Drug Metabolism

Question 1

Define drug metabolism?

Answer 1

Biochemical modification of pharmaceutical substances by living organisms usually through specialised enzyme activity.

Question 2

Why is drug metabolism essential?

Answer 2

Limits the life of a substance in the body.

Question 3

Are drugs usually metabolised before or after excretion?

Answer 3

Before

Question 4

Where are the important sites of drug metabolism?

Answer 4

Liver
Lining of gut
Kidneys
Lungs

Question 5

What are the 2 purposes of metabolism?

Answer 5

Increase water solubility

Deactivate compounds

Question 6

What are the 3 effects of metabolism?

Answer 6

Loss of pharmacological activity
Decrease of activity
Increase of activity

Question 7

What are the 3 productions of toxic metabolites?

Answer 7

Direct toxicity
Carcinogenesis
Teratogenesis

Question 8

Enzymes in drug metabolism are very specific/have a wide specificity.

Answer 8

Wide

Question 9

How are some enzymes expressed?

Answer 9

Constitutively.

Question 10

How are other enzymes expressed or induced?

Answer 10

In the presence of a particular substrate.

Question 11

How many phases are there?

Answer 11

2

Question 12

What are the phase 1 reactions?

Answer 12

Oxidation
Reduction
Hydrolysis

Question 13

What is increased in phase 1?

Answer 13

Polarity of compound, providing an active site for phase 2.

Question 14

What are the most important super family of metabolising enzymes?

Answer 14

P-450

Question 15

Is specificity usually relative or absolute?

Answer 15

Relative

Question 16

What is a major constitutive enzyme in human liver?

Answer 16

CYP3A4

Question 17

What drug is responsible for the metabolism of antidepressants?

Answer 17

CYP2D6

Question 18

Why are 5-10% of the population immune to analgesic actions of codeine?

Answer 18

Reduced or absent expression of CYP2D6

Question 19

What is CYP1A2 induced by?

Answer 19

Smoking

Question 20

What is CYP1A2 important in?

Answer 20

Metabolism of theophylline.

Question 21

What does phase 2 include?

Answer 21

Conjugation

Question 22

What does conjugation increase?

Answer 22

Water solubility, enhancing excretion of the metabolised compound.

Question 23

What factors affect metabolism?

Answer 23

Other drugs/herbals/natural substances
Genetics
Hepatic blood flow
Liver disease
Age
Sex
Ethnicity
Pregnancy

Question 24

What happens when a drug is induced?

Answer 24

Increases metabolism of drugs metabolised by that enzyme.

Question 25

Induction is a ______ process.

Answer 25

Slow

Question 26

What are the 2 most common enzyme inducers?

Answer 26

Alcohol | Smoking

Question 27

What may inhibit drug metabolising enzymes?

Answer 27

Commonly used drugs, herbal medicines and food stuffs.

Question 28

What are common drug metabolising inhibitors?

Answer 28

Cimetidine Ketoconazole Grapefruit

Question 29

What can be the consequences of genetic variation?

Answer 29

Therapeutic failure | Adverse drug reactions

Question 30

How are pharmacogenetics often expressed?

Answer 30

In multiple forms

Question 31

What are common differences in gene expression?

Answer 31

Interindividual

Question 32

What does a lack/decreased activity of an enzyme result in?

Answer 32

Increased drug toxicity

Question 33

Approx __ nucleotide polymorphisms are known?

Answer 33

70

Question 34

What are the 4 phenotype subpopulations of metabolisers?

Answer 34

Poor Intermediate Extensive Ultrarapid

Question 35

How many drugs does CYP2C9 commonly metabolise?

Answer 35

16

Question 36

What are 2 substrates of CYP2C9?

Answer 36

Warfarin | Phenytoin

Question 37

What are drug metabolising enzymes are often ______ or ______ in the fetus or premature infant.

Answer 37

Deficient | Reduced

Question 38

What builds up due to renal function being deficient in children?

Answer 38

Metabolites to toxic level

Question 39

By what age can children metabolise drugs more than adults?

Answer 39

2

Question 40

Who are more prone to drug toxicity?

Answer 40

Women

Question 41

What does pregnancy induce?

Answer 41

Certain drug metabolising enzymes.

Question 42

What factors can decrease and alter drug metabolism in the elderly?

Answer 42

Plasma protein Lean body mass Liver weight

Question 43

Why are the elderly more likely to be on multiple drug therapy?

Answer 43

Chronic disease

Question 44

Where are the difference in racial genetic expression?

Answer 44

Cytochrome P-450

Question 45

What do steroids do to your blood sugars?

Answer 45

Increases it