-
European Journal of Pharmacology Mar 2024Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to...
Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT, 5-HT, H, NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome.
Topics: Mice; Male; Animals; Fibromyalgia; Mast Cells; Hyperalgesia; Serotonin; Reserpine; Mastocytosis
PubMed: 38311276
DOI: 10.1016/j.ejphar.2024.176385 -
Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
Food Chemistry Jun 2024The prohibition of antipsychotic drugs in animal foodstuffs has raised significant concerns. In this study, a novel matrix purification adsorbent comprising a polymer...
The prohibition of antipsychotic drugs in animal foodstuffs has raised significant concerns. In this study, a novel matrix purification adsorbent comprising a polymer (polyaniline and polypyrrole)-functionalized melamine sponge (Ms) was employed for the high performance liquid chromatography-diode array detector (HPLC-DAD) detection of three phenothiazines (chlorpromazine, thioridazine, and promethazine), and a tricyclic imipramine in milk. The as-prepared functionalized Ms was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle measurements. Excellent linearity with a coefficient of determination (R) of 0.999 was achieved for all drugs within the concentration range of 0.01-47.00 μg mL. The recoveries of the four analytes ranged from 92.1 % to 106.9 % at the three spiked levels. These results demonstrate the successful application of the proposed method for the determination of the four drugs. Cost-effective polymer-functionalized Ms is a viable alternative for matrix purification, enabling rapid determination of drug residues in diverse food samples.
Topics: Animals; Milk; Antipsychotic Agents; Chromatography, High Pressure Liquid; Polymers; Pyrroles; Solid Phase Extraction; Triazines
PubMed: 38309075
DOI: 10.1016/j.foodchem.2024.138553 -
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 -
Environment International Feb 2024Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6...
Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6 antihistamines and 4 metabolites in treated wastewater effluents, rivers, stormwater, and seawater in Hong Kong, with special focus on chirality. The average levels of ∑pharmaceuticals ranged from 0.525 to 1070 ng/L in all samples and the total annual mass load of target pharmaceuticals in the marine environment of Hong Kong was 756 kg/y. Antihistamines accounted for >80 % of ∑pharmaceuticals, with diphenhydramine and fexofenadine being predominant. The occurrence and enantiomeric profiles of brompheniramine and promethazine sulfoxide were reported in global natural waters for the first time. Among chiral pharmaceuticals, mirtazapine and fexofenadine exhibited R-preference, while others mostly exhibited S-preference, implying that the ecological risks derived from achiral data for chiral pharmaceuticals may be biased. The joint probabilistic risk assessment of fluoxetine revealed that R-fluoxetine and rac-fluoxetine presented different ecological risks from that of S-fluoxetine; Such assessment also revealed that target pharmaceuticals posed only minimal to low risks, except that diphenhydramine posed an intermediate risk. As estimated, 10 % aquatic species will be affected when the environmental level of diphenhydramine exceeds 7.40 ng/L, which was seen in 46.9 % samples. Collectively, this study highlights further investigations on the enantioselectivity of chiral pharmaceuticals, particularly on environmental behavior and ecotoxicity using local aquatic species as target organisms.
Topics: Fluoxetine; Water Pollutants, Chemical; Environmental Monitoring; Antidepressive Agents; Histamine Antagonists; Diphenhydramine; Risk Assessment; Rivers; Pharmaceutical Preparations; Terfenadine
PubMed: 38237506
DOI: 10.1016/j.envint.2024.108434 -
Frontiers in Pharmacology 2023Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive...
Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive landscape of culprit-drug of QT prolongation and TdP is currently lacking. To identify the top drugs reported in association with QT prolongation and TdP and provide information for clinical practice. We reviewed the reports related to QT prolongation and TdP in the FDA Adverse Event Reporting System (FAERS) database from January 1, 2004 to December 31, 2022, and summarized a potential causative drug list accordingly. Based on this drug list, the most frequently reported causative drugs and drug classes of QT prolongation and TdP were counted, and the disproportionality analysis for all the drugs was conducted to in detect ADR signal. Furthermore, according to the positive-negative distribution of ADR signal, we integrated the risk characteristic of QT prolongation and TdP in different drugs and drug class. A total of 42,713 reports in FAERS database were considered to be associated with QT prolongation and TdP from 2004 to 2022, in which 1,088 drugs were reported as potential culprit-drugs, and the largest number of drugs belonged to antineoplastics. On the whole, furosemide was the most frequently reported drugs followed by acetylsalicylic acid, quetiapine, citalopram, metoprolol. In terms of drug classes, psycholeptics was the most frequently reported drug classes followed by psychoanaleptics, analgesics, beta blocking agents, drugs for acid related disorders. In disproportionality analysis, 612 drugs showed at least one positive ADR signals, while citalopram, ondansetron, escitalopram, loperamide, and promethazine were the drug with the maximum number of positive ADR signals. However, the positive-negative distribution of ADR signals between different drug classes showed great differences, representing the overall risk difference of different drug classes. Our study provided a real-world overview of QT prolongation and TdP to drugs, and the presentation of the potential culprit-drug list, the proportion of reports, the detection results of ADR signals, and the distribution characteristics of ADR signals may help understand the safety profile of drugs and optimize clinical practice.
PubMed: 38186652
DOI: 10.3389/fphar.2023.1259611 -
Analytical Methods : Advancing Methods... Feb 2024An electrochemical sensor was developed based on a glassy carbon electrode (GCE) modified with multi-walled carbon nanotubes (MWCNTs) and gold nanoparticles (AuNPs) for...
An electrochemical sensor was developed based on a glassy carbon electrode (GCE) modified with multi-walled carbon nanotubes (MWCNTs) and gold nanoparticles (AuNPs) for the determination of promethazine (PMZ) in 'purple drank', pharmaceutical formulations, and synthetic saliva. The oxidation of PMZ at the modified electrode occurred at a higher cathodic potential and produced a higher sensitivity compared to the unmodified GCE. The morphology of the modified electrode was characterized using field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and transmission electron microscopy (TEM). The presence of MWCNTs and AuNPs was confirmed. The optimized parameters included the concentration and pH of the supporting electrolyte, amount of modifiers used to fabricate the electrode, deposition potential, and time. Using these optimized conditions, the method has a linear range from 0.5 to 100 μmol L, with a value of 0.9991. The limit of detection (3SD/slope) was 0.13 μmol L. The proposed electrochemical sensor was successfully applied for the determination of PMZ in 'purple drank', pharmaceutical formulations, and spiked synthetic saliva samples. The results obtained from this sensor were in statistical agreement with the values obtained using the reference gas chromatography-flame ionization method.
Topics: Promethazine; Gold; Nanotubes, Carbon; Metal Nanoparticles; Limit of Detection; Electrochemical Techniques; Pharmaceutical Preparations
PubMed: 38168774
DOI: 10.1039/d3ay01706k -
Cureus Dec 2023Belly dancer's dyskinesia (BDD) is an unusual neurological disorder characterized by focal dyskinesia that results in involuntary, rhythmic movements of the anterior...
Belly dancer's dyskinesia (BDD) is an unusual neurological disorder characterized by focal dyskinesia that results in involuntary, rhythmic movements of the anterior abdominal wall. This case report comprehensively examines the presentation, potential medication-induced etiology, and therapeutic response of a 64-year-old male diagnosed with schizophrenia. The patient developed BDD-like symptoms resembling hiccups, experiencing recurrent episodes that endured for hours and occurred nearly daily, significantly affecting wakefulness and sleep. Importantly, the patient's medical history included the utilization of fluphenazine and benztropine for schizophrenia management. Following a thorough multidisciplinary neurology consultation, a tailored treatment regimen involving clonazepam, promethazine, and baclofen was initiated, culminating in a noteworthy reduction in symptom frequency. This report substantially enriches the existing knowledge of BDD, highlighting the critical necessity to elucidate its intricate pathophysiology for the advancement of refined diagnostic and therapeutic strategies.
PubMed: 38161556
DOI: 10.7759/cureus.49796 -
Frontiers in Pharmacology 2023The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during...
The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during pregnancy (NVP) or hyperemesis gravidarum (HG). However, treatment guidelines for NVP or HG do not address the use of antiemetics in women who are breastfeeding while becoming pregnant again. Our objective was to characterize inquiries to describe the need for lactation risk information among women with NVP or HG and also to raise awareness of this topic. We conducted a review of inquiries to the Norwegian web-based medicines information service, SafeMotherMedicine. In total, 97 inquiries addressing the use of antiemetics for NVP or HG during breastfeeding were identified. The following medications were addressed in the inquiries ( = 97): meclizine (51%), metoclopramide (33%), promethazine (16%), ondansetron (9%), and others (6%). The breastfed child was older than 6 months and 1 year in 96% and 71% of the inquiries, respectively. There was a preponderance of general inquiries (unclear motivation/double checking) (64%); however, one-third of the inquiries were generated by restrictive information from sources such as product information. Based on our small review of spontaneous inquiries, there seems to be an information need about the use of antiemetics during lactation among women breastfeeding an older infant whilst suffering from NVP or HG. Addressing such use in guidelines for NVP and HG and/or other easily available information sources may be considered in order to balance out the restrictive information provided by the manufacturers. This could avoid potential unnecessary weaning of breastfeeding in an otherwise challenging situation.
PubMed: 38094894
DOI: 10.3389/fphar.2023.1238875