Novel Approaches to the Treatment of Nausea and Vomiting

Abstract

Nausea and vomiting are debilitating symptoms complicating many clinical conditions. Conventional antiemetic agents act as muscarinic, histamine, and dopamine receptor antagonists in the central nervous system. In a retrospective analysis, tricyclic antidepressant drugs demonstrated efficacy in long-term treatment of functional nausea. Some cases of vomiting result from impaired gastrointestinal motor activity. Agents which act on gastric serotonin (5-HT₄), dopamine, and motilin receptors accelerate gastric emptying and relieve symptoms in gastroparesis. Recent investigations suggest that some patients with refractory gastroparesis may benefit from gastric electrical pacing. The treatment of acute chemotherapy-induced emesis was revolutionized by 5-HT₃ receptor antagonists; however, these agents are less efficacious in delayed vomiting. Neurokinin (NK-1) receptor antagonists show promise in treating delayed chemotherapy-evoked emesis. Furthermore, animal studies indicate a broad spectrum of action for NK-1 antagonists in treating diverse causes of nausea and vomiting. The cyclic vomiting syndrome is characterized by discrete episodes of relentless vomiting separated by asymptomatic intervals and is associated with migraine headaches. Antimigraine therapies including the 5-HT_1D receptor agonists sumatriptan reduce the severity of cyclic vomiting attacks. Investigations into these and other novel treatments may provide important advances in the care of difficult cases of nausea and vomiting resulting from disparate illnesses.

The role of substance P in inflammatory disease

“…SP acts on NK‐1R cholinergic vagal neurons in the dorsal motor nucleus of the vagus nerve, which control enteric NANC motor inhibition of the gastric fundus (Chang et al, 1999). Therefore, an antiemetic site of action of NK‐1R antagonists may be in the dorsal motor nucleus to prevent excitation of neurons controlling fundic relaxation (Ladabaum and Hasler, 1999). Tachykinins stimulate duodenal contraction and bicarbonate secretion and are potent pancreatic circulatory stimulants and secretagogues (Pawlik et al, 1992).…”

Control of nausea and vomiting after chemotherapy: what is the evidence?

“…Several other agents have been studied for their ­­anti‐emetic potential including: (i) domperidone, (ii) cisapride, (iii) cannabinoids and (iv) transdermal fentanyl. These trials have generally either yielded disappointing results or have been too small to make valid conclusions (level of evidence III) 1,33−39 …”

Pathophysiology of headache

“…Connections between the trigeminal nucleus caudalis and the nucleus of the tractus solitarious may account for it. Experimental drugs such as NK-1 receptor antagonists or 5-HT1A receptor agonists, acting in the dorsal vagal complex, have been shown to be effective antiemetic drugs, reinforcing the role of these receptors in the pathogenesis of migraine [49].…”