Chemotherapeutic agents

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

How anticancer drugs work – Molecular mechanism of action of doxorubicin or adriamycin

How anticancer drugs work – Molecular mechanism of action of doxorubicin or adriamycin

The cytotoxic antibiotics are a varied group of drugs that have various mechanisms of action. The group includes the anthracyclines and other drugs including actinomycin, bleomycin, plicamycin, and mitomycin. Doxorubicin and daunorubicin were the first two anthracyclines, and were obtained from the bacterium Streptomyces peucetius. Derivatives of these compounds include epirubicin and idarubicin. Other clinically used drugs in the anthracyline group are pirarubicin, aclarubicin, and mitoxantrone. The mechanisms of anthracyclines include: • DNA intercalation (molecules insert between the two strands of DNA) • Iron-mediated generation of highly reactive free radicals that damage cellular molecules • Topoisomerase inhibition • Induction of histone eviction from chromatin that deregulates DNA damage response, epigenome and transcriptome Actinomycin is a complex molecule that intercalates DNA and prevents RNA synthesis. Doxorubicin (INN, AAN, BAN, USAN; trade name Adriamycin; pegylated liposomal form trade name Doxil; nonpegylated liposomal form trade name Myocet), also known as hydroxydaunorubicin and hydroxydaunomycin, is a drug used in cancer chemotherapy and derived by chemical semisynthesis from a bacterial species. It is an anthracycline antitumor antibiotic closely related to the natural product daunomycin and like all anthracyclines, it works by intercalating DNA, with the most serious adverse effect being heart damage. It is commonly used in the treatment of a wide range of cancers, including hematological malignancies (blood cancers, like leukemia and lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It is often used in combination chemotherapy as a component of various chemotherapy regimens. * Crystal structure provides more accurate structural information but less accurate chemical information (such as bond order, polar contacts etc.). You should be careful about this.

Anthracyclines for HER2-Positive Early Breast Cancer

Anthracyclines for HER2-Positive Early Breast Cancer

The continued use of anthracyclines in the adjuvant treatment of patients with early-stage HER2-positive breast cancer is an area that has posed many questions in recent years. Moderator, Debu Tripathy, MD, explains that some physicians are considering abandoning the use of anthracyclines, due to recent clinical trials and the toxicity profile. For more from this discussion, visit http://www.onclive.com/peer-exchange/early-breast-cancer

Anthracycline Chemistry and Biology II Mode of Action, Clinical Aspects and New Drugs Topics in Curr

Anthracycline Chemistry and Biology II Mode of Action, Clinical Aspects and New Drugs Topics in Curr

Anthracyclines - doxorubicin, daunorubicin, idarubicin, Lang Pharm Cards

Anthracyclines - doxorubicin, daunorubicin, idarubicin, Lang Pharm Cards

via YouTube Capture

Cancer Drugs - Learn with Visual Mnemonics!

Cancer Drugs - Learn with Visual Mnemonics!

Website: http://VisualLearner.net/ Facebook: http://www.facebook.com/visuallearnerstudios Twitter: https://twitter.com/VL_Studios Alright...today, we will go over some common classes of drugs used in treating cancer and examples within each class. To remind you of this, this picture is a scene out of the latest sci-fi movie starring my main man...VIN EASEL. The plot?...Vin Easel and his crew battling a giant cancer crab. Vinca alkaloids: Vinblastine, Vincristine First up, are the Vinca alkaloids represented by Vin Easel. VIN BLASTING the crab is VINBLASTINE, and VIN with the CROSS is VINCRISTINE. Antimetabolites - Methotrexate, Fluorouracil, Mercaptopurine Next, we have the antimetabolites, represented by the T-Rex. The METH smoking T-REX is METH-O-TREX-ATE, his FLORAL shorts is FLUORO-URACIL, and his MERCEDES CAP is MER-CAP-TOPURINE. *we do not condone smoking meth* Taxanes: Paclitaxel Another class are the Taxanes, represented by the Tax Man. He’s is wearing a PACK of TAXES, which is PAC-LITAXEL. Alkylating Agents - Cyclophosphamide, Carboplatin, Cisplatin, Busulfan Lastly, we have the Alkylating agents, these are represented by the vehicles in the back line. The CYCLONE CYCLER on his PHOSPHATE bike is CYCLOPHOSPHAMIDE. The CAR of PLATINUM is CARBOPLATIN, and his SISter car is CIS-PLATIN. The BUS wielding FANS is BUS-UL-FAN. Alright folks, that’s it for this video! To learn more about visual mnemonics and Cancer drugs, including mechanisms of action and side effects, please check out our website at VisualLearner.net. Happy studying!

Anthracyclines - Focus for the Cure

Anthracyclines - Focus for the Cure

Dr. Elisabeth McKeen, FACP Medical Oncologist, Palm Beach Cancer Institute

Anticancer Chemotherapy - Topoisomerase Inhibitors Part 1

Anticancer Chemotherapy - Topoisomerase Inhibitors Part 1

In this video we discuss the use of topoisomerase inhibitors in anticancer chemotherapy.

Doxorubicin-induced Cardiotoxicity

Doxorubicin-induced Cardiotoxicity

How Chemotherapy Drugs Work

How Chemotherapy Drugs Work

Learn how different types of chemotherapy drugs work. Dr. Meschino explains the process of cell division & explains the stages of cell division that different chemotherapy drugs target to stop the replication of cancerous cells. Visit http://www.meschinohealth.com/ArticleDirectory/How_Chemotherapy_Drugs_Work to read Dr. Meschino's full article on this topic.

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