Antiemetic Research Articles

A multicenter, phase II trial of triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for highly emetogenic chemotherapy in breast cancer (PATROL-II)

Dexamethasone is an antiemetic drug widely used to prevent nausea and vomiting caused by anticancer drugs. However, dexamethasone can cause several side effects even after short-term administration. Therefore, the development of dexamethasone-free antiemetic therapies has been recognized as an important challenge. The objective of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine. Patients who were chemotherapy-naïve and scheduled to receive highly emetogenic chemotherapy for breast cancer were enrolled and assessed for nausea and vomiting occurring within 120 h after the start of chemotherapy. The primary endpoint was the total control (TC) rate of overall phases. Secondary endpoints included the complete response (CR) rate, which was evaluated during the acute, delayed, and overall phases. A total of 88 patients were enrolled from eight centers in Japan, of whom 84 were included in the analysis. The proportion of patients achieving TC throughout the overall period was 17.1%. Similarly, CR and CC rates for the overall period were 43.4% and 39.5%, respectively. Frequently reported adverse events were loss of appetite and constipation, with rates of 52.4% and 50.0%, respectively. The primary endpoint was not achieved. Therefore, antiemetic therapy without dexamethasone shows an inadequate effect on nausea, and it is generally advisable to avoid omitting dexamethasone. However, in the overall period, both CR and CC were comparable to conventional three-drug combination therapy. Thus, in patients unable to use dexamethasone, replacing it with olanzapine could be an option.Trial registration number: UMIN 000038644, November 20, 2019. The date of first trial registration: 13/03/2020.

Overcoming amphotericin B resistance in Candida auris using the antiemetic drug rolapitant.

The emergence of Candida auris poses a significant health challenge that has led to a new era of multidrug-resistant fungal infections. Invasive infections caused by C. auris are usually associated with remarkable morbidity and mortality. For many years, amphotericin B (AmB) remained the most efficient and the last line of treatment against most hard-to-treat fungal infections. However, strains of C. auris possess extraordinary resistance to most antifungal agents, including AmB. In this study, we screened ~2,600 FDA-approved drugs and clinical compounds to identify the antiemetic drug rolapitant as a promising enhancer to AmB against C. auris. Rolapitant exhibited potent synergistic interactions with AmB against all tested (29/29) C. auris isolates. In a time-kill assay, rolapitant restored the fungicidal activity of AmB within 4 h. Additionally, the synergistic relationship between rolapitant and AmB was observed against other medically crucial Candida, Cryptococcus, and Aspergillus species. A transcriptomic study revealed that exposure to rolapitant affects oxidation reduction processes, ion transporters, and ATP production. Rolapitant triggers an elevation in cytosolic and mitochondrial calcium levels and induces oxidative stress within fungal cells. An ATP luminescence assay confirmed that rolapitant, at sub-inhibitory concentrations, significantly interfered with ATP production in C. auris. Moreover, rolapitant enhanced the in vivo activity of AmB in a mouse model of disseminated C. auris infection, as the combination reduced the fungal burden in murine kidneys by ~1 log (~90%) colony forming units. Our findings warrant further investigation of using rolapitant to overcome AmB resistance in C. auris and other fungal species.

[11C]Metoclopramide PET can detect a seizure-induced up-regulation of cerebral P-glycoprotein in epilepsy patients

BackgroundP-glycoprotein (P-gp) is an efflux transporter which is abundantly expressed at the blood-brain barrier (BBB) and which has been implicated in the pathophysiology of various brain diseases. The radiolabelled antiemetic drug [11C]metoclopramide is a P-gp substrate for positron emission tomography (PET) imaging of P-gp function at the BBB. To assess whether [11C]metoclopramide can detect increased P-gp function in the human brain, we employed drug-resistant temporal lobe epilepsy (TLE) as a model disease with a well characterised, regional P-gp up-regulation at the BBB.MethodsEight patients with drug-resistant (DRE) TLE, 5 seizure-free patients with drug-sensitive (DSE) focal epilepsy, and 15 healthy subjects underwent brain PET imaging with [11C]metoclopramide on a fully-integrated PET/MRI system. Concurrent with PET, arterial blood sampling was performed to generate a metabolite-corrected arterial plasma input function for kinetic modelling. The choroid plexus was outmasked on the PET images to remove signal contamination from the neighbouring hippocampus. Using a brain atlas, 10 temporal lobe sub-regions were defined and analysed with a 1-tissue-2-rate constant compartmental model to estimate the rate constants for radiotracer transfer from plasma to brain (K1) and from brain to plasma (k2), and the total volume of distribution (VT = K1/k2).ResultsDRE patients but not DSE patients showed significantly higher k2 values and a trend towards lower VT values in several temporal lobe sub-regions located ipsilateral to the epileptic focus as compared to healthy subjects (k2: hippocampus: +34%, anterior temporal lobe, medial part: +28%, superior temporal gyrus, posterior part: +21%).Conclusions[11C]Metoclopramide PET can detect a seizure-induced P-gp up-regulation in the epileptic brain. The efflux rate constant k2 seems to be the most sensitive parameter to measure increased P-gp function with [11C]metoclopramide. Our study provides evidence that disease-induced alterations in P-gp expression at the BBB can lead to changes in the distribution of a central nervous system-active drug to the human brain, which could affect the efficacy and/or safety of drugs. [11C]Metoclopramide PET may be used to assess or predict the contribution of increased P-gp function to drug resistance and disease pathophysiology in various brain diseases.Trial registrationEudraCT 2019-003137-42. Registered 28 February 2020.

A Method to Determine Metoclopramide Hydrochloride in Oral Dosage Forms by Micellar Liquid Chromatography

Background: Metoclopramide is a widely prescribed antiemetic drug. Its analysis in pharmaceutical formulations often involves procedures using high amounts of toxic chemicals. Objective: A method based on micellar liquid chromatography to determine metoclopramide hydrochloride in several oral dosage forms has been developed. Methods: The drug was resolved from matrix compounds within 6 min using a C18 column with isocratic elution at 1 mL/min utilizing a solution of 0.10 mol/L sodium dodecyl sulfate – 6 % 1- pentanol phosphate buffered at pH 7 as mobile phase, and detection by absorbance at 210 nm. Samples were dissolved or diluted in the mobile phase and directly injected; thus, only one solution had to be prepared for the entire procedure. Besides, it contained mainly harmless chemicals and a minimal amount of organic solvent. Results The procedure was validated by the International Council of Harmonization guidelines and the results were: specificity, calibration range (0.5 – 5.0 mg/L), linearity (r2 > 0.9990), trueness (98.1 – 100.3 %), precision (< 0.7%), robustness, carry-over effect, and system suitability. It was used to analyze commercial samples. Otherwise, it was found the influence of the surfactant on elution strength was nearly three times stronger than that of 1-pentanol. Conclusion: The procedure was reliable, easy-to-conduct, safe, eco-friendly, short-time, widely available and highly sample-throughput, and then useful for routine analysis of metoclopramidebased dosage forms in pharmaceutical quality control.

Tropisetron, an Antiemetic Drug, Exerts an Anti-Epileptic Effect Through the Activation of α7nAChRs in a Rat Model of Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE), a prevalent chronic neurological disorder, affects millions of individuals and is often resistant to anti-epileptic drugs. Increasing evidence has shown that acetylcholine (ACh) and cholinergic neurotransmission play a role in the pathophysiology of epilepsy. Tropisetron, an antiemetic drug used for chemotherapy in clinic, has displayed potential in the treatment of Alzheimer's disease, depression, and schizophrenia in animal models. However, as a partial agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), whether tropisetron possesses the therapeutic potential for TLE has not yet been determined. In this study, tropisetron was intraperitoneally injected into pilocarpine-induced epileptic rats for 3 weeks. Alpha-bungarotoxin (α-bgt), a specific α7nAChR antagonist, was applied to investigate the mechanism of tropisetron. Rats were assessed for spontaneous recurrent seizures (SRS) and cognitive function using video surveillance and Morris's water maze testing. Hippocampal impairment and synaptic structure were evaluated by Nissl staining, immunohistochemistry, and Golgi staining. Additionally, the levels of glutamate, γ-aminobutyric acid (GABA), ACh, α7nAChRs, neuroinflammatory cytokines, glucocorticoids and their receptors, as well as synapse-associated protein (F-actin, cofilin-1) were quantified. The results showed that tropisetron significantly reduced SRS, improved cognitive function, alleviated hippocampal sclerosis, and concurrently suppressed synaptic remodeling and the m6A modification of cofilin-1 in TLE rats. Furthermore, tropisetron lowered glutamate levels without affecting GABA levels, reduced neuroinflammation, and increased ACh levels and α7nAChR expression in the hippocampi of TLE rats. The effects of tropisetron treatment were counteracted by α-bgt. In summary, these findings indicate that tropisetron exhibits an anti-epileptic effect and provides neuroprotection in TLE rats through the activation of α7nAChRs. The potential mechanism may involve the reduction of glutamate levels, enhancement of cholinergic transmission, and suppression of synaptic remodeling. Consequently, the present study not only highlights the potential of tropisetron as an anti-epileptic drug but also identifies α7nAChRs as a promising therapeutic target for the treatment of TLE.

Brain mitochondrial damage attenuation by quercetin and N-acetyl cysteine: peripheral and central antiemetic effects.

Nausea serves as a protective mechanism in organisms to prevent excessive consumption of toxic substances. Due to the adverse effects of chemical anti-nausea drugs, there is a growing interest in using herbal remedies and natural antioxidants. In this study, we evaluated the neuroprotective effects of quercetin (QU) and N-acetylcysteine (NAC) against oxidative damage induced by nausea. Emesis was induced in chickens using ipecac and copper sulfate (600 and 60mg/kg, orally, respectively). QU and NAC (with doses of 50, 100, 200mg/kg), and their combination were administered, along with a standard therapy (metoclopramide; MET 2mg/kg) for one-time. Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC), glutathione level (GSH), and reactive oxygen species (ROS) as oxidative damage biomarkers were evaluated in the chicken's brain mitochondria. QU and NAC significantly reduced emesis induced by copper sulfate and ipecac compared to the control group (P<0.001). Significant differences in oxidative damage were observed in the groups received of copper sulfate and ipecac compared with control group. Levels of LPO, ROS, and PC were significantly decreased after the administration of QU and NAC in emesis induced by copper sulfate and ipecac. While, mitochondrial function and GSH levels were increased after the administration of QU and NAC. Combination therapy with QU and NAC yielded the most effective results. This study suggests that QU and NAC possess antiemetic effects through both peripheral and central mechanisms and exhibit neuroprotective effects against oxidative brain damage induced by emesis by increasing plasma antioxidants or scavenging free radicals.

Effects of adding intravenous midazolam to a dual postoperative nausea and vomiting regimen in patients undergoing breast surgery: A pragmatic randomized controlled trial.

For high-risk patients, adding a third antiemetic drug to dual postoperative nausea and vomiting (PONV) prophylaxis is controversial. Given the established antiemetic properties of midazolam, this study compared the combination of low-dose dexamethasone-ondansetron and midazolam with high-dose dexamethasone-ondansetron. A total of 300 female patients scheduled for breast surgery were recruited and randomly assigned to two groups. The DO group received dexamethasone 8 mg and ondansetron 4 mg, whereas the DOM group received dexamethasone 4 mg, ondansetron 4 mg, and midazolam 0.04 mg/kg. The primary outcome was the incidence of PONV within 24 h. Secondary outcomes were PONV severity, antiemetic requirement, blood glucose levels, satisfaction and sedation scores, time to eye opening and extubation, pain outcome, and sore throat. Primary outcome analysis included 298 patients. Incidence of PONV within the first 24 h after surgery occurred in 52 of 150 (35%) patients in the DO group and 33 of 148 (22%) patients in the DOM group (adjusted risk ratio, 0.63; 95% confidence interval, 0.45-0.88; P = 0.007). The antiemetic requirement was significantly greater in the DO group compared with the DOM group (P = 0.034). However, a significantly higher sedation level and longer time for eye-opening and extubation were observed in the DOM group (P < 0.05). Compared to high-dose dexamethasone and ondansetron alone, midazolam combined with low-dose dexamethasone and ondansetron decreased the incidence of PONV in patients undergoing breast surgery; however, it increased the sedation level in the early postoperative period.

Patient Profile-Based Management with Nintedanib in Patients with Idiopathic Pulmonary Fibrosis.

A severe and progressive interstitial lung disease (ILD) known as idiopathic pulmonary fibrosis (IPF) has an unknown etiology with poorly defined mechanisms of development. Among the currently prescribed pharmacological interventions for IPF, nintedanib demonstrates the ability to decelerate the deterioration of lung function and yield positive clinical outcomes. Multiple randomized placebo-controlled trials have confirmed the efficacy and acceptable safety profile of nintedanib. Real-world evidence studies also support the use of nintedanib in IPF, being an efficient and well-tolerated treatment option. It has the potential to stabilize the disease progression in patients with ILD. Patients with IPF frequently have comorbidities like diabetes and hypertension, which can exacerbate the course of disease, reduce quality of life, and decrease treatment adherence. For well-informed decision-making, it is important for healthcare professionals to recognize the position of nintedanib therapy in IPF with comorbidities. The gastrointestinal adverse effects, notably diarrhea, dominate the nintedanib safety profile. These can be effectively controlled by closely monitoring side effects, administering anti-diarrheal and anti-emetic drugs, reducing the nintedanib dose, and discontinuing it in case of severe symptoms with an option to reintroduce the treatment after side effects subside. Symptomatic interventions and monitoring of liver enzymes may reduce the occurrence of permanent treatment discontinuations.

Can a Continuous Wound Infiltration System Replace Intravenous Patient-Controlled Analgesia for Postoperative Pain Management after a Single-Port Access Laparoscopy?

Background: The aim of this study was to determine whether continuous wound infiltration (CWI) can replace intravenous patient-controlled analgesia (IV PCA) and to investigate effective pain control strategies after a single-port access (SPA) laparoscopy for adnexal disease. Methods: A total of 470 patients (the CWI group [n = 109], the IV PCA group [n = 198], and the combined group [n = 163]) who underwent an SPA adnexal laparoscopy and who received CWI or IV PCA for postoperative pain management were retrospectively reviewed. The numeric rating scale (NRS) pain score at 6, 12, 24, and 48 h (h) after surgery and the total amount of fentanyl administered via IV PCA were collected. The incidence of postoperative nausea and vomiting (PONV) and the total amount of rescue antiemetic drugs administered were also evaluated. Results: The mean NRS pain scores at 6 h (combined vs. PCA vs. CWI, 3.08 vs. 3.44 vs. 3.96, p < 0.001), 12 h (2.10 vs. 2.65 vs. 2.82, p < 0.001), and 24 h (1.71 vs. 2.01 vs. 2.12, p < 0.001) after surgery were significantly lower in the combined group. CWI showed a similar pain-reduction effect after surgery compared to IV PCA, except for the acute phase (within 6 h after surgery). The incidence of PONV during the entire hospitalization period was significantly lower in the CWI group compared to the groups using IV PCA (p < 0.05). The combined group had a significantly lower incidence of PONV and use of rescue antiemetics than the IV PCA group (p < 0.05). The combined group required significantly less total PCA fentanyl compared to the IV PCA group (combined vs. PCA, 622.1 μg vs. 703.1 μg, p < 0.001). Conclusions: CWI is an effective alternative to IV PCA and has fewer side effects. Combined use of CWI and IV PCA may be an ideal pain management strategy, offering a strong pain-reduction effect and only moderate side effects.

Bilateral Ultrasound-Guided External Oblique Intercostal Block Vs. Modified Thoracoabdominal Nerve Block Through Perichondrial Approach for Postoperative Analgesia in Patients Undergoing Laparoscopic Sleeve Gastrectomy Surgery: A Randomized Controlled Study.

The objective of the present study was to evaluate morphine consumption and pain scores 24h postoperatively to compare the effects of a bilateral External Oblique Intercostal (EOI) block with those of a Modified Thoracoabdominal Nerve Block Trough Perichondrial Approach (M-TAPA) block in laparoscopic sleeve gastrectomy (LSG). Fifty-eight patients aged between 18 and 65years of with American Society of Anesthesiologists class II-III were included in this randomized, double-blinded study. Patients were assigned into two groups either EOI block or M-TAPA block. The primary outcome was cumulative morphine consumption within the first postoperative 24h. Secondary outcomes were numerical rating scale (NRS) scores at rest and during activity, QoR-15 Patient Questionnaire scores, incidence of postoperative nausea and vomiting (PONV), number of patients requiring rescue analgesic and antiemetics drugs, and complications. There was no statistically significant difference between the groups in terms of morphine consumption in the first 24h (EOI block; 10.74 ± 3.94mg vs. M-TAPA block; 11.67 ± 4.66mg, respectively). In addition, no significant difference between the two groups in the NRS and PONV scores, total QoR-15 scores, and the number of patients requiring rescue analgesics and antiemetics. EOI block and M-TAPA block showed similar effectiveness for morphine consumption within 24h postoperatively and in pain scores in LSG.

Review of Intranasal Active Pharmaceutical Ingredient Delivery Systems.

In recent decades, there has been an increased interest in the development of intranasal delivery systems for active pharmaceutical ingredients (APIs) not only for treating local nasal diseases but also for treating systemic diseases, central nervous system (CNS) disorders, and vaccine delivery. The nasal cavity possesses a unique set of anatomical characteristics for delivering active pharmaceutical ingredients, but there are several limitations that recent research in the field of the intranasal administration of APIs aims to overcome. For the effective delivery of nasal preparations, active pharmaceutical ingredients are incorporated into various micro- and nanosystems. Some of the most commonly encountered API delivery systems in the scientific literature include liposomal systems, polymer particles with mucoadhesive properties, in situ gels, nano- and microemulsions, and solid lipid particles. This article provides a review of research on the development of nasal preparations for treating local nasal cavity diseases (in particular, for antibiotic delivery), systemic diseases (analgesics, drugs for cardiovascular diseases, antiviral and antiemetic drugs), CNS disorders (Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, depression), and vaccine delivery. The literature data show that active research is underway to reformulate drugs of various pharmacotherapeutic groups into a nasal form.

Comparison of olanzapine 2.5 mg and 5 mg in the prevention of chemotherapy-induced nausea and vomiting: a Japanese nationwide database study

BackgroundOlanzapine is prescribed as prophylaxis for chemotherapy-induced nausea and vomiting at a dose of 2.5 or 5 mg in Asian countries. We compared the effectiveness of olanzapine 2.5 mg and 5 mg in preventing chemotherapy-induced nausea and vomiting among patients receiving high-emetogenic chemotherapy for lung cancer.MethodsUsing a Japanese national inpatient database, we identified patients who received olanzapine doses of 2.5 or 5 mg during high-emetogenic chemotherapy for lung cancer between January 2016 and March 2021. We conducted a 1:1 propensity score-matched analysis with adjustment for various factors, including those affecting olanzapine metabolism. The outcomes were additional antiemetic drug administration (within 2–5 days after chemotherapy initiation), length of hospital stay, and total hospitalization costs.ResultsOlanzapine 2.5 and 5.0 mg were used in 2905 and 4287 patients, respectively. The propensity score-matched analysis showed that olanzapine 2.5 mg administration was significantly associated with a higher proportion of additional antiemetic drug administration (36% vs. 31%, p < 0.001) than olanzapine 5 mg. The median length of hospital stay was 8 days in both groups. Total hospitalization cost did not differ significantly between the two doses of olanzapine (5061 vs. 5160 USD, p = 0.07). The instrumental variable analysis demonstrated compatible results.ConclusionProphylactic use of olanzapine 2.5 mg during chemotherapy for lung cancer was associated with a higher rate of additional antiemetic drugs than olanzapine 5 mg.

Comparison of aprepitant versus ondansetron for prevention of postoperative nausea and vomiting: A systematic review and meta-analysis with trial sequential analysis.

Postoperative nausea and vomiting (PONV) is a common complication after surgery. Preventing PONV in high-risk patients often requires a multimodal approach combining antiemetic drugs with diverse mechanisms. While aprepitant, a neurokinin-1 receptor antagonist, is recognised as highly effective for PONV prevention, uncertainties remain regarding its effectiveness. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The analysis assessed the effectiveness of aprepitant (A), aprepitant plus ondansetron (AO) and aprepitant plus dexamethasone and ondansetron (ADO) in preventing PONV compared to ondansetron alone (O) or in combination with dexamethasone (DO). In the analysis of 12 studies involving 2729 patients, aprepitant demonstrated significant efficacy in preventing PONV compared to ondansetron alone (A versus [vs.] O: PONV incidence 12.5% vs. 28.5%, relative risk [RR] = 0.45, P < 0.001; complete response rate 55.97% vs. 50.35%, RR = 1.13, P = 0.010). The combination of aprepitant with ondansetron (AO) also showed a significantly lower incidence of PONV compared to ondansetron alone (11.3% vs. 26.8%, RR = 0.43, P < 0.001) and a higher complete response rate (38.1% vs. 26.84%, RR = 1.41, P = 0.020). In addition, ADO significantly reduced PONV incidence compared to DO (ADO vs. DO: 13.63% vs. 35.38%, RR = 0.38, P = 0.006). Aprepitant, whether used alone or in combination with ondansetron or both ondansetron and dexamethasone, consistently outperforms ondansetron in achieving a complete response as it lowers vomiting rates and reduces the need for rescue therapy during the crucial 24-48-h postoperative period.

Diagnosa Penyakit Chikungunya Menggunakan Metode Certainty Factor

Chikungunya is a disease caused by the Chikungunya virus (CHIKV) transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Some of the symptoms are sudden fever, chills, pain in the joints, muscle pain in the neck, shoulders and limbs, rash. Treatment of sufferers is aimed at complaints and symptoms that arise and the drugs given are generally only to relieve existing symptoms, such as giving Antipyretic drugs to relieve fever, Antiemetic drugs to relieve nausea / vomiting, or Analgetics to relieve joint pain only, from these problems many people also do not understand the handling of chikungunya disease, therefore it is necessary to have a system that can collect information to collect information and conduct counseling activities on the treatment of Chikungunya disease to the general public and especially to the elderly to provide knowledge about Chikungunya disease using the Certainty Factor method. The purpose of this research is to provide information and knowledge to the public about Chikungunya Disease Treatment and the Elderly know the medicine for Chikungunya Disease treatment. From the results of applying the certainty factor method to diagnose chikungunya disease, it can be obtained that the diagnosis result is acute chikungunya disease with a confidence level of 95.19%.

Medication-based profiling of older orthopedic patients: a multicenter cross-sectional study

BackgroundManaging medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern.MethodsWe retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs.ResultsA total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11–1.44] and 1.12 [CI: 1.00–1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14–56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05–1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients.ConclusionsMore than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions.

Postoperative Nausea and Vomiting in the Ambulatory Surgery Center: A Narrative Review.

Postoperative nausea and vomiting (PONV) is a common complication of ambulatory surgery, leading to numerous deleterious effects such as decreased patient satisfaction, prolonged recovery unit stays, and rarely, more serious complications such as aspiration pneumonia or wound dehiscence. In this paper, we present a narrative review of the literature regarding common risk factors for PONV including patient factors, surgical factors, and anesthetic factors. We then will review anesthetic techniques and antiemetic drugs demonstrated to mitigate the risk of PONV. Finally, we discuss the potential economic benefits of PONV prophylaxis in the perioperative ambulatory setting.

Comparison of postoperative analgesia effects between subcostal anterior quadratus lumborum block and transversus abdominis plane block in bariatric surgery: a prospective randomized controlled study

BackgroundCurrently, the prevalence of obesity is on the rise annually. Bariatric surgery stands out as the most efficacious approach for addressing obesity. Obese patients are more prone to experience moderate to severe pain after surgery due to lower pain thresholds. Regional block, as an important component of multimodal analgesia in bariatric surgery, is crucial in reducing opioid consumption and alleviating postoperative pain in patients undergoing bariatric surgery.Transversus abdominis plane block (TAPB) has gained widespread utilization in bariatric surgery; however, its limitation of inadequate reduction of visceral pain in obese patients remains a significant concern. Therefore, it is imperative to explore new and more efficient strategies for analgesia. Quadratus lumborum block (QLB) has emerged as a popular nerve block in recent years, frequently utilized in conjunction with general anesthesia for abdominal surgery. In the cadaver study of QLB, it was confirmed that the dye level could reach up to T6 when using the subcostal anterior quadratus lumborum muscle approach, which could effectively reduce the incision pain and visceral pain of bariatric surgery patients during the perioperative period.However, there is currently a lack of research on the use of subcostal anterior QLB in patients undergoing bariatric surgery. Our study aims to investigate whether subcostal anterior QLB can provide superior perioperative analgesic efficacy for bariatric surgery under general anesthesia compared to TAPB, leading to reduced postoperative opioid consumption and a lower incidence of postoperative nausea and vomiting (PONV).Methods and designThis study is a prospective, randomized controlled trial aiming to recruit 66 patients undergoing bariatric surgery. The participants will be randomly allocated into two groups in a 1:1 ratio: subcostal anterior QLB group (n = 33) and TAPB group (n = 33). The study aims to investigate the efficacy of subcostal anterior QLB and TAPB in obese patients who are scheduled to undergo bariatric surgery. Our primary outcome is to observe the amount of opioids used in the two groups 24 h after operation. The secondary outcomes included VAS of pain during rest/activity after operation, the type and dose of additional analgesics, the occurrence and severity of PONV, the type and dose of additional antiemetic drugs, postoperative anesthesia care unit (PACU) time, time of first postoperative exhaust, time to first out of bed activity, time to first liquid diet and postoperative admission days.DiscussionOpioid analgesics are prone to causing adverse reactions such as nausea, vomiting, and respiratory depression, especially in obese patients. Multimodal analgesia, including nerve block, can effectively reduce the dose of opioids and alleviate their adverse effects. Currently, TAPB is the most prevalent nerve block analgesia method for abdominal surgery. Recent studies have indicated that subcostal anterior QLB offers advantages over TAPB, including a wider block plane, faster onset, and longer maintenance time. It is not clear which of the two nerve block analgesia techniques is better for postoperative analgesia in patients undergoing bariatric surgery. Our objective in this investigation is to elucidate the superior method between TAPB and subcostal anterior QLB for postoperative pain management in bariatric surgery.Trial registrationChiCTR ChiCTR2300070556. Registered on 17 April 2023.

UNIFAC and Wilson models to correlate solubility of pharmaceutical compounds in supercritical carbon dioxide

New thermodynamic correlations were proposed for the solubility of pharmaceutical compounds in supercritical carbon dioxide based on the solid-liquid equilibrium model. The activity coefficient models proposed in the study were based on Universal quasi-chemical Functional Group Activity Coefficient and Wilson models. The pharmaceutical drug compounds used in this study belong to anticancer, antibiotics, anti-androgenic, non-steroidal anti-inflammatory drugs, anti-prostatic tumour drugs and antiemetic drugs. The correlating ability of the proposed models was discussed in terms of various statistical parameters. Further, the proposed model results were compared with six existing solid-fluid equilibrium model results. It was found that the newly proposed models were more promising than those of existing solid-fluid equilibrium models. The correlating ability of the proposed models was discussed in terms of various statistical parameters.

Signal mining of adverse reactions in the antiemetic drug ondansetron during pregnancy:A Real-World analysis of the FDA adverse Event Reporting System (FAERS)

ABSTRACT Background The aim of this study is to assess the risks associated with the use of ondansetron in pregnant women in real-world based on the Food and Drug Administration adverse Event Reporting System (FAERS). Methods The FAERS data from the 2017Q1 to the 2023Q1, which was used by the ratio-of-reporting (ROR) and Bayesian confidence interval progressive neural network (BCPNN) to assess the safety of ondansetron in pregnancy. Results A total of 15,727 pregnancy population reports were reported, with a total of 1,064 reports of adverse reactions with ondansetron as the primary suspected drug. Ondansetron was involved in a total of 10 system organ classifications (SOCs) of signal generation, and the top three signal intensities were Congenital, familial and genetic disorders (ROR=19.1, ROR025=17.03; IC=1.23, IC025=1.16), Ear and labyrinth disorders (ROR=17.11, ROR025=12.46; IC=1.22, IC025=1.03), and Cardiac disorders (ROR=9.48, ROR025=8.38; IC=1.12, IC025=1.03); signals of adverse reactions obtained of 216, of which the main ones were Anhedonia (IC=1.34, IC025=1.08), Injury (IC=1.34, IC025=1.19), Left-to-right cardiac shunt (IC=1.33, IC025=1.05). Conclusion The adverse reactions of Ondansetron involve multiple systems and organs, which should cause clinical vigilance. However, due to the limitations of the data, the causal relationship and risk level of adverse reactions cannot be accurately inferred.

The domperidone dilemma in Pakistan: Balancing access and safety concerns.

Madam, Domperidone is used in the treatment of nausea and vomiting as an antiemetic and prokinetic drug. Its pro-kinetic effects mainly manifest in the upper gastrointestinal tract by acting as a dopamine receptor antagonist [1]. However, the drug has been banned by the FDA in the USA due to its association with cardiac arrhythmias and cardiac arrest. A recent meta-analysis has shown a statistically significant association between sudden cardiac death [2] and the use of domperidone which raises the question of drug usage in Pakistan as an over-the-counter medication. The meta-analysis considers six different case-control studies, between 2005 and 2016, that have shown an increase in the risk of sudden cardiac death and ventricular arrhythmias associated with domperidone. The observational studies were conducted in North America, Asia, and Europe, proving that it is a global phenomenon, stemming from the use of the drug. The forest plot of the studies has been mentioned later in the abstract showing heterogeneity at 0%, OR ratio 1.69 with 95% CI (1.46-1.95). To further highlight the risks associated with domperidone, another study has reported that the safety index of the drug is 5.25, which is remarkably lower than the international safety ratio of 30[3]. The safety index, or therapeutic index, is the ratio of the toxic dose in 50% of the population (TD50) and the effective dose in 50% of the population (ED50) with the same therapeutic effect. A wider safety index indicates more room for error in the drug's therapeutic effect; essentially a larger barrier before the drug is toxic. With a safety index of 5.25, the action potential duration is markedly increased, resulting in arrhythmias. The author also comments on restricting the drug only to patients where the potential benefit is proven to justify the risks. In Pakistan, Domperidone is readily available as an over-the-counter drug. The casual availability raises the concern that the associated safety issues must be critically evaluated to determine whether the uses of the drug outweigh the risk of sudden cardiac death and ventricular arrhythmias [4] mentioned in these studies.