3.1:9 Metabolism of drugs

Question 1

How are drugs eliminated from the body?

Answer 1

Excretion and metabolism (major route)

Question 2

What are the most common metabolic reactions ?

Answer 2

Oxidation, reduction, hydrolysis and conjugation

Question 3

What is sequential metabolism?

Answer 3

Further (secondary) metabolism ie conjugation reaction. These reactions occur in series

Question 4

What is competitive metabolism?

Answer 4

When a drug simultaneously undergoes metabolism by several competing (primary) pathways.

The fraction depends on the relative rates of each pathway.

Question 5

What are phase I reactions?

Answer 5

Reactions that often occur first (oxidation,reduction and hydrolysis)

Phase I reactions are commonly considered to be preparation of the drug molecule for phase II

Question 6

What are phase II Reactions?

Answer 6

Reactions that often occure second (conjugations)

Question 7

What are chytochrome P450-dependant mixed-functional oxidation (MFO) reactions ?

Answer 7

They cataluse the oxidation of many drugs and chemicals

Metabolised molecule usually has a reasonably high degree of lipophilicity

Question 8

What is the percentage of similarity in a the cytochrome family

Answer 8

40%

Question 9

What is the percentahe opf silimarity in the cytochrome sunb-family ?

Answer 9

70%

Question 10

Where is CYP3A found ?

Answer 10

Highly active in the small intestine (especially duodenum) and much less in the large intestine

Question 11

State the oxidations involving CYP450

Answer 11

• Aromatic hydroxylation
• Aliphatic hydroxylation
• Epoxidation
• Dealkylation- N,-O, -S
• Oxidative deamination
• Dehalogenation
• N-oxidation
• S-oxidation
• Phosphothianate oxidation

Question 12

What enzyme is used to convert ethanol to acetaldehyde?

Answer 12

Alcohol dehydrogenase 1B

Question 13

True/False . Acetaldehyde is a highlt unstable compound and forms free readical structures which are highlt toxic

Answer 13

True

Question 14

What enzyme is used to convert acetyldehyde to acetic acid ?

Answer 14

Alcohol dehydrogenase 2

Question 15

What do 1/3 of east asians lack and what is the result of this?

Alcohol flushing response

Answer 15

Alcohol dehydrogenase 2 resulting in prolonged period of time of acetaldehyde in their system.

This causes extreme toxisity to the body and can damage the body

Question 16

Name a reductive metabolism

Answer 16

Azo-compounds
Nitro-compounds
Hydrolysis
Amide hydrolysis

Question 17

In phase I metabolism what functional grtoups do the final products usually have ?

Answer 17

-OH, -NH2, -SH, -COOH (these are ready to react for phase II)

Question 18

Why is it difficult to predict the exact pathway of a drug?

Answer 18

Drugs can undergo a number of phase I reactions therefore it is really difficult to predict the exact pathway from their chemical structure

Question 19

What do phase II metabolism generally lead to ?

Answer 19

Water soluble products which can be excreted in bile and urine

Question 20

What is the major route of sugar conjugation?

Answer 20

Glucuronidation (conjugation with a- D-glucuronic acid)

Question 21

What is the difference between:

a. UDP-Glucuronosyltransferase (UGT)
b. UPD-glucuronic acid

Answer 21

a. Enzyme

b. Co-factor

Question 22

Name the phase II pathways

Answer 22

O- Glucuronidation
N-Glucuronides 
Sulfation
Acetylation
Aminoiacid conjugation

Question 23

What ios the difference between sulfation and Glucuronidation?

Answer 23

Most drugs that can be glucuronidated, can also be sulfated which leads to a possibility of competition for the sunstrate between these two pathways

Sulfate conjugation predominateds at low subsrate conc where as glucuronide conjugation predominates at high concentration

Question 24

True/false? The liver is the mainorgan responmsible for phase I and pahse II metabolism ?

Answer 24

True but other organs are involved in drug metabolism

Question 25

What does drug localisation and metabolism depend on?

Answer 25

Physiochemical properties of the drug (pKa, lipid solubility, MW)

Chemical composition of a metabolising organ

Presence of specific uptake mechanism (transporters)