58° Congresso Nazionale SCIVAC: Oncologia veterinaria

58° Congresso Nazionale SCIVAC • Milano, 7-9 Marzo 2008 • Oncologia veterinaria - Alle soglie del III Millennio
ANTIMICROTUBULE AGENTS
The antimicrotubule agents include the vinca alkaloids, compounds that are
derived from the periwinkle (Cantharanthus roseus, or Vinca rosea) plant. The
mechanism of action of the vinca alkaloids is through binding microtubular
proteins, which results in dissolution of the mitotic spindle and mitotic arrest.
Drug resistance is due to mutation of the alpha or beta subunits of tubulin, or
through increased expression of a cell membrane pump (P-glycoprotein).
VINCRISTINE
A naturally occuring vinca alkaloid, is an antimicrotubule antineoplastic
agent. It is the dimeric alkaloid salt isolated from Cantharanthus roseus (Vinca
rosea linn). The drugs vinblastine and vincristine were introduced in the 1960’s.
Mechanism of action
Inhibition of microtubule assembly occurs as a result of binding to tubulin
subunits. Vincristine arrests cells in the G2/M phase of the cell cycle.
Pharmacokinetics
The principle route of administration of vincristine is intravenous. Doses used
in veterinary medicine range from 0.5-0.75 mg/m 2 body surface area. The drug is
rapidly and widely distributed following IV administration. Vincristine is excreted
through the bile. Peak bile concentration occurs 2-4 hours after rapid IV injection.
Toxicity
Vincristine can cause myelosuppression, especially at the high end of the
dosage range. Perivascular injection can result in tissue irritation and sloughing.
Because of effects on microtubule function, the drug can result in neurotoxicity
due to impairment of axonal transport, often manifested at GI ileus.
Indications
Vincristine is most often used in combination to treat lymphoma, leukemia,
and sarcomas in dogs and cats. Vincristine is a successful single-agent
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