ANTIMICROTUBULES PHL 417 ANTIMICROTUBULE AGENTS 1 VINCA ALKALOIDS

ANTIMICROTUBULES PHL 417

ANTIMICROTUBULE AGENTS

1. VINCA ALKALOIDS Vinblastine Vincristine Vinorelbine

VINCA ALKALOIDS They are plant alkaloids extracted from Periwinkle plant (Vinca Rosa) 3 3

VINCA ALKALOIDS MECHANISM OF ACTION act by binding to and tubulin and inhibit its polymerization into microtubules leading to preventing spindle formation in mitosing cells. They Resulting in mitotic arrest at metaphase, dissolution of the mitotic spindle, and interference with chromosome segregation. CCS agents- M phase

VINCA ALKALOID MECHANISM OF RESISTANCE 1 - Pleiotropic drug resistances i. e. cross-resistant to a wide range of chemically dissimilar agents: vinca alkaloid, epidophyllotoxin, anthracyclines and colchicine. Due to: High level of P-glycoprotein o 2 - Mutation in either and tubulin that prevent effective binding of vinca alkaloids

VINCA ALKALOID THERAPEUTIC USES Vincristine Vinblastine With Lymphomas and prednisone for Systemic remission of Hodgkin’s Acute disease Leukemia Vinorelbine Non-small cell lung cancer

VINCA ALKALOID SIDE EFFECTS Vincristine -Hair loss -Neuromuscular abnormalities -parathesia Vinblastine Vinorelbine -Myelosupression Granulocytopenia -GIT ulceration

2. TAXANES Paclitaxel (Taxol) Docetaxel Alkaloid esters derived from the bark of ash tree (Taxus brevifolia).

TAXANES (CONT. ) MECHANISM OF ACTION Taxanes enhance assembly of microtubules and stabilize them against depolymerization. It binds to tubulin (at a site distinct from that used by vinca alkaloids) and promotes assembly of microtubules giving non-functional microtubule network.

TAXANES (CONT. ) TOXICITY Paclitaxel Neutropenia, thrombocytopenia Peripheral neuropathy Docetaxel Bone marrow suppression Neurotoxicity Fluid retention