L28 Pharmacology II and III

Question 1

Define ‘xenobiotic’

Answer 1

Foreign compound with no nutritional value

Drugs are examples of xenobiotics

Question 2

What factors affect distribution of drugs in the body?

Answer 2

Molecular size of drug

Ability to cross membranes

Binding to plasma proteins

Question 3

How does elimination of drugs occur?

Answer 3

• Renal excretion
• Liver metabolism
• Chemical transformation

Question 4

Which two types of compounds are not metabolised; cleared almost exclusively by glomerular filtration?

Answer 4

Small, water-soluble molecules

Complex carbohydrates

Question 5

Which type of compounds are extensively metabolised?

Answer 5

Lipophilic drugs

If they were not metabolised they would be endlessly recycled through glomerular or enterohepatic reabsorption.

Question 6

What are the 3 pathways of metabolism?

Answer 6

Phase I metabolism: Functionalisation reactions

Phase II metabolism: Conjugation reactions

Phase III metabolism: Formation of xenobiotic-macromolecule adducts

Question 7

What is a functionalisation reaction?

Answer 7

Addition or unmasking of a functional polar group

Question 8

True or false:Drug-metabolising enzymes generally have a high substrate specificity

Answer 8

False.

Generally have a low substrate specificity - not specific for one compound or group of compounds

Question 9

True or false: Drug-metabolising enzymes may have low reaction specificity

Answer 9

True. They may catalyse different types of reactions

Question 10

True or false: Substrates of drug-metabolising enzymes are usually lipophilic

Answer 10

True.

Question 11

True or false: Drug-metabolising enzymes have lower catalytic rates and are usually present in lower concentrations.

Answer 11

False.

Drug-metabolising enzymes have lower catalytic rates and are usually present in higher concentrations.

Question 12

In which subcellular hepatic compartments does drug metabolism take place?

Answer 12

Smooth endoplasmic reticulum (contain microsomes)

Cytosol

Question 13

Which of the following is a microsomal enzyme:

a) Aldehyde oxidase
b) Flavin monooxygenase
c) Monoamine oxidase
d) Sulphotransferase

Answer 13

b) Flavin monooxygenase

Aldehyde oxidase and sulphotransferase are cytosolic enzymes.

Monoamine oxidase is a mitochondrial enzyme.

Question 14

Which are the mitochondrial enzymes from the lecture slides?

Answer 14

Aldehyde dehydrogenase (also a cytosolic enzyme)

Monoamine oxidase

Question 15

Which are the cytosolic enzymes from the lecture slides?

Answer 15

Aldehyde oxidase

Aldehyde dehydrogenase (also a mitochondrial enzyme)

Alcohol dehydrogenase

Glutathione transferase

Sulphotransferase

Question 16

What are the microsomal enzymes from the lecture slides?

Answer 16

Cytochrome P450

Flavin monooxygenase (FMO)

Glucuronosyl transferase

Epoxide hydrolase

Question 17

What common, non-medicinal substance inhibits cytochrome P450 3A4?

Answer 17

Grapefruit juice

Question 18

Terfenadine is a prodrug. What is its active form, and what problem was found with taking the drug?

Answer 18

Terfenadine oxidised to fexofenadine in the liver.

Patients taking substances that inhibit CP450 3A4 had high levels of terfenadine as it couldn’t be metabolised. Resulted in cardiotoxicity.

Question 19

Erythromycin, clarithromycin, ketoconazole, itraconazole and cimetidine all inhibit which enzyme?

Answer 19

Cytochrome P450 3A4

Question 20

Define drug selectivity

Answer 20

Selectivity describes the ability of a drug to bind to a particular receptor.

If it binds to multiple receptors, it has a low selectivity.

Question 21

What is a quantal response?

Answer 21

An all or nothing response - compare quantal responses of patients to determine median effective dose (dose that caused the desired effect in 50% of patients)