Anticancer Drugs Flashcards
Malignant
Tumor invades nearby tissue or spreads throughout the body
Anticancer drug classes
Cytotoxic drugs, hormonal drugs and targeted drugs
Cytotoxic Drug Toxicity Impacts on body systems
- Bone marrow: Neutropenia (decrease WBC’s) which results in infections. Fever. The “nadir”, Thrombocytopenia (decrease in platelets)
- Hair follicles: Alopecia
- GI tract: stomatitis, diarrhea, nausea and vomiting
- Gonads: menstrual irregularities and impaired spermatogenesis
- Wounds: impaired healing
- Fetus: teratogenesis
Cytotoxic Drug Therapy
Combination drug therapy is most effective: less drug resistance, increased effectiveness, less toxic to normal cells because drugs with non overlapping toxicities are used
Hodgkins Drug Therapy
ABVD- adriamycin, bleomycin, vinblastine, decarbazine
Breast Cancer Drug Therapy
CMF- cyclophosphamide, methotrexate, 5-fluorouracil
Cytotoxic drug types or classes
Alkylating agents, platinum compounds (alkylating “like”), antimetabolites, anti tumor antibiotics, mitotic inhibitors, topoisomerase inhibitors, miscellaneous cytotoxic drugs
Alkylating Agents
- CYCLOPHOSPHAMID, CISPLATIN (alkylating “like”)
- Highly reactive compounds
- Cells killed by alkalization of DNA
Cyclophosphamide
- Used orally and IV with a half life of 7 hours
- Requires activation in the liver to activate metabolites. Suppresses the immune system
Adverse Effects and Uses of Cyclophosphamide
Bone marrow suppression, nausea and vomiting, alopecia, sterility, immunosuppression, hemorrhagic cystitis, bladder toxicity, Mesna as an antidote
Uses: leukemia, lymphoma, multiple myeloma; breast, lung, ovarian, neuroblastoma, retinoblastoma, sarcoma,
Cisplatin-Alkylating like agent
- Platinum-guanine DNA crosslinking
- Used by IV infusion
- Adverse effects: nausea and vomiting, bone marrow suppression, irreversible HEARING loss (ototoxicity), peripheral neuropathy, use is limited by renal toxicity which is treated with fluid and diuretics
- Uses: testicular, ovarian, bladder, lung, head and neck cancers
Cochlear explants cultures
Protection of hair cells in the inner ear from cisplatin-induced death
Antimetabolites
Drugs that resemble natural substrate molecules and inhibit or substitute for those molecules to interfere with DNA or RNA synthesis groups include: PYRIMIDINE ANALOGS-5-fluorouracil
PURINE ANALOGS- 6 mercaptopurine
Antitumor Antibiotics-DOXORUBICIN
Only used IV to treat cancer
MOA: Inserts into DNA
-Used to treat many tumor types: Hodgkin’s, cancers of lung, ovary, breast, thyroid, testes
- Can cause acute (arrhythmias) and delayed, months to years, (heart failure) cardiac toxicity. Vesicant
Mitotic Inhibitors
MOA: Block mitosis by inhibiting microtubules that move chromosomes during cell division, given IV
Vincristine and Paclitaxel
Vincristine
Causes peripheral nerve toxicity but little bone marrow depression. Common use in combo cancer therapy. Vesicant
Paclitaxel
Commonly used, ovarian and lung cancer. Causes bone marrow suppression, peripheral neuropathy and cardiac toxicity
Topoisomerase Inhibitors
Etoposide and Asparaginase (enzyme)
ETOPOSIDE
Etoposide inhibits topoisomerase. Topoisomerase alters the shape of supercoiled DNA to allow replication and repair. This drug causes hypotension, dilute in large volume of i.v. fluid
ASPARAGINASE
Converts asparagine to aspartic acid which depletes the amino acid asparagine inhibiting protein synthesis. Only LEUKEMIC cells.
Atypical adverse: altered blood coagulation, liver and kidney damage, immune hypersensitivity reactions. NO BONE MARROW EFFECTS
TAMOXIFEN
Antiestrogens block estrogen receptors in breast tumors (ER +) in women and men.
MOA: blocks estrogen receptors in some tissues (breast) but stimulates those receptors in other tissues (bone and liver). Selective estrogen receptor modulator
Adverse Effects of Tamoxifen
Menstrual irregularities, hot flashes, thromboembolism (deep vein thrombosis), endometrial cancer risk, may cause damage to developing embryos
Aromatase Inhibitors-Letrozole, Anastrozole and Exemestane
MOA: block synthesis of estrogen from androgens
Oral drugs. Treatment for 5 years.
Adverse: musculoskeletal pain is common, hot flashes, GI disturbances, osteoporosis
Trastuzumab
- Human epidermal growth factor receptor 2 (HER2) monoclonal antibody
- Trastuzumab binds to HER2 to inhibit cell growth and causes antibody induced cell death
- Adverse effects: cardio toxicity, fatal hypersensitivity reactions, flu like symptoms (40%)
Hormonal Drugs for Prostate Cancer
- Prostate glands tumors require androgen for tumor growth
- Prostate cancer drugs include: Gonadotropin releasing hormone antagonists, androgen receptor blockers
GnRH Antagonists
- Degarelix is a GnRH antagonist. Blocks GnRH receptors and inhibits FSH and LH hormones release, thus blocking testes production of androgens
- Adverse effects: hot flashes, loss of libido, gynecomastia, reduced muscle mass, osteoporosis
Androgen Receptor Blockers
Flutamide- oral
MOA: blocks androgen receptors in tumor cells to inhibit androgen dependent cell growth
Adverse: hot flashes, loss of libido, gynecomastia, reduced muscle mass, osteoporosis, liver failure
Gefitinib or Erlotinib
MOA: small molecules which block an enzyme called tyrosine kinase thus suppressing cell proliferation and promoting apoptosis
Indication: cancer resistant to cisplatin or paclitaxel therapy
Adverse: GI, skin rash
