Metabolism

Question 1

What is metabolism?

Answer 1

The enzymatic conversion of one chemical compound to another

Question 2

Where does most drug metabolism occur?

Answer 2

Liver

Question 3

Where in the body does metabolism occur?

Answer 3

Gut wall, lungs and blood plasma

Question 4

What is drug metabolism?

Answer 4

Conversion of drug into a more water soluble compound by increasing its polarity

Question 5

How does age affect metabolism?

Answer 5

Increased age results in a decline in hepatocyte number and enzyme activity

Question 6

How does disease affect metabolism?

Answer 6

Disease state:
Reduces hepatic blood flow
Increases heart failure or shock which reduces metabolic potential of the liver

Question 7

How does genetics affect metabolism?

Answer 7

Genetic can result in over-expression or deficiency of a particular enzyme

Question 8

How do diet and lifestyle affect metabolism?

Answer 8

Grapefruit juice and St John’s Wort inhibit CYP450 activity
Cigarette smoke and Brussel Sprouts increase CYP450 activity

Question 9

Explanation for the Rate vs Substrate Conc graph flattening out

Answer 9

The enzyme becomes saturated with substrate

Question 10

Why is there almost no curvature in rate vs drug conc graph?

Answer 10

Therapeutically relevant doses only appear at the very start of the graph

Question 11

What happens to drug conc with a drug that follows non-linear or zero order kinetics?

Answer 11

A small increase in dose may cause a disproportionately large increase in plasma concentration

Question 12

What group do the main drug metabolising enzymes belong to?

Answer 12

CYP450s

Question 13

Where are CYP450s found?

Answer 13

Smooth endoplasmic reticulum of cells

Question 14

What is involved in Phase I of Metabolism?

Answer 14

Reduction, hydrolysis or oxidation

Question 15

What is oxidation catalysed by in Phase I of metabolism?

Answer 15

CYP450s

Question 16

Nomenclature of CYPs

Answer 16

Nomenclature is genetically based and has no functional implication
CYP2 - Family
CYP2D - Sub-family
CYP2D6 - Specific gene

Question 17

What is involved in Phase II metabolism?

Answer 17

Conjugation with the attachment of an ionised group to the drug

Question 18

Where does Phase II metabolism occur?

Answer 18

In hepatocyte cytoplasm

Question 19

What does the attachment of an ionised group mean?

Answer 19

Makes the metabolite more water soluble and facilitates excretion and decreases pharmacological activity

Question 20

What is the first pass effect?

Answer 20

Any drug taken orally will go into the stomach and pass through the liver via portal circulation before getting into systemic circulation

Question 21

What does a high degree of first-pass metabolism mean?

Answer 21

A large proportion of dose is metabolised before it gets to systemic circulation

Question 22

How can first pass be avoided?

Answer 22

Buccal medications
Rectal
Parenterals

Question 23

What happens to CYP450 activity down the GI tract?

Answer 23

Decreases down the GI Tract
Duodenum - 50%
Jejunum - 30%
Ileum - 10%
Colon - 2%

Question 24

What happens to pro-drugs?

Answer 24

Metabolised to the active form by enzymes in Phase I metabolism

Question 25

What occurs in paracetamol overdose?

Answer 25

Not enough glutathione to conjugate Accumulation causes toxicity and can result in hepatitis Compounds that increase levels of gluthione are administered to allow conjugation

Question 26

What happens in drug metabolism induction?

Answer 26

Drug A increases the rate of metabolism of Drug B Blood concentration of drug B falls below normal therapeutic levels and drug B is ineffective

Question 27

What happens in drug metabolism inhibition?

Answer 27

Drug A reduces the rate of metabolism of Drug B Blood concentration of Drug B increases above safe levels and becomes toxic

Question 28

What happens in CYP450 enzyme inhibition?

Answer 28

Quantity of CYP450 is not reduced but existing CYP405s are made less effective

Question 29

What is special about Quinidine?

Answer 29

It inhibits a specific CYP even though it is not metabolised by it

Question 30

Is alcohol an inducer or an inhibitor?

Answer 30

Both Inhibitory effect is instant Inducing effect occurs with long-term alcohol use due to time needed to synthesise new enzymes

Question 31

What herbal remedies are inhibitors?

Answer 31

Garlic Peppermint Oil Milk Thistle

Question 32

What herbal remedies are inducers?

Answer 32

St John's Wort Reduces effectiveness of certain drugs as they are cleared from the body more quickly

Question 33

Grapefruit Juice

Answer 33

Antioxidants inhibit CYP3A4 in the gut wall and liver Increases blood levels of Ca2+ channel blockers

Question 34

Cranberry Juice

Answer 34

Antioxidants inhibit CYP450s Warfarin levels can increase significantly