Pharmacokinetics 2

Question 1

If drug A is bound to proteins in plasma and then drug B is administered with a characteristic such that: Protein affinity of drug B > Protein affinity of drug A What will happen to the plasma concentration of free drug A? What will happen to the plasma concentration of bound drug of A?

Answer 1

Free drug plasma conc of A: It will transiently increase. Bound drug plasma conc of A: It will transiently decrease.

Question 2

There are how many binding sites per albumin molecule?

Answer 2

2

Question 3

Give an example of how drug binding to tissue components can produce adverse effects.

Answer 3

Thiopentone binds to fat > Longer anaesthesia Tetracycline binds to calcium > Bone/tooth decay Chlorquinine binds to melanin granules in the retina. Carbon monoxide binds to RBC Haemoglobin > Hypoxia

Question 4

What is ‘body burden’?

Answer 4

The amount of drug in the body.

Question 5

If a drug does have extensive protein binding, what does this mean for patient dosing?

Answer 5

It means that minimal increases in drug dosage can have large effects on plasma concentration. i.e. The fraction of drug will suddenly increase due to the albumin/protein binding sites becoming saturated.

Question 6

What is the formula for Vd?

Answer 6

Vd = A / Cp = Q / Cp Such that A = Q = Amount of drug (mass)

Question 7

Can one drug inhibit the elimination of another? If not, explain why. If so, give an example.

Answer 7

It can. An example is that phenylbutazone inhibits the elimination of warfarin, leading to internal bleeding.

Question 8

If a drug binds well to tissues, it’s Vd will most likely be: (a) < 3L (b) > 3L

Answer 8

(b) > 3L

Question 9

True or false, most assays can determine the proportion of a drug that is free or bound in a patient’s body.

Answer 9

False, most assays cannot.

Question 10

Name four factors affecting drug plasma-protein binding?

Answer 10

1. Less protein synthesis (cirrhosis, liver dz) 2. More protein catabolism (shock, trauma, surgery) 3. Movement of albumin to extracellular place (e.g. burns) 4. Excess secretion of protein (renal dz)

Question 11

What is the four ways in which drugs can leave the body and which one is most common?

Answer 11

1. Kidneys > Urinated out = most common 2. Lungs 3. Biliary system 4. Breast milk

Question 12

The plasma compartment has the Vd of approximately how many litres?

Answer 12

3 litres.

Question 13

What is the approximate volume of all fluid in the body?

Answer 13

41L

Question 14

Do most drugs exceed or not meet the maximal albumin drug binding concentration?

Answer 14

Most drugs do not meet the maximal drug concentration of albumin binding.

Question 15

Which protein makes up 55-60% of the plasma proteins?

Answer 15

Albumin

Question 16

It’s important for renal dz pts if the fraction of free-drug is low or high?

Answer 16

Low. Because then the drug’s amount of free drug skyrockets, causing a way higher Emax

Question 17

A drug that binds to bodily tissues will have the following characteristics: 1. ________ concentration in body fat 2. Does/doesn’t cross the blood brain barrier 3. Likely to have a small/large t1/2

Answer 17

1. Significant concentration in body fat 2. Doescross the blood brain barrier 3. Likely to have a large t1/2

Question 18

What is another formula for loading dose?

Answer 18

Ld = Vd*Cp*m

Question 19

The Vd of all compartments and fat is approximately?

Answer 19

40L

Question 20

Regarding the figure below, the x-axis is time.
One colour is a drug with high-protein-binding affinity, one is a drug with low-protein-binding affinity and one is the amount of the drug with high-protein-binding affinity that isin the bloodstream.

Answer 20

Red = Drug with low-protein-binding affinity.

Green = Drug with high-protein-binding affinity.

Blue = Amount of Green that is bound to proteins.

Question 21

A drug will have a very similar Vd as blood volume (3L) if it satisfies either one of which two characteristics?

Answer 21

1. It tightly binds to plasma proteins.

2. It is a very ionised drug.

Question 22

The Vd of the plasma compartment and extracellular fluid is approximately?

Answer 22

15L