LIVER - DETOXIFICATION Flashcards Preview

PHASE 1 REVISION GUIDE > LIVER - DETOXIFICATION > Flashcards

Flashcards in LIVER - DETOXIFICATION Deck (42)
Loading flashcards...
1

what is the function of detoxification of drugs?

to make it more polar and therefore more soluble
this means it can be excreted in urine

2

what is the method of detoxification in the liver?

via phase I and phase II reactions

3

what are phase I reactions?

- the addition/exposure of a functional group
- it is non-synthetic

4

what is the effect of phase I reactions on hydrophilicity?

it produces only a small increase of hydrophilicity

5

what types of reactions are involved in phase 1 detoxification?

oxidation
reduction
hydrolysis

6

give examples of oxidation reactions involved in phase 1 reactions?

hydroxylation (addition of -OH group)
N- and O- dealkylation (removal of -CH side chains)
deamination (removal of NH side chain)
epoxidation

7

give examples of reduction reactions involved in phase 1 reactions?

hydrogenation (unsaturated -> saturated)

8

give examples of hydrolysis reactions involved in phase 1 reactions?

splitting amide and ester bonds

9

what are phase II reactions?

conjugation to produce hydrophilic metabolites
is biosynthetic

10

what is the effect of phase II reactions on hydrophilicity?

produce a large increase in hydrophilicity

11

give examples of phase II reactions

glucuronidation
sulphation

12

what are xenobiotics?

foreign substances that have no nutritional value so need to be excreted

13

how are xenobiotics ingested?

through eating
air pollution
drugs

14

what are the dangers of xenobiotics?

they damage proteins, lipids and can bind to DNA (are carcinogens)
they react with O2 and release free radicals

15

where are microsomal enzymes found?

in smooth ER of liver, kidneys and intestinal mucosa

16

give examples of microsomal enzymes?

cytochromes (CYPs)
FMOs

17

what reactions are microsomal enzymes involved in?

the majority of drug biotransformation reactions

18

are microsomal enzymes inducible?

yes - by drugs and diet

19

where are non-microsomal enzymes found?

in cytoplasm and mitochondria of hepatocytes

20

give examples of non-microsomal enzymes

protein oxidases, esterases etc

21

what reactions are non-microsomal enzymes involved in?

non-specific enzymes for conjugation

22

are non-microsomal enzymes inducible?

no

23

what are cytochrome P450?

there are at least 10 main groups
they are encoded by a superfamily of 60 different genes

24

where are CYP450 found?

in smooth ER

25

what reactions are CYP450 involved in?

phase I biotransformation reactions
oxidise substrates and reduce oxygen
they are inducible

26

what are the properties of CYP450?

have cytochrome reductase subunit - uses NADPH
they generate a free radical
they have affinity for CO and O2

27

which is the most common cytochrome?

CYP3A4 - it is responsible for 2/3 of all drug reactions

28

how is cytochrome P450 induced?

- molecule binds to intracellular receptor within cytoplasm
- the molecule receptor complex migrates to nucleus
- this increases transcription of mRNA for cytochrome P450
- this increases the effect of the cytochrome

29

what is the mechanism of action of cytochrome P450?

- CYPs contain haem component which is capable of oxidising molecules (-OH addition) by becoming reduced themselves
- the reductases use NADPH to become active
- the reductases reduce CYPs allowing oxidation of the foreign molecule
- the reaction forms water and has an intermediate of a haem free radical

30

where does drug metabolism occur?

in smooth ER in the liver
(can also occur in lung and small intestine)