Antimetabolites

Question 1

What is 5FU

Answer 1

Antimetabolite
Fluropyrimidine analog

Question 2

Cell cycle in which sfu acts

Answer 2

S phase

Question 3

Moa of 5Fu

Answer 3

Inhibition of thymidylate synthase by metabolite FdUMP which leads to accumulation of dUMP , which is incorporated into DNA as dUTP, which results in DNA Synthesis and function as well as alterations in RNA processing and m RNA translation

Question 4

Absorption of 5 fu

Answer 4

I’ve Route only

Question 5

Distribution of 5FU

Answer 5

Highest concentrations in GI mucosa , bone marrow liver, also in third space fluid collections and csf and brain

Question 6

Excretion of 5FU

Answer 6

Urine

Question 7

Half life of 5 fu

Answer 7

10 to 20 ins

Question 8

What is MTX

Answer 8

Anti metabolite
Anti folate
Folic acid analogue

Question 9

Mechanism of action of MTX

Answer 9

Inhibits the di hydro folic acid reductase that converts DHFA to THFA

Inhibits the de novo synthesis of purines thereby inhibits the DNA synthesis and function

Active on the S phase

Question 10

What is folinic acid rescue

Answer 10

Folinic acid is given 1 day after high dose MTX to rescue the normal cells, from the toxic effect of MTX

Question 11

Mechanism of folinic acid rescue

Answer 11

Selective uptake in normal cells due to the low levels of MTX poly Glutamates

It can be converted to Formyl THFA without the action of DHFA reductase enzyme

Question 12

Routes of administration MTX

Answer 12

Oral and Iv

Question 13

Uses of oral MTX

Answer 13

Given once a week

Inflammatory bowel, crowns , Rheumatoid arthritis

Along with folks acid

MTX on mondays and folic acid on fridays

Question 14

Dose limiting side effects of MTX and how would u treat it

Answer 14

Mucositis and stomatitis

Oral cryotherapy
Benzydamine mouth wash

Grade 4- parenteral treatment

Question 15

Emetogenic potential of MTX

Answer 15

Minimal MTX less than 50 mg/m2

Low MTX 50 to 250

Moderate MTX more than 250

Question 16

Does MTX cross Bbb

Answer 16

At high doses

Question 17

Metabolism of MTX

Answer 17

Liver

Question 18

Excretion of MTX

Answer 18

Urine

Question 19

Indications of MTX

Answer 19

Breast
HNC
All
Hl
Primary CNS lymphoma
Bladder
Gtc

Question 20

Dose of MTX

Answer 20

Low dose :
Weekly - 25 mg/m2 IV
Monthly - 10 TO 50 mg/m2

Moderate dose
100 to 500 mg/m2 every 2-3 weekly

High dose
1 to 12 gram per m2 over 3 to 24 hours Q 1-3 weeks

Question 21

Others routes of MTX

Answer 21

Intra thecal : 10 to 15 mg twice weekly till CSF is clear
Followed by weekly for 4 weeks
Followed by monthly dose

IM :
25 mg per m2 every 3 weeks

Question 22

Dose reduction in MTX

Answer 22

Renal impairment

Question 23

Other dose limiting toxicity of MTX

Answer 23

Myelosuppression

Question 24

MOA of pemetrexed

Answer 24

Inhibits - thymidalate synthase - resulting in decreased thymidine available for DNA synthesis

inhibits DHFR and GARFT which are required for synthesis of purine de novo

Question 25

Cell cycle of pemetrexed

Answer 25

G1/S

Question 26

Excretion of pemetrexed

Answer 26

Urine 80%

Question 27

Indications and doses of pemetrexed

Answer 27

NSCLC - non squamous locally advanced / metastatic along with cisplatin or second line agent Mesothelioma Dose 500 mg/ m2 every 3 weeks

Question 28

Caution before pemetrexed

Answer 28

Folic acid 400 microgram per oral 7 days before starting pemetrexed and 21 days after the completion of pemetrexed Vitamin B12 1000 microgram IM 7 days prior to the first dose then every 9 weeks until 3 cycles are completed

Question 29

Toxicity of pemetrexed

Answer 29

Myelosuppression dose limiting Skin toxicity : rashes Dexa 4mg PO 4 mg

Question 30

What is capecitabine

Answer 30

Fluropyrimidine analogue Antimetabolite Active is S phase

Question 31

Dose limiting of capecitabine

Answer 31

Diarrhoea Withhold if grade 2/3 Start loperamide

Question 32

Other toxicities and how do you prevent

Answer 32

Hand foot syndrome ( palmar plantar erythrodesesthesia ) VIT b6 50 to 150 mg orally to prevent Followed by dose reduction

Question 33

Dose and indications

Answer 33

1250 mg/ m2 Po bd with food In breast cancer and colorectal ca Dose reduction to 825 mg/ m2 in case of toxicity

Question 34

Metabolism of capecitabine

Answer 34

Liver Converted to 5FU with thymidine phosphorylase followed by 5FdUMP to inhibit DNA synthesis and FUTP to inhibit RNA synthesis and FBAL INACTIVE METABOLITE by DPD