Pharmacology
Summary
Mitotic inhibitors are chemotherapeutic agents that disrupt the function of microtubules--- crucial parts of the cytoskeleton and mitotic spindle that play a critical role in cell division, intracellular transport, and structural support within cells--- and inhibit mitosis, which effectively slows down the proliferation of cancer cells.
Vincristine and vinblastine are examples of mitotic inhibitors and are classified as vinca alkaloids.Vincristine works by binding to tubulin subunits in the microtubule, preventing their polymerization and leading to reduced microtubule formation, which disrupts the assembly of the mitotic spindle. Similarly, vinblastine also disrupts mitotic spindle formation, which causes an arrest in cell division and leads to cell death. In contrast, taxanes--- a group of plant alkaloid derivatives that bind directly to microtubules, such as paclitaxel, docetaxel, and cabazitaxel--- inhibits cellular proliferation by stabilizing microtubules and preventing their degradation. Despite the differing mechanisms, all these mitotic inhibitors lead to an arrest in the M phase of the cell cycle and prevent further cell division.
Lesson Outline
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FAQs
Vincristine and Vinblastine belong to a group of drugs called vinca alkaloids. They inhibit microtubule production and mitotic spindle assembly, which disrupts the formation of the spindle fibers that separate the chromosomes during cell division (mitosis), preventing cell division and thus arresting the cell in the M phase of the cell cycle. This makes them effective in treating various hematologic and solid malignancies.
Vinca alkaloids like vincristine and vinblastine are used for treating many hematologic and solid malignancies, including leukemias, lymphomas, pediatric tumors, breast cancer, and germ cell cancer. These drugs can be used alone or in combination with other cancer therapies depending on the type and stage of the cancer.
Vincristine can potentially produce a number of adverse side effects, including neurotoxicity, which can manifest as peripheral sensory neuropathy. It may also cause autonomic dysfunction that can present as paralytic ileus or constipation. Another common side effect of vinca alkaloids, which includes vincristine, is alopecia or hair loss.
Taxanes, which include drugs like paclitaxel, docetaxel, and cabazitaxel, have a mechanism of action that is opposite to that of vinca alkaloids. While vinca alkaloids inhibit microtubule production and prevent assembly of the mitotic spindle, taxanes enhance microtubule production and prevent their degradation. This results in the stabilization of the microtubule and prevention of its disassembly, leading to improper mitotic spindle function and the cessation of cell division at the M phase of the cell cycle.
