Chemotherapy drugs from plant origins

• Microtubules inhibitors:

  • vinca alkaloids

  - vincristine

  - vinblastine

  - vinorelbine

  • taxanes

  - docetaxel

  - paclitaxel

  - carbazitaxel

  • epipodophyllotoxins

  - podophyllins
• Topoisomerase inhibitors:

  1. epipodophyllotoxins

  - etoposide

  - teniposide

  
  

  2. camptothecins

  - topotecan

  - irinoteca
• MOA of vinca alkaloids:

  1.acts on tubulin

  • main constituents of microtubules of living cells
  • important in nerve conduction and signal transduction

  2.cell cycle specific

  • acts on S phase and M phase
  • disrupt the normal balance between polymerization & depolymerization of microtubules
  • inhibiting the assembly of microtubules
  • interfering with the formation of spindle fibers
  • causing cells to arrest at metaphase
  • thereby halt the cell division
• Vincristine

  • active in leukemia

  SE: neurotoxicity
• Vinblastine:

  1. Active in :

  • lymphoma
  • testicular cancer

  SE: myelosuppression
• Vinorelbine

  • active in lung cancer

  SE: neurotoxic and myelosuppression
• vinca alkaloids act on S phase and M phase
• Taxanes act on late G2 mitotic phase
• Paclitaxel and docetaxel act by:

  1. binding to tubulin, interfere with tubulin assembly (unlike vincas, they do not interfere tubulin assembly)
  2. induce tubulin polymerization
  3. results in formation of inappropriately stable, nonfunctional microtubules (inhibit dissemble)
• Both vincas and taxanes act on tubulin. What is the difference?

  Vincas do not interfere with tublulin assembly, but taxanes do.
• What is the common toxicity of taxanes?

  myelosuppression
• Adverse effects of docetaxel?

  -myelosuppression

  -increase fluid retention
• Adverse effects of paclitaxel?

  -myelosuppression

  -increase neurotoxicity

  -hypersensitivity reactions
• How to manage hypersensitivity reaction in paclitaxel?

  require premedication

  • steroid, H2-blocker, diphenhydramine
  • new formation: albumin-bound paclitaxel
• MOA of Podophyllin

  • binds to tubulin
  • interferes with microtubule formation
• What is the difference between the MOA of podophyllin and etoposide, teniposide ?

  Podophyllin is microtubule inhibitors while etoposide and teniposide are topoisomerase inhibitors
• MOA of Etoposide and Teniposide:

  - they are semisynthetic epipodophyllotoxin derivatives

  - extracted from mayapple plant & mandrake plant

  • damage tumor cells b causing strand breakage via inhibiting topoisomerase II
  • cross-resistant

  - acts on S phase and early G2 phase

  • activity is greater in divided dose rather than in large single dose
• Etoposide an Teniposide act on s phase and early G2 phase