Drug Metabolism

Question 1

Pharmacokinetics

Answer 1

Studies of drug metabolism

Question 2

Metabolism

Answer 2

Process which body makes compounds that are too hydrophobic to be excreted

Question 3

Phase 1 metabolism

Answer 3

Functionalisation
Prepare for phase 2 usually by creation for more polar metabolite

Question 4

Phase II metabolism

Answer 4

Conjugation reactions
Further increase aqueous solubility so drug can be excreted

Question 5

Phase I processes

Answer 5

Oxidation
reduction
Hydrolysis

Question 6

Summary of phase II processes

Answer 6

Glucuronidation
Sulfation
Acetylation

Question 7

What enzyme is involved in oxidation

Answer 7

Cytochrome P450
Catalyse the transfer of oxygen from heme to the substrate

Question 8

What other roles to CYP have

Answer 8

Fatty acid metabolism
Biosynthesis of important lipid derived compounds

Question 9

Isoform

Answer 9

Similar proteins which have small differences in primary structure and different functions

Question 10

Why do all CYP have different substrate preferences

Answer 10

Different active sites because of different primary structure which leads to different tertiary structures

Question 11

CYP and their individual substrate preferences

Answer 11

CYP3A4= large molecul substrates
CYP2D6= basic drugs
CYP2C9= acidic drugs
CYP1A2= planar amines+ amides

Question 12

Aliphatic hydroxylation

Answer 12

CYP adds a hydroxyl group to an aliphatic carbon centre

Question 13

Benzylic hydroxylation

Answer 13

Hydroxylation at benzylic position (aliphatic car bottom atom directly next to a benzene ring)

Question 14

Aromatic hydroxylation

Answer 14

Hydroxylates an aromatic ring, aromatic carbon atom

Question 15

Heteroatom dealkylations N

Answer 15

Removal of Alkyl group that is connected directly to a heteroatom (any atom that is not C or H) and replaced with H

Question 16

What is produced as a by product of the alkyl group is methyl in heteroatom dealkylation N

Answer 16

Formaldehyde

Question 17

O- dealkylation

Answer 17

Removal of an alkyl from O
Formation of formaldehyde

Question 18

Nitro reduction

Answer 18

Nitro group is reduced to amino group

Question 19

Hydrolysis of esters produce what and what enzyme

Answer 19

Carboxylic acid and an alcohol
Esterase

Question 20

Hydrolysis of amides produces what using what enzymes

Answer 20

Carboxylic acid and amine
peptidases

Question 21

Glucuronidation

Answer 21

Glucuronic acid molecule is transferred to a nucleophilic group in the drug/metabolite
Metabolite is now highly water soluble and is excreted

Question 22

What is Glucuronidation catalysed by

Answer 22

Enzymes called UDP- glucuronosyltransferases (UGTs)

Question 23

Sulfation

Answer 23

Sulfation group is transferred to a nucleophilic group in the drug/metabolite

Question 24

Why is Sulfation high affinity, low capacity

Answer 24

Enzymes have high affinity for the substrate which leads to rapid reactions
Limited availability of sulphate

Question 25

Why is Glucuronidation a low affinity high capacity

Answer 25

Enzyme has lower affinity for its substrates leading to slower reactions Huge supply of glucuronic acid

Question 26

N- acetylation

Answer 26

Acetyl group is transferred to a nucleophilic group in the drug/metabolite

Question 27

N- acetyltransferase

Answer 27

Catalyse the transfer of acetate from acetyl coA to a nitrogen nucleophilic in the drug/metabolite, producing coA as a byproduct product

Question 28

Acetylation polymorphism

Answer 28

High variability in the rate of drug acetylation populations

Question 29

Metabolic drug drug interaction

Answer 29

Compound that inhibit/induce the activity of a metabolic enzyme has the potential to influence the metabolism of another drug

Question 30

Drug drug interactions

Answer 30

CYP Inhibition CYP induction Phase II inhibition