6. Liver: Detoxification and Excretion

Question 1

What is meant by drug metabolism?

Answer 1

Process where drugs undergo transformations catalysed by enzymes

Question 2

Why are lipophilic drugs converted to hydrophilic ones?

Answer 2

Increases solubility

Increases renal excretion and decreases tubular reabsorption

Question 3

Why might a drug be metabolised?

Answer 3

Allow for excretion
Termination of drug action
Metabolite may have its own pharma activity
Pro-drug

Question 4

Where in the body can drugs be metabolised?

Answer 4

Liver,
GIT
Lungs
Skin 
Kidneys

Question 5

What is the first pass effect?

Answer 5

When a drug is taken orally, the liver can break it down before it exerts its effects

Question 6

What reactions commonly take place at phase 1?

Answer 6

Oxidation
Reduction
Dealkylation
Hydrolysis

Question 7

Where does phase 1 take place?

Answer 7

ER of hepatocytes

Question 8

What is needed for an oxidation reaction?

Answer 8

cytochrome P450
NADPH
O2

Question 9

Name a drug that is hydroxylated

Answer 9

Lidocaine

Question 10

Name a drug that is dehydrogenated

Answer 10

Ethanol

Question 11

Described the dehydrogenation of ethanol to acetate

Answer 11

Ethanol is oxidated to ethanal by Alcohol DeHydrogenase

Ethanal is converted to acetate by ALdehyde DeHydrogenase

Question 12

How does disulphiram exert its effects?

Answer 12

Binds to ALDH to prevent conversion of ethanal to acetate

Results in hangover-like side effects, intended to encourage abstinence from alcohol

Question 13

Name a drug which is dealkylated

Answer 13

Alkyl group on codeine is oxidised to an aldehyde, making morphine

Question 14

Name a drug that is reduced

Answer 14

Chloramphenicol

Catalysed by nitro-reductases

Question 15

Name a drug that is hydrolysed

Answer 15

Procaine

Question 16

What are phase 1 compounds often conjugated with?

Answer 16

Glucaronic acid
Sulfate
Acetic acid
Amino acids

Question 17

Which functional groups are conjugated with glucaronic acid?

Answer 17

OH
COOH
NH2

Question 18

What enzyme conjugates drugs with glucaronic acid?

Answer 18

Glucaronyl transferase

Question 19

Which functional groups are conjugated with sulfate?

Answer 19

NH2

OH

Question 20

Where is sulfate taken from?

Answer 20

PAPs

Question 21

What enzyme conjugates drugs with sulfate?

Answer 21

Sulfotransferase

Question 22

Which functional group is conjugated with glycine?

Answer 22

COOH

Question 23

What enzyme conjugates drugs with glycine?

Answer 23

Glycine transferase

Question 24

How is aspirin metabolised?

Answer 24

1. Hydrolysed to ethanoic acid and salicylate
   (These are excreted at very high doses)
2. Low doses are conjugated with glycine/ high doses are conjugated with glucuronic acid

Question 25

What 3 ways is paracetemol metabolised?

Answer 25

45-50%: Sulfation 45-50%: Glucuronidation 4-5%: Oxidised to NAPQI (toxic to the liver)

Question 26

How is NAPQI cleared at low doses?

Answer 26

Conjugates with glutathionine

Question 27

What is the toxicity antidote for NAPQI?

Answer 27

N-acetylcysteine | Stimulates the production of glutathionine

Question 28

What is a pro-drug?

Answer 28

Inactive precursor to an active drug

Question 29

What is sulfasalazine used to treat?

Answer 29

Ulcerative colitis

Question 30

What is sulfasalazine composed of?

Answer 30

5-ASA (active drug) | Sulphapyridine

Question 31

Why is 5ASA not given directly?

Answer 31

Absorbed before it reaches the colon | Sulfasalazine is broken down by azoreductase enzymes in the colon

Question 32

What is haloperidol decenoate used for?

Answer 32

Slow conversion to haloperidol over 1 month | Anti-psychotic