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Clinical Surgery Journal 2022Cannabinoid Hyperemesis Syndrome (CHS) is a form of cyclic vomiting syndrome characterized by episodic vomiting occurring every few weeks or months and is associated...
BACKGROUND
Cannabinoid Hyperemesis Syndrome (CHS) is a form of cyclic vomiting syndrome characterized by episodic vomiting occurring every few weeks or months and is associated with prolonged and frequent use of high-dose cannabis. CHS in the pediatric population has been increasingly reported over the last decade and can lead to life-threatening complications such as pneumomediastinum, which warrant careful consideration for surgical intervention.
CASE PRESENTATION
A 17-year-old female with no significant past medical history presented to the emergency department with abdominal pain, nausea, and vomiting for 24 hours. She had four episodes of green-yellow emesis followed by dry heaves. She also complained of chest and back pain, worse with deep inspiration. Upon further history, the patient reported a similar episode of abdominal pain and repetitive vomiting six months prior to the current episode. She smoked cannabis at least once daily and has done so for the past two years. Chest X-ray revealed a subtle abnormal lucency along the anteroposterior window and anterior mediastinum, consistent with a small amount of pneumomediastinum without any other acute intrathoracic abnormalities. Follow-up chest computed tomography with contrast showed multiple foci of air within the anterior and posterior mediastinum tracking up to the thoracic inlet. There was no evidence of contrast extravasation; however, small esophageal perforation could not be excluded. Given uncomplicated pneumomediastinum without frank contrast extravasation, the patient was treated medically with piperacillin-tazobactam, metronidazole, and micafungin for microbial prophylaxis; hydromorphone for pain control; as well as with pantoprazole, ondansetron, and promethazine. Nutrition was provided via total parenteral nutrition. The patient was intensely monitored for signs of occult esophageal perforation, but none were detected. She was advanced to a soft diet on hospital day eight, solid food diet on day nine, at which point antibiotics were discontinued, and the patient was subsequently discharged.
CONCLUSION
CHS in an increasingly common disorder encountered in the pediatric setting due to rising prevalence of cannabis use. The management of CHS and potentially life-threatening complications such as pneumomediastinum should be given careful consideration. Pneumomediastinum can be a harbinger of more sinister pathology such as esophageal perforation, which may warrant urgent surgical intervention.
PubMed: 36438163
DOI: No ID Found -
Biomolecules Jun 2022Stroke is a leading threat to human life. Metabolic dysfunction of glucose may play a key role in stroke pathophysiology. Pharmacological hypothermia (PH) is a potential...
Stroke is a leading threat to human life. Metabolic dysfunction of glucose may play a key role in stroke pathophysiology. Pharmacological hypothermia (PH) is a potential neuroprotective strategy for stroke, in which the temperature is decreased safely. The present study determined whether neuroprotective PH with chlorpromazine and promethazine (C + P), plus dihydrocapsaicin (DHC) improved glucose metabolism in acute ischemic stroke. A total of 208 adult male Sprague Dawley rats were randomly divided into the following groups: sham, stroke, and stroke with various treatments including C + P, DHC, C + P + DHC, phloretin (glucose transporter (GLUT)-1 inhibitor), cytochalasin B (GLUT-3 inhibitor), TZD (thiazolidinedione, phosphoenolpyruvate carboxykinase (PCK) inhibitor), and apocynin (nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor). Stroke was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 6 or 24 h of reperfusion. Rectal temperature was monitored before, during, and after PH. Infarct volume and neurological deficits were measured to assess the neuroprotective effects. Reactive oxygen species (ROS), NOX activity, lactate, apoptotic cell death, glucose, and ATP levels were measured. Protein expression of GLUT-1, GLUT-3, phosphofructokinase (PFK), lactate dehydrogenase (LDH), PCK1, PCK2, and NOX subunit gp91 was measured with Western blotting. PH with a combination of C + P and DHC induced faster, longer, and deeper hypothermia, as compared to each alone. PH significantly improved every measured outcome as compared to stroke and monotherapy. PH reduced brain infarction, neurological deficits, protein levels of glycolytic enzymes (GLUT-1, GLUT-3, PFK and LDH), gluconeogenic enzymes (PCK1 and PCK2), NOX activity and its subunit gp91, ROS, apoptotic cell death, glucose, and lactate, while raising ATP levels. In conclusion, stroke impaired glucose metabolism by enhancing hyperglycolysis and gluconeogenesis, which led to ischemic injury, all of which were reversed by PH induced by a combination of C + P and DHC.
Topics: Adenosine Triphosphate; Animals; Chlorpromazine; Gluconeogenesis; Glucose; Hypothermia; Infarction, Middle Cerebral Artery; Ischemic Stroke; Lactates; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Stroke
PubMed: 35740974
DOI: 10.3390/biom12060851 -
Anti-cancer Agents in Medicinal... 2020Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role...
BACKGROUND
Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs.
OBJECTIVES
We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1) pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa).
METHODS
Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav, CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa cell lines.
RESULT
We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects when tested in DU145 and PC3 cell lines. Diphenhydramine, which shares its targets with promethazine, except the CaM, failed to exhibit oncocidal effects.
CONCLUSION
Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized, or these two drugs could be re-purposed after human trials in PCa.
Topics: ATP Binding Cassette Transporter, Subfamily B; Androgens; Antineoplastic Agents; Calcium Channels, L-Type; Calmodulin; Cell Proliferation; Diphenhydramine; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Loperamide; Molecular Structure; Promethazine; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 32271699
DOI: 10.2174/1871520620666200409142239 -
Brachytherapy 2021The COVID-19 pandemic presents serious challenges for brachytherapists, and in the time-sensitive case of locally advanced cervical cancer, the need for curative...
PURPOSE
The COVID-19 pandemic presents serious challenges for brachytherapists, and in the time-sensitive case of locally advanced cervical cancer, the need for curative brachytherapy (BT) is critical for survival. Given the high-volume of locally advanced cervical cancer in our safety-net hospital, we developed a strategy in close collaboration with our gynecology oncology and anesthesia colleagues to allow for completely clinic-based intracavitary brachytherapy (ICBT).
METHODS AND MATERIALS
This technical report will highlight our experience with the use of paracervical blocks (PCBs) and oral multimodal analgesia (MMA) for appropriately selected cervical ICBT cases, allowing for completely clinic-based treatment.
RESULTS
18 of 19 (95%) screened patients were eligible for in-clinic ICBT. The excluded patient had significant vaginal fibrosis. 38 of 39 intracavitary implants were successfully transitioned for entirely in-clinic treatment utilizing PCBs and oral MMA (97% success rate). One case was aborted due to inadequate analgesia secondary to a significantly delayed case start time (PO medication effect diminished). 95% of patients reported no pain at the conclusion of the procedure. The median (IQR) D for rectum and bladder were 64.8 (58.6-70.2) Gy and 84.1 (70.9-89.4) Gy, respectively. Median (IQR) CTV high-risk D was 88.0 (85.6-89.8) Gy.
CONCLUSIONS
In a multidisciplinary effort, we have successfully transitioned many ICBT cases to the clinic with the use of PCB local anesthesia and oral multimodality therapy in direct response to the current pandemic, thereby mitigating exposure risk to patients and staff as well as reducing overall health care burden.
Topics: Ambulatory Surgical Procedures; Analgesics; Anesthesia, Local; Anesthesia, Obstetrical; Anti-Anxiety Agents; Antiemetics; Brachytherapy; COVID-19; Female; Gabapentin; Humans; Hydromorphone; Ibuprofen; Lorazepam; Organs at Risk; Pain, Procedural; Pandemics; Promethazine; Radiotherapy Dosage; Rectum; SARS-CoV-2; Urinary Bladder; Uterine Cervical Neoplasms
PubMed: 32891569
DOI: 10.1016/j.brachy.2020.08.002 -
Effectiveness of promethazine on preoperative and intraoperative sequelae in cleft palate surgeries.Orthodontics & Craniofacial Research Jun 2024Anxiety and nosocomial infection are the most common reported problems in children undergoing cleft surgeries. Research shows that there is an enigma in the use of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Anxiety and nosocomial infection are the most common reported problems in children undergoing cleft surgeries. Research shows that there is an enigma in the use of antihistamine therapy in children for the management of upper respiratory tract infection. 'Promethazine' is a first-generation H1 receptor antagonist, and antihistamine also has strong sedative effects. Our study aims at evaluating the Effectiveness of Promethazine (Phenergan) in preoperative and intra operative sequelae in cleft surgeries.
MATERIALS AND METHODS
This is a single-centre, parallel, randomized, double-blinded randomized control clinical trial, which was conducted among 128 children between 2 and 4 years of age undergoing cleft palate surgery under general anaesthesia. After randomization, the case group was subjected to promethazine syrup 1 mg/kg body weight twice a day, orally for 3 days. The primary outcomes were preoperative anxiety levels which were recorded by children fear scale. The secondary outcomes include preoperative sleep quality and cough rate of children which are recorded by using sleep and cough objective scale respectively. The intraoperative heart rate is monitored with an ECG connected to a monitor.
RESULTS
Promethazine causes a reduction in the anxiety level by 70%, 64% reduction in cold and cough, improvement in sleep score by 70% and the heart rate was found to be stable throughout the surgery when compared to the control group.
CONCLUSION
As the benefits of promethazine in cleft palate surgery rule over its adverse effects, promethazine is considered safe to be used as premedication for children undergoing cleft palate surgeries.
Topics: Humans; Promethazine; Cleft Palate; Child, Preschool; Male; Female; Double-Blind Method; Histamine H1 Antagonists; Anxiety; Preoperative Care; Treatment Outcome; Heart Rate; Preoperative Period
PubMed: 38265116
DOI: 10.1111/ocr.12743 -
PloS One 2024The concoction known as "lean" containing codeine and promethazine, holds a prominent cultural presence and is often referenced in mass media platforms (e.g., music and...
BACKGROUND
The concoction known as "lean" containing codeine and promethazine, holds a prominent cultural presence and is often referenced in mass media platforms (e.g., music and social media). Surprisingly, there's a scarcity of national data characterizing the use of lean. Therefore, the current study investigated the use of lean using national survey data and online forum participant input, and focused on identifying concurrent substance use, exploring co-administration with other substances (e.g., alcohol, cannabis), and determining lean-related experiences.
METHODS
We analyzed data from the National Survey on Drug Use and Health (NSDUH) spanning 2007-2019, identifying persons who used lean (weighted N = 42,275). Additionally, we conducted a Reddit-based study to gather insights about lean consumtion (N = 192).
RESULTS
The NSDUH data indicated that lean use was most prevalent among teenagers and young adults (ages 13-21), accounting for 66% of the sample. This trend was more pronounced in male respondents (75%) compared to females. Additionally, the use was predominantly observed among Black/African American (29%), Hispanic (28%), and White (33%) populations, with these groups also reporting higher levels of concurrent alcohol and cannabis use. Similarly, findings from Reddit showed that individuals who used lean were predominantly male (67%) and exhibited elevated concurrent rates of alcohol (83%) and cannabis (46%) use in the past 30 days. Moreover, approximately 66% of respondents met criteria for severe lean use disorder, and 37% acknowledged driving under its influence.
CONCLUSION
The NSDUH data found that mostly young adult males reported consuming lean in the past twelve months, though the racial/ethnic breakdown of persons who used lean was diverse. The Reddit data found that most individuals in the sample met the criteria for a substance use disorder pertaining to their lean consumption. These findings underscore the clinical significance and necessity for further controlled research on lean.
Topics: Adolescent; Female; Humans; Male; Young Adult; Cannabis; Codeine; Health Surveys; Hispanic or Latino; Promethazine; Substance-Related Disorders; United States; White; Black or African American
PubMed: 38527052
DOI: 10.1371/journal.pone.0301024 -
Cell Transplantation Feb 2019Ischemic stroke destroys blood-brain barrier (BBB) integrity. There are currently no effective treatments available in the clinical setting. Post-ischemia treatment with...
Ischemic stroke destroys blood-brain barrier (BBB) integrity. There are currently no effective treatments available in the clinical setting. Post-ischemia treatment with phenothiazine drugs [combined chlorpromazine and promethazine (C+P)] has been shown to be neuroprotective in stroke. The present study determined the effect of C+P in BBB integrity. Sprague-Dawley rats were divided into the following groups ( n=8 each): (1) stroke, (2) stroke treated by C+P with temperature control, and (3) stroke treated by C+P without temperature control. Infarct volume and neurological deficits were measured to assess the neuroprotective effect of C+P. BBB permeability was determined by brain edema and Evans blue leakage. Expression of BBB integral molecules, including proteins of aquaporin-4 and -9 (AQP-4, AQP-9), matrix metalloproteinase-2 and -9 (MMP-2, MMP-9), zonula occludens-1 (ZO-1), claudin-1/5, occludin, and laminin were determined by Western blot. Stroke caused brain infarction and neurological deficits, as well as BBB damage, which were all attenuated by C+P through drug-induced hypothermia. When the reduced temperature was controlled to physiological levels, C+P still conferred neuroprotection, suggesting a therapeutic effect independent of hypothermia. Furthermore, C+P significantly attenuated the increase in AQP-4, AQP-9, MMP-2, and MMP-9 levels after stroke, and reversed the decrease in tight junction protein (ZO-1, claudin-1/5, occludin) and basal laminar protein (laminin) levels. This study clearly indicates a beneficial effect of C+P on BBB integrity after stroke, which may be independent of drug-induced hypothermia. These findings further prove the clinical target and cell-signal communication of C+P treatment, which may direct us closer toward the development of an efficacious neuroprotective therapy.
Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Chlorpromazine; Male; Promethazine; Rats; Rats, Sprague-Dawley; Stroke
PubMed: 30569751
DOI: 10.1177/0963689718819443 -
Spectrochimica Acta. Part A, Molecular... Jun 2018The binding nature of amphiphilic drugs viz. promethazine hydrochloride (PMT) and adiphenine hydrochloride (ADP), with human hemoglobin (Hb) was unraveled by...
The binding nature of amphiphilic drugs viz. promethazine hydrochloride (PMT) and adiphenine hydrochloride (ADP), with human hemoglobin (Hb) was unraveled by fluorescence, absorbance, time resolved fluorescence, fluorescence resonance energy transfer (FRET) and circular dichroism (CD) spectral techniques in combination with molecular docking and molecular dynamic simulation methods. The steady state fluorescence spectra indicated that both PMT and ADP quenches the fluorescence of Hb through static quenching mechanism which was further confirmed by time resolved fluorescence spectra. The UV-Vis spectroscopy suggested ground state complex formation. The activation energy (E) was observed more in the case of Hb-ADP than Hb-PMT interaction system. The FRET result indicates the high probability of energy transfer from β Trp37 residue of Hb to the PMT (r=2.02nm) and ADP (r=2.33nm). The thermodynamic data reveal that binding of PMT with Hb are exothermic in nature involving hydrogen bonding and van der Waal interaction whereas in the case of ADP hydrophobic forces play the major role and binding process is endothermic in nature. The CD results show that both PMT and ADP, induced secondary structural changes of Hb and unfold the protein by losing a large helical content while the effect is more pronounced with ADP. Additionally, we also utilized computational approaches for deep insight into the binding of these drugs with Hb and the results are well matched with our experimental results.
Topics: Binding Sites; Diphenylacetic Acids; Fluorescence; Fluorescence Resonance Energy Transfer; Hemoglobins; Humans; Hydrogen Bonding; Molecular Docking Simulation; Molecular Dynamics Simulation; Promethazine; Protein Binding; Spectrometry, Fluorescence
PubMed: 29562212
DOI: 10.1016/j.saa.2018.03.023 -
Lakartidningen Sep 2021Overdoses with the sedating antihistamines alimemazine, hydroxyzine, promethazine and propiomazine have received attention in recent years in Sweden. The Poisons...
Overdoses with the sedating antihistamines alimemazine, hydroxyzine, promethazine and propiomazine have received attention in recent years in Sweden. The Poisons Information Center has noted an increase in calls regarding intoxications, and the National Board of Forensic Medicine has concluded that these substances have directly contributed to a large number of poisoning deaths. When prescribing alimemazine, hydroxyzine, promethazine and propiomazine, their pharmacological properties, such as antihistaminergic and anticholinergic effects, and their anti-arrhythmic potential must be considered. Furthermore, it is important to also consider the risks of severe intoxication in case of overdose. The lowest possible amount should be prescribed. Special attention is required when prescribing alimemazine oral solution.
Topics: Cholinergic Antagonists; Drug Overdose; Histamine H1 Antagonists; Humans; Promethazine; Sweden
PubMed: 34590703
DOI: No ID Found -
Medical Mycology Nov 2018The aim of this study was to evaluate the effect of promethazine on the antifungal minimum inhibitory concentrations against planktonic cells and mature biofilms of...
The aim of this study was to evaluate the effect of promethazine on the antifungal minimum inhibitory concentrations against planktonic cells and mature biofilms of Candida tropicalis, as well as investigate its potential mechanisms of cell damage against this yeast species. Three C. tropicalis isolates (two azole-resistant and one azole-susceptible) were evaluated for their planktonic and biofilm susceptibility to promethazine alone and in combination with itraconazole, fluconazole, voriconazole, amphotericin B, and caspofungin. The antifungal activity of promethazine against C. tropicalis was investigated by performing time-kill curve assays and assessing rhodamine 6G efflux, cell size/granularity, membrane integrity, and mitochondrial transmembrane potential, through flow cytometry. Promethazine showed antifungal activity against planktonic cells and biofilms at concentrations of 64 and 128 μg/ml, respectively. The addition of two subinhibitory concentrations of promethazine reduced the antifungal MICs for all tested azole drugs against planktonic growth, reversing the resistance phenotype to all azoles. Promethazine decreased the efflux of rhodamine 6G in an azole-resistant strain. Moreover, promethazine decreased cell size/granularity and caused membrane damage, and mitochondrial membrane depolarization. In conclusion, promethazine presented synergy with azole antifungals against resistant C. tropicalis and exhibited in vitro cytotoxicity against C. tropicalis, altering cell size/granularity, membrane integrity, and mitochondrial function, demonstrating potential mechanisms of cell damage against this yeast species.
Topics: Antifungal Agents; Biofilms; Candida tropicalis; Cell Membrane; Drug Resistance, Fungal; Drug Synergism; Flow Cytometry; Humans; Membrane Potentials; Microbial Sensitivity Tests; Microbial Viability; Mitochondria; Promethazine
PubMed: 29420801
DOI: 10.1093/mmy/myx088