CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV)

R.A.S HEMAT, MB;BCh, FRCSI, DUL.

Nausea and vomiting remain among the most distressing side effects of anticancer chemotherapy. The fear of chemotherapy-induced nausea and vomiting (CINV) can result in patients receiving suboptimal dosing of chemotherapeutic agents or even in patients refusing to continue potentially curative therapy because of anticipatory nausea and vomiting. Nausea is accompanied by gastric stasis. Emesis is defined as the forceful expulsion of gastrointestinal contents through the mouth. Retching is associated with negative deflections in the thorax coinciding with positive deflections in the abdomen.

Cytotoxic drugs and other emesis-stimulating agents form free radicals that activate enterochromaffin cells, which release serotonin. The serotonin stimulates 5-HT3 receptors located along the gut vagal afferent nerves, and the impulse is propagated to the brain, stimulating the CTZ and generating the emetic response.

Free-radical generation by biotoxins, cytotoxic drugs, or x-irradiation initiates a series of events that almost certainly involve activation of gut mucosal interneurons and alteration in neurotransmitter-receptor sensitivities in the gut.
The close proximity of enterochromaffin cells to vagal neurons suggests that serotonin released from enterochromaffin cells can reach 5-HT3 receptors on sensory neurons before entering the circulation.

The acute (sensitive to 5HT3-receptor antagonists) phase lasts about 16 hours, followed by delayed (insensitive to 5HT3-receptor antagonists) phase from 19-50 hours.

Because granisetron and ondansetron are rapidly absorbed after oral administration, absorption almost certainly occurs predominantly in the proximal gut, which is also where the concentration of 5-HT3 receptors is greatest.

A 20-mg oral dose of dexamethasone administered once before chemotherapy may be considered equivalent to a 20-mg iv. dose.

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Dr. R.A.S HEMAT declares no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, stock holdings, gifts, or honoraria.