Drug Metabolism

Question 1

Define Drug Metabolism:

Answer 1

A biochemical modification to pharmaceutical substance by livin organisms, ususally through activity of specialzed enzymes.

Question 2

4 main sites of drug metabolism?

Answer 2

Liver
Lungs
Gut Lining
Kidneys

Question 3

What is a prodrug?

Answer 3

A precursor to a drug which is converted to its active form by metabolism. e.g. Codeine

Question 4

What are the 3 outcomes of metabolism on a drug?

Answer 4

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

Question 5

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

Answer 5

It means many drugs can be metabolized by more than one enzyme

Question 6

What are the 3 types of phase 1 metabolism reaction? [HOR}

Answer 6

Hydrolysis
or Oxidation
or Reduction

Question 7

Whats the function of phase 1 metabolism?

Answer 7

To increase polarity of the compound and provide an active site for phase 2 to occur

Question 8

What family of enzymes carries out phase 1 metabolism?

Answer 8

P-450 family of enzymes

Question 9

Prefix for the enzymes in phase 1 metabolism?

Answer 9

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

Question 10

3 enzymes in phase 1 metabolism?

Answer 10

CYP3A4
CYP2D6
CYP1A2

Question 11

Where is CYP3A4 found?

Answer 11

In the Liver

Question 12

What does CYP2D6 metabolize?

Answer 12

CYP2D6 metabolizes antidepressants, antipsychotics & ocnverts codeine to morphine

Question 13

How does smoking affect CYP2D6?

Answer 13

CYP2D6 is induced by Smoking.

Question 14

What does CYP1A2 metabolize?

Answer 14

Theophylline

Question 15

Which phase 1 enzyme isnt induced by smoking?

Answer 15

CYP3A4 isnt induced by smoking

Question 16

What phase involves conjugation?

Answer 16

Phase 2 metabolism involved conjugation

Question 17

What is conjugation?

Answer 17

Conjugation is combining drugs with other substances to terminate their activity

Question 18

How does conjugation make excretion of the drug easier?

Answer 18

Conjugated drugs have an increased water solubility

Question 19

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

Answer 19

Glucuronic Acid
Glutathione
Sulphate
Acetate

Question 20

Does conjugation deactivate all dru metabolites?

Answer 20

Most but not all are inactivated

Question 21

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

Answer 21

Other drugs & herbals can cause enzyme induction & inhibition. Therfore affecting metabolic rates

Question 22

What is enzyme induction?

Answer 22

One substance causes an increased synthesis of the enzyme leading to a greater metabolic rate.

Question 23

What are some commmon inducers?

Answer 23

Other drugs, herbals, smoking & alcohol.

Question 24

How long does induction take to become apparent?

Answer 24

Weeks -> months

Question 25

Is enzyme inhibition reversible?

Answer 25

Some enzyme inhibition is reversible but not all

Question 26

What are some common substances htat imhibit durg metabolizing enzymes?

Answer 26

Erythromycin & Clarythromycin Grapefruit

Question 27

What is pharmacogenetics?

Answer 27

The wide genetic variability in pharmcokinetic & pharmacodynamic reponse to drugs between individuals

Question 28

What are the consequences of 'bad' pharmacogenetics?

Answer 28

Therapeutic failure Adverse reactions

Question 29

How can genetic variation lead to drug toxicity?

Answer 29

Genetic variation -> abscence/deficiency in an enzyme -> Overly high drug level -> Drug toxicity

Question 30

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

Answer 30

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

Question 31

What two aspects of the liver can effect drug metabolism?

Answer 31

Liver Disease Hepatic Blood Flow

Question 32

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

Answer 32

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

Question 33

How is a pubescant childs metabolism differnt to an adults?

Answer 33

By puberty a childs metabolism is faster than an adults

Question 34

Which parameters affecting drug metabolism are affected in the elderly?

Answer 34

The elderly have a lower liver weight, renal function, plasma protein & lean body mass

Question 35

How does chronic disease in the elderly affect drug metabolism?

Answer 35

Chronically ill elderly people ar eon multiple meds which can interact or simply overpower the body.

Question 36

How does gender affect drug metabolism?

Answer 36

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

Question 37

How does pregnancy effect drug metablism?

Answer 37

Hormonla changes in 2nd/3rd trimester induce some durg metabolizing enzymes

Question 38

How does ethnicity effect drug metabolism?

Answer 38

Variation in expression of P-450 genes leading to different levels of drug metabolizing enzymes between races

Question 39

What is knwing ADME importnat for?

Answer 39

- Choosing methd of administrstion - Choosing safe & effect Dosaes/Frequency - Making changes based on drugs, illness or physioloical factors