Antineoplastic Agents (Conventional cytotoxins) Flashcards
Alkylating Agents (Nitrogen mustard agents) MoA
Bind to nucleotides and alkylate them (add a methyl group), this forms: (Inter-strand & Intra-strand) crosslinking, interfering with DNA & RNA synthesis
Alkylating Agents (Nitrogen mustard agents) cell cycle target
Non-specific
Alkylating Agents (Nitrogen mustard agents) indications
Non-Hodgkin lymphoma
Leukemia
Sarcoma
Alkylating Agents (Nitrogen mustard agents) examples
Cyclophosphamide
Ifosfamide
Platinum Coordination Complexes MoA
Add platin group to guanine, this forms: (Inter-strand & Intra-strand) crosslinking
Platinum Coordination Complexes cell cycle target
Non-specific, but favors (G1) and (S) phases
Platinum Coordination Complexes examples
Cisplatin “Parent drug”
Carboplatin
Oxaliplatin
Anti-metabolites MoA
Inhibit the synthesis of nucleotides by competing with their precursors
Anti-metabolites cell cycle target
(S) phase
Anti-metabolites examples
5-Fluorouracil (5-FU)
Capecitabine
5-Fluorouracil (5-FU) cell cycle target
(S) phase
5-Fluorouracil (5-FU) synergism
5-FU is combined with Leucovorin → this enhances its binding to thymidine synthase
5-Fluorouracil (5-FU) indications
Colorectal cancer
Breast cancer
Ovarian cancer
Pancreas cancer
Gastric carcinoma
5-Fluorouracil (5-FU) mechanisms of resistance
(1) Cancer cells are unable to convert 5-FU into its active form (5-FdUMP)
(2) increased the levels of thymidylate synthase
Capecitabine RoA
Given orally as a prodrug that gets activated in the liver
Capecitabine cell cycle target
(S) phase
Capecitabine MoA
Converted inside the cell to 5-FU; (then same MoA as 5-FU)
Capecitabine indications
Colorectal cancer
Breast cancer
Anthracyclines cell cycle target
non-specific
Anthracyclines MoA
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
Anthracyclines examples and indications
A. Doxorubicin: Sarcoma, Lung cancer, Breast cancer, Acute lymphocytic leukemia
B. Epirubicin: Gastric carcinoma, Esophageal carcinoma
Topoisomerase inhibitors examples
Camptothecins (Irinotecan/Topotecan)
Etoposide
Camptothecins cell cycle target and MoA
- Cell cycle target: (S) phase
- MoA: Camptothecins inhibit Topoisomerase I in DNA replication, leading to Single-strand breaks
Camptothecins synergy
these drugs are used with 5-FU and leucovorin for Colorectal cancer
Camptothecins examples
→ Irinotecan, a prodrug that gets converted by CYT P450 3A4 to (SN-38), a metabolite x1000 potent than Irinotecan
→ Topotecan
Etoposide MoA and cell cycle target
→ MoA: Etoposide inhibits Topoisomerase II in DNA replication, leading to Double-strand breaks
→ Cell cycle target: (S) phase & (G2) phase
Microtubule Inhibitors examples
→ Taxanes (Paclitaxel and Docetaxel)
→ Vinca alkaloids (Vincristine and Vinblastine)
Taxanes (Paclitaxel and Docetaxel) cell cycle target and MoA
→ 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
Vinca alkaloids (Vincristine and Vinblastine) cell cycle target and MoA
→ Cell cycle target: (M) phase
→ MoA: they inhibit the polymerization of microtubules of the mitotic spindles
Associated drug of Myelosuppression
5-Fluorouracil & Capecitabine “Anti-metabolites”
Associated drug of Renal toxicity
Cisplatin
Associated drug of Cardiotoxicity
Doxorubicin
Associated drug of Neurotoxicity
Vincristine & Vinblastine “the V’s”
Associated drug of GI toxicity
5-Fluorouracil & Capecitabine “Anti-metabolites”
Associated drug of Alopecia
Doxorubicin & Etoposide
