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Preventing Chemotherapy-Induced Nausea and Vomiting (CINV)…

Preventing Chemotherapy-Induced Nausea and Vomiting (CINV)…

Hello. My name is Jim Koeller. I’m a professor of pharmacy medicine and oncology
out of the University of Texas at Austin and the Health Science Center in San Antonio. Today I’m going to talk about the pathophysiology
of chemotherapy-induced nausea and vomiting, also referred to as CINV. Now when you talk about the proposed pathophysiology
of CINV, there are basically three types of mechanisms for chemotherapy-induced nausea
and vomiting. We have central, we have peripheral and then
we have a combination of the two. Let’s start at the top with the central mechanism. Central mechanism is, you start with activation
of the chemotherapy trigger zone. The activation of the chemotherapy trigger
zone invokes the release of neurotransmitters and those stimulate the vomiting center. Once the vomiting center is stimulated a person
then gets efferent transmission into the body, into the diaphragm, into the stomach, into
breathing and you throw up. The peripheral mechanism is chemotherapeutic
agents cause an irritation and damage to GI mucosa. When you see this damage to the GI mucosa,
this also results in the release of neurotransmitters. These transmitters, again, through the vagus
nerve, feed up into the vomiting center and you also can throw up from a peripheral mechanism,
also activating the vomiting center causing the same vagal afferents. Then there’s the combined mechanism where
chemotherapy agents can both act centrally and peripherally, which is probably seen with
many of the agents. This next slide shows the pictorial of that
and you can see here where we talked about cell damage to the GI tract in the bottom
part of the picture and that damage then causes activation of the vagus nerve. That vagus nerve then activates the CTZ zone
that I mentioned up in the brain and that then activates the vomiting center and the
vomiting center then will cause efferent or impulses out of the brain that then hit target
organs and cause you to vomit. You can also see that you can have direct
activation through the blood because chemotherapy drugs are in the blood stream and they can
directly activate the brain, and/or through the cerebral spinal fluid, causing the same
activation of the vomiting center. This next picture shows in detail the chemicals
being released as part of this process. If you look at the bottom of the slide, in
the left-hand corner, you can see this is the gut. These are the luminal cells of the GI tract. Chemotherapy, as we mentioned, can act peripherally. They can cause damage to the cells called
enterochromaffin cells and these cells then will release a substance called serotonin. Serotonin is a substance that then activates
the receptors in the vagus nerve and that vagus nerve then feeds up into the area postrema
and that, again, is in the brainstem and that then activates the CTZ, the chemotherapy trigger
zone, that will activate the vomiting center. So it’s those neurotransmitters there that
are responsible for this activation. If you look up on the right side of this,
you can see again the central pathway, you have this vagal feed and you can see here
you have substance P being released and that substance P will activate the neurokinin receptor
and that neurokinin receptor centrally in the brain can also activate the vomiting center,
causing a person to vomit. So those are the two neurotransmitters that
seem to be related to vomiting. The peripheral one from the GI tract is more
associated with acute vomiting and the central and mediated substance P, or the neurokinin
receptor, is more responsible for delayed vomiting, which we see often with chemotherapy
administration. So summarizing this part of the pathophysiology,
chemotherapy can act both centrally and peripherally to induce nausea and emesis from chemotherapy. The enterochromaffin cells in the GI mucosa
are stimulated to release serotonin and serotonin then stimulates the afferent vagus nerve fibers,
which leads to the CTZ, the chemotherapy trigger zone, and that in turns stimulates the vomiting
center, causing one to vomit. Also, though, through blood and CSF, you can
have chemotherapy, they connect directly on the vomiting center through a central mechanism,
causing a patient to also vomit. So there can be two mechanisms, both central
and peripheral for nausea and vomiting induced by chemotherapy. That activation of the vomiting center then,
once stimulated, causing an efferent or going away from the brain that stimulates salivation,
breathing changes and then stomach muscle contraction and that stomach muscle contraction
makes you vomit. Thank you very much. That is the end of this session.

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