Liver and drug Metabolism

Question 1

What is Metabolism?

Answer 1

Metabolism is the enzymatic conversion of one chemical compound into another.

Question 2

Where does most drug Metabolism take place?

Answer 2

The Liver

though some process do take place in Gutwall, lungs and blood plasma

Question 3

What group of enzymes housed in the liver hepacytes are involved in the metabolism of drugs?

Answer 3

cytochrome P450 group

Question 4

Where are these enzymes found?

Answer 4

smooth endoplasmic reticulum of the cell.

Question 5

How many phases of Drug Metabolism are there?

Answer 5

Two

Phase 1 Metabolism
Phase 2 Metabolism

Question 6

What is Phase 1 Metabolism?

Answer 6

Phase 1 Metabolism
can involve reduction or hydrolysis of the drug but more likely oxidation.

(Oxidation is the chemical reaction that occurs when apples turn brown when exposed to the oxygen in air).

this is triggered by P450 enzymes and results in the loss of electrons from the drug.

Question 7

What is Phase 2 Metabolism?

Answer 7

Phase 2 metabolism involves conjugation -, the attachment of an ionised group to the drug.

This makes the metabolite more more water soluble.

This facilitates excretion as well as decreasing the pharmacological activity.

Let’s look at aspirin as example of a drug being metabolised.

E.g:

Aspirin undergoes phase 1 hydrolysis to salicylic acid. In phase 2 it is congugated with either glycine or glucoronic acid forming a range of ionised metabolytes that can then be excreted in the urine.

Question 8

What factors can affect Metabolism

Answer 8

Age
Genetiis
Environment
Drugs/alcohol
Disease
Nutrition

Question 9

What can inhibit Cytochrome P450 Activity?

Answer 9

Grapefruit juice
St John’s Wort

Question 10

What can increase Cytochrome P450 activity?

Answer 10

cigarette smoke
brussel sprouts

Question 11

Where does most Drug Metabolism occur?

Answer 11

A: the kidney
B: the liver
C: the blood plasma

Question 12

What is the most common biochemical process in phase 1 metabolism?

Answer 12

A: oxidation
B: reduction
C: hydrolysis

Question 13

What does Conjugation do?

Answer 13

A: increases pharmacological activity
B: decreases pharmacological activity
C: causes the retention of metabolites

Question 15

A patient requires a high dose of a new antihypertensive medication because the new
medication has a significant first-pass effect. What does this mean?

Answer 15

The medication is extensively metabolized in the patient’s liver.