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Journal of Dental Anesthesia and Pain... Oct 2021Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of... (Review)
Review
BACKGROUND
Migraine headaches are the second leading cause of disability worldwide and are responsible for significant morbidity, reduction in the quality of life, and loss of productivity on a global scale. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of ketamine on migraines and other primary headache disorders compared to placebo and other active interventions, such as midazolam, metoclopramide/diphenhydramine, and prochlorperazine/diphenhydramine.
METHODS
An electronic search of databases published up to February 2021, including Medline via PubMed, EMBASE, Web of Science, and Cochrane Library, a hand search of the bibliographies of the included studies, as well as literature and systematic reviews found through the search was conducted to identify randomized controlled trials (RCTs) investigating ketamine in the treatment of migraine/headache disorders compared to the placebo. The authors assessed the risk of bias according to the Cochrane Handbook guidelines.
RESULTS
The initial search strategy yielded 398 unduplicated references, which were independently assessed by three review authors. After evaluation, this number was reduced to five RCTs (two unclear risk of bias and three high risk of bias). The total number of patients in all the studies was 193. Due to the high risk of bias, small sample size, heterogeneity of the outcomes reported, and heterogeneity of the comparison groups, the quality of the evidence was very low. One RCT reported that intranasal ketamine was superior to intranasal midazolam in improving the aura attack severity, but not duration, while another reported that intranasal ketamine was not superior to metoclopramide and diphenhydramine in reducing the headache severity. In one trial, subcutaneous ketamine was superior to saline in migraine severity reduction; however, intravenous (I.V.) ketamine was inferior to I.V. prochlorperazine and diphenhydramine in another study.
CONCLUSION
Further double-blind controlled studies are needed to assess the efficacy of ketamine in treating acute and chronic refractory migraines and other primary headaches using intranasal and subcutaneous routes. These studies should include a long-term follow-up and different ketamine dosages in diagnosed patients following international standards for diagnosing headache/migraine.
PubMed: 34703891
DOI: 10.17245/jdapm.2021.21.5.413 -
Journal of Nuclear Medicine : Official... Dec 2023Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed...
Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed to evaluate the potential of an anti-GPC1 monoclonal antibody (GPC1 mAb) labeled with Zr or At as a theranostic target in pancreatic ductal adenocarcinoma. GPC1 mAb clone 01a033 was labeled with Zr or At with a deferoxamine or decaborane linker, respectively. The internalization ability of GPC1 mAb was evaluated by fluorescence conjugation using a confocal microscope. PANC-1 xenograft mice ( = 6) were intravenously administered [Zr]GPC1 mAb (0.91 ± 0.10 MBq), and PET/CT scanning was performed for 7 d. Uptake specificity was confirmed through a comparative study using GPC1-positive (BxPC-3) and GPC1-negative (BxPC-3 GPC1-knockout) xenografts (each = 3) and a blocking study. DNA double-strand breaks were evaluated using the γH2AX antibody. The antitumor effect was evaluated by administering [At]GPC1 mAb (∼100 kBq) to PANC-1 xenograft mice ( = 10). GPC1 mAb clone 01a033 showed increased internalization ratios over time. One day after administration, a high accumulation of [Zr]GPC1 mAb was observed in the PANC-1 xenograft (SUV, 3.85 ± 0.10), which gradually decreased until day 7 (SUV, 2.16 ± 0.30). The uptake in the BxPC-3 xenograft was significantly higher than in the BxPC-3 GPC1-knockout xenograft (SUV, 4.66 ± 0.40 and 2.36 ± 0.36, respectively; = 0.05). The uptake was significantly inhibited in the blocking group compared with the nonblocking group (percentage injected dose per gram, 7.3 ± 1.3 and 12.4 ± 3.0, respectively; = 0.05). DNA double-strand breaks were observed by adding 150 kBq of [At]GPC1 and were significantly suppressed by the internalization inhibitor (dynasore), suggesting a substantial contribution of the internalization ability to the antitumor effect. Tumor growth suppression was observed in PANC-1 mice after the administration of [At]GPC1 mAb. Internalization inhibitors (prochlorperazine) significantly inhibited the therapeutic effect of [At]GPC1 mAb, suggesting an essential role in targeted α-therapy. [Zr]GPC1 mAb PET showed high tumoral uptake in the early phase after administration, and targeted α-therapy using [At]GPC1 mAb showed tumor growth suppression. GPC1 is a promising target for future applications for the precise diagnosis of pancreatic ductal adenocarcinoma and GPC1-targeted theranostics.
Topics: Humans; Animals; Mice; Glypicans; Positron-Emission Tomography; Precision Medicine; Positron Emission Tomography Computed Tomography; Cell Line, Tumor; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; DNA; Zirconium
PubMed: 37827841
DOI: 10.2967/jnumed.123.266313 -
Die Pharmazie Jan 2018Phenothiazine derivatives possess biological properties very useful for cancer therapy, such as antiemetic and sedative activity as well as good blood-brain barrier...
Phenothiazine derivatives possess biological properties very useful for cancer therapy, such as antiemetic and sedative activity as well as good blood-brain barrier permeability. Our goal was to determine if perphenazine and prochlorperazine are possessing cytotoxic activity towards U87-MG cells. It has been shown that the analyzed drugs induce concentration-dependent loss in cell viability, what correlates with their chemical structure. The calculated EC50 values for perphenazine (0.98 μM) and prochlorperazine (0.97 μM) are related to their toxic concentrations in human plasma. The obtained results suggest that perphenazine and prochlorperazine may have a potential for the development of new and effective anticancer therapies.
Topics: Antineoplastic Agents; Antipsychotic Agents; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Glioblastoma; Humans; Perphenazine; Prochlorperazine
PubMed: 29441946
DOI: 10.1691/ph.2018.7806 -
Pakistan Journal of Pharmaceutical... Jan 2022The study aimed at simultaneous quantification of sumatriptan succinate (SUM) and prochlorperazine maleate (PCP) in an orodispersible film using two validated...
The study aimed at simultaneous quantification of sumatriptan succinate (SUM) and prochlorperazine maleate (PCP) in an orodispersible film using two validated spectroscopic methods viz. simultaneous equation (Method I) and the Q-absorption ratio (Method II). The Method I involved measurement of absorbances at λ of both drugs while in Method II, absorbances were measured at isosbestic wavelength and λ of one of the two components. Method validation were accomplished as per the ICH guidelines. A 1:1 mixture of the drugs and an orodispersible film (ODF) containing these drugs were assayed by both methods. The absorbance data of SUM and PCP in both methods were linear at respective wavelengths with correlation coefficient values >0.995. Both methods were precise as % RSD in repeatability, interday and intraday precision was less than 2. The estimation of SUM and PCP from the film dosage form by method I was104.74% and 98.34% and by method II was 103.45% and 98.85%, respectively, with a standard deviation <2. The study concluded that both the methods were simple, reliable and robust and can be applied successfully for the simultaneous quantification of SUM and PCP in mixture and orodispersible film dosage form.
Topics: Administration, Oral; Antiemetics; Membranes, Artificial; Prochlorperazine; Spectrophotometry, Ultraviolet; Sumatriptan; Surface Properties; Vasoconstrictor Agents
PubMed: 35228176
DOI: No ID Found -
The Journal of Emergency Medicine Apr 2018Headache is a common complaint managed in the emergency department (ED), with emergency physicians focusing on evaluation for life-threatening conditions while treating...
BACKGROUND
Headache is a common complaint managed in the emergency department (ED), with emergency physicians focusing on evaluation for life-threatening conditions while treating pain and nausea.
OBJECTIVE
This review evaluates the treatment of benign, primary headaches in the ED, with recommendations provided based on the literature.
DISCUSSION
Headaches are a major cause of disability in the United States and a common condition managed in the ED. The primary objectives of emergency evaluation of these patients include evaluation for a life-threatening, secondary cause of headache, with treatment of primary headaches. Close evaluation for a secondary cause of headache include consideration of red flags and focused neurologic examination. The diagnosis of primary headaches is clinical. Literature has evaluated medication efficacy in headache treatment, with antidopaminergic medications demonstrating high rates of efficacy when used in combination with nonsteroidal inflammatory drugs or acetaminophen. Dexamethasone can be used for the reduction of headache recurrence. If dehydration is present, intravenous fluids should be provided. Diphenhydramine is not recommended for analgesia but may reduce akathisia associated with prochlorperazine. Ketamine, propofol, and nerve blocks demonstrate promise. Triptan agents are also efficacious, provided absence of contraindications. Most patients are appropriate for discharge with pain improvement.
CONCLUSIONS
A variety of medications is available for the treatment of primary headaches in the ED. Antidopaminergic agents demonstrate the highest efficacy and should be provided with acetaminophen and nonsteroidal inflammatory drugs. Dexamethasone may reduce headache recurrence. Other treatments include ketamine, propofol, and nerve blocks.
Topics: Cluster Headache; Emergency Service, Hospital; Headache; Humans; Migraine Disorders; Pain Management; Tension-Type Headache; United States
PubMed: 29395690
DOI: 10.1016/j.jemermed.2017.12.023 -
Obesity Surgery May 2018Postoperative nausea and vomiting (PONV) is problematic in bariatric surgery patients and has negative impacts on perioperative outcome. Antiemetic prophylaxis may... (Observational Study)
Observational Study
BACKGROUND
Postoperative nausea and vomiting (PONV) is problematic in bariatric surgery patients and has negative impacts on perioperative outcome. Antiemetic prophylaxis may reduce PONV. Perioperative antiemetic prophylaxis or therapy is crucial and may enhance fast-track bariatric surgery. This study examined the impact of intraoperative multimodal antiemetic prophylaxis on fast-track bariatric surgery.
METHODS
This prospective observational clinical study explored the perioperative data of 400 consecutive laparoscopic bariatric surgery patients, over a 6-year period. Perioperative outcomes and variables were analyzed and compared between different intraoperative antiemetic modes.
RESULTS
The mean BMI was 49, mean age was 42, and male:female ratio was 1:4. About 70% of patients received intraoperative multimodal antiemetic, comprising combinations of prochlorperazine, dexamethasone, ondansetron, or cyclizine. PONV occurred in 19.5% of patients. Intraoperative multimodal antiemetic was associated with significantly less PONV, shorter post-anesthesia care unit duration, earlier postoperative drinking, and shorter hospital stay (p = 0.001). Compared to other multimodal antiemetic modes, dexamethasone + cyclizine + prochlorperazine provided the best prophylaxis and outcome: p = 0.002.
CONCLUSION
PONV is a common and peculiar problem in bariatric surgery patients. However, intraoperative multimodal antiemetic prophylaxis effectively minimizes PONV. Intraoperative multimodal antiemetic enhances fast-track bariatric surgical care, patient satisfaction, and perioperative outcomes.
Topics: Adult; Antiemetics; Bariatric Surgery; Chemoprevention; Critical Pathways; Dexamethasone; Drug Administration Schedule; Female; Humans; Laparoscopy; Length of Stay; Male; Middle Aged; Obesity, Morbid; Ondansetron; Perioperative Care; Postoperative Nausea and Vomiting; Preoperative Period; Prospective Studies; Time Factors; Treatment Outcome
PubMed: 29116559
DOI: 10.1007/s11695-017-3009-7 -
The Journal of the Association of... Feb 2020Considering the prevailing concerns about extrapyramidal symptoms (EPS) associated with oral prochlorperazine, this study was conducted to assess the safety of oral... (Observational Study)
Observational Study
BACKGROUND
Considering the prevailing concerns about extrapyramidal symptoms (EPS) associated with oral prochlorperazine, this study was conducted to assess the safety of oral prochlorperazine (in recommended dose/duration) in the management of acute dizziness. Effectiveness was also assessed in the Indian real-world setting.
METHODS
A prospective, multicentric, single-arm observational study was conducted across 20 centers in India. Data from 500 patients were analyzed. Patients presenting with a complaint of dizziness, receiving prochlorperazine (Stemetil® MD-5 mg, t.i.d.) as per the routine clinical practice were enrolled. Safety and effectiveness at Week-1, compared to baseline, were assessed.
RESULTS
The mean (SD) age of the population was 43.3 (11.93) years with a marginally higher proportion of women (women: 52.2% Vs men 47.8%). The mean (SD) dose of prochlorperazine was 14.9 (0.24) mg/day. Only three patients (0.006%) reported adverse drug reactions (headache, asthenia, somnolence) during the conduct of the study, which were mild in severity and were completely resolved. Further, a significant reduction in the number of episodes of dizziness was noted at the end of Week-1(p<.0001). Moreover, improvement in the number of episodes from baseline to Week-1 was significant for nausea, vomiting, lightheadedness, and headache.
CONCLUSION
Prochlorperazine was well-tolerated in the management of acute dizziness when administered at a mean dose of 14.9 mg/day, and mean duration of 7.2 days. Additionally, prochlorperazine was effective in providing significant symptomatic relief from dizziness and associated vomiting and nausea.
Topics: Antiemetics; Dizziness; Female; Humans; India; Male; Prochlorperazine; Prospective Studies; Vomiting
PubMed: 32009365
DOI: No ID Found -
PeerJ 2020Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We...
BACKGROUND
Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We aimed to identify potential biomarkers and small-molecule drugs for MB.
METHODS
Gene expression profile data sets were obtained from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using the Limma package in R. Functional annotation, and cell signaling pathway analysis of DEGs was carried out using DAVID and Kobas. A protein-protein interaction network was generated using STRING. Potential small-molecule drugs were identified using CMap.
RESULT
We identified 104 DEGs (29 upregulated; 75 downregulated). Gene ontology analysis showed enrichment in the mitotic cell cycle, cell cycle, spindle, and DNA binding. Cell signaling pathway analysis identified cell cycle, HIF-1 signaling pathway, and phospholipase D signaling pathway as key pathways. SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were the prominent hub genes and their expression level were verified by RT-qPCR. Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB. The five hub genes may be targets for diagnosis and treatment of MB, and the small-molecule compounds are promising drugs for effective treatment of MB.
CONCLUSION
In this study we obtained five hub genes of MB, SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were confirmed as hub genes. Meanwhile, Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB.
PubMed: 32328342
DOI: 10.7717/peerj.8670 -
Frontiers in Cellular and Infection... 2023The coronavirus disease 2019 (COVID-19) pandemic, stemming from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has persistently threatened the global...
INTRODUCTION
The coronavirus disease 2019 (COVID-19) pandemic, stemming from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has persistently threatened the global health system. Meanwhile, tuberculosis (TB) caused by () still continues to be endemic in various regions of the world. There is a certain degree of similarity between the clinical features of COVID-19 and TB, but the underlying common pathogenetic processes between COVID-19 and TB are not well understood.
METHODS
To elucidate the common pathogenetic processes between COVID-19 and TB, we implemented bioinformatics and systematic research to obtain shared pathways and molecular biomarkers. Here, the RNA-seq datasets (GSE196822 and GSE126614) are used to extract shared differentially expressed genes (DEGs) of COVID-19 and TB. The common DEGs were used to identify common pathways, hub genes, transcriptional regulatory networks, and potential drugs.
RESULTS
A total of 96 common DEGs were selected for subsequent analyses. Functional enrichment analyses showed that viral genome replication and immune-related pathways collectively contributed to the development and progression of TB and COVID-19. Based on the protein-protein interaction (PPI) network analysis, we identified 10 hub genes, including IFI44L, ISG15, MX1, IFI44, OASL, RSAD2, GBP1, OAS1, IFI6, and HERC5. Subsequently, the transcription factor (TF)-gene interaction and microRNA (miRNA)-gene coregulatory network identified 61 TFs and 29 miRNAs. Notably, we identified 10 potential drugs to treat TB and COVID-19, namely suloctidil, prenylamine, acetohexamide, terfenadine, prochlorperazine, 3'-azido-3'-deoxythymidine, chlorophyllin, etoposide, clioquinol, and propofol.
CONCLUSION
This research provides novel strategies and valuable references for the treatment of tuberculosis and COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Computational Biology; Genes, Regulator; Tuberculosis; Mycobacterium tuberculosis; Gene Expression Profiling; MicroRNAs
PubMed: 38162574
DOI: 10.3389/fcimb.2023.1280223 -
Headache May 2019The aim of this review was to evaluate the efficacy and safety of prochlorperazine (PCP) in patients with acute migraine headache in the emergency department (ED). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this review was to evaluate the efficacy and safety of prochlorperazine (PCP) in patients with acute migraine headache in the emergency department (ED).
METHODS
Electronic databases (Medline, Scopus, Web of Science, and Cochrane) were searched for randomized clinical trials that investigated the effect of PCP on headache relief. The outcomes were the number of patients without headache or with reduced headache severity, the number of adverse events, and the need for rescue analgesia.
RESULTS
From 450 citations, 11 studies (n = 771) with 15 comparison arms met the inclusion criteria. Overall, PCP was more effective than placebo (OR = 7.23; 95% CI = 3.82-3.68), metoclopramide (OR = 2.89; 95% CI = 1.42-5.86), and other active comparators (OR = 3.70; 95% CI = 2.41-5.67) for headache relief. The odds ratio of experiencing adverse events with PCP compared with placebo was 5.79 (95% CI = 2.43-13.79). When PCP compared with other active comparators, no statistical difference was found regarding the overall number of adverse events (OR = 1.88; 95% CI = 0.99-3.59). However, PCP significantly increased the odds of akathisia/dystonia (OR = 2.55; 95% CI = 1.03-6.31). The request for rescue analgesia was significantly lower in the PCP group compared with other groups (16% vs 84%; OR = 0.16; 95% CI = 0.09-27).
CONCLUSIONS
For adult patients with acute migraine, PCP could effectively abort the acute attack and reduce the request for rescue analgesia in the ED. However, compared with placebo, PCP could increase the risk of adverse events.
Topics: Acute Disease; Akathisia, Drug-Induced; Dopamine Antagonists; Drug Therapy, Combination; Emergency Service, Hospital; Humans; Hypotension, Orthostatic; Migraine Disorders; Prochlorperazine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30990883
DOI: 10.1111/head.13527