Pharmacokinetics and Drug Metabolism

Question 1

State the five stages of the journey of a drug through the body.

Answer 1

Administration 
Absorption 
Distribution 
Metabolism 
Excretion 
(Voiding)

Question 2

What is the difference between enteral and parenteral administration?

Answer 2

Enteral – using the GI tract

Parenteral – everything except the GI tract

Question 3

What are the advantages of intravenous administration?

Answer 3

It gives rapid systemic exposure and a high bioavailability

Question 4

State the two ways in which drug molecules move around the body.

Answer 4

Bulk Flow Transfer – in the bloodstream it will move in bulk to the tissues
Diffusion Transfer – molecule by molecule over short distances

Question 5

State four methods by which drugs can cross lipid membrane barriers.

Answer 5

Diffusion through the lipid membrane (if appropriately lipophilic)
Diffusion through aqueous pores
Carrier molecules
Pinocytosis

Question 6

Finish the sentence: most drugs are either …… or ……

Answer 6

Weak acids or weak bases

Question 7

Which factors affect the ratio of ionized to non-ionized drug?

Answer 7

pKa of the drug

pH of the environment

Question 8

Describe and explain the difference in absorption of aspirin in the stomach and the small intestine.

Answer 8

Aspirin has a pKa of 3.4
The stomach has a pH of around 1 so when the aspirin enters the stomach, as the pH of the stomach is lower than the pKa of aspirin, the equilibrium of the aspirin is shifted towards the unionized state
So in the stomach, aspirin mainly exists in the unionized state and is rapidly absorbed
Eventually, the aspirin will reach the small intestines which has a muchmore basic pH (which is greater than the pKa of aspirin)
This means that aspirin in the small intestine is mainly ionized and hence absorption is SLOWER in the small intestine

Question 9

What is ion trapping?

Answer 9

Some ionized aspirin will enter the systemic circulation, which is an aqueous environment
As it is ionized it will not be able to move into the tissues and hence is ‘trapped

Question 10

State four factors affecting drug distribution.

Answer 10

Regional blood flow
Extracellular binding (plasma-protein binding)
Capillary permeability
Localisation in tissue

Question 11

In which state can albumin bind to drugs? Ionized or non-ionized?

Answer 11

Both ionised and unionised

Question 12

State three types of capillary architecture.

Answer 12

Continuous
Fenestrated
Discontinuous

Question 13

Give a broad example of localization of a drug in tissue.

Answer 13

Lipophilic drugs tend to localise in fatty tissues e.g. brain and testes

Question 14

What are the two main routes of drug excretion?

Answer 14

Kidneys (mainly)

Liver

Question 15

What types of molecule tend to get excreted via the biliary route?

Answer 15

Large molecule weight molecules

The liver allows concentration of large molecular weight molecules that are very lipophilic

Question 16

Via what form of molecular movement do most drugs tend to getexcreted into urine?

Answer 16

Active secretion

Question 17

What happens to drug-protein complexes at the glomerulus?

Answer 17

They are not filtered into the filtrate

Question 18

Where does active secretion of acids and bases occur in the nephron?

Answer 18

Proximal convoluted tubule

Question 19

What can happen to lipid soluble drugs in the proximal and distal convoluted tubules?

Answer 19

They could be reabsorbed

Question 20

Why might treatment with I.V. sodium bicarbonate increase aspirin excretion?

Answer 20

IV sodium bicarbonate will increase the pH of the blood
This will increase the amount of aspirin that is ionised
Becoming ionised will mean that the aspirin is more water-soluble and less lipid-soluble so the kidneys can more easily excrete it and less aspirin is reabsorbed in the proximal and distal tubules
This increases the rate of aspirin excretion

Question 21

What is the main purpose of the active transport systems that secrete drugs into bile?

Answer 21

They are meant to be for the active transport of glucuronides and bileacids into the bile but drugs can hitch a ride on this mechanism

Question 22

What is a potential problem with biliary excretion of xenobiotics?

Answer 22

Enterohepatic cycling – it can become reabsorbed and return to the liver via the enterohepatic circulation
This leads to drug persistence

Question 23

Define bioavailability.

Answer 23

The proportion of the administered drug that is available within thebody to exert its pharmacological effect

Question 24

Define apparent volume of distribution.

Answer 24

The volume in which a drug appears to be distributed – an indicator of pattern of distribution

Question 25

Define biological half-life.

Answer 25

The time taken for the concentration of a drug (in blood/plasma) to fall to half its original value

Question 26

Define clearance.

Answer 26

The volume of plasma cleared of a drug per unit time

Question 27

Define First-Order kinetics.

Answer 27

When the rate of drug excretion is proportional to the concentration of drug remaining within the body
Log of drug concentration is proportional to time

Question 28

State the equation for half-life in first-order kinetics reactions.

Answer 28

T1/2 = Vd x log(2)/Cl 
Vd = volume of distribution  
Cl = clearance

Question 29

Define Zero-Order kinetics.

Answer 29

A constant amount of drug is removed from the body per unit time

Question 30

What does zero-order kinetics suggest about the enzymes involved?

Answer 30

It suggests that the enzymes are saturated
Once the enzymes are saturated, the rate of removal of a drug peaks and remains constant
NOTE: most drugs follow first-order kinetics