Tuesday, January 30, 2007

UKALL 2003 - Vincristine

Another drug derived from a natural source – the Madagascan Periwinkle Caranthus roseus. The plant has been in use in traditional medicine for centuries treating anything from diabetes to wasp stings to eye infections. When scientists began looking at it in the 1950s, they discovered over
70 alkaloids among which was vincristine.

Microtubules form part of the structural network, or cytoskeleton, of a cell's cytoplasm. They are made of a protein called tubulin. They form various structures and have various functions. One of these is the formation of a structure called a mitotic spindle (mitosis = cell division). This segregates chromosomes correctly during cell division so that each daughter cell receives the correct number of chromosomes. In the picture below the mitotic spindle is green and the chromosomes are blue.

Vincristine binds to tubulin and prevents the formation of microtubules and, in particular, the mitotic spindle. Thus the cell dies without being able to divide.

Unlike our other chemotherapy agents so far, this is not working directly on the cell nucleus and DNA but within the cell's cytoplasm surrounding the nucleus.

It has, like all our drugs, many side-effects. Particularly, noticeable are neurological effects – Kezia developed tingling feet making her unwilling to walk. Others report similar effects.

If given intrathecally (in the spine), it is fatal. For this reason the UKALL 2003 protocol gives the following warning:

All medical staff involved in the care of patients with leukaemia MUST be aware that the inadvertent administration of vincristine by the intrathecal route is invariably FATAL. Vincristine should NOT BE AVAILABLE when an intrathecal needle is in situ. This protocol has been written to provide separation of intrathecal methotrexate administration from intravenous vincristine administration in time. An additional precaution is that the two drugs should not be administered in the same place.”

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