(8) Antineoplastics: Antimetabolites (1.1-1.3)

Question 1

What is the precursor to dTMP?

Answer 1

dUMP

Question 2

What cofactor does Thymidylate Synthase require?

Answer 2

THF

(tetrahydrofolate)

Question 3

MOA: Methotrexate

Answer 3

Inhibits dihydrofolate reductase

Question 4

Cell Cycle Specificity: Hydroxyurea

Answer 4

S phase

(Same for MTX and 5-FU)

Question 5

Indications - Non-neoplastic (5) : Methotrexate

Answer 5

(1) Abortifacient
(2) Ectopic pregnancy
(3) Molar pregnancy
(4) Psoriasis
(5) Rheumatoid arthritis
* (And the neoplastic indications of trophoblastic tumors and choriocarcinomas)*

Question 6

Adverse Effects (7) : Methotrexate

Answer 6

(1) Megaloblastic anemia
(2) Pulmonary fibrosis
(3) Hepatotoxicity
(4) Alopecia
(5) Mucositis
(6) Pancytopenia
(7) ⇒ Immunosuppression

Question 7

What drug can be used to reverse the toxic effects of Methotrexate?

Answer 7

Folinic acid

(Trade name: Leucovorin ≠ Folate)

Question 8

MOA: 5-Fluorouracil

Answer 8

Inhibits thymidylate synthase

(After activation by THF)

Question 9

Name 2 adverse effects more common with 5-FU than MTX

Answer 9

(1) Severe diarrhea
(2) Cutaneous complications

Question 10

Can you use Folinic Acid to treat 5-FU toxicity?

Answer 10

No

(It actually potentiates 5-FU)

Question 11

What reaction does ribonucleotide reductase catalyze?

Answer 11

UDP ⇒ dUDP

(Notice progression from UDP → dUDP → dUMP)

Question 12

MOA: Hydroxyurea

Answer 12

Ribonucleotide reductase inhibitor

(Also prevents HbS polymerization by ↑ [HbF])

Question 13

What non-neoplastic indication does Hydroxyurea have?

Answer 13

Sickle cell anemia

(⇒ ↑ [HbF])

Question 14

In purine synthesis, what is the precursor to IMP?

Answer 14

PRPP

(“Pentagon-shaped pedestal”)

Question 15

What is a pro-drug of 6-mercaptopurine?

Answer 15

Azathioprine

Question 16

What enzyme activates 6-mercaptopurine?

Answer 16

HGPRT

Question 17

The synthesis of what purine intermediate is inhibited by 6-mercaptopurine?

Answer 17

IMP

Question 18

Cell Cycle Specificity: Azathioprine

Answer 18

S phase

Question 19

What is the primary neoplastic indication for AZA/6-MP?

Answer 19

Hematologic malignancies

Question 20

Indications - Non-neoplastic (3) : AZA/6-MP

Answer 20

(1) Immunosuppressive
(2) Rheumatoid arthritis
(3) IBS
* (Note: AZA is NOT as effective as MTX in treating RA)*

Question 21

Adverse Effects (4) : AZA/6-MP

Answer 21

(1) Myelosuppression
(2) ⇒ Immunosuppression
(3) Pancreatitis
(4) Hepatitis

Question 22

What notable drug interaction does AZA/6-MP have?

Answer 22

Xanthine oxidase inhibitors

(I.e., Allopurinol, Febuxostat)

Question 23

MOA: Mycophenolate mofetil

Answer 23

Inhibits IMP Dehydrogenase ⇒ ↓ GMP

Question 24

What cell population is particularly vulnerable to Mycophenolate mofetil?

Answer 24

Lymphocytes

(Which require de novo synthesis of nucleotides. 6-MP/AZA likely has a similar profile)

Question 25

Indications - Non-neoplastic (2) : Mycophenolate mofetil

Answer 25

(1) Immunosuppressive
(2) Rheumatoid arthritis

Question 26

Adverse Effects (2) : Mycophenolate mofetil

Answer 26

(1) Severe GI distress
(2) Immunosuppression

Question 27

Is Cladribine a purine or pyrimidine analog?

Answer 27

Purine

(Purines have 2 rings, purines = pu-‘rings’)

Question 28

Cell Cycle Specificity: Cytarabine

Answer 28

S phase

Question 29

MOA: Cladribine

Answer 29

Inhibits DNA polymerase

Question 30

What is the most effective pharmacologic treatment for hairy cell leukemia?

Answer 30

Cladribine

Question 31

Adverse Effects (2) : Cladribine/Gemcitabine

Answer 31

(1) Myelosuppression

(2) ⇒ Immunosuppression

Question 32

Is Cytarabine a purine or pyrimidine analog?

Answer 32

Pyrimidine

Question 33

What type of cancers is Cytarabine effective against?

Answer 33

Hematologic malignancies only

Question 34

Is Gemcitabine a purine or pyrimidine analog?

Answer 34

Pyrimidine

Question 35

What is the difference in the type of cancers Gemcitabine and Cytarabine treat?

Answer 35

(1) Gemcitabine: Hematologic AND solid tumors
(2) Cytarabine: Only hematologic

Question 36

What type of cancers does Cytarabine treat?

Answer 36

Hematologic malignancies