Vinca Alkaloids

Question 1

Example drug of a Vinca Alkaloids

Answer 1

Vincristine

Question 2

Mechanism of action of Vincristine

Answer 2

Vincristine works partly by binding to the tubulin protein, stopping the tubulin dimers from polymerizing to form microtubules, causing the cell to be unable to separate its chromosomes during the metaphase. The cell then undergoes apoptosis. The vincristine molecule inhibits leukocyte production and maturation. A downside, however, to Vincristine is that it does not only affect the division of cancer cells. It affects all rapidly dividing cell types, making it necessary for the very specific administration of the drug

Question 3

Metabolism of Vincristine

Answer 3

Dennison et al 2007
Liver, Vincristine is preferentially metabolized to a secondary amine, M1, by CYP3A5 with a 9- to 14-fold higher intrinsic clearance than CYP3A4 using cDNA-expressed enzymes. The genetically polymorphic expression of CYP3A5 may contribute to interindividual variability in vincristine efficacy and toxicity.

Question 4

Tumor type of Vincristine

Answer 4

Acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin’s disease, neuroblastoma, and small cell lung cancer

Question 5

Toxicity of Vincristine

Answer 5

The main side effects of vincristine are chemotherapy-induced peripheral neuropathy, hyponatremia, constipation, and hair loss.

Chemotherapy-induced peripheral neuropathy can be severe, and may be a reason to reduce or avoid using vincristine. The symptoms of this are progressive and enduring tingling numbness, pain and hypersensitivity to cold, beginning in the hands and feet and sometimes affecting the arms and legs. One of the first symptoms of peripheral neuropathy is foot drop: A person with a family history of foot drop and/or Charcot-Marie-Tooth disease (CMT) should avoid the taking of vincristine.