Lecture 4 - Metabolism

Question 1

Biotransformations?

Answer 1

Two phases, phase 1 from drug into intermediate, then phase 2 conjugation into excretory product

Question 2

Major enzyme systmes?

Answer 2

phase I - cytochrome P450; phase II - transferases (glucuronyl-, sulphate-, acetate-)

Question 3

Locations of cytochrome P450?

Answer 3

gut wall, liver

Question 4

CYP1A2?

Answer 4

theophylline, bronchodilator, induced by smokes (e.g. tobacco and BBQ) and inhibited by cimetidine

Question 5

CYP2E1?

Answer 5

ethanol, paracetamol, induced by ethanol

Question 6

CYP2C9?

Answer 6

s-warfarin, anticoagulants, adverse effect of increased bleeding risk managed by lower dose, 25% caucasian variance and 1% asian

Question 7

CYP2C19?

Answer 7

omeprazole, acid-pump inhibitor, GORD treatment, counters prodrugs, asian’s more clearance than caucasian

Question 8

CYP2D6 - marker drug?

Answer 8

debrisoquine

Question 9

CYP2D6 - clinically relevant durgs?

Answer 9

tricyclic-antidepressants, beta blockers, prodrug analgesics

Question 10

CYP2D6 - drug interactions?

Answer 10

fluoxetine, quinidine

Question 11

CYP3A4 - marker drug?

Answer 11

metabolises 30% medicines, simvastatin

Question 12

CYP3A4 - clinically relevant drugs?

Answer 12

simvastatin, protease inhibitor, immunosuppresant

Question 13

CYP3A4 - interactions?

Answer 13

grapefruit juice, iopinavir, St John’s Wort

Question 14

Clinical applications of CYP?

Answer 14

drug interaction awareness, dose individualisation