Vinca alkaloids

Vinca alkaloids

Vinca alkaloids are nitrogenous bases derived from the periwinkle plant. These drugs are cell cycle’specific for the M phase and include:

• vinblastine
• vincristine
• vinorelbine.

Pharmacokinetics

After I.V. administration, the vinca alkaloids are well distributed throughout the body.

Metabolism and excretion

Vinca alkaloids undergo moderate liver metabolism before being eliminated through different phases, primarily in stool with a small percentage eliminated in urine.

Pharmacodynamics

Vinca alkaloids may disrupt the normal function of the microtu-bules (structures within cells that are associated with the movement of DNA) by binding to the protein tubulin in the microtu-bules.

Separation anxiety

With the microtubules unable to separate chromosomes properly, the chromosomes are dispersed throughout the cytoplasm or arranged in unusual groupings. As a result, formation of the mitotic spindle is prevented, and the cells can’t complete mitosis (cell division).

 

Under arrest

Cell division is arrested in metaphase, causing cell death. Therefore, vinca alkaloids are cell cycle’specific for the M phase. Interruption of the microtubule function may also impair some types of cellular movement, phagocytosis (engulfing and destroying micro-organisms and cellular debris), and CNS functions.

 

Pharmacotherapeutics

Vinca alkaloids are used in several therapeutic situations:

• Vinblastine is used to treat metastatic testicular cancer, lymphomas, Kaposi’s sarcoma (the most common acquired immunodeficiency syndrome [AIDS]–related cancer), neuroblastoma (a highly malignant tumor originating in the sympathetic nervous system), breast cancer, and choriocarcinoma.
• Vincristine is used in combination therapy to treat Hodgkin’s disease, non-Hodgkin’s lymphoma, Wilms’ tumor, rhabdomyosarcoma, and acute lymphocytic leukemia.
• Vinorelbine is used to treat non’small-cell lung cancer. It may also be used in the treatment of metastatic breast cancer, cisplatin-resistant ovarian cancer, and Hodgkin’s disease.

Drug interactions

Vinca alkaloids can interact with other drugs.

• Erythromycin may increase the toxicity of vinblastine.
• Vinblastine decreases the plasma levels of phenytoin.
• Vincristine reduces the effects of digoxin.
• Asparaginase decreases liver metabolism of vincristine, increasing the risk of toxicity.
• Calcium channel blockers enhance vincristine accumulation, increasing the tendency for toxicity. (See Adverse reactions to vinca alkaloids.)

Warning!

Adverse reactions to vinca alkaloids

Nausea, vomiting, constipation, and stomatitis may occur in patients taking vinca alkaloids. Tissue necrosis may also occur with extravasation.

Toxic topics

Vinblastine and vinorelbine toxicities occur primarily as bone marrow suppression.

Muscle matters

Neuromuscular abnormalities commonly occur with vincristine and vinorelbine and, occasionally, with vinblastine therapy.

Tumor trouble

Vinblastine may produce tumor pain described as an intense stinging or burning in the tumor bed, with an abrupt onset 1 to 3 minutes after drug administration. The pain usually lasts 20 minutes to 3 hours.

Less hair there

Reversible alopecia occurs in up to one-half of patients receiving vinca alkaloids; it’s more likely to occur with vincristine than with vinblastine.