Drug Metabolism

Question 1

State what is meant by ‘drug metabolism’.

Answer 1

The biochemical modification of pharmaceutical substances by living organisms usually through specialised enzymatic activity

Question 2

Describe the effects of metabolism.

Answer 2

• Loss of pharmacological activity
• Decrease in activity, with metabolites that show some activity
• Increase in activity, more active metabolites - activation of a prodrug
• Production of toxic metabolites (direct toxicity, carcinogenesis and teratogenesis)

Question 3

State what is meant by a ‘prodrug’

Answer 3

A drug that is activated after metabolism

Question 4

What is the purpose of drug metabolism?

Answer 4

• To increase water solubility

- To deactivate compounds

Question 5

State the most important family of metabolising enzymes involved in first pass metabolism.

Answer 5

Cytochrome P-450 enzymes

Question 6

CYP3A4:

Answer 6

• Found in the human liver

- Metabolises a wide range of drugs e.g diazepam, methadone and simvastatin

Question 7

CYP2D6:

Answer 7

• Metabolises antidepressants, antipsychotics and converts codeine to morphine
• Reduced/absent expression in 5-10% of people.
• Some induction by smoking

Question 8

CYP1A2:

Answer 8

• Induced by smoking

- Important in the metabolism of theophylline

Question 9

Phase 1 metabolism can involve which 3 reactions?

Answer 9

Hydrolysis, oxidation or reduction

Question 10

In phase 2 metabolism, conjugation:
Increases/decreases water solubility,
Results in activation/inactivation

Answer 10

Increases water solubility (makes excretion easier)

Results in inactivation

Question 11

In phase 2 metabolism, conjugation can involve the attachment of (4)

Answer 11

• Glucuronic acid
• Glutathione
• Acetate
• Sulphate

Question 12

State the factors which affect drug metabolism.

Answer 12

Sex
Hepatic blood flow
Ethnicity

Genetics
Other drugs/herbals/natural substances
Age
Liver Disease

Pregnancy