E1 non specific

Question 1

Name 3 types of non specific immunosuppressers

And what do all three lead to

Answer 1

1. False metabolites:
   substitute normal nucleotide in growing nucleotide chain to stop it forming
2. Alkylating agents:
   stage at which DNA unwinds: covalently bind nucleotides to prevent unwinding/ synthesis
3. Inhibitors of nucleotide synthesis:
   stop nucleotide flux into DNA synthesis

lead to cytotoxicity

Question 2

‘side effects’ of non specific immunosuppressers

Answer 2

Hair loss
GI damage
Skin damage

(Above cells have fast turn over, now unable to divide –> cytotoxicity

Question 3

Describe Azathioprine (imuran)
- What class of non-specific immunosuppressor

Answer 3

Azathioprine converted to 6-mercaptopurine
(nitrogen group removed)

Cleaved after absorbed
- false metabolite
= cytotoxicity

Question 4

What else can Azathioprine be converted to

- what inhibits the undesired conversion

Answer 4

(purine synthesis) OR thiobarbituric acid via xanthine oxidase
converted to inactive molecule, excreted by kidney

allopurinol blocks

Question 5

What type of agent is cyclophosphamide

• what is the bifunctional group
• what is it converted to

Answer 5

Alkylating agent

• 2 chlorines which are the correct distance for intercalating into DNA to covalently bind 2 guanine bases
• converted to aldophosphamide (active form)
• prodrug

((first converted by cytP450 to 4-OH-cpa then to aldo))

Question 6

what can aldophosphamide be converted to?

Answer 6

carboxylic acid and excreted by urine

Question 7

describe the covalent binding of aldophosphamide

Answer 7

2 +ve charges in each nitrogen covalently bound to Cl - links two molecules together
N7 groups are covently bound

Question 8

what type of drug is mycophenolic acid: MPA

- what is converted to give MPA

Answer 8

Inhibitor of nucleotide synthesis
(prodrug)

mycophenolate mofetil is hydrolyses to mycophenolic acid

Question 9

Describe mechanism of action of MPA

Answer 9

non competitive enzyme inhibitor (binds allosterically)

- prevents inosine converted to guanosine by blocking IMP dehydrogenase enzyme