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!!!
Used in Advanced breast and ovarian cancers, lung cancer, gastroesophageal cancer, gastric cancer, prostate cancer, bladder cancer, head and neck cancer
Paclitaxel, docetaxel (TOPNOTCH)
Acts primarily in M phase of cancer cell cycle
Vinca alkaloid: Vincristine, Vinblastine (TOPNOTCH)
Intercalates between base pairs. Inhibits topoisomerase II. Generates free radicals → single and double-stranded DNA breaks. Cell cycle non-specific.
- Anthracycline: Doxorubicin, daunorubicin, idarubicin, epirubicin, mitoxantrone (TOPNOTCH)
- Side effects: Alopecia, Nausea, Vomiting, Dilated Cardiomyopathy, Congestive heart failure, red urine (Doxorubicin), myelosuppression
- Rescue therapy is DEXRAZOXANE
Rescue therapy for Doxorubicin
dexrazoxane (TOPNOTCH)
Most specific for the G2 phase of cell cycle
Bleomycin (TOPNOTCH)
Generates free radicals, which cause DNA strand breaks. Intercalates with DNA. Cell cycle specific.
SE: Pneumonitis, Pulmonary fibrosis, Mucocutaneous reactions (blisters, hyperkeratosis), Alopecia, Hypersensitivity, Fever and chills , hypotension
BLEOMYCIN [D], MITOMYCIN [D]
Binds to double stranded DNA, inhibits DNA-dependent RNA synthesis, cell cycle non-specific
Actinomycin D (TOPNOTCH)
*Other name of actinomycin is dactinomycin. It is the oldest antitumor
antibiotic.
MOA: Inhibits tyrosine kinase activity of the protein product of bcr-abl oncogene in CML. Inhibits c-kit tyrosine kinase in GIST.
Tyrosine Kinase Inhibitors: IMATINIB [D], DASATINIB [D], NILOTINIB [D], CRIZOTINIB [D], AFATINIB [D], NINTEDANIB [D], REGORAFENIB [D]
MOA: Acts against breast cancer cells that overexpress the HER-2/neu receptor for epidermal growth factor
Monoclonal antibody: TRASTUZUMAB [B], PERTUZUMAB [D], LAPATINIB [D]
*Just like doxorubicin, it can cause cardiomyopathy. This drug has a trade name Herceptin. MNEMONIC: Heartceptin or if you want Trastuzumab “tinuzuk ang puzu”
MOA: Inhibits binding of VEGF to VEGFR leading to inhibition of VEGF signaling. Inhibits tumor vascular permeability but enhances tumor blood flow and drug delivery.
Bevacizumab
SIMD: SORAFENIB [D], SUNITINIB [D], PAZOPANIB [D], LENVATINIB [D]
* MNEMONIC: BV BeVacizumab for blood vessel. It inhibits angiogenesis!
Binds to a surface protein in NHL cells, induces complement-mediated lysis, direct cytotoxicity and induction of apoptosis
Rituximab (TOPNOTCH)
Endogenous glycoproteins with antineoplastric, immunosuppressive and antiviral actions
Interferon alpha (TOPNOTCH)
Depletes serum asparagines ; For ALL, T-cell auxotrophic CA (leukemia and lymphomas) that require asparagine for growth
Asparaginase (TOPNOTCH)
Only vitamin that can cure cancer
MOA: Allows DNA transcription and differentiation of immature leukemic promyelocytes into mature granulocytes (differentiation therapy).
All-Trans retinoic acid
REVIEW:
- What leukemia is this drug used? ACUTE PROMYELOCYTIC LEUKEMIA!!
- What do you call the needle-like azurophilic granules seen in APL? AUER RODS!!
- What do you call cells with numerous auer rods? FAGGOT CELLS!!
- t(15;17)!!!!!
For acute promyelocytic leukemia
All-Trans retinoic acid (TOPNOTCH)
Suppresses inflammation and immune response, may trigger apoptosis and work on nondividing cancer cells
Prednisone (TOPNOTCH)
Estrogen antagonist actions in breasts tissue and CNS
Estrogen agonist effects in uterus, liver and bone
Selective Estrogen Receptor Modulator: TAMOXIFEN [D], TOREMIFENE [D]
*Prevents osteoporosis in post-menopausal women and decreases risk of atherosclerosis at the risk of causing endometrial cancer.
FLUVESTRANT is a FULL ESTROGEN RECEPTOR ANTAGONIST (No agonist effect) used in hormone receptor positive metastatic breast cancer.
Torimefene is structurally related to Tamoxifen
Androgen antagonist ; For prostate cancer
Flutamide (TOPNOTCH)
Increased LH, FSH secretion with intermittent administration, reduced LH and FSH secretion with prolonged continuous administration ; For prostate cancer
GnRH Analog: LEUPROLIDE [D], GONADORELIN [B], NAFARELIN [X]
* Must be co-administered with flutamide (androgen antagonist) to prevent tumor flare-up on initiation of treatment
Reduces estrogen synthesis by inhibiting aromatase; For breast cancer
Anastrazole (TOPNOTCH)
Effective againsts breast cancer that have become resistant to tamoxifen
Anastrazole (TOPNOTCH)
Causes Nephrotoxicity and acoustic nerve damage
Cisplatin, Carboplatin
Causes peripheral neuropathy
VIncristine
Causes cardiotoxicity
Doxorubicin (Dilated cardiomyopathy) and Transtuzumab
Causes pulmonary fibrosis
Bleomycin
Causes hemorrhagic cystitis
Cyclophosphamide
Causes myelosuppression
Methotrexate, 5 FU, 6 Mercaptopurine
