Pharm 2 Exam 3: sasha

• Growth Fraction


  ratio of proliterating cells to G0 cells

  High growth fraction = high % of proliferating cells

  - Chemo is more effective on tissues with high growth fraction (skin, hair, bone marrow, sperm, GI)
• Obstacles to chemotherapy


  Toxicity to normal cells

  Cure requires 100% cell kill

  If not early detected - more aggressive tx is needed

  Solid tumors respond poorly - surgery is better
• Strategies for maximum chemo benefits - intermittent chemotherapy


  normal cells can recover between doses, only partial regrowth of cancer cells
• Strategies for maximum chemo benefits - combination therapy

  suppresses drug resistance, increases cancer cell kill and decreases injury to normal cells
• What blood counts to monitor for cancer

  low platelets (watch bleeding)

  low rbcs (watch anemia)

  low wbcs (neutropenic precautions)
• What do you do if the chemo is not working

  stop chemo
• What infection indicator is critical to assess in a patient on chemotherapy

  fever - is a medical emergency in someone on neutropenic precautions
• What is extravasation and why do you monitor it in someone on chemotherapy

  Chemo is a toxic med and can cause necrosis if it leaks into surrounding tissues

  1. remove the extra med

  2. administer antidote

  3. remove IV
• When is cancer treatment okay in pregnancy

  Chemo - 2nd and 3rd trimester

  Radiation - poses risk to fetus throughout entire pregnancy
• Cell-cycle phase specific drugs


  Must be in blood continuously for a long time

  Toxic only to cells in a particular phase
• Non-specific cell cycle drugs

  More toxic than phase-specific
• Classes for cell cycle phase specific drugs (4)

  - antimetabolites

  - hypo methylating agents

  - mitotic inhibitors

  - topoisomerase inhibitors
• Classes for non-phase specific drugs (3)

  - alkylating agents

  - platinum compounds

  - antitumor antibiotics
• Antimetabolite classes (3) and MOA

  - folate antagonists

  - Pyridimine antagonists

  - Purine antagonists

  
  

  S-phase specific; impacts DNA synthesis
• Folate antagonist - METHOTREXATE moa


  - blocks conversion of folic acid to its active form (folate)

  - s phase specific
• What does methotrexate treat

  RA and psoriasis
• What is the rescue med for methotrexate?

  LEUCOVORIN - given with high doses of methotrexate to allow normal cells to synthesize thymidylate and other compounds minimizing risk of normal cell kill

  FAILURE TO ADMINISTER LEUCOVORIN AT THE RIGHT DOSE AND RIGHT TIME CAN BE FATAL
• Pyridamine antagonist - FLUOROURACIL (5-PU)

  inhibits biosynthesis of pyridines, DNA & RNA
• What does fluorouracil treat?

  Solid tumors
• Route of fluouracil


  IV only - MONITOR EXTRAVASATION

  - enters CNS with ease
• Purine antagonists - MERCAPTOPURINE


  s-phase specific

  ORAL only

  prodrug - converts to active form within the cell
• What does mercaptopurine treat?


  leukemias, UC, crohns
• Mitotic inhibitors class

  - vinca alkaloids
• What phase are mitotic inhibitors blocking


  m-phase specific where cell division is prevented (mitosis)
• Vinca alkaloids drugs (2)

  Vincristine

  Vinblastine
• Vinca alkaloid drug that is toxic to peripheral nerves, but doesn't suppress bone marrow function?

  Vincristine
• Vinca alkaloid drug that causes significant bone marrow suppression, but is harmless to peripheral nerves?

  Vinblastine (remember by bone marrow, blast cell vinBLASTine)
• Cycle non-phase specific drug classes (1 with 2 subclasses)

  Alkalating agents

  - nitrogen mustard

  - nitrosourea
• Alkalating agents - how do they kill cells

  By alkalization of DNA
• Where do toxicities occur when administering alkalizing agents

  They occur in tissues with a high growth fraction - bone marrow, hair, GI mucosa, sperm
• Nitrogen mustard: CYCLOPHOSPHAMIDE


  Alkalating agent AND cross-links DNA

  - Prodrug: converted to active form by the liver
• Nitrosurea: CARMUSTINE


  Alkalating agent and cross-links DNA

  - crosses BBB easily
• How is nitrosurea (carmustine) administered


  Topical or IV (monitor for phlebitis and extravasation)
• Platinum compounds drug


  cisplatin
• How are platinum compounds administered?

  IV only
• Adverse effects of cisplatin


  KIDNEY DAMAGE - dose limiting

  - can be minimized by hydration, diuretics and amifostine

  HIGHLY EMATOGENIC
• Antitumor antibiotics subclasses (2)

  - anthracyclines

  - nonanthracyclines
• What type of culture are antitumor antibiotics isolated from?

  Streptomycin cultures

  - DO NOT TREAT INFECTION ONLY CANCER
• How do antitumor antibiotics cause cell injury?

  Through direct interaction with DNA
• Why are antitumor antibiotics given through IV


  Poor GI absorption