Substance P (Neurokinin-1) Antagonist Prevents Postoperative Vomiting after Abdominal Hysterectomy Procedures

Gesztesi, Zsuzsanna; Scuderi, Phillip E.; White, Paul F.; Wright, William C.; Wender, Ronald H.; D’Angelo, Robert; Black, L; Dalby, Patricia L.; MacLean, David B.

doi:10.1097/00000542-200010000-00009

Cited by 88 publications

(56 citation statements)

References 18 publications

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“…89 In humans, NK1 receptor antagonists were effective for the prophylaxis and treatment of PONV (IIIA). 90,91 In one study in females undergoing gynecologic surgery, the NK1 receptor antagonist provided better prophylaxis against vomiting compared with ondansetron. The combination of both agents also significantly prolonged the time to administration of rescue antiemetics compared with either drug alone, and was associated with a very low incidence of emesis (2%).…”

Section: Future Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

Evidence-based management of postoperative nausea and vomiting: a review

Habib

Gan

2004

Can J Anesth/J Can Anesth

195

106

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P Pu ur rp po os se e: : To provide evidence-based guidelines for the prophylaxis and treatment of postoperative nausea and vomiting (PONV).S So ou ur rc ce e: : Literature from randomized controlled trials, systematic reviews, logistic regression analyses and expert opinion in the management of PONV.P Pr ri in nc ci ip pa al l f fi in nd di in ng gs s: : The etiology of PONV is multifactorial. Patient, anesthesia, and surgery related risk factors have been identified. Universal PONV prophylaxis is not cost-effective. Identification of patients at high-risk of PONV allows targeting prophylaxis to those who will benefit most from it. No prophylaxis is needed for patients at low risk for PONV. For patients at moderate risk for PONV, prophylaxis using a single antiemetic or a combination of two agents should be considered. Double and triple antiemetic combinations should be considered for patients at high risk for PONV. Furthermore, a multimodal approach should be adopted incorporating steps to keep the baseline risk of PONV low. The optimum cost-effective approach to the management of PONV will differ between an ambulatory centre and an inpatient hospital setting. For the treatment of established PONV in patients who failed prophylaxis, patients should not receive a repeat dose of the prophylactic antiemetic. Rather, a drug acting at a different receptor should be used. Beyond six hours after surgery, patients can be treated with any of the agents used for prophylaxis, except dexamethasone and transdermal scopolamine.C Co on nc cl lu us si io on n: : PONV are common after anesthesia and surgery. We provided evidence-based guidelines for the management of this problem based on the available literature. Objectif : Énoncer des lignes de conduite fondées sur des données probantes pour la prévention et le traitement des nausées et des vomissements postopératoires (NVPO). Source : Les publications d'essais contrôlés et randomisés, les études méthodiques, les analyses de régression logistique et l'opinion d'experts sur le traitement des NVPO. Constatations principales : L'origine des NVPO est multifactorielle. Les facteurs de risque reliés au patient, à l'anesthésie et au type de chirurgie sont connus. La prévention universelle des NVPO n'est pas rentable. L'identification des patients à haut risque de NVPO permet

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Section: Future Therapiesmentioning

confidence: 99%

“…The combination of both agents also significantly prolonged the time to administration of rescue antiemetics compared with either drug alone, and was associated with a very low incidence of emesis (2%). 91 …”

Section: Future Therapiesmentioning

confidence: 99%

Evidence-based management of postoperative nausea and vomiting: a review

Habib

Gan

2004

Can J Anesth/J Can Anesth

195

106

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“…4 NK1 receptor antagonists have been shown in clinical trials to be effective in treating depression, 5 chemotherapy-induced emesis and postoperative emesis. 6 One NK1 antagonist, aprepitant (MK869, Emend), is an approved treatment for chemotherapy-induced emesis. 7,8 Sequence polymorphisms in genes that encode receptors, phase I and phase II metabolizing enzymes, and drug transporters have the potential to affect many aspects of drug efficacy, metabolism and safety.…”

Section: Introductionmentioning

confidence: 99%

Identification of single-nucleotide polymorphisms of the human neurokinin 1 receptor gene and pharmacological characterization of a Y192H variant

Randolph¹,

Simon²,

Arreaza³

et al. 2004

Pharmacogenomics J

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Neurokinin receptors in the central nervous system are involved in the neural circuitry of anxiety, depression and emesis. This has led to the development of nonpeptidic NK1 receptor antagonists as therapeutic agents. Clinical trials have shown that NK1 receptor antagonists have efficacy in chemotherapyinduced emesis and depression. Sequence polymorphisms can potentially influence the efficacy of drugs in patient populations and are an important consideration in the drug development process. To identify DNA sequence variants in the NK1 receptor, comparative DNA sequencing was performed on a population of 93 individuals. In total, 19 single-nucleotide polymorphisms (SNPs) were identified with one SNP (g.78351T4C) resulting in a tyrosine to histidine subsitution at residue 192 (Y192H). The Y192H variant was expressed using site-directed mutagenesis and was characterized with respect to affinity, receptor kinetics, functional calcium response and receptor internalization. In all cases the Y192H variant was found to display properties similar to those of the wild-type receptor.

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“…For the prevention of PONV, evidence from a double-blind RCT of females listed for abdominal hysterectomy demonstrated that 100 mg or 200 mg of oral CP122721, administered 60 to 90 min preoperatively, was more effective than placebo for prevention of PONV within 8 h and 72 h into the postoperative period [83]. Within the first 8 h, the higher dose of this NK-1 antagonist was more effective than the lower dose (the incidences of PONV being 10% and 33%, respectively).…”

Section: Methods To Prevent and Treat Ponvmentioning

confidence: 99%

“…of ondansetron has been compared with the individual drugs in a double-blind RCT [83]. There was a significant improvement in the median emesis-free time for 75% of patients in the combination group compared with the findings in the patients receiving CP1222721 or ondansetron separately.…”

Section: Combination Antiemetic Therapymentioning

confidence: 99%