Metabolism

Question 1

When does metabolism occur?

Answer 1

Prior to and during absorption

Question 2

What is first pass metabolism?

Answer 2

Drugs go via liver and liver breaks down drug

Question 3

What 4 major metabolic barriers much drug pass before reaching general circulation?

Answer 3

1. Intestinal lumen
2. Intestinal wall
3. Liver
4. Lung

Question 4

What does intestinal lumen do?

Answer 4

• Digestive enzyme secreted by mucosal cells and pancreas

- Certain enzymes break down proteins and stop them being absorbed

Question 5

What does intestinal wall do?

Answer 5

Rich in enzymes that further metabolise drugs

Question 6

What do lungs to?

Answer 6

Cells of lungs have high affinity for many drugs and are site of metabolism for many local hormones

Question 7

What does liver do?

Answer 7

Major site of drug metabolism

Question 8

What are the 2 phases of metabolism?

Answer 8

Phase 1 –> Oxidation, reduction and hydrolysis

Phase 2 –> Conjunction

Question 9

What is result of phase 1?

Answer 9

Forms more reactive products, sometimes toxic

Question 10

What is result of phase 2?

Answer 10

Usually forms inactive and readily excretable products (hydrophilic drug)

Question 11

What are the family of enzymes in the liver called?

Answer 11

Cytochrome P450 (CYP450) system

Individual one called isoenzyme

Question 12

What are enzyme inducers in regards to CYP450 system?

When are they given?

Answer 12

Enhance production of liver enzymes which breakdown drugs

Given alongside drugs

Question 13

What is result of enzyme inducers?

Answer 13

Faster rate of drug breakdown

Can lead to drug not being in system long enough

Question 14

What are enzyme inhibitors in regards to CYP450 system?

Answer 14

Inhibit production of enzymes that breakdown drugs

Question 15

What is result of enzyme inhibitors?

Answer 15

Reduced rate of drug breakdown

End up with too much drug in system

Question 16

What is result of too much warfarin?

Answer 16

Bleeding

Question 17

What happens during paracetamol overdose?

Answer 17

1. All receptors become saturated
2. Paracetamol cannot go down normal conjunction route
3. Goes back to oxidation route via phase 1
4. Production of toxic metabolite (NAPQI)

Question 18

What is given during paracetamol overdose?

Answer 18

Acetyl cysteine - push it back down conjugation route

Question 19

What is bioavailability?

Answer 19

Proportion of dose that reaches systemic circulation (only really applies to oral medication)

Question 20

What is bioequivalence?

What is benefit?

Answer 20

2 or more products are chemically/pharmaceutically equivalent

May replace one with another without causing clinical problems

Question 21

What is metabolism?

Answer 21

• Process to alter drugs to facilitate their removal from the body
• The activation of inactive drug
• Production of active drug with increased activity from active drug
• Inactivation of active drug change in nature of activity

Question 22

What is warfarin?

Answer 22

Anticoagulant, or blood thinner. It makes your blood flow through your veins more easily. This means your blood will be less likely to make a dangerous blood clot.

Question 23

If a patient on warfarin is given an inducer, what is effect on warfarin levels?

Answer 23

Decrease

Question 24

What is normal metabolism of paracetamol?

Answer 24

Paracetamol –> paracetamol glucuronide / paracetamol sulphate

Goes down conjugation route

Question 25

What is the toxic metabolite of paracetamol?

Answer 25

NAPQI

Question 26

What is the difference in metabolism in children and elderly?

Answer 26

Children –> reduced capacity due to immature liver, drug effects prolonged and excessive

Elderly –> slight reduction due to impaired liver function, drug effects more pronounced and longer lasting