Regulation of Emesis

Emesis, or vomiting, is the expulsion of the contents of the stomach up through the oral cavity. Nausea is the sick feeling that precedes emesis. Vomiting is an adaptive behavior that can work to eliminate toxic substances that have been ingested. However, nausea and vomiting can also be problematic side effects of anesthesia used in surgery (postoperative nausea and vomiting) or cancer treatments (chemotherapy and radiation) and can substantially interfere with treatment and recovery.

Emesis is an automatic behavior controlled by nuclei in the brainstem, referred to as the vomiting center. During retching, the lower esophageal sphincter relaxes, abdominal skeletal muscles contract, and strong peristaltic contractions of the muscularis externa operate in reverse of the normal pattern, forcing the contents of the stomach and even the small intestine upward into the esophagus. Emesis occurs when these contractions are strong enough to expel the contents of the GI tract past the upper esophageal sphincter.

There are several ways that emesis can be triggered as shown in the figure.


emesis

Cancer treatments induce nausea and vomiting because they cause serotonin release by the specialized cells in the intestinal epithelium. Chemotherapy and radiation cause the formation of free radicals. Free radicals induce serotonin release, and serotonin stimulates afferents projecting to the vomiting center. Chemotherapeutic agents may also stimulate emesis systemically by stimulating the area postrema. Opioids and other anesthetics are thought to trigger postoperative nausea and vomiting through the activation of opioid receptors found in the area postrema.

Drugs used to prevent nausea and vomiting are called antiemetics. Most work by blocking neurotransmitters involved in the neural pathways underlying emesis. One group of powerful antiemetic drugs are 5-HT3 antagonists (drugs that block specific serotonin receptors) such as ondansetron (ZofranŽ) and palonosetron (AloxiŽ). These drugs block the effect of serotonin on afferents from the GI tract, but they also work centrally to block the effects of serotonin in brain regions involved in emesis. Another powerful antiemetic is the drug aprepitant (EmendŽ), which is a non-peptide antagonist of neurokinin receptor 1, the receptor for substance P.  Aprepritant is very effective at preventing emesis due to a variety of stimuli.  This suggests that the peptide substance P is an important neurotransmitter in the vomiting center.

There are several other neurotransmitters besides serotonin and substance P that are involved in the pathways controlling nausea and vomiting. Other drugs that are used as antiemetics include antagonists for dopamine, histamine and acetylcholine.  Examples are the dopamine antagonists promethazine (PhenerganŽ) and prochlorperazine (CompazineŽ); the histamine anatagonist dimenhydrinate (DramamineŽ); and the muscarinic anatagonist scopolamine.  Cannabinoid agonists such as tetrahydrocannabinol (THC; the principal psychoactive ingredient in marijuana) are also used to reduce nausea and vomiting.      



Quick Quiz


Fill in Answer Correct False Correct Answer
1. Name the regulatory molecule that is released in response to toxins or irritants in the GI tract.
2. Name the region of the brain that is directly stimulated by factors in the circulation that trigger emesis.
3. Factors in the circulation can affect this region of the brain because it has an incomplete _______.
4. The drug aprepitant (EmendŽ) is an antagonist for which neurotransmitter? (Hint: this neurotransmitter is typically associated with pain).
5. Which of the following drugs is used to prevent nausea and vomiting? [dopamine antagonist; muscarinic antagonist; cannabinoid agonist; histamine antagonist; all of the above]


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