The Gastrointestinal Tract in Chemotherapy-induced Emesis

Summary

The objective of this paper is to summarize current knowledge of gastrointestinal motility and to describe those alterations which emetic agents induce, or may induce, which result in vomiting.

The proximal stomach (fundus and orad corpus) acts as a reservoir, regulates intragastric pressure and controls gastric emptying of liquids. On the other hand, distal gastric motility is regulated by a myogenous pacemaker located along the greater curvature in the proximal corpus. The electrical activity controls the rate, strength, and direction of gastric peristalsis. The proximal and distal stomach differ in their responses to ingested substances according to the texture of the ingesta. Therefore, ‘baseline contractile activity’ is a function of the nature of ingesta (solid or liquid).

The electrical pattern of the small bowel is controlled by a pacemaker located in the first centimetre of the duodenum. As pacesetter potentials spread from the duodenum to the distal small bowel, they phase the onset and direction of contractions in the bowel.

Apomorphine and morphine at emetic doses decrease the amplitude of pacesetter potentials and cause retrograde propagation of action potentials resulting in jejuno-duodenogastric reflux and vomiting. After a characteristic latency period, cisplatin administration results in similar disorganisation of gastrointestinal motility and vomiting. Emetic episodes can be predicted as they are associated with orad sequences of action potentials which are propagated from the small bowel, through the duodenum, and then well into the proximal corpus.

Metoclopramide effectively blocks cisplatin emesis while it induces brisk bursts of action potentials in the stomach which are propagated distally into the terminal antrum. Antroduodenal electrical bursts are coordinated by metoclopramide. It appears that the most potent dopamine antagonists, domperidone and metoclopramide, are the most effective antiemetics. Both drugs increase the frequency of action potentials in the distal stomach and duodenum and appear to improve gastrointestinal coordination, thus improving gastric emptying and aboral transit.

The ‘central’ effects of chemotherapeutic drugs may be projected on the gastrointestinal tract by direct or indirect neural and/or humoral pathways. Indeed it is likely that there are direct motility pathways to the gastrointestinal tract from multiple central areas. The roles of gastrointestinal hormones, endogenous opiates, and dopamine as potential neurotransmitters influencing gut motility are being studied. Their relationship to emesis is currently only conjectural. However, it is evident that simple mechanical relationships between intrathoracic and intra-abdominal pressure do not explain all the phenomena observed during nausea and vomiting. It is likely that the rhythmic contractions of the muscles of respiration and the other phenomena associated with emesis occur in parallel with the gastrointestinal alterations. The coordination of these phenomena is so exquisite that the retching and other movements of the respiratory muscles may facilitate emetic expulsion. To the point of expulsion, gastrointestinal retroperistalsis appears to be the final common pathway to all emesis.