Anti-Metbolites Flashcards Preview

(UNI) Chemotherapy & Selective Toxicity (3rd Year) > Anti-Metbolites > Flashcards

Flashcards in Anti-Metbolites Deck (25)
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1
Q

What are anti-metabolites?

A

They are chemicals that inhibit the use of a metabolite where the metabolite is a naturally occurring chemical that is part of normal metabolism. Thus, they are similar in structure to the metabolite they interfere with.

2
Q

Comment on the selectivity of anti-metabolites.

A

They are similar in structure to the metabolite they interfere with. Because of this, they have poor selectivity and are also effective against healthy tissues.

3
Q

Chemically, what are anti-metabolites often?

A

They are often purine, pyridine, and pteridine (folate) analogues.

4
Q

During what phase of the cell replication cycle do anti-metabolites have an effect?

A

The S phase.

5
Q

Why is it often necessary to give supplements with anti-metabolite therapy?

A

It is often required to give supplements to reduce the effect of these anti-metabolites on healthy cells.

6
Q

Are anti-metabolites restricted to use in the treatment of cancer?

A

No. Sulphonamides are also antimetabolites and they are used as antibacterials.

7
Q

Describe fludarabine.

A

Fludarabine is a purine anti-metabolite given orally or IV. It interferes with ribonucleotide reductase and DNA polymerase enzymes. It is active against both dividing and resting cells.

8
Q

Describe the structure of fludarabine.

A

It is a fluorinated analogue of adenine attached to an arabinose sugar C2’ OH has the beta configuration (up) compared with ribose (down).

9
Q

Fludarabine is used in the treatment of non-Hodgkin’s lymphomas in combination with which drugs?

A

Cyclophosphamide, mitoxantrone, dexamethasone, rituximab.

10
Q

Describe cyclophosphamide.

A

A DNA alkylator acting at the N7 of guanine.

11
Q

Describe mitoxantrone.

A

Topoisomerase II inhibitor, interferes with DNA replication/repair.

12
Q

Describe dexamethasone.

A

A steroid to counteract the side effects of chemotherapy.

13
Q

Describe rituximab.

A

A monoclonal antibody, destroys excessive, overactive B lymphocytes.

14
Q

Describe purine anti-cancer agents.

A

Purine bases are prodrugs that exploit the purine salvage pathway.

15
Q

What are purine anti-cancer agents used against?

A

Purine anticancer agents are used against leukaemia and non-Hodgkin’s lymphoma, as well as others.

16
Q

What drug has an interaction with mercaptopurine? What is the result of this reaction?

A

There is a drug interaction with allopurinol (a xanthine oxidase inhibitor) that can exacerbate mercaptopurine toxicity.

17
Q

Describe anti-folates.

A

These are agents which mimic the structure of folic acid and inhibit dihydrofolate reductase. They are made up of a section that mimics the folic acid base, and a section that mimics the side chain.

18
Q

Describe methotrexate.

A

This is an anticancer agent which is the most tightly binding DHFR inhibitor. It is an irreversible DHFR antagonist.

19
Q

Describe premetrexed.

A

This is an agent used to treat lung cancer. It is combined with cisplatin and the steroid dexamethasone.

20
Q

Describe leucovorin (folinic acid).

A

This is an agent used in rescue therapy. It combats the toxicity caused by the use of methotrexate and purine antimetabolits. It kickstarts the ‘folate pool’.

21
Q

By what other name is leucovorin known?

A

Folinic acid.

22
Q

What compound is also known as folinic acid?

A

Leucovorin.

23
Q

5-FU is a prodrug, what is it converted to? By what mechanism does this occur?

A

5-FU is a prodrug that is converted to active 5-FdU by pyrimidine salvage.

24
Q

How does 5-FdU inhibit thymidylate synthase?

A

The molecule has an F atom. The removal of the F+ is impossible as it can’t accept a positive charge. Hence, the compound stays in the enzymes active site and the reaction remains incomplete.

25
Q

What enzyme does 5-FdU inhibit?

A

Thymidylate synthase.