Drug Metabolism

Question 1

What is the significance of biotransformation?

Answer 1

Major route of drug elimination
Often activates/inactivates drugs
May produce toxic products
Source of patient variability
Explains drug interactions

Question 2

How many phases are there in biotransformations?

Answer 2

Two

Question 3

Which enzymes are responsible for each phase?

Answer 3

Phase 1: Cytochrome P450 (CYP)- 70% of drugs

Phase 2: Transferases (glucuronyl, sulphate, acetate-)

Question 4

Where is cytochrome P450 found?

Answer 4

Gut and liver

Question 5

What are the CYP substrates (what do they break down)?

Answer 5

CYP 123 = medicines
CYP 458 = fatty acids and prostaglandins
CYP 71117212427 = steroids

Question 6

Describe the enzyme CYP1A2

Answer 6

Marker drug: theophylline

Drug interaction: tobacco, green veges, BBQ and cimetidine

Question 7

Describe the enzyme CYP2E1

Answer 7

Marker drug: ethanol
Clinically relevant drug: paracetamol
Drug interaction: ethanol

Question 8

Describe the enzyme CYP2C9

Answer 8

Marker drug: s-warfarin
Clinically relevant drug: warfarin
Can cause increased bleeding risk
Most common in whiteys

Question 9

Describe the enzyme CYP2C19

Answer 9

Marker drug: s-mephenytoin
Clinically relevant drug: omeprazole
Cure of GORD
Drug interaction: clopidogrel
Most common in asians

Question 10

Describe the enzyme CYP3A4

Answer 10

Marker drug: simvastatin
Clinically relevant drugs: simvastatin, lopinavir and cyclosporine
Drug interaction: grape fruit juice and lopinavir

Question 11

Describe the enzyme CYP2D6

Answer 11

Marker drug: debrisoquine
Clinically relevant drugs: tricyclic antidepressants, beta blockers and analgesics
Drug interactions: Fluoxetine and quinidine

Question 12

What is the difference between induction and inhibition?

Answer 12

Induction: Increased activity
Inhibition: Decreased activity