Pharmacokinetics 2

Question 1

Describe Phase 1 metabolism in the liver?

Answer 1

• It is generally oxidation, reduction or hydrolysis, introducing or revealing a reactive chemical group (functionalisation). Products are often more reactive

Question 2

Describe Phase 2 metabolism in the liver

Answer 2

Hydrophilic, inactive compounds generated by changing the chemical properties. This makes the body more likely to get rid of it.

Question 3

How are hydrophilic compounds excretes?

Answer 3

in urine via the kidneys

Question 4

What enzymes mediate phase 1 metabolism?

Answer 4

Cytochrome P450 enzymes (mixed function monooxygenases)

Question 5

What are the functions of Cytochrome P450 enzymes?

Answer 5

Biosynthesis of steroids, fatty acids and bile acids. Metabolism of endogenous and exogenous substrates

Question 6

Describe the metabolism of paracetamol

Answer 6

It can be conjugated with sulphate or glucoronide (main ways) or some of it is metabolised by cytochrome P450 enzymes.

Question 7

Describe the metabolism of paracetamol via cytochrom P450 enzymes

Answer 7

The enzymes turn it into a toxic metabolite which will combine with glutathione if there are normal levels which then gets conjugated and excreted. If there are depleted levels of glutathione it will combine with hepatic proteins and become toxic.

Question 8

Describe the interaction between Warfarin and Phenobarbital

Answer 8

Phenobarbital increases the expression of Cytochrome P450 and Warfarin is metabolised by cytochrome P450 so it will decrease the effect of warfarin

Question 9

Describe the effects of grapefruit juice on statins

Answer 9

It prevents the metabolism of statins by blocking the enzyme that metabolises it. (CYP3A4)

Question 10

What is the importance of drugs being metabolised differently?

Answer 10

It allows for patient-specific choices to be made, for example Vecuronium is metabolised by the liver so this drug wouldn’t be suitable for a patient with poor liver function.

Question 11

Metabolism can affect what?

Answer 11

The bioavailability of drugs

Question 12

How are drugs eliminated?

Answer 12

Either unchanged or as metabolited. Hydrophilic drugs are eliminated more readily than lipophilic except for in the lungs

Question 13

What are the possible sources of excretion?

Answer 13

Breath, Urine, Saliva, Perspiration, Feces, Milk, Bile and hair

Question 14

What is the minimum effective concentration

Answer 14

The min plasma conc that needs to be achieved before evidence of a therapeutic effect could be observed.

Question 15

What is the minimum toxic concentration?

Answer 15

The min plasma conc required to observe unwanted or toxic effects of the drug

Question 16

What is the theraputic window? how can you calculate it from a graph

Answer 16

The gap between the minimum effective concentration and the minimum toxic concentration. Calculated by drawing a line at both values and the space in between is therapeutic window

Question 17

What is the onset of action? How can u calculate it on a graph?

Answer 17

How long it takes the drug plasma conc to reach the min effective conc. Draw line at value for min effective conc and where the curve breaches that line is the onset of action

Question 18

How can you calculate on a graph the duration of action?

Answer 18

Draw line at the min effective concentration. Mark when the curve breaches the line and then another mark when it descends back below the line.

Question 19

What is Cmax?

Answer 19

The peak plasma concentration achieved after administering the drug

Question 20

What is Tmax?

Answer 20

The time taken to reach the Cmax

Question 21

What is the plasma clearance half life (elimination half life)? How is it calculated?

Answer 21

How quickly the drug is removed from the body. Start at Tmax and work out how long it takes for 50% of Cmax to be reached (towards the right of Tmax)