Ingestion of toxin, traumatic events, adverse drug reactions, and motion can all result
in nausea and emesis. In addition, cyclic vomiting syndrome is quite prevalent in
the pediatric population. Coordination of the various autonomic changes associated
with emesis occurs at the level of the medulla oblongata of the hindbrain. Chemosensitive
receptors detect emetic agents in the blood and relay this information by means of
neurons in the area postrema to the adjacent nucleus tractus solitarius (NTS). Abdominal
vagal afferents that detect intestinal luminal contents and gastric tone also terminate
in the NTS (gelatinosus, commissural, and medial subnuclei). The NTS is viscerotopically
organized into subnuclei that subserve diverse functions related to swallowing (subnucleus
centralis), gastric sensation (subnucleus gelatinosus), laryngeal and pharyngeal sensation
(intermediate and interstitial NTS), baroreceptor function (medial NTS), and respiration
(ventrolateral NTS). Neurons from the NTS project to a central pattern generator (CPG),
which coordinates the sequence of behaviors during emesis, as well as directly to
diverse populations of neurons in the ventral medulla and hypothalamus. Thus, it is
critical to realize that there is not an isolated "vomiting center," but rather groups
of loosely organized neurons throughout the medulla that may be activated in sequence
by a CPG. The newer antiemetic agents appear to block receptors in the peripheral
endings of vagal afferents to reduce "perception" of emetic stimuli and/or act in
the dorsal vagal complex. A primary site of action of 5-HT(3)-receptor antagonists
is by means of the vagal afferents. Neurokinin-1 receptor (NK(1)R) antagonists are
antiemetics, because they act at a site in the dorsal vagal complex. Part of their
effectiveness may be the result of inhibition of the NK(1)R on vagal motor neurons
to prevent fundic relaxation, which is a prodromal event essential for emesis. Delta(9)-tetrahydrocannabinol
(Delta(9)-THC), the major psychoactive component of marijuana, can be therapeutically
useful as an antiemetic. The site of action of Delta(9)-THC is on cannabinoid CB1
receptors in the dorsal vagal complex. However, it decreases fundic tone and antral
motility. It is not easy to predict the potential antiemetic effects of drugs that
alter motility. Although antiemetic drugs are available for management of acute chemotherapeutic-induced
emesis, few treatments are effective for delayed emesis or cyclic vomiting syndrome.