Drug metabolism

Question 1

Define drug metabolism

Answer 1

A biochemical modification to pharmaceutical substances by living organisms, usually through activity of specialised enzymes.

Question 2

4 main sites of drug metabolism?

Answer 2

Liver
Lungs
Gut linings
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

• activation (prodrugs)
• deactivation/ loss of activity
• production of toxic metabolites

Question 5

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

Answer 5

Many drugs can be metabolism by more than one enzyme

Question 6

What are the 3 types of phase 1 metabolism? (HOR)

Answer 6

Hydrolysis
or Oxidation
or Reduction

Question 7

Whats the functions of phase 1 metabolism?

Answer 7

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

Question 8

What family of enzymes carry out phase 1 metabolism?

Answer 8

P-450 family of enzymes

Question 9

What is the prefix for the enzymes in phace 1 metabolism?

Answer 9

CYP is the prefix followed by no-letter-no

Question 10

What are the 3 enzymes in phase 1 metabolism?

Answer 10

CYP3A4

CYP2D6

CYP1A2

Question 11

Where is CYP3A4 found?

Answer 11

Liver

Question 12

What does CYP2D6 metabolise?

Answer 12

• antidepressants and antipyschotics

- convert codeine to morphine

Question 13

How does smoking affect CYP2D6?

Answer 13

CYP2D6 is induced by smoking

Question 14

What does CYP1A2 metabolise?

Answer 14

Theophylline

Question 15

Which phase 1 enzyme isn’t induced by smoking?

Answer 15

CYP3A4 isn’t induced by smoking

Question 16

What phase involves conjugation?

Answer 16

Phase 2 metabolism involves conjugation

Question 17

What is conjugation?

Answer 17

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

• Glucoronic acid
• Glutathione
• Sulphate
• Acetate

Question 20

Does conjugation deactivate all drug 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

-Enzyme induction
-Enzyme inhibition
, therefore 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 common inducers?

Answer 23

Other drugs, herbals, smoking and alcohol

Question 24

How long does it take for enzyme induction to become apparent?

Answer 24

Weeks -> months

Question 25

Is enzyme inhibition reversible?

Answer 25

Some enzyme inhibition is reversible but not all and some are irreversible

Question 26

What are some common substances that inhibit drug metabolising enzymes?

Answer 26

- Erythromycin - Clarythromycin - Grapefruit

Question 27

What is pharmacogenetics?

Answer 27

The wide genetic variability in pharmacokinetics and pharmacodynamic response 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 - > absence/deficiency in an enzyme. - >overly high drug level

Question 30

How can genetic variation lead to therapeutic failure without adverse reactions?

Answer 30

- over production of an enzyme - overly high metabolic activity - low drug conc. in blood - failure of therapy

Question 31

What two aspect of the liver can effect drug metabolism?

Answer 31

- liver disease | - hepatic blood flow

Question 32

What are the two main differences in the drug metabolism of infants to adults?

Answer 32

infants have - reduced or absent drug metabolising enzymes - reduced renal function

Question 33

How is a pubescent Childs metabolism different 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 - lower liver weight - lower renal function - lower plasma protein - lower lean body mass

Question 35

How does chronic disease in the elderly affect drug metabolism?

Answer 35

-Chronically ill elderly people are on multiple medication which can interact or simply overpower the body

Question 36

How does gender affect drug metabolism?

Answer 36

Affects all 4 areas of pharmacokinetics: - absorption - dsitrubtion - metabolism - excretion

Question 37

How does pregnancy affect drug metabolism?

Answer 37

Hormonal Changes in 2nd/3rd trimester induces some Drug metabolsing enzymes

Question 38

How does ethnicity affect drug metabolism

Answer 38

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

Question 39

What is knowing ADME important for?

Answer 39

- choosing method of administration - choosing safe and effective dosages/frequencies - making changes based of drugs, illnesses or physiological factrs