Metabolism Flashcards Preview

BMSC1212 Introduction to pharmacology > Metabolism > Flashcards

Flashcards in Metabolism Deck (44):
1

What is elimination the sum of?

Metabolism and excretion

2

Give two examples of drugs which are removed from the body unchanged

1. Benzylpenicillin
2. Gentamicin

3

What is biotransformation?

The chemical modification of drugs and other foreign compounds (xenobiotics)

4

What is the main site of action for metabolism?

The liver

5

Give 3 examples of less important sites of action for metabolism

1. Kidney
2. Epithelial cells of the GIT
3. The skin

6

What is the purpose of biotransformations?

Convert the drug into a more excretable form which the body can recognise.

7

What are the metabolites in comparison to the drugs

Less pharmacologically active and less toxic

8

What is the drug Tamoxifen (TAM) used for?

Chemotherapy drug used to treat breast cancer

9

What is a pro drug?

Must be modified before it is in its most active form.

10

How is TAM modified?

A methyl groups is removed and a hydroxyl group is added to form Endoxifen

11

What does the addition of a -OH group to TAM allow?

It to form an interaction with the Estrogen receptor.

12

What are cytochrome P450s?

A group of enzymes responsible for metabolic reactions.

13

Which cyt P450 adds the hydroxyl group to TAM?

CYP2D6

14

Which cyt P450 removes the methyl group from TAM?

CYP3A4/5

15

What is the primary metabolic pathway for paracetamol?

Glucuronidation

16

What is the toxic (to hepatocytes) intermediate formed from paracetamol?

NAPQI

17

How is NAPQI inactivated?

Conjugation by glutathione (will be used up if too much is taken resulting in liver failure). `

18

What is phase 1 biotransformation?

Modify the drug by oxidation, reduction or hydrolysis.

19

What is phase 2 biotranformation?

Involve the addition of a new chemical group to the drug or to its phase one metabolite - a conjugation reaction.

20

What is the most important phase 1 reaction?

Oxidation

21

What is the main organ involved in oxidation metabolism?

Liver

22

What is the reaction for oxidation?

RH + NADPH + H+ + O2 --> R-OH +NADP+ + H2O

23

What are the 6 cytochrome p450s that are used in oxidative metabolism?

CYP1A2
CYP2C9
CYP2C19
CYP2D6
CYP2E1
CYP3A4

24

Where is the hydroxyl group added?

Often at the site at which phase 2 takes place

25

How are phenactin and acetanilide converted into paracetamol?

Phenacetin --> De-alkylated
Acetanilide --> hydroxylated

26

What type of drugs often undergo reduction reactions?

Those containing Nitro or azo groups

27

What is chloroamphenicol and what reaction does it undergo?

Antibacterial eyedrop, has a nitro group which results in an amine group when metabolised.

28

What sort of drugs undergo hydrolysis?

Those which contain ester or amide bonds

29

What are the enzymes which catalyse hydrolysis called?

Esterases

30

What does aspirin form when hydrolysed?

Salicyclic acid and acetic acid

31

What does phase 1 metabolism result in?

Formation of more polar, less lipid soluble metabolites.

32

What is the most important phase 2 reaction?

Glucuridation

33

Give two other phase 2 reactions

1. Sulphation
2. N-acetylation

34

What is glucuronidation catalysed by?

UDP-glucuronosyltransferases (UTGs)

35

What drugs can glucuronidation occur for?

Those containing -OH, -COOH and -NH2 groups

36

What drugs can sulphation occur for?

-OH and -NH2

37

What is the source of sulfur?

Cofactor, 3'-phosphoadenosine-5'-phosphpsulphate.

38

What does N-acetyl action occur for and what is it catalysed by?

-NH2 groups, N-acetyltransferases.

39

Give 3 classifications of drugs which act as enzyme inducers

1. Anticonvulsants
2. Antimicrobial agents
3. Steriods

40

What does induction involve?

Binding of drug or doreign compound to either cytosolic or nuclear receptors and the interaction of the sensor with specific regions of DNA to switch on transcription of genes for enzymes.

41

What does Rifampicin do?

Reduces the expression of a large number of cytochrome P450s

42

What do phenytoin and carbamazepine do?

Promote the induction of the same metabolic enzymes that would metabolise themselves.

43

What is osteomalacia?

Some anticonvulsants increase the metabolism of vitamin D3 resulting in demineralisation of bone

44

What is Cimetidine?

Inhibits gastric acid, inhibits metabolic enzymes responsible for biotransformations of warfarin. Increases chance of haemorrhaging by enhancing anticoagulent effect.