The homozygous ABCB1 diplotype (GG-CC) conferred an odds ratio of 0.12 (95% confidence interval, 0.01-0.98) with regard to the use of ondansetron for postoperative nausea or vomiting.
In this review, we update the involvement of the SP/NK-1 receptor system in the physiopathology of the above-mentioned pathologies and we suggest valuable future therapeutic interventions involving the use of NK-1 receptor antagonists, particularly in the treatment of emesis, depression, cancer, neural degeneration, inflammatory bowel disease, viral infection and pruritus, in which that system is upregulated.
Our results indicate associations between cisplatin's peak immediate- and delayed-phase vomiting frequency with increased: (1) expression levels of NK(1) receptor mRNA and its protein level, and (2) downstream NK(1) receptor-mediated phosphorylation of ERK1/2 and PKA signaling.
Loss-of-function mutations of the MR are responsible for renal pseudohypoaldosteronism type 1 (PHA1), a rare disease of mineralocorticoid resistance presenting in the newborn with weight loss, failure to thrive, vomiting and dehydration, associated with hyperkalemia and metabolic acidosis, despite extremely elevated levels of plasma renin and aldosterone.
We suggest that in MCADD (1) a newborn screening C8 level of 6micromol/L or greater represents particular risk of sudden death; (2) that MCAD genotypes other than homozygosity for the c.985A>G mutation are also associated with sudden death; (3) that vomiting is a frequent symptom preceding sudden death; and (4) social support and medical follow-up of these families are crucial in reducing the occurrence of sudden death.
The incidence rate of grade 3-4 toxicities of EGFR-TKI-based regimens was significantly higher for rash (OR =10.17, 95% CI 2.37-43.63, <i>P</i>=0.002) but lower for vomiting (OR =0.08, 95% CI 0.01-0.61, <i>P</i>=0.02).
Oral gavage with selective agonists for CaSR (R-568) or TRPA1 (allyl isothiocyanate; AITC) rapidly elicited emesis in the mink in dose-dependent fashion.
The antiemetics recommended in these guidelines (5-hydroxytryptamine type 3 receptor antagonists, neurokinin-1 receptor antagonists, dexamethasone) have significantly reduced emesis but not nausea.
LMN-NKA unexpectedly activated NK1 receptors at doses that stimulated voiding, causing emesis and hypotension that may limit the clinical utility of nonselective NK2 receptor agonists.
Serotonin (5-HT) and substance P immunostaining revealed FPL64176-induced emesis was accompanied by an increase in 5-HT but not SP-immunoreactivity in the dorsomedial subdivision of the NTS.
Netupitant and rolapitant are second-generation neurokinin-1 receptor antagonists that provide effective prophylaxis against delayed chemotherapy-induced vomiting and also have an antinausea benefit.
Knowledge of the involvement of the neurokinin substance P in emesis has led to the development of the neurokinin-1 receptor antagonists (NK-1 RAs) for control of chemotherapy-induced nausea and vomiting (CINV), in combination with serotonin type 3 receptor antagonists and corticosteroids.
This study was undertaken to further establish Cryptotis parva as an emesis model, by sequencing and characterizing SP mRNA, and then comparing the least shrew tachykininergic system to other mammalian species (vomiting and non-vomiting).
The introduction of second generation serotonin 5-HT<sub>3</sub> receptor (5-HT<sub>3</sub>) antagonist palonosetron combined with long-acting substance P neurokinin NK<sub>1</sub> receptor (NK<sub>1</sub>) antagonists (e.g. netupitant) has substantially improved antiemetic therapy against early- and delayed-phases of emesis caused by highly emetogenic chemotherapeutics such as cisplatin.
Cisplatin-evoked emesis is predominantly due to release of serotonin and substance P (SP) in the gut and the brainstem which subsequently stimulate their corresponding 5-HT<sub>3</sub>-and neurokinin NK<sub>1</sub>-receptors to induce vomiting.
The latter led to identification of selective 5-HT<sub>3</sub> receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) <i>Neurokinin</i><sub>1</sub><i>receptor antagonists</i>-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis.
According to current ESMO - MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus.
Capecitabine and RT was well tolerated with low-grade palmar plantar erythrodyesthesia, increased alanine aminotransferase, cytopenias, and vomiting the most commonly reported toxicities.