Cancer Drugs

Question 1

Anti-metabolite drugs

Answer 1

• Folate antagonist
  
  • Methotrexate
• Purine Analogs
  
  • 6-thiopurines
    
    • 6-mercaptopurine
    • 6-guanopurine (?)
  • Fludarabine ==> CLL tx
  • Cladribine ==> HCL tx
• Pyrimidine Ananologs
  
  • 5-FU
  • Capecitabine
  • Cytarabine
  • Gemcitabine

Question 2

Vinblastine: MOA, SE

Answer 2

• MOA:
  
  • inhibits MT formation of mitotic spindle
• SE:
  
  • alopecia
  • constipation
  • myelosuppression
  • neurotoxicity (rare)

Question 3

Cancer drugs that act in the M phase of the cell cycle

Answer 3

• vinca alkaloids=inhibit MT fxn/spindle formation
  
  • vincristine
  • vinblastine
• paclitaxel
  
  • binds to tubulin and hyperstabilizes MTs that have already polymerized ==> prevents spindle breakdown

Question 4

5-fluorouracil: MOA, use

Answer 4

• anti-metabolite
• prevents formation of thymidine vua inhibition of thymidylate synthase
• uses
  
  • slow-growing solid tumors:
  • breast
  • ovarian
  • pancreatic
  • colorectal
  • gastric carcinomas

Question 5

6-mercaptopurine: MOA, use

Answer 5

• anti-metabolite
• inhibits formation of purines
• use = cancer drug

Question 6

Methotrexate: MOA, use

Answer 6

• anti-metabolite
• inhibts dihydrofolate reductase ==> inhibition of DNA synthesis (via same pathway as 5-fluorouracil)
• use = cancer drug

Question 7

Busulfan: MOA, use

Answer 7

• DNA alkylating agent (cell cyle nonspecific)
• use = CML

Question 8

Bleomycin: MOA, use, SE

Answer 8

• inhibit replication by inducing DNA strand breaks via free radical formation
• strand breakage interrupts G2 phase of cell cycle (after DNA synthesis)
• uses: testicular tumors, lymphomas, squamous cell carcinoma
• SE
  
  • rales, cough
  • infiltration ==> fibrosis

Question 9

Cyclophosphamide: MOA, uses, SE

Answer 9

• DNA alkylating agent (cell cycle nonspecific)
  
  • activated by CYP450
  • ==> apoptosis via DNA crosslinking
• uses
  
  • leukemias, lymphomas
  • testicular and gyn cancers
• SE
  
  • hemorrhagic cystitis

Question 10

How to prevent major side effect of cycloposphamide

Answer 10

• prevent hemorrhagic cystitis via:
  
  • adequate hdration
  • IV injection of mesna

Question 11

Methotrexate rescue

Answer 11

• folinic acid aka n-formyl-xxxx aka leucovorin
• acts synergystically with 5FU

Question 12

Common method of chemotherapy resistance

Answer 12

• human multi-drug resistance gene (MDR1)
• p-glycoprotein = transmembrane ATP-dependent efflux pump
  
  • broad specificity for hydrophobic compounds
  • decreases drug entry and increases efflux