Doxorubacin

Other Anthracyclines

• Cell-cycle nonspecific
  • Block DNA and RNA synthesis
  • Produce free radicals
  • Disrup fluid and ion transport
• Side effects
  • BM suppression
  • Cardiac tox (give with dexrazoxane)
  • Extravasation reaction

• Cell-cycle specific
  • Forms oxygen radicals
  • Accumulates cells in G₂
• Side effects
  • Allergic reactions
  • Pulm. fibrosis

• Cell-cycle nonspecific
  • Alkylating agent (cross-links DNA)
• Also used for rheumatoid arthritis
• Side effects
  • Hemorrhagic cystitis
  • Bone marrow suppression

• Cell-cycle non-specific
  • Alkylating agent
• Side effects
  • GI upset
  • Nephro and ototoxicity

• Cell-cycle dependent
  • Inhibits dihydrofolate reductase --> decreased DNA synthesis
  • Given with Leucovorin (folinic acid)
• Other uses
  • Treatment of rheumatoid arthritis
  • Abortifacient
• Side effects
  • Bone marrow suppression
  • Nephrotox

• Cell-cycle specific
  • Converted to thio-IMP
  • Inhibits purine synthesis
• Side effects
  • Bone marrow suppression
  • Hepatotox

• Cell-cycle specific
  • Converted to 5-FdUMP
  • Inhibits thymidylate synthase
  • Incorpated into RNA --> misreading
• Side effects
  • Bone marrow suppression
  • Oral ulcerations

• Cell-cycle specific
  • Inhibits DNA polymerase
  • Can be incorporated into DNA --> chain termination
• Side effects
  • Bone marrow suppression

Vincristine

Vinblastine

• Cell-cycle specifc (M phase)
  • Cause depolymerization of the mitotic spindle
• Side effects
  • Only vinblastine causes bone marrow suppression
  • Peripheral neuropathy