Biotransformation of Drugs

Question 1

Mechanisms of Elimination

Answer 1

Biotransformation: Chemical

Excretion: Physical

Question 2

General Process of Biotransformation

Answer 2

Drug converted to one or more metabolite

Sites:
Liver
Colon by bacteria
Other ex intestinal mucosa

Example
Chloramphenicol

Question 3

Phase I
General
Steps

Answer 3

Catabolic process
Products often more chemically reactive
Increases water solubility-> slightly faster excretion
Functional group is added; if drug already has
appropriate functional group: can skip Phase 1

Oxidation
Dehydrogenation
Reduction
Hydrolysis

Question 4

Phase I

Oxidation

Answer 4

Either microsomal (in sER) or non microsomal (other parts)

Microsomal
CYP450
Microsomal Flavin cont. Monooxygenase (FMO)
not as vertasile

Non Microsomal
Monoamine Oxidases (MAO): Mitochondrial
oxidative deamination of amines

Alcohol and aldehyde dehydrogenases: cytosolic
methanol-> formaldehyde-> formic acid

Mo containing oxidases: Ex: Xanthine oxidase: cytosolic
ex hypoxanthine-> xanthine-> uric acid

Question 5

Phase I

Oxidation: CYP

Answer 5

A heme containing protein
Constitutes a superfamily of enzymes
Req partner enzyme: NADPH-CYP
Main: CYP1-3

Catalyse
Oxidation: insertion of O atom into C-H or C=C bonds

Dehydrogenation

Reduction

Question 6

Phase I

Oxidation: Variations

Answer 6

1) Insertion of Oxygen to produce stable metabolite
Hydroxylation
Insertion of O into C-H or N-H bond
C- Hydroxylation and N- Hydroxylation respectively

Epoxidation
Insertion of O into C=C bond
–> formation of epoxide

2) Insertion of O to produce an unstable metabolite
Spontaneously breaks into 2 molecules

Oxidative Dealkylation
Metabolite dealkylated and aldehyde formed

Oxidative Deamination
Larger part of molecule oxidised while NH3+ is
produced

Oxidative Dehalogenation

CONTINUE