Antineoplastic Agents (Conventional cytotoxins)

Question 1

Alkylating Agents (Nitrogen mustard agents) MoA

Answer 1

Bind to nucleotides and alkylate them (add a methyl group), this forms: (Inter-strand & Intra-strand) crosslinking, interfering with DNA & RNA synthesis

Question 2

Alkylating Agents (Nitrogen mustard agents) cell cycle target

Answer 2

Non-specific

Question 3

Alkylating Agents (Nitrogen mustard agents) indications

Answer 3

Non-Hodgkin lymphoma
Leukemia
Sarcoma

Question 4

Alkylating Agents (Nitrogen mustard agents) examples

Answer 4

Cyclophosphamide
Ifosfamide

Question 5

Platinum Coordination Complexes MoA

Answer 5

Add platin group to guanine, this forms: (Inter-strand & Intra-strand) crosslinking

Question 6

Platinum Coordination Complexes cell cycle target

Answer 6

Non-specific, but favors (G1) and (S) phases

Question 7

Platinum Coordination Complexes examples

Answer 7

Cisplatin “Parent drug”
Carboplatin
Oxaliplatin

Question 8

Anti-metabolites MoA

Answer 8

Inhibit the synthesis of nucleotides by competing with their precursors

Question 9

Anti-metabolites cell cycle target

Answer 9

(S) phase

Question 10

Anti-metabolites examples

Answer 10

5-Fluorouracil (5-FU)
Capecitabine

Question 11

5-Fluorouracil (5-FU) cell cycle target

Answer 11

(S) phase

Question 12

5-Fluorouracil (5-FU) synergism

Answer 12

5-FU is combined with Leucovorin → this enhances its binding to thymidine synthase

Question 13

5-Fluorouracil (5-FU) indications

Answer 13

Colorectal cancer
Breast cancer
Ovarian cancer
Pancreas cancer
Gastric carcinoma

Question 14

5-Fluorouracil (5-FU) mechanisms of resistance

Answer 14

(1) Cancer cells are unable to convert 5-FU into its active form (5-FdUMP)
(2) increased the levels of thymidylate synthase

Question 15

Capecitabine RoA

Answer 15

Given orally as a prodrug that gets activated in the liver

Question 16

Capecitabine cell cycle target

Answer 16

(S) phase

Question 17

Capecitabine MoA

Answer 17

Converted inside the cell to 5-FU; (then same MoA as 5-FU)

Question 18

Capecitabine indications

Answer 18

Colorectal cancer
Breast cancer

Question 19

Anthracyclines cell cycle target

Answer 19

non-specific

Question 20

Anthracyclines MoA

Answer 20

1) inhibits DNA helicase → it is the enzyme that separates the two DNA strands of DNA
2) inhibits Topoisomerases (II) → it the enzyme that re-joins the two DNA strands
3) produces free ROS, which causes cell injury

Question 21

Anthracyclines examples and indications

Answer 21

A. Doxorubicin: Sarcoma, Lung cancer, Breast cancer, Acute lymphocytic leukemia
B. Epirubicin: Gastric carcinoma, Esophageal carcinoma

Question 22

Topoisomerase inhibitors examples

Answer 22

Camptothecins (Irinotecan/Topotecan)
Etoposide

Question 23

Camptothecins cell cycle target and MoA

Answer 23

• Cell cycle target: (S) phase
• MoA: Camptothecins inhibit Topoisomerase I in DNA replication, leading to Single-strand breaks

Question 24

Camptothecins synergy

Answer 24

these drugs are used with 5-FU and leucovorin for Colorectal cancer

Question 25

Camptothecins examples

Answer 25

→ Irinotecan, a prodrug that gets converted by CYT P450 3A4 to _(SN-38)_, a metabolite x1000 potent than Irinotecan → Topotecan

Question 26

Etoposide MoA and cell cycle target

Answer 26

→ MoA: Etoposide inhibits Topoisomerase II in DNA replication, leading to Double-strand breaks → Cell cycle target: (S) phase & (G2) phase

Question 27

Microtubule Inhibitors examples

Answer 27

→ Taxanes (Paclitaxel and Docetaxel) → Vinca alkaloids (Vincristine and Vinblastine)

Question 28

Taxanes (Paclitaxel and Docetaxel) cell cycle target and MoA

Answer 28

→ Cell cycle target: (M) phase → MoA: they bind to the mitotic spindles of the cell, inhibiting their depolymerization so the cells will be stuck in the metaphase of the cell cycle

Question 29

Vinca alkaloids (Vincristine and Vinblastine) cell cycle target and MoA

Answer 29

→ Cell cycle target: (M) phase → MoA: they inhibit the polymerization of microtubules of the mitotic spindles

Question 30

Associated drug of Myelosuppression

Answer 30

5-Fluorouracil & Capecitabine “Anti-metabolites"

Question 31

Associated drug of Renal toxicity

Answer 31

Cisplatin

Question 32

Associated drug of Cardiotoxicity

Answer 32

Doxorubicin

Question 33

Associated drug of Neurotoxicity

Answer 33

Vincristine & Vinblastine “the V’s”

Question 34

Associated drug of GI toxicity

Answer 34

5-Fluorouracil & Capecitabine “Anti-metabolites”

Question 35

Associated drug of Alopecia

Answer 35

Doxorubicin & Etoposide