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01-12-2016 | Nausea and vomiting | Book chapter | Article

2. The Physiology and Pharmacology of Nausea and Vomiting Induced by Anticancer Chemotherapy in Humans

Authors: DSc Paul L. R. Andrews, PhD John A. Rudd

Publisher: Springer International Publishing

Abstract

The basic pathways inducing vomiting, the brainstem sites of integration and the main motor components had all been described by the early 1950s but relatively little was known about how cancer chemotherapeutic agents induced emesis until research was prompted by the clinical use of cisplatin thirty years later. The acute phase of cisplatin-induced emesis is predominantly driven by 5-hydroxytryptamine released from enterochromaffin cells in the small intestine activating 5-HT3 receptors located on vagal afferent terminals. Other substances such as prostanoids and substance P also interact with receptors on the afferents and are proposed to be involved in local inflammatory responses. Although for the delayed phase of cisplatin-induced emesis a contribution of the vagal afferents driven by an inflammatory response in the gut cannot be excluded, the evidence supports release of an endocrine mediator (unidentified) from the gut but acting on the area postrema to activate central pathways. The potential mechanisms by which cisplatin and other chemotherapeutic agents act on the gut epithelium and enteric neurones are reviewed. The sites and mechanisms of action of 5-HT3 and NK1 receptor antagonists are discussed in relation to the emetic pathways. The biologically significant, aversive, unpleasant sensation of nausea is a focus of the chapter because it impacts on the patient’s quality of life. The potential roles of vasopressin secretion, disturbance of gastric myoelectric activity and central pathways implicated in the genesis of the sensation are discussed in the wider context of the relative efficacy of anti-emetic drugs against nausea as compared to retching and vomiting.

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