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Heliyon Jan 2024Montelukast, an approved leukotriene receptor 1 (Cys-LT 1) antagonist with anti-inflammatory properties is used for the treatment of asthma and allergic rhinitis. In the...
Anti-enzymatic and DNA docking studies of montelukast: A multifaceted molecular scaffold with investigations, molecular expression analysis and molecular dynamics simulations.
Montelukast, an approved leukotriene receptor 1 (Cys-LT 1) antagonist with anti-inflammatory properties is used for the treatment of asthma and allergic rhinitis. In the present studies, montelukast was subjected to inhibitory assays followed by kinetic and investigations. Montelukast demonstrated inhibitory activity against yeast α-glucosidase (IC 44.31 ± 1.21 μM), jack bean urease (JB urease, IC 8.72 ± 0.23 μM), human placental alkaline phosphatase (hPAP, IC 17.53 ± 0.19 μM), bovine intestinal alkaline phosphatase (bIAP, IC 15.18 ± 0.23 μM) and soybean 15-lipoxygenase (15-LOX, IC 2.41 ± 0.13 μM). Kinetic studies against α-glucosidase and urease enzymes revealed its competitive mode of inhibition. Molecular expression analysis of montelukast in breast cancer cell line MCF-7 down-regulated AP by a factor of 0.27 (5 μM) compared with the 0.26 value for standard inhibitor levamisole (10 μM). Molecular docking estimated a binding affinity ranging -8.82 to -15.65 kcal/mol for the enzymes. Docking against the DNA dodecamer (ID: 1BNA) observed -9.13 kcal/mol via minor groove binding. MD simulations suggested stable binding between montelukast and the target proteins predicting strong inhibitory potential of the ligand. Montelukast features a chloroquinoline, phenyl ring, a cyclopropane group, a carboxylic group and a sulfur atom all of which collectively enhance its inhibitory potential against the said enzymes. These and computational investigations demonstrate that it is possible and suggested that the interactions of montelukast with more than one targets presented herein may be linked with the side effects presented by this drug and necessitate additional work. The results altogether suggest montelukast as an important structural scaffold possessing multitargeted features and warrant further investigations in repurposing beyond its traditional pharmacological use.
PubMed: 38298631
DOI: 10.1016/j.heliyon.2024.e24470 -
Proceedings (Baylor University. Medical... 2023Patients with chronic kidney disease (CKD) are at increased risk for adverse drug events due to medication dosing errors. We studied the awareness and knowledge among...
BACKGROUND
Patients with chronic kidney disease (CKD) are at increased risk for adverse drug events due to medication dosing errors. We studied the awareness and knowledge among internal medicine housestaff (IMHS) of proper dose adjustment of commonly used rheumatology and allergy/immunology medications for patients with CKD.
METHODS
We surveyed 353 IMHS to evaluate their awareness of the need for medication dose adjustments for patients with CKD and knowledge for medication adjustment by level of glomerular filtration rate for common rheumatology and allergy/immunology medications.
RESULTS
There was lack of awareness and knowledge for both rheumatology and allergy/immunology medications. Incorrect awareness and knowledge were as follows: allopurinol, 21.2%, 73.4%; colchicine, 19.0%, 75.9%; diphenhydramine, 34.0%, 34.0%; loratadine, 82.2%, 93.2%; and montelukast, 34.0%, 34.0%, respectively. Exploratory logistic regression analyses showed that PGY1 residents had higher odds for lack of awareness for allopurinol (odds ratio [OR] 24.57, 95% CI [confidence interval] 4.69, 99.13, < 0.001), colchicine (OR 3.98, 95% CI 1.50, 10.51, < 0.01), diphenhydramine (OR 2.24, 95% CI 1.10, 4.54, < 0.04), and montelukast (OR 2.45, 95% CI 1.20, 5.00, < 0.05) than PGY3 residents. A nephrology rotation in medical school was associated with lower odds for incorrect knowledge for allopurinol (OR 0.46, 95% CI 0.25, 0.87, < 0.05) and montelukast (OR 0.50, 95% CI 0.27, 0.92, < 0.05).
CONCLUSION
Overall, awareness and knowledge were poor among IMHS for dose adjustments of rheumatology and allergy/immunology medications in patients with CKD. Proper education and exposure to nephrology during training may improve quality and safety of care for patients with CKD.
PubMed: 37663380
DOI: 10.1080/08998280.2023.2228172 -
Journal of Medical Case Reports Oct 2023Clopidogrel and ticagrelor are rarely reported to cause vasculitis via drug hypersensitivity reaction, largely mediated by T cells and immunoglobulin E (IgE). Despite... (Review)
Review
BACKGROUND
Clopidogrel and ticagrelor are rarely reported to cause vasculitis via drug hypersensitivity reaction, largely mediated by T cells and immunoglobulin E (IgE). Despite therapeutic advances, the etiology of refractory vasculitides remains incompletely understood. Recently, (non)immunological mechanisms bypassing T cells and IgE have been proposed to explain resistance to standard immunosuppressants. Herein, we report a case of refractory drug-induced systemic small-vessel vasculitis with varied extracutaneous manifestations and incorporate multiple sources of data to provide detailed accounts of complex (non)immunological phenomena involved in this case. Study objectives are to provide an insight about rare presentations of commonly used drugs, upgrade the pathophysiological concepts of drug-induced vasculitis, raise need for further investigation to define causes and risk factors for refractory vasculitis, and discuss most of the current knowledge suggesting novel therapeutic approaches to treat this vasculitis. To our knowledge, this is the first case of the two flares of systemic small-vessel vasculitis in a single patient in response to clopidogrel and ticagrelor exposure, respectively. However, this report is limited by attribution/observer bias.
CASE PRESENTATION
We herein report a 24-year-old Caucasian male student with a medical history of mild seasonal allergic rhinoconjunctivitis, tension-type headaches, posttraumatic arterial stenosis, and previous exposure to ibuprofen, acetylsalicylic acid, and mRNA coronavirus disease 2019 (COVID-19) vaccine who suffered largely from acute urticaria and dyspnea after 20 days of acetylsalicylic acid and clopidogrel introduction. A skin punch biopsy confirmed leukocytoclastic vasculitis. Serologic antibody testing, complement analysis, microbiologic testing, and cancer biomarkers revealed no abnormalities. Regarding the patient's medical history, both acetylsalicylic acid and clopidogrel were exchanged for ticagrelor. Furthermore, the addition of naproxen, cyclosporine, bilastine, prednisolone, and montelukast resulted in complete recovery. After 7 days, diarrhea and hematuria occurred. Urinalysis and computed tomography showed reversible proteinuria with gross hematuria and hypodense changes in kidney medulla, respectively, associated with discontinuation of ticagrelor and naproxen. In addition, the patient recovered completely without any immunosuppression up-titration.
CONCLUSIONS
This case highlights the role of clopidogrel and ticagrelor as possible triggering agents for systemic small-vessel vasculitis and offers an insight into novel therapeutic strategies for refractory vasculitides. Further research is needed to build on the findings of a current report.
Topics: Humans; Male; Young Adult; Aspirin; Clopidogrel; Hematuria; Immunoglobulin E; Naproxen; Ticagrelor; Vasculitis
PubMed: 37885023
DOI: 10.1186/s13256-023-04174-8 -
Iranian Journal of Otorhinolaryngology Mar 2024Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications...
INTRODUCTION
Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications and more convenience. The present study investigated the effect of adding oral montelukast to mometasone nasal spray in treating adenoid hypertrophy.
MATERIALS AND METHODS
This was a randomized, double-blind, placebo-controlled study conducted at a referral teaching hospital (Tehran, Iran) from September 2020 to September 2021. Children aged 2 to 14 years with clinical and radiological findings of adenoid hypertrophy were enrolled. Patients were randomly divided into two groups: mometasone nasal spray with oral montelukast (case group) or mometasone with placebo (control group). Then, the clinical scores were compared before and two months after the intervention.
RESULTS
Ninety-six patients completed the study [62.5% male (n=60)]. Of these, 51 were in the case and 45 in the control group. The clinical score in each group decreased significantly after the intervention (P<0.001), but the decrease in clinical score in the case group was not significantly different from the control (p=0.576).
CONCLUSION
The results showed that the combination therapy with mometasone and montelukast has the same efficacy as mometasone and placebo in treating adenoid hypertrophy. Adding montelukast to mometasone has no additional effect.
PubMed: 38476566
DOI: 10.22038/IJORL.2024.73906.3490 -
Health Science Reports Nov 2023To reduce death rates for critical patients hospitalized in intensive care units (ICUs), coronavirus (COVID-19) lacks proven and efficient treatment methods. This...
BACKGROUND AND AIMS
To reduce death rates for critical patients hospitalized in intensive care units (ICUs), coronavirus (COVID-19) lacks proven and efficient treatment methods. This cross-sectional study aims to evaluate how physicians treat severe and suspected COVID-19 patients in the ICU department in the absence of an established approach, as well as assess the rational use of the medication in the ICU department.
METHODS
Between June 16, 2021, and December 10, 2022, a total of 428 prescriptions were randomly gathered, including both suspected (yellow zone) and confirmed (red zone) COVID-19 patients. For data management, Microsoft Excel 2021 was utilized, while STATA 17 provided statistical analysis. To find associations between patients' admission status and demographic details, exploratory and bivariate analyses were conducted.
RESULTS
Of the 428 patients admitted to the ICU, 228 (53.27%) were in the yellow zone and 200 (46.73%) were in the verified COVID-19 red zone. The majority of patients were male (54.44%), and the age range from 41 to 60 was the most common (41.82%). No significant deviation was detected to the yellow and red groups' prescription patterns. A total of 4001 medicines (mean 9.35/patient) were prescribed. Antiulcerants, antibiotics, respiratory, analgesics, anticoagulants, vitamins and minerals, steroids, cardiovascular, antidiabetic drugs, antivirals, antihistamines, muscle relaxants, and antifungal treatments were widely prescribed drugs. Enoxaparin (67.06%) appeared as the most prescribed medicine, followed by montelukast (60.51%), paracetamol (58.41%), and dexamethasone (51.64%).
CONCLUSION
The prescription patterns for the yellow and red groups were comparable and mostly included symptomatic treatment. Respiratory drugs constituted the most frequent therapeutic class. Polypharmacy should be taken under considerations. In ICU settings, the outcomes emphasize the need of correct diagnosis, cautious antibiotic usage, suitable therapy, and attentive monitoring.
PubMed: 38028685
DOI: 10.1002/hsr2.1711 -
The Primary Care Companion For CNS... May 2024
Topics: Humans; Sulfides; Cyclopropanes; Acetates; Quinolines; Male; Psychoses, Substance-Induced; Child; Female; Adolescent; Asthma
PubMed: 38815271
DOI: 10.4088/PCC.23cr03694 -
Indian Journal of Endocrinology and... 2024Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its...
BACKGROUND
Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy.
METHODS
40 Wistar rats of either sex were randomly divided into four groups . 1. Vehicle control group, 2. Enalapril (5 mg/kg), 3. Montelukast low-dose (10 mg/kg) and 4. High-dose (20 mg/kg) group. On day 1, diabetes was induced using a single dose of STZ (60 mg/kg) intraperitoneally. Diabetes induction was verified based on fasting blood glucose (FBG) levels on day 7 and from day 8 to day 42, rats were given study drugs. FBG, serum creatinine, blood urea nitrogen (BUN) and urine microalbumin levels were assessed pre-study and post-study. Assessments of kidney malondialdehyde (MDA), reduced glutathione (GSH) and renal histopathology were carried out at the end of the study.
RESULTS
Montelukast 10 mg/kg group showed significantly lower urine microalbumin levels compared to the vehicle control group (p < 0.05). Montelukast 20 mg/kg group showed significantly lower levels of FBG, serum creatinine, BUN and urine microalbumin compared to the vehicle control group (p < 0.05). In addition, Montelukast 20 mg/kg group also showed better effects on kidney MDA and GSH levels (p < 0.05) and histopathological scores compared to the vehicle control group.
CONCLUSION
Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.
PubMed: 38533280
DOI: 10.4103/ijem.ijem_414_22 -
Frontiers in Medicine 2024This network meta-analysis was to analyze and rank the efficacy and safety of different systemic drugs in the treatment of uremic pruritus (UP) among hemodialysis...
Efficacy and safety of different systemic drugs in the treatment of uremic pruritus among hemodialysis patients: a network meta-analysis based on randomized clinical trials.
AIM
This network meta-analysis was to analyze and rank the efficacy and safety of different systemic drugs in the treatment of uremic pruritus (UP) among hemodialysis patients.
METHOD
PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to 10 July 2023 for randomized controlled trials (RCTs) investigating different drugs in the treatment of UP among hemodialysis patients. Drugs including cromolyn sodium, dexchlorpheniramine, difelikefalin, gabapentin, hydroxyzine, ketotifen, melatonin, montelukast, nalbuphine, nalfurafine, nemolizumab, nicotinamide, pregabalin, sertraline, thalidomide, and placebo were assessed. Outcome measures, including pruritus relief, response, and adverse events, were analyzed. Network plots, forest plots, league tables, and the surface under the cumulative ranking (SUCRA) probabilities were depicted for each outcome.
RESULTS
The network meta-analysis retrieved 22 RCTs. Gabapentin (69.74%) had the highest likelihood to be the most effective drug for pruritus relief in UP patients receiving hemodialysis, followed by cromolyn sodium and hydroxyzine. Thalidomide (60.69%) and gabapentin (58.99%) were associated with significantly more drug responses for treating UP among patients receiving hemodialysis. Patients who were treated with gabapentin (40.01%) were likely to have risks of adverse events and dizziness. Lower risks of adverse events, nausea, and diarrhea were found in patients who received cromolyn sodium and lower risks of somnolence.
CONCLUSION
This study suggests considering gabapentin treatment when facing a patient suffering from UP. This study provides a reference for the selection of drug therapy for UP patients receiving hemodialysis.
PubMed: 38646551
DOI: 10.3389/fmed.2024.1334944 -
Postepy Dermatologii I Alergologii Feb 2024Atopic dermatitis (AD) is one of the most common chronic skin conditions affecting about 20% of children and 5% of adults. However, the studies assessing novel therapies...
INTRODUCTION
Atopic dermatitis (AD) is one of the most common chronic skin conditions affecting about 20% of children and 5% of adults. However, the studies assessing novel therapies for AD have been focused mainly on paediatric patients and only few studies have involved adult participants.
AIM
To compare the treatment outcomes between the antihistamine monotherapy and combined intervention with an antihistamine agent and a cysteinyl leukotriene receptor antagonist in adult patients with atopic dermatitis.
MATERIAL AND METHODS
Patients were randomized into two groups to receive 5 mg oral desloratadine or the combined therapy with 5 mg oral desloratadine and 10 mg montelukast. Both groups were also administered topical treatment using the same protocol (topical Elocon and moisturizer). To estimate the efficacy of the implemented therapy methods, different skin health scores (SCORAD, GISS, EASI, PPNRS and DLQI) and skin functional assessment outcomes (corneometry, pH and transepidermal water loss) were evaluated before and after the treatment.
RESULTS
Significant differences were revealed in compared measurement results for scales of the Extent and Severity of Eczema assessment, Global Individual Signs Score, Eczema Area and Severity Index, Pruritus Numerical Rating Scale, Dermatology Life Quality Index and Skin Functional Properties (p > 0.05).
CONCLUSIONS
Comparison of data presenting the therapy outcomes in two groups showed that administration of the combined therapy was significantly more effective compared to the antihistamine monotherapy. The results revealed considerable efficacy of the combined therapy reinforced by the use of cysteinyl leukotriene receptor antagonist, montelukast.
PubMed: 38533375
DOI: 10.5114/ada.2023.135759 -
Cureus Jul 2023Eosinophilic gastrointestinal disorders (EGIDs) are a spectrum of disorders including eosinophilic esophagitis, eosinophilic gastroenteritis, and eosinophilic colitis....
Eosinophilic gastrointestinal disorders (EGIDs) are a spectrum of disorders including eosinophilic esophagitis, eosinophilic gastroenteritis, and eosinophilic colitis. We report a case of EGID involving the esophagus, small intestine, and large intestine simultaneously. A 38-year-old male patient presented with chronic diarrhea, abdominal pain, and unquantified weight loss for the last two months, which not improving with routine empirical treatment. Endoscopy revealed erosions in the stomach, duodenum, terminal ileum, and proximal colon. Biopsy revealed eosinophilic infiltration in the esophagus, terminal ileum, and proximal colon. Contrast-enhanced CT showed multiple skip areas of short- and long-segment circumferential mural thickening with enhancement in the jejunum and ileal loops, causing mild luminal narrowing with pelvic ascites, indicating involvement of muscular and probably serosal layer to a lesser degree (absence of obstructive symptoms with minimal ascites) along with predominant mucosal involvement (responsible for clinical symptoms). The patient was treated with elimination diet, systemic corticosteroids, and montelukast. Diarrheal episodes decreased, and the treatment was shifted to oral budesonide. We believe it to be one of the first reports to show a simultaneous involvement of the esophagus, small intestine, and large intestine, along with mucosal and mural involvement. It strengthens the fact that a common underlying pathogenesis causes EGIDs and an underlying muscular layer involvement in patients with predominant mucosal disease.
PubMed: 37621796
DOI: 10.7759/cureus.42349