lecture 4 - drug metabolism

Question 1

importance of understanding biotransformation

Answer 1

• major route of drug elimination
• often activates/inactivates drugs
• may produce toxic products
• source of between patient variability
• explains many drug-drug interactions

Question 2

phase 1 of biotransformation

Answer 2

metabolism
oxygen inserted into molecules

major enzyme systems = cytochrome p450 (CYP)

Question 3

phase 2 of biotransformation

Answer 3

conjugation, addition of another alkyl group

typically involves sugars, acetates, sulfates being added

major enzyme systems, transferases

Question 4

describe cytochrome P450

Answer 4

• found in gut wall and liver
• > 70% of drugs metabolized by CYPs
• contains Heme

Question 5

CYP2E1

Answer 5

marker drug = ethanol

clinically relevant substrate = analgesic substrate

drug interaction = ethanol

Question 6

CYP1A2

Answer 6

marker drug = theophylline

clinically relevant substrate = bronchodilator

drug interaction =
tobacco, green veges, BBQ (inducer)
cimetidine (inhibitor)

Question 7

CYP2C9

Answer 7

marker drug = s-warfarin

clinically relevant = anticoagulant

adverse event risk = lower dose & increased bleeding

Question 8

CYP2C19

Answer 8

marker drug = mephenytoin

clinically relevant = acid-pump inhibitor (omeprazole)

Question 9

omeprazole

Answer 9

used for GORD, cures 86% in poor metabolizers

inhibits CYP2C19

side effect = it decreases effectiveness of clopidogrel when combined with omeprazole

Question 10

CYP3A4

Answer 10

marker drug = simvastatin

clinically relevant substrates =

- HMG-CoA inhibitor
- protease inhibitor
- immunosuppressant

drug interaction

- ketoconazole, grapefruit juice (inhibitor)
- St johns Wort (inducor)

Question 11

CYP activity

Answer 11

induction

• increased activity
• many substances can induce (e.g. tobacco & CYP1A2)

inhibition

• decreased activity
• usually competitive (e.g. grapefruit & CYP3A4 in gut)

Question 12

cytochrome P450 inhibitor

Answer 12

reduces the metabolism of the substrate, thereby increasing its concentration and physiologic effect.