Antimetabolites

Question 1

3 Types of antimetabolites

Answer 1

Folate antagonist
Pyrimidine antagonist
Purine antagonist

Question 2

3 Folate antagonist types

Answer 2

Methotrexate
Pralatraxate
Pemetrexed…

Question 3

Types of purine antagonist

Answer 3

6- Mercaptopurine
6- Thioguanine

Question 4

Eg of pyrimidine antagonist

Answer 4

5 Flurouracil…

Question 5

3 Folate transport system

Answer 5

Folate receptor
Folate transport which is main transient protein for methotrexate
A transport which activates at low PH

Question 6

Reduced folate transportar gene resides on

Answer 6

Chromosome 21
Which is present in hyperdiploid subtype of acute lymphoblastic leukemia

Question 7

How folic acid is used in the body

Answer 7

Folic acid - tetrahydrofolate cofactors - methyl groups - DNA precursor - Thymidylate and purines ..

Question 8

MOA of methotrexate

Answer 8

Active catalytic site of dihydrofolate reductase ( DHFR )

Question 9

Inhibition of DHFR cause depletion of which FH4 co factors

Answer 9

5-10 methylene tetrahydrofolic acid
N 10 formyl tetrahydrofolic acid

Question 10

Other effect of methotrexate

Answer 10

Effect folate dependent enzyme of denovo purines and Thymidylate

Question 11

Methotrexate targets which phase

Answer 11

S phase
Only partially selective for tumor cells

Question 12

How methotrexate resistance is developed

Answer 12

Impaired transport of methotrexate
Increase in conc. Of DHFR
Altered forms of DHFR
Decrease ability to synthesize methotrexate

Question 13

Therapeutic uses of methotrexate

Answer 13

ALL in children
Acute lymphoblastic leukemia
Meningeal leukemia and carcinomatosis

Question 14

Methotrexate is used in combination with

Answer 14

Dactinomyocin…

Question 15

ADRs of methotrexate

Answer 15

Nephrotoxicity
Neurotoxicity
Allergic reactions
Dermatitis
Alopecia
Haemorrhage
Bone marrow suppression

Question 16

How toxic effects of methotrexate can be terminated..

Answer 16

By administration of leucovorin which is a fully reduced folate co-enzyme and and fill intracellular pool of FH4 cofactors but doesn’t reverse neurotoxicity

Question 17

6 MP is metabolized into and by who and what’s it’s effect

Answer 17

Monophosphate nucleotide 6- thioinosinic acid..
By
Hypoxanthine guanine phosphoribosyl transferases
Which by inhibiting different enzyme inhibit denovo purines nucleotide synthesis

Question 18

What are 2 significant active metabolites of 6 Mercaptopurine

Answer 18

Thioguanylic acid and 6 methyl Mercaptopurine Ribonucleotide

Question 19

Inactive metabolites of 6 Mercaptopurine

Answer 19

6 Thio uric acid formed by xanthine oxidase

Question 20

Main use of 6 Mercaptopurine

Answer 20

Childhood acute leukemia

Question 21

1st thiopurine analog found

Answer 21

6 Mercaptopurine

Question 22

How thiopurine are metabolized

Answer 22

By thiopurine methyl transferase

Question 23

MOA of 5 FU

Answer 23

dTMP is required for DNA synthesis
dUMP is converted dTMP by enzyme Thymidylate synthetase..

5 Flurouracil is converted to 5 fluro deoxy uridine monophosphate Thymidylate synthetase

Question 24

How 5 Flurouracil interfere with RNA processing

Answer 24

5 FU converted to 5 Fluoroudine triphosphate which incorporates into RNA…

Question 25

Therapeutic uses of Pyrimidine antagonist

Answer 25

Rarely used alone..
Upper GIT carcinoma, breast and colon carcinoma

Question 26

How 5 FU is used in colorectal cancer

Answer 26

Combination with leucovorin and oxaliplatin or irrinotecan…

Question 27

Alopecia, Diarrhea, severe ulceration and bone marrow suppression
Toxicities