X - CHEMOTHERAPEUTIC DRUGS Flashcards
Forms DNA cross-links, resulting in inhibition of DNA synthesis and function, Cell-cycle nonspecific
Alkylating agents
*Alkylating agents are inserted in the DNA of the cancer cells. They will cause chain termination because the cancer cell will lack 3’OH. As a general concept, in terms of side effect they will cause bone marrow suppression (take a look at the following alkylating agents to appreciate this generality. Bone marrow suppression manifested by pancytopenia)
Alkylating agents
- CYCLOPHOSPHAMIDE [D], IFOSFAMIDE [D], CHLORAMBUCIL [D], MECHLORETHAMINE [D]
- CISPLATIN [D], CARBOPLATIN [D], OXALIPLATIN [D]
- PROCARBAZINE [D]
- DACARBAZINE [C]
- BUSULFAN [D]
- CARMUSTINE [D]
SE: bone marrow suppression, hemorrhagic cystitis, hepatotoxicity, alopecia, SIADH, pulmonary toxicity
Cyclophosphamide
*Rescue therapy is MESNA. Cystitis can be prevented with adequate hydration
Rescue therapy for cyclophosphamide
MESNA (TOPNOTCH)
Rescue therapy for Cisplatin
Amifostine (TOPNOTCH)
MOA: Forms hydrogen peroxide, which generates free radicals that cause DNA strand scission. Cell cycle nonspecific.
- can penetrate the CSF, For Hodgkin’s lymphoma, non-hodgkin’s lymphoma, brain tumors
Procarbazine
* Procarbazine has the highest carcinogenic potential amongst alkylating agent. Imagine an anticancer drug that can actually cause cancer. This one is to remember.
SE: pulmonary fibrosis, adrenal insufficiency, skin pigmentation
Busulfan (TOPNOTCH)
Highly lipophilic allowing ease of passage through BBB into the CNS ; For brain tumors, melanoma, skin cancer
Carmustine, lomustine (TOPNOTCH)
Inhibits dihydrofolate reductase, decreases synthesis of thymidylate, amino acids, purine nucleotides; cell cycle specific
Methotrexate (TOPNOTCH)
Rescue therapy for methotrexate
Leucovorin (Folinic acid) (TOPNOTCH)
MOA: Inhibits de novo purine nucleotide synthesis. Activated by HGPRT. Cell cycle specific.
USES: Acute leukemias (AML, ALL), Chronic myelogenous leukemia, Lymphomas
6-MERCAPTOPURINE [D], 6-THIOGUANINE [D], AZATHIOPRINE [D]
Inhibits thymidylate synthase, causes thymineless death of cells, cell cycle specific
5-Fluorouracil (TOPNOTCH)
Inhibits DNA synthesis and repair. Inhibits ribonucleotide reductase with reduced formation of dNTPs. Cell-cycle specific.
Antimetabolite (pyrimidine): GEMCITABINE [D], CAPECITABINE [D]
* Gemcitabine is an evolution of antimetabolite because it can be used for solid tumors. Think of Pancreatic cancer as the most common indication.
MOA: Inhibits DNA synthesis and repair. Inhibits ribonucleotide reductase with reduced formation of dNTPs. Cell-cycle specific.
Most specific for the S-phase of the cell cycle
USES: Acute leukemias (AML, ALL), CML in blast crisis
Cytarabine
Prevents microtubule assembly, causes cell arrest at metaphase, cell cycle specific
Vinca alkaloid: Vincristine, Vinblastine
* Vincristine will not likely cause bone marrow suppression rather it will cause neuropathy. Vincristine will cause crispy nerves.
* vinBLASTine BLASTS the Bone marrow. vinblastine causes myelosuppression
Inhibits DNA topoisomerase II (DNA Gyrase). Inhibits mitochondrial electron transport. Cell cycle specific.
Class: Podophyllotoxin
ETOPOSIDE [D], TENIPOSIDE [D]
SE: Bone marrow suppression, GI irritation, Alopecia
MOA: Inhibits topoisomerase I. Cell cycle specific.
Class: Camptothecin
TOPOTECAN [D], IRINOTECAN [D]
Topotecan: Advanced ovarian cancer (2nd line), Small cell lung cancer
Irinotecan: Metastatic colorectal cancer (MNEMONIC: Irinotecan! Inire! Inire! Colorectal cancer)
Interferes with mitotic spindle, prevents microtubule DISASSEMBLY into tubulin monomers, cell cycle specific
PACLITAXEL [D], DOCETAXEL [D], CABAZITAXEL [D]
NOTE: They will prevent microtubule DISASSEMBLY. What drugs will inhibit microtubule ASSEMBLY? VINCRISTINE AND VINBLASTINE!!!
