Chemotherapeutic agents

This is a brief overview of chemotherapeutic agents, their mechanism of action, and some related side effects. I created this presentation with Google Slides. Image were created or taken from Wikimedia Commons I created this video with the YouTube Video Editor. ADDITIONAL TAGS: Chemotherapeutic agents Classes of chemical agents used in the treatment of cancer Alkylating agents Antimetabolites Microtubule targeting agents Topoisomerase inhibitors Anthracyclines Monoclonal antibodies Other agents Alkylating agents Attach alkyl groups to DNA, allows cross linking of base pairs, damaging DNA; cell cycle nonspecific Typical alkylating agents: cyclophosphamide, ifosfamide, melphalan, busulfan, mechlorethamine, chlorambucil, thiotepa Side effects: myelosuppression drop in WBC, Hb, crit, nausea/vomiting, secondary malignancies, infertility/impaired fertility, hemorrhagic cystitis hematuria, dysuria from direct irritation of bladder by acrolein metabolite Atypical alkylating agents Platinum compounds covalently bind purine DNA bases. Drugs and side effects: cisplatin causes nephrotoxicity and n/v carboplatin causes thrombocytopenia oxaliplatin causes cold sensitivity all cause peripheral neuropathies, paresthesia Nitrosoureas: BCNu, CCNu both cause pulmonary toxicity, phlebitis. CNS Alkylating agents Antimetabolites Microtubule targeting agents Topoisomerase inhibitors Anthracyclines Monoclonal antibodies Other agents Antimetabolites Inhibit DNA replication or repair by mimicking normal cell compounds; S phase specific Folate inhibitor: Methotrexate inhibits DHFR, prevents regeneration of THF Adjuvant leucovorin to protect healthy cells adjuvant Side effect is mucositis, myelosuppression Pyrimidine inhibitors 5-fluorouracil inhibits thymidylate synthetase Bolus dose causes myelosuppression Continuous dose causes GI problems mucositis, diarrhea Synergistic leucovorin potentate mechanism of action synergistic Capecitabine is essentially an oral prodrug for 5-FU Side effect: hand-foot syndrome - palms and hands and feet become red, can start blistering Cytarabine AraC is a DNA chain terminator Side effects: conjunctivitis and cerebellar neural defects The 7 in 7+3 chemotherapy Purine analog is 6-mercaptopurine Alkylating agents Antimetabolites Microtubule targeting agents Topoisomerase inhibitors Anthracyclines Monoclonal antibodies Other agents Microtubule targeting agents These drugs inhibit mitosis, specifically M phase Vinca alkaloids destroy microtubules, obviously preventing their function Vincristine, vinblastine, and vinorelbine Side effects: peripheral neuropathy, myelosuppressive blast others Fatal if given intrathecally Taxanes stabilize microtubules, preventing their function Paclitaxol, docetaxol Side effects: myelosuppression, peripheral neuropathies Hypersensitivity from diluent: Cremophor diluent in paclitaxel Tween80 in docetaxel Avoid hypersenitivity with abraxane, protein-bound paclitaxol particles less sensitivity but more neuropathy Topoisomerase inhibitors Topoisomerase I inhibitors prevent relaxation of supercoiled DNA Topotecan, irinotecan Both have side effect of myelosuppression Irinotecan causes diarrhea: “I ran to the can” Topoisomerase II inhibitors prevent recoiling of DNA after transcription Etoposide, teniposide Both have side effects of myelosuppression, mucositis, secondary malignancies AML Etoposide also causes hypotension Anthracyclines Various mechanisms of action: intercalate DNA, inhibit topo II, generate ROS, perhaps alkylation -rubicins: doxorubicin, daunorubicin, idarubicin, epirubicin Side effects: biventricular heart failure, necrotic with extravasation The 3 in 7+3 chemotherapy Monoclonal antibodies Origin determined from suffixes: -omab from mouse; -ximab is chimeric cross between human/mouse; -umab is humanized; -mumab is fully human mAb Target Treats: Toxicity Rituximab CD20 lymphoma - Trastuzumab Her-2 breast cancer - Cetuximab EGFR solid tumors initially for colorectal cancer Acneiform rash Bevacizumab VEGF solid tumors initially for colorectal/lung cancers GI perforation, Other chemotherapeutic agents Bleomycin causes lung toxicity Side effects: pulmonary fibrosis, interstitial pneumonitis, hypersensitivity pneumonitis cough, infiltrates Hormonal therapies Antiestrogens block estrogen stimulation of breast cancer Tamoxifen, fulvestrant, megestrol acetate Aromatase inhibitors block synthesis of estrogen Anastrozole, letrozole Antiandrogens block androgen stimulation of prostate cancer Other targets for prostate cancer are LHRH agonists prevent testosterone production, GnRH antagonist, CYP17 inhibitor