A Review of Granisetron, 5-Hydroxytryptamine3 Receptor Antagonists, and Other Antiemetics

Abstract

Nausea and vomiting are 2 of the most upsetting adverse reactions of chemotherapy. Current guidelines propose 5-hydroxytryptamine3 (5-HT3) receptor antagonists as a pharmacologic intervention for acute and delayed nausea and vomiting [chemotherapy-induced nausea and vomiting (CINV)] associated with moderately and highly emetogenic chemotherapy. Meanwhile, both postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting are challenging situations after surgeries and procedures. Prophylactic and therapeutic combinations of antiemetics are recommended in patients at high risk of suffering from PONV and postdischarge nausea and vomiting. Granisetron (Kytril) is a selective 5-HT3 receptor antagonist that does not induce or inhibit the hepatic cytochrome P-450 system in vitro. There are also 4 other antagonists of 5-HT3 receptor (dolasetron, ondansetron, palonosetron, and tropisetron) being metabolized via the CYP2D6 and are subject to potential genetic polymorphism. The launch of a new class of antiemetics, the substance P/neurokinin1 receptor antagonists, was attributed to the scientific update on the central generator responsible for emesis and role of substance P. There has been mounting interest in exploring integrative medicine, either acupuncture or acustimulation of P6 (Nei-Kuwan), to complement the western medicine for prevention and management of nausea and vomiting. The potential application of cannabinoids, either alone or in combination with other agents of different mechanism, could contribute further to improve outcome in CINV. Implementation of future treatment guidelines for more effective management of CINV and PONV could certainly improve the efficacy and outcome of cancer and postoperative care.

Effects and Mechanisms of Transcutaneous Electroacupuncture on Chemotherapy‐Induced Nausea and Vomiting

“…However, different subtypes of 5-HT receptors are believed to be involved in the antiemetic effect and the prokinetic effect of acupuncture. The prokinetic effect of acupuncture is believed to involve 5-HT 4 mechanism, whereas the antiemetic effect of acupuncture is believed to involve 5-HT 3 mechanisms [29, 31]. In addition, a reduction in circulating dopamine was also noted after the treatment of TEA.…”

Safety and efficacy of commonly used antiemetics

“…administration, with a mean half-life of 3 --6 h. Granisetron is metabolized by hepatic P4503A enzymes. Inducers or inhibitors of P450 enzymes may alter the clearance and halflife of granisetron [98].…”

Interference with acute nausea and anticipatory nausea in rats by fatty acid amide hydrolase (FAAH) inhibition through a PPARα and CB1 receptor mechanism, respectively: a double dissociation

“…Chemotherapy patients frequently experience nausea and vomiting, and often report nausea as the most debilitating symptom associated with treatment (Griffin et al 1996;de Boer-Dennert et al 1997;Grunberg 2004;Aapro et al 2005;Janelsins et al 2013). Current antiemetic therapies are effective in reducing chemotherapy-induced vomiting but are less effective in reducing acute and delayed nausea and completely ineffective in reducing anticipatory nausea (AN, Morrow et al 1995Morrow et al , 1998bHesketh 2008;Hsu 2010). Nausea is poorly treated and understood, because of the lack of selective preclinical models of nausea to evaluate effective treatments.…”