Drug Metabolism

Question 1

CYP1A2

Answer 1

Marker Drug: Theophylline (his favourite one so its for 1A2)

Clinically relevant drugs: TC
Theophylline
Clozapine

Drug interactions:
Tobacco; diet. Tobacco induces CYP1A2 so if someone is a smoker then you need to give them a larger dose of TC. But if they cease smoking and remain on the high dose then it may cause overdose.

Question 2

CYP2E1

Answer 2

MD: Ethanol (E for Ethanol)

Clinically relevant drug: Paracetamol (think of Jiddo)

Drug interactions:
Chronic ethanol consumption increases the expression of CYP2E1, so may increase the formation of the toxic metabolite of paracetamol. So you need less Paracetamo to OD.

Question 3

CYP2C19

Answer 3

When Salam (2) was 19 OME wanted PRAZOLE, and I met toby who was pro GUAnipigs but I had nil of it.

MD: proguanil and omeprazole.

Clinically relevant drugs:

• Omeprazole
• Clopidigrel
• Cyclophosphamide

Genetic polymorphisms may play an important role.

Question 4

CYP2D6

Answer 4

Debby and Quine

MD: Debrisquine

Clinically relevant drugs:
Codeine
Tricyclic antidepressants
beta blockers

Genetic polymorphisms may be important

Question 5

CYP3A4

Answer 5

CYP3A4

• Marker drug: erythromycin
• Clinically relevant drugs:
  o Major enzyme for ~30% of drugs currently on the market
  o Calcium channel blocker (felodipine)
  o HMG-CoA reductase inhibitor (simvastatin)
  o Immunosuppressant (ciclosporine)
• Drug-drug interactions rather than genetic polymorphism are the major concern
  o Grapefruit juice an inhibitor
  St John’s Wort an inducer; is a highly accessible drug, can be used for self-

Question 6

What is first pass metabolism?

Answer 6

Drugs taken orally may be metabolised as they pass through the gut wall or in the liver before they reach the target site.

This may limit the usefulness of oral administration of the drug.
- Morphine - you give a far bigger dose orally than intravenously.