Austin Drug Metabolism

What are the metabolism genralizations?

What are the metabolism genralizations?

1. Decreases lipophilicity

2. Decreases or removes biological activity

3. Oxidation state is usually increased or unchanged

Following chemical modification (metabolism), a drug may…

Lose all biological activity, reduce biological activity, increase biological activity, and bring about new biological activity.

What forms are metabolites found in?

1. Active

2. Inactive

3. Toxic

Where is the site of metabolism?

Liver

WHat types of metabolism is involved in phase 1?

Oxidation

Reduction

Hydrolysis

What type of metabolism is in phase 2?

Conjugatation

T/F: A drug must go through phase 1 to get to phase 2.

False: Can go through, either, both, or none. But they usually go through phase 1 then phase 2

What type of reaction is this?

Oxidation

In regards to drugs, oxidation usually implies…

the removal of hydrogen or carbon with an oxygen.

In oxidation, are the active metabolites toxic or nontoxic and why?

Active metabolites are toxic because the added oxygen increases its reactivity.

What is required for an oxidation reaction?

Drug, Enzyme, Oxidizing agent

What enzyme family is responsible for oxidation reactions?

CYP450

What are the types of oxidation?

alipathic/aromatic hydroxylation (adding O to chain or ring)

N or S oxidation

N, O, S dealkylation

N-Deamination

Identify what type of reactions these are

1) Aliphatic Hydroxylation

2) Aromatic Hydroxylaion

What type of reaction is this?

N-Dealkylation

What type of reaction is this?

Deamination

Hydrolysis is done on what groups?

Ester and Amide

What is conjugation?

A conjugate binds to the H group of the drug

What enzyme is required for Conjugation?

Transferase

What are examples of conjugates?

Glucuronate

Glutathione

What is the most common phase 2 pathway?

Glucuronidation

How is glutathione protective against carcinogens?

Antioxidant reducing agent

What type of reaction is this?

Glucouronidation

Compare Phase 1 and Phase 2

Speed:

Capacity:

Phase 1 slower and Phase 2 faster

Phase 1 unlimited and Phase 2 limited