Metabolic reactions

There are four main patterns of drug metabolism.

These are:

1) oxidation

2) reduction

3) hydrolysis

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4) conjugation

The first three are often lumped together as phase I reactions, while the fourth process, conjugation, is called phase II metabolism. A common scheme in the overall metabolism of drugs is that metabolites are metabolized. In particular a drug maybe oxidized, reduced or hydrolyzed and then another group may be added in a conjugation step.A common cause of capacity limited metabolism is a limit in the amount of the conjugate added in the conjugation step.

Phase I

Oxidation

Common reactions include :-

Alkyl group ----> alcohol

for example phenobarbitone

Aromatic ring ----> phenol

for example phenytoin

Oxidation at S or N

sulfoxide

for example chlorpromazine

in two steps oxidative dealkylation is possible

for example phenacetin

Outside the microsomes - in liver and brain

Monoamineoxidaze

for example 5-hydroxytryptamine

Alcohol dehydrogenase - in liver, kidney, lung

Reduction

Add a hydrogen or remove oxygen

azo (-N=N-) or nitro groups (-NO₂) -----> amines (-NH₂)

for example nitrazepam

Hydrolysis

Addition of water with breakdown of molecule. In blood plasma (esterases) and liver

Esters ---> alcohol and acid

for example aspirin to salicylic acid

Amides to amine and acid

for example procainamide

Copyright 2001 David W.A. Bourne