?

Answer 13

the time taken between when the rug is administered and the minimum effective concentration

Question 14

what is the duration of action?

Answer 14

the time between the drug first reaches the minimum effective concentration and the the second time it passes this concentration as its level decreases

Question 15

what is Cmax?

Answer 15

peak plasma concentration of a drug

Question 16

what is Tmax?

Answer 16

time to reach peak plasma concentration

Question 17

what is the absorption half life?

Answer 17

the time taken to reach half of Cmax

Question 18

what factor decrease with absorption half life?

Answer 18

peak plasma concentration

Question 19

what factor increase with absorption half life?

Answer 19

duration of action

Question 20

what is the plasma clearance half life?

Answer 20

the time taken to eliminate half of the peak plasma concentration of drug

Question 21

what pharmacokinetic parameters affect elimination half life?

Answer 21

distribution, metabolism and elimination

Question 22

what is Css in terms of IV infusion of drug?

Answer 22

the ‘steady state’ concentration of plasma drug when the rate of drug in equals the rate of drug out