Τόμος 5 (1987) – Τεύχος 1 – Άρθρο 3 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 5 (1987) – Issue 1 – Article 3 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

5: 23-31 (1987)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

5: 23-31 (1987)

The Vinca Alkaloids (Vincristine, Vinblastine, Vindesine) are closely related chemical structures, with some differences in their spectrum of cli­nical action and toxicity. The Vinca Alka­loids possess cytotoxic activity by virtue of their binding to tubulin. They have the same cellular mode of action because tubulin is their target molecule. Through their binding to tubulin, they inhibit the assembly of microtubules, and lead to the dissolution of the mitotic spindle. They block tubulin polymerization and interact with performed microtubules in vitro. The primary action of Vinca Alkaloids is an arrest of cells in the metaphase of mito­sis. They inhibit the invasion of the can­cer and sarcoma cells. The anti-invasive effect is ascribed to interference of these drugs with the assembly of the cytopla­smic microbutule complex, resulting in in­hibition of the cells capacity to perform directional migration. Vinca Alkaloids inhi­bit the calmodulin – dependent fraction of Ca²⁺ – transport ATPase. With respect to other ATPases the action of them on Ca2⁺-transport ATPase seems to be specific sin­ce Mg²⁺-ATPase and Na⁺/Κ⁺-ATPase are hardly affected. Since Ca²⁺ and cyclic AMP concentration both regulated by calmodu­lin, which plays a role in assembly-dissas­sembly of microtubules during mitosis. The mechanism by which the Vinca Alkaloids permeate cells is uncertain. The main fea­tures of drug disposition are similar for these agents and include the achievement of peak plasma concentrations, with their administration by i.v. bolus. Total doses often associated with progressive and di­sabling neurotoxicity (peripheral neuropa­thy, autonomic neuropathy and cranial nerves). Vincristine causes little myelo­suppresion, mucositis is another frequent side effect, and neurotoxicity rarely is ob­served at conventional doses. Vindesine, causes both myelosuppression and mild but consistent neurotoxicity, similar to that caused by Vincristine; since it is less toxic than Vincristine. It is anticipated that it would be a more acceptable agent for chronic administration. Vinblastine is less toxic than both of the others. The Vinca Alkaloids play an important role in the management of malignant diseases becau­se of their spectrum of activity. They are included in many combination chemothe­rapeutic regimens. Unfortunately these drugs are often deleted after several cour­ses because of their neurotoxicity.

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