Question | Answer |
Chemotherapy Uses | 1) Advanced Disease: No other tx possible. Chemo alone. Metastatic disease. Improve QOL. 2) Localized disease: Chemo + radiation. Neo-Adjuvant therpay. Other tx available but not totally effective. Anal, bladder, esophagea, laryngeal Ca 3) Adjuvent therapy: Surgery + radiation. REduce systemic and local effects and imrpove patient survival. Breast, Lung, Colon, Gastric, Wilm's tumor, Astrocytoma |
Primary Resistance | No response with drug therapy indicates towards a primary resistance (Malignant melanoma, renal cell cancer, and brain cancers). as been blamed on loss of p53 Tumor suppressor gene |
Acquired Resistance | In response to exposure of chemotherapeutic agent. Usually a multidrug resistance occurs. Increased expression of MDR1 gene in certain tumors |
Classes of Anticancer Drugs | Alkylating AGents Antimetabolites Natural Anticancer drugs Anticancer Abx Misc. Anticancer Drugs |
Alkylating Agents Examples | Chlorambucil, Melphalan, Cyclophosphamide, Busulphan, Thiotepa, Cisplatin, Dacarbazine |
Antimetabolites Examples | Methotrexate, 5 fluroacil, Cytarabine, Fludarabine |
Natural Anticancer Drugs Examples | Vinblastine, Vincristine, Epipodophyllotoxins |
Anticancer Antibiotics Examples | Anthracyclines, Mitomycin Bleomycin |
Misc. Anticancer Drugs Examples | Imatinib, Niclotinib, Cetuximab |
Alkylating Agents MOA | Transfer their Alkyl groups to DNA w/in the nucleus causing cell death. React chemically w/ sulfhydryl, amino, hydroxyl, and phosphate groups 2ndary Mechanism: Carbamoylation of lysine proteins thus inhibiting protein chains and DNA strand breakage |
Alkylating Agents Adverse Effects | Dose related. Bone marrow, GIT, and reproductive system affected most d/t rapid cell division N/V are severe Injection abscess and induration Carcinogenic |
Cyclophosphamide [Clinical applications & Toxicity] | Clinical Applications: Inactive drug acted upon by CYP450 breast, ovarian, non hodgkins, CLL, Wilm's tumor, Neuroblastoma Toxicity: Hemorrhagic cystitis, BM depression, leukopenia |
Chlorambucil [Clinical Applications & Toxicity] | Clinical Application: CLL, NHL Toxicity: N/V |
Melphalan [Clinical Applications & Toxicity] | Clinical Applicaitons: MM, Breast, Ovarian Ca Toxicity: N/V |
Busulphan [Clinical Applications & Toxicity] | Clinical Applicaitons: CML Toxicity: Skin pigmentation, pulmonary fibrosis, adrenal insufficiency |
Carmustine/Lomustine [Clinical Applications & Toxicity] | Clinical Applications: Brain Cancer Toxicity: N/V, myelosuppression |
Dacarbazine/Procarbazine [Clinical Applications & Toxicity] | Clinical Applications: Hodgkins & NHL Toxity: Myelosuppression |
Cisplatin/Carboplatin [Clinical Applications & Toxicity] | Clinical Applications: Small cell and non small cell lung, breast, bladder, Head, and neck cancer Toxicity: Nephrotoxicity, Ototoxicity |
Methotrexate [MOA] | Folic Acid Analog Binds to DHFR (Dihydrofolate Reductase) Inhibits production of THFR Inhibits formation of cellular proteins needed by Cancer cells to grow and proliferate |
Methotrexate [Delivery] | Oral, IV, intrathecal Oral erratic absorption Renal excretion: Penicillin, ASA, cephalosporins, and NSAIDs inhibit renal excretion of methotrexate, cause toxicity |
Methotrexate [Clinical Applications & Toxicity] | Clinical Application: Breast, head and neck, osteogenic sarcoma, NHL, Bladder Ca Toxicity: Mucositis, myelosuppression, neutropenia |
5-Flurouracil [Clinical Applications & Toxicity] | Clinical Applications: Colorectal, anal, breast, head and neck, hepatocellular Toxicity: Nausea, mucositis, diarrhea, neurotoxicity |
Fludarabine [Clinical Applications & Toxicity] | Clinical Applications: NHL Toxicity: Immunosuppresion, fever, myalgia, arthralgia |
6-Mercaptopurine [Clinical Applications & Toxicity] | Clinical Application: AML Toxicity: Myelosuppression, Hepatotoxicity |
Cytarabine [Clinical Applications & Toxicity] | Clinical Applications: ALL, AML, CLL, blast crisis Toxicity: N/V/D, Myelosuppression, Neutropenia |
Gemcitabine [Clinical Applications & Toxicity] | Clinical Applications: pancreatic, bladder, breast, ovarian Toxicity: N/V/D, myelosuppression |
Natural Anticancer Drugs [Examples] | Vinblastine, Vincristine, Vinorelbine Paclitaxel Daunorubicin, Doxorubicin Etoposite, Podophyllotoxin Bleomycin Mitomyin |
Vinblastine, Vincristine, Vinorelbine (Vinca rosea-Periwinkle) [MOA, Clinical Applications & Toxicity] | -MOA-Inhibition of Tubulin, loss of mitotic spindle -Clinical Applications: HL/NHL, Breast, Kaposie's, Wilms, ALL -Toxicity: N/V, Myelosuppression, Mucositis, SIADH, Neurotoxicity, Paralytic ileus |
Paclitaxel [Clinical Applications & Toxicity] | -Clinical Applications: Breast, non small cell, Ovarian, Prostate, Bladder -Toxicity: Myelosuppression, Peripheral Neuropathy |
Daunorubicin/Doxorubicin [Clinical Applications & Toxicity] | -MOA: Oxygen free radicals bind to DNA causing breaks -Clinical Applications: Breast, Hodgkin's, AML, ALL, Thyroid, Wilms -Toxicity: Cardiotoxicity, Red Urine, Myelosuppression |
Etoposide Podophyllotoxin [MOA, Clinical Applications, & Toxicity] | -MOA: Inhibits Topoisomerase -Clinical Applications: Lung, Hodgkins, Gastric Ca -Toxicity: Alopecia, Myelosuppression |
Bleomycin [Clinical Applications & Toxicity] | -Clinical Applications: HL, NHL -Toxicity: Alopecia, Skin toxicity |
Mitomycin [Clinical Applications & Toxicity] | -Clinical Applications: Bladder, gastric, breast -Toxicity: Myelosuppression, Hemolytic-Uremic syndrome |
Imatinib, Nilotinib | Inhibitors of tyrosine kinase and prevent phosphorylation of the cell kinase substrates by ATP. |
Nilotinib | Second generation 50x more potent than imatinib |
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