Drug Metabolism

Question 1

Describe phase 1 metabolism

Answer 1

Creating/modifying functional group
Creation - oxidation
Modifying - hydrolysis

Question 2

Describe phase 2 metabolism

Answer 2

Products:

Less active
More hydrophilic
Larger
Weak acids
More likely to bind albumin

Availability of co-factor determines reaction capacity

Question 3

Define Drug Metabolism:

Answer 3

Biochemical modification to pharmaceutical substance by living organisms
Usually through activity of specialised enzymes

Question 4

4 main sites of drug metabolism?

Answer 4

Liver
Lungs
Gut Lining
Kidneys

Question 5

What is a prodrug?

Answer 5

Precursor to a drug
Activated by metabolism e.g. Codeine

Question 6

What are the 3 outcomes of metabolism on a drug?

Answer 6

Production of toxic metabolites
Activation (prodrugs)
Deactivation/loss of activity

Question 7

What does the “wide substrate specificty” of metabolic enzymes mean?

Answer 7

Many drugs can be metabolised by more than one enzyme
Substrate is specific to many different enzymes

Question 8

What are the 3 types of phase 1 metabolism reaction?

Answer 8

Hydrolysis
Oxidation
Reduction
[HOR]

Question 9

Whats the function of phase 1 metabolism?

Answer 9

Increase polarity of compound
Provide active site for phase 2 to occur

Question 10

What family of enzymes carries out phase 1 metabolism?

Answer 10

P-450 family of enzymes

Question 11

What is the Prefix for the enzymes in phase 1 metabolism?

Answer 11

CYP- is prefix followed by no.-letter-no.

Question 12

3 enzymes in phase 1 metabolism?

Answer 12

CYP3A4
CYP2D6
CYP1A2

Question 13

Where is CYP3A4 found?

Answer 13

In Liver

Question 14

What does CYP2D6 metabolise?

Answer 14

Antidepressants
Antipsychotics
Converts codeine to morphine

Question 15

How does smoking affect CYP2D6?

Answer 15

CYP2D6 is induced by Smoking

Question 16

What does CYP1A2 metabolize?

Answer 16

Theophylline

Question 17

Which phase 1 enzyme isnt induced by smoking?

Answer 17

CYP3A4 isn’t induced by smoking

Question 18

What phase involves conjugation?

Answer 18

Phase 2 metabolism involved conjugation

Question 19

What is conjugation?

Answer 19

Combining drugs with other substances to terminate their activity

Question 20

How does conjugation make excretion of the drug easier?

Answer 20

Conjugated drugs have an increased water solubility

Question 21

What substances are used to conjugate the metabolites formed in phase 1?

Answer 21

Glucuronic Acid
Glutathione
Sulphate
Acetate

Question 22

Does conjugation deactivate all drug metabolites?

Answer 22

Most, but not all are inactivated

Question 23

In what two ways do other drugs/herbal meds affect drug metabolism?

Answer 23

Other drugs/herbals can cause enzyme induction & inhibition, affecting metabolic rates

Question 24

What is enzyme induction?

Answer 24

Substance causes increased synthesis of enzyme leading to greater metabolic rate

Question 25

What are some commmon inducers?

Answer 25

Other drugs, herbals, smoking & alcohol.

Question 26

How long does induction take to become apparent?

Answer 26

Weeks -> months

Question 27

Is enzyme inhibition reversible?

Answer 27

Some enzyme inhibition is reversible but not all

Question 28

What are some common substances that inhibit drug metabolising enzymes?

Answer 28

Erythromycin & Clarithromycin (Grapefruit)

Question 29

What is pharmacogenetics?

Answer 29

Wide genetic variability in pharmacokinetics Role of genome in drug response

Question 30

What are the consequences of 'bad' pharmacogenetics?

Answer 30

Therapeutic failure Adverse reactions

Question 31

How can genetic variation lead to drug toxicity?

Answer 31

Genetic variation can cause: Absence/deficiency in enzymes Overly high drug level Drug toxicity

Question 32

How can genetic variation lead to tehrapeutic failure without adverse effectS?

Answer 32

Over production of an enzyme Overly high metabolic activity Low drug conc. in blood Failure of therapy

Question 33

What two aspects of the liver can effect drug metabolism?

Answer 33

Liver Disease Hepatic Blood Flow

Question 34

What are the 2 main differnces in the drug metabolism of infants to adults?

Answer 34

Infants have: - reduced or absent drug metabolizing enzymes - Reduced renal function

Question 35

How is a pubescant childs metabolism differnt to an adults?

Answer 35

By puberty a childs metabolism is faster than an adults

Question 36

Which parameters affecting drug metabolism are affected in the elderly?

Answer 36

Lower liver weight, renal function, plasma protein & lean body mass

Question 37

How does chronic disease in the elderly affect drug metabolism?

Answer 37

Chronically ill elderly people are on multiple meds which can interact or overpower the body.

Question 38

How does gender affect drug metabolism?

Answer 38

It effects all 4 areas of pharmacokinetics: - Absorption - Distribution - Metabolism - Excretion

Question 39

How does pregnancy effect drug metabolism?

Answer 39

Hormonal changes in 2nd/3rd trimester induce some drug metabolising enzymes

Question 40

How does ethnicity effect drug metabolism?

Answer 40

Variation in expression of P-450 genes leads to different levels of drug metabolising enzymes between races

Question 41

What is knowing ADME important for?

Answer 41

- Choosing method of administration - Choosing safe & effect Doses/Frequency - Making changes based on drugs, illness or physiological factors