Drug Metabolism

Question 1

How does metabolism increase the rate of excretion?

Answer 1

By increasing water solubility (polarity)

Question 2

Where does metabolism occur?

Answer 2

Liver > hepatocytes > SER

Question 3

What is phase 0 of metabolism?

Answer 3

Transport of drug from blood to liver

Question 4

What is Phase I of metabolism?

Answer 4

Functionalization reactions

Question 5

What is Phase II of metabolism?

Answer 5

Conjugation or synthetic reactions

Question 6

What are functionalization reactions?

Answer 6

Oxidation
Reduction
Hydrolysis

Question 7

What do phase II reaction do when they follow phase I?

Answer 7

Up polarity, down pharmacological activity and toxicity

Question 8

What is the most common conjugation reaction?

Answer 8

Glucuronide

Question 9

What is the second most important conjugation reaction?

Answer 9

Sulfate (SULTs)

Question 10

What are the 5 phase II conjugation reactions?

Answer 10

Glucuronide
Sulfate
N-acetylation
Methylation
Glutathione/amino acid

Question 11

What do amino acid conjugation reaction happen with?

Answer 11

Only -COOH reactive center

Question 12

What is enzyme induction?

Answer 12

An increase in enzyme levels (CYP450) caused by a drug or environmental compounds

Question 13

What are the consequences of enzyme induction and how do we treat it?

Answer 13

Drug metabolism goes up which causes drug effect to go down.

To treat this you must up the dose

Question 14

What is an example of Herb interactions involving enzyme induction?

Answer 14

St. John’s Wort

Question 15

What does St. John’s Wort do?

Answer 15

It’s a powerful inducer of CYP 3A4 and P-GP

Question 16

What are the consequences of enzyme inhibition and how do we treat it?

Answer 16

Down drug metabolism which increases drug effect

Treat this by decreasing dose

Question 17

What are some other factors that can affect drug metabolism?

Answer 17

Age
Diet
Genetic Differences