Chemo Drugs - non-cell cycle specific

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ehamm
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145126
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Chemo Drugs - non-cell cycle specific
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2012-04-01 19:05:38
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Chemo Drugs non cell cycle specific
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Chemo Drugs - non-cell cycle specific
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  1. Alkylating Agents
    • Damage DNA by adding alkyl group
    • –Results in impaired cell reproduction
    • Platinums
    • Nitrogen Mustards
    • –Cyclophosphamide, Ifosphamide, Melphalan, Chlorambucil
    • •Side effects:
    • –Myelosuppression
    • –Nausea/Vomiting (severe and common)
    • –Increased risk of secondary malignancies (AML and myelodysplasia)
    • –Neurotoxicity: tremors, confusion and ataxia (chlorambucil and ifosphamide)
    • –Hemorrhagic cystitis (cyclophosphamide)
    • Temozolomide
    • •Class: non-classic alkylating agent
    • •Mechanism of action
    • –Methylation of guanine residues in DNA which inhibit DNA, RNA, and protein synthesis
    • •Side effects
    • –Leukopenia, thrombocytopenia
    • –N/V, anorexia
    • –Headache, and dizziness
    • –Elevated LFTs (40%)
    • –Skin: rash, itching, photosensitivity
    • –Increased incidence of PCP
  2. Platinum Toxicities
  3. Anti Tumor Antibiotics
    • •Dactinomycin
    • •Mitomycin-C
    • •Bleomycin: (testicular ca) oxidation of DNA produces free radicals
    • –Pulmonary toxicity
    • •Resistance: MDR
  4. Arsenic Trioxide
    • •Mechanism of Action
    • –Apoptosis of APL cells
    • –Degradation of the fusion protein PML/RAR-a
    • •Clinical Use: Acute Promyelocytic leukemia (APL)
    • •Side Effects
    • –CV: Prolonged QT interval
    • –GI: Nausea, vomiting, diarrhea, or constipation
    • –HA, myalgias, and bone pain
    • –Leukocytosis (50% of pts)
    • –Neuro: neuropathy, tremors, insomnia
    • –Pulmonary: cough, SOB, pleural effusions
    • –Electrolyte abnormalities
    • –APL differentiation syndrome
  5. Trentinoin (ALL-Trans Retinoic Acid)
    • •Mechanism: induces maturation of promyelocytes to myelocyte; thus decreasing proliferation
    • •Clinical use: APL
    • •Side effects
    • –Vitamin A toxicity symptoms: HA, fever, bone pain,nausea, vomiting, sweating, dry skin, mucositis, rash
    • –GI: abdominal pain, diarrhea or constipation
    • –Neuro: dizziness, confusion, depression
    • –Increasing leukocyte count
  6. Steroids
    • •Prednisone
    • •Dexamethasone
    • •Action
    • –Inhibit tumor growth (NHL)
    • –Reduce inflammation
    • –Reduce CNS edema
    • –Antiemetic
  7. Tamoxifen
    • Mechanism
    • Competitively binds ER inhibiting transcriptional processes in breast cancer cells
    • Systemic estrogen receptor modulator (SERM)
    • Estrogen antagonist in breast cancer tissue
    • Estrogen agonist in endometrium and bone
    • Conversion by CYP2D6 to active drug 4-hydroxytamoxifen
    • •Use(s): Pre/Postmenopausal women with ER+ breast cancer
    • –History of ER+ DCIS/LCIS
    • –Beneficial for prophylaxis in women at high risk of developing breast cancer.
    • Serious risks: Thromboembolic events, endometrial cancers
    • Adverse effects: Hot flashes, fluid retention, vaginal bleeding
    • Drug interactions: Strong inhibitors of CYP2D6
    • SSRI’s: Paxil>Prozac>Zoloft>>Effexor
    • Genetics: CYP2D6 *10 genotype shown to have lower 4-OHT levels
  8. Aromatase inhibitors
    • •Mechanism
    • –Inactivates aromatase and blocks the conversion of adrenal androgens to estrogen
    • •Common Toxicities
    • –Hot flashes
    • –Arthralgias (15%)
    • –Headache
    • –Flu-like symptoms
    • •Examples
    • –Anastrozole
    • –Letrozole
    • –Exemestane
  9. Fulvestrant
    • •Mechanism
    • –ER antagonist
    • –Downregulates ER expression
    • •Common Toxicities
    • –Asthenia (25%)
    • –Hot flashes (20%)
    • –Flu-like symptoms (10%)
    • –Headaches
  10. LHRH Antagonists
    • •Common Toxicities
    • –Hot flashes (50%)
    • –Impotence (10%)
    • –Decreased libido (10%)
    • –Tumor Flare (20%) – increased bone pain, urinary retention or back pain
    • •Examples
    • –Leuprolide
    • –Goserelin
  11. Antiandrogens
    • •Mechanism
    • –Binds to Androgen receptor and inhibits androgen uptake
    • •Common Toxicities
    • –Hot flashes
    • –Decreased libido
    • –Gynecomastia
    • –Myalgias
    • –Hepatotoxicity
    • •Examples
    • –Bicalutimide
    • –Nilutamide
    • –Flutamide

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