The role of neurokinin-1 (substance P) antagonists in the prevention of postoperative nausea and vomiting

Okafor, Dionne; Kaye, Alan D.; Kaye, Rachel; Urman, Richard D.

doi:10.4103/0970-9185.222511

Cited by 19 publications

(5 citation statements)

References 35 publications

(44 reference statements)

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“…Our study cohort had an incidence of PONV of 11.8%, which was at the lower end of the reported range for children post-surgery. This result was consistent with results from studies of aprepitant preoperative use in adults that ranged from 9.7% to 22% [17,18], suggesting aprepitant is as effective an antiemetic in children as it is in adults. In addition, our study found no serious adverse effects of aprepitant in the 144 children who received it.…”

Section: Discussionsupporting

confidence: 89%

Preoperative Administration of Aprepitant to Prevent Postoperative Nausea and Vomiting in Children

Kukura¹,

Slenkovich²,

Shafy³

et al. 2022

J Curr Surg

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Background: Aprepitant (Emend ® ), a neurokinin-receptor antagonist, has seen increased use in the treatment of nausea and vomiting in various clinical scenarios. To date, there are limited data regarding its use in the pediatric population. We retrospectively reviewed our experience with aprepitant after its addition to the operating room formulary for prevention of postoperative nausea and vomiting (PONV). Methods:The anesthetic records of patients who received aprepitant were retrospectively reviewed. Demographic, surgical, medication, and efficacy data were retrieved. Results:The study cohort included 144 patients ranging in age from 7 to 17 years and in weight from 24.7 to 208.9 kg. The most common surgical procedures included gastrointestinal surgery, orthopedic surgery, and otolaryngologic procedures. Reasons for the administration of aprepitant included PONV prophylaxis due to risk factors such as type of surgery, duration of surgery, previous history of significant PONV, female gender, and family history of PONV. The majority of the patients (98.6%) received aprepitant in capsule form in a dose of 40 mg (97.9%). Seventeen patients (11.8%) had PONV or received antiemetic agents postoperatively. There were no unplanned admissions related to PONV. No adverse effects related to aprepitant were noted.Conclusions: Aprepitant was effectively introduced to the preoperative regimen as an additional agent for the prevention of PONV. The overall tolerability and efficacy of aprepitant was similar to previous studies, even in a patient population at high risk for PONV.

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Section: Discussionsupporting

confidence: 89%

Preoperative Administration of Aprepitant to Prevent Postoperative Nausea and Vomiting in Children

Kukura¹,

Slenkovich²,

Shafy³

et al. 2022

J Curr Surg

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“…A plausible explanation could be that canine IL-31, after intradermal administration, enters the systemic circulation and induces itch by directly targeting spinal cord circuits, which has been observed in rodents after the intrathecal administration of IL-31 [9]. Interestingly, intradermal injections of substance P, a neurokinin-1 receptor agonist [26], induced vomiting in healthy dogs (10 out of 20 dogs tested), confirming the idea that some of the intradermally injected compounds can be systemically absorbed by dogs [27].…”

Section: Discussionmentioning

confidence: 99%

Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis

Pearson

Leon

Starr

et al. 2023

Veterinary Sciences

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Pruritic models in healthy dogs utilizing intravenous administration of interleukin 31 (IL-31) bypass the “natural” itch sensation in AD, which is initiated by pruriceptive primary afferent neurons in the skin. This study aimed to evaluate the immediate/delayed pruritus responses and the pruritic behaviors observed in an intradermal IL-31-induced pruritic model of healthy dogs and the anti-pruritic effect of oclacitinib on said model. In Phase 1, all the dogs were randomized and video-recorded for 300 min after intradermal canine recombinant IL-31 injections (1.75 µg/kg) and vehicle (phosphate-buffered saline) injections. In Phase 2, all the dogs received oral oclacitinib (0.4–0.6 mg/kg, twice daily for 4 consecutive days and once daily on day 5), with the intradermal IL-31 injection performed on day 5. Two blinded investigators reviewed the pruritic behaviors in all the video recordings. Intradermal IL-31 administration to healthy dogs caused a significant increase in the total (p = 0.0052) and local (p = 0.0003) seconds of pruritic behavior compared to the vehicle control. Oral oclacitinib administration significantly reduced the total (p = 0.0011) and local (p = 0.0156) intradermal IL-31-induced pruritic seconds; there was no significant difference in pruritic seconds between the vehicle and oclacitinib within the IL-31 groups. Significant delayed pruritic responses at 150–300 min after IL-31 injections were observed, and intradermal IL-31 failed to induce acute itch (first 30 min). Intradermal injection of IL-31 induces delayed itch responses in dogs that are diminished by the effect of oclacitinib, an oral JAK inhibitor.

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“…Expression of NK-1R was demonstrated in brain regions associated with the emetic reflex, such as the nucleus solitary tract and area postrema. Since NK-1R activation leads to nausea and vomiting, its specific antagonists are utilized as antiemetic agents in practice [4,27]. Currently, the specific NK-1R antagonists allowed for use in clinical practice, generally needed for chemotherapy and post-operative patients, are aprepitant (administered orally) and fosaprepitant (an intravenous prodrug of aprepitant) [14].…”

Section: Discussionmentioning

confidence: 99%

The effect of aprepitant, a neurokinin-1 receptor antagonist, on epileptiform activity in the penicillin model of epilepsy

Cirrik,

Dogan,

Aslan

et al. 2024

Med-Science

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Substance P (SP) is a peptide neurotransmitter that plays a role in pain transmission, stress, inflammation, and emesis through neurokinin-1 receptor (NK-1R). Previous studies of NK-1R antagonists suggest that SP can have either convulsant or anticonvulsant effects. Aprepitant, an NK-1R antagonist, is clinically used to prevent nausea and vomiting in chemotherapy and post-operative patients. However, the effects of aprepitant on epilepsy have not been studied yet. Therefore, the objective of this study was to explore the influence of aprepitant on epileptiform activity in a rat model of epilepsy induced by penicillin. Male Wistar rats, aged 2.5 to 3 months, were divided into 5 groups (n=6): Control, Vehicle, Aprepitant, Substance P, and Aprepitant+Substance P. Aprepitant was administered intragastrically (30 mg/kg) 24 hours and 3 hours before surgery. Substance P (10 pmol) was administered intraventricularly during the surgical procedure. Induction of epileptiform activity was achieved by the injection of penicillin G (500 IU) into the cortex. Electrocorticography (ECoG) recording was conducted online using the PowerLab data acquisition system for over 3 hours. The disparity in spike frequency and amplitude among groups for each 10-minute interval was assessed through One-Way ANOVA and subsequent Tukey post-hoc tests, utilizing the SPSS 15.0 software package. Epileptiform activity was observed in all rats within 3 minutes after the injection of penicillin into the cortex. No significant difference was found between groups in terms of spike frequency and amplitude. When the percentage changes in mean spike frequency and amplitude values were calculated, no significant difference was shown between the groups. Using a penicillin-induced epilepsy model, the present study showed that aprepitant does not affect epileptiform activity in the presence or absence of exogenous SP. Further studies are needed to understand possible anticonvulsant or proconvulsant properties of aprepitant.

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The role of neurokinin-1 (substance P) antagonists in the prevention of postoperative nausea and vomiting

Cited by 19 publications

References 35 publications

Preoperative Administration of Aprepitant to Prevent Postoperative Nausea and Vomiting in Children

Preoperative Administration of Aprepitant to Prevent Postoperative Nausea and Vomiting in Children

Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis

The effect of aprepitant, a neurokinin-1 receptor antagonist, on epileptiform activity in the penicillin model of epilepsy

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