Chemo Drugs III: Antimetabolites

Question 1

Methotrexate

MOA

Answer 1

Binds dihydrofolate reductase and decreases THF synthesis

Inhibits purine and thiamine synthesis

Question 2

How can cells be rescued during Methotrexate treatment?

Answer 2

Administer THF during the methotrexate treatment to save the cells that do NOT have polyglutamated methotrexate

Question 3

What happens when methotrexate gets polyglutamated?

Answer 3

Polyglutamated methotrexate will hang around in the cell much longer, increasing its inhibitory effects

Question 4

Methotrexate

Indications

Answer 4

Lymphoma
Leukemia
Brian tumors
Breast CA

Rheumatoid arthritis
Psoriasis

Question 5

Methotrexate

AEs

Answer 5

N/V
Stomatitis
Myelosuppression

Reduce dose in renal insufficiency

Question 6

Methotrexate

Contraindications

Answer 6

Methotrexate is highly protein bound, so use caution with aspirin, sulfa drugs, penicillins, etc

Ascites
Pleural effusions

Probenecid (used for uric acid underexcreters) will interfere with Methotrexate’s elimination

Question 7

Methotrexate with Leucovorin rescue

Uses

Answer 7

Leucovorin is given after a high dose methotrexate intake

You cannot rescue cancer cells with leucovorin, because they will polyglutamate methotrexate

Normal cell will not polyglutamate methotraxate, allowing leucovorin to competitively prevent methotrexate’s harmful effects in normal cells

Question 8

Pemetrexed

MOA and Indications

Answer 8

Inhibit thymidylate synthase, which stops nucleic acid synthesis

Used in lung cancer and mesothelioma

Question 9

Pemetrexed

AEs

Answer 9

Myelosuppression is dose limiting

Hand foot syndrome - painful rash on palms and soles

Question 10

Pemetrexed

How to diminish AEs

Answer 10

Pretreatment with Vit B12 and oral folic acid decreases the myelosuppression

Question 11

Cytosine Arabinoside

MOA

Answer 11

Pyrimidine analog that gets incorporated into DNA and inhibits DNA polymerase and chain elongation

Has a schedule-dependent cytotoxicity (3 days IV anthrocycline + 7 days IV Cytosine Arabinoside) for AML

Question 12

Cytosine Arabinoside

Indication

Answer 12

AML

Question 13

Cytosine Arabinoside

AEs

Answer 13

Myelosuppression
Cerebellar toxicity
Conjunctivitis

Question 14

What two drugs are approved for intrathecal administration?

Answer 14

Cytosine Arabinoside

Methotrexate

Question 15

5-FU

MOA

Answer 15

inhibits both DNA and RNA pathways

FdUMP is made, which inhibits thymidylate synthase (S phase specific)

Question 16

5-FU

What enhances the cytotoxicity of 5-FU?

Answer 16

Leucovorin enhances 5-FU cytotoxicity

Question 17

5-FU

Metabolism

Answer 17

Liver

Metabolized by dihydropyrimidine dehydrogenase (DPD)

Question 18

5-FU

Indications

Answer 18

GI malignancy

Head and neck tumors

Question 19

What is Capecitabine?

Answer 19

Oral form of 5-FU

-Gets cleaved and releases 5-FU intracellularly

Question 20

Capecitabine

AE

Answer 20

Hand-Foot Disease
Painful thickening and desquamation of the skin

Fissures and cracking of skin

Question 21

6-Mercaptopurine

MOA

Answer 21

Gets metabolized to 6-thioinosinic acid, which inhibits purine synthesis

Question 22

6-Mercaptopurine

Metabolism

Answer 22

Activation: Gets metabolized to 6-thioinosinic acid, which inhibits purine synthesis

Inhibition: metabolized by xanthine oxidase (so you need to decrease 6-Mercaptopurine dose when the patient is on allopurinol)

Question 23

6-Mercaptopurine

Indication

Answer 23

Childhood leukemia

Question 24

6-Mercaptopurine

AEs

Answer 24

Myelosuppression

Toxicity occurs when given with allopurinol