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Pharmaceuticals (Basel, Switzerland) Aug 2022Increasing environmental distress is associated with a growing asthma incidence; no treatments are available but montelukast (MTK)-an antagonist of the cysteinyl... (Review)
Review
Increasing environmental distress is associated with a growing asthma incidence; no treatments are available but montelukast (MTK)-an antagonist of the cysteinyl leukotrienes receptor 1-is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions (ADRs). Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as a modulator of leukotriene pathways and systematize the current knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.
PubMed: 36145259
DOI: 10.3390/ph15091039 -
Journal of Research in Pharmacy Practice 2016Pyelonephritis is an inflammatory process, and oxidative stress plays a major role in it. Anti-inflammatory or antioxidant therapy given concomitantly with antibiotics... (Review)
Review
Pyelonephritis is an inflammatory process, and oxidative stress plays a major role in it. Anti-inflammatory or antioxidant therapy given concomitantly with antibiotics should lower the risk of postpyelonephritic scarring. As the lack of review studies in the use of antioxidants in urinary tract infections was detected, this study was designed. We conducted a review of available articles in PubMed and Google Scholar with a simple review, using keywords of "antioxidant" and "pyelonephritis" with all their possible synonyms and combinations. Only interventional studies were collected. There were neither limitations on time, nor the location of the study, type of subjects, administration rout of the antioxidant drug, and the antioxidant drug used. After studying the abstracts or in some cases the full text of articles, they were categorized based on the type of antioxidant, type and number of subjects, rout of administration, dosing, duration of treatment, year of publication of the paper, and the results. A total of 66 articles published from 1991 to 2015 were found by studying just the title of the papers. Studying the abstracts reduced this number to 51 studies. Antioxidants used for this condition were Vitamins A, E, and C, cytoflavin, caffeic acid phenethyl ester, ebselen, allopurinol, melatonin, N-acetylcysteine, oleuropein, montelukast, oxytocin, ozon, dapsone, pentoxifyllin, tadalafil, bilirubin, cranberry, meloxicam, L-carnitine, colchicine, perfluoran, methylprednisolone, and dexamethasone. Studies show that antioxidants are capable of reducing oxidative stress and can be used effectively along with antibiotics to reduce the scar formation.
PubMed: 27162800
DOI: 10.4103/2279-042X.179567 -
Heliyon Aug 2022Knowing the level of active ingredients in an expired drug is a matter of concern irrespective of its final disposition. This is also a matter of national security and...
BACKGROUND
Knowing the level of active ingredients in an expired drug is a matter of concern irrespective of its final disposition. This is also a matter of national security and defense as it has important implications on the nation's stockpile of prescription medications. Current literature has limited information about the strength of expired medications and any relevant trends.
OBJECTIVE
To utilize high performance liquid chromatography (HPLC) to determine the strength of selected drugs for asthma and chronic obstructive pulmonary disease (COPD) as a class of therapeutic agents commonly used in free clinics.
METHODS
Samples from expired lots of montelukast and albuterol pharmaceutical products were analyzed for their levels of their respective active ingredients. Two HPLC methods were developed, validated, and applied to achieve this goal. Quantitative analysis of each drug was performed using two different reversed phase C18 columns with a linear gradient of acetonitrile in 0.1% aqueous formic acid at a flow rate of 1 mL/min for both methods. Detection wavelength for montelukast and albuterol was 280 and 277 nm, respectively.
RESULTS
Expiry dates of analyzed batches ranged from 2003 to 2019. Despite the extended time range beyond expiry dates, levels of both drugs were relatively consistent and exceeded 90% of the listed strength in most analyzed lots.
CONCLUSIONS
Our results introduce a new perspective towards reducing the financial burden resulting from disposal of expired medications with retained strength. They also offer supporting evidence to extend the use of out-of-date montelukast and albuterol preparations at home and in free clinics.
PubMed: 36016533
DOI: 10.1016/j.heliyon.2022.e10104 -
BMJ Open Jan 2022National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of...
BACKGROUND
National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP).
OBJECTIVE
To systematically review evidence regarding deprescribing montelukast in CYP with established asthma.
DESIGN
Systematic review.
DATA SOURCES
Embase, Medline, PubMed and CINAHL were searched up to October 2020.
STUDY SELECTION
Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included.
RESULTS
The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased.
CONCLUSION
Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP.
PROSPERO REGISTRATION NUMBER
CRD42020213971.
Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Cyclopropanes; Deprescriptions; Forced Expiratory Volume; Humans; Infant; Infant, Newborn; Quinolines; Sulfides
PubMed: 35105629
DOI: 10.1136/bmjopen-2021-053112 -
International Immunopharmacology Feb 2022Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a...
Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins, cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19. Clinical data to date with an associated six-month follow-up, suggests the combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of 'Long COVID,' thereby cost effectively reducing both morbidity and mortality. To investigate patient outcomes, 53 consecutive COVID-19 test (+) cases (ages 3-90) from a well-established, single-center practice in Boston, Massachusetts, between March - November 2020, were treated with levocetirizine and montelukast in addition to then existing protocols [2]. The data set was retrospectively reviewed. Thirty-four cases were considered mild (64%), 17 moderate (32%), and 2 (4%) severe. Several patients presented with significant comorbidities (obesity: n = 22, 41%; diabetes: n = 10, 19%; hypertension: n = 24, 45%). Among the cohort there were no exclusions, no intubations, and no deaths. The pilot study in Massachusetts encompassed the first COVID-19 wave which peaked on April 23, 2020 as well as the ascending portion of the second wave in the fall. During this period the average weekly COVID-19 case mortality rate (confirmed deaths/confirmed cases) varied considerably between 1 and 7.5% [37]. FDA has approved a multicenter, randomized, placebo-controlled, Phase 2 clinical trial design, replete with electronic diaries and laboratory metrics to explore scientific questions not addressed herein.
Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Cetirizine; Child; Child, Preschool; Cyclopropanes; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Retrospective Studies; SARS-CoV-2; Sulfides; Treatment Outcome; Young Adult; COVID-19 Drug Treatment
PubMed: 34942461
DOI: 10.1016/j.intimp.2021.108412 -
Asian Pacific Journal of Allergy and... Mar 2022Leukotriene receptor antagonists are recommended to treat asthma and allergic rhinitis. Although they had been used for a long time, recent studies have reported...
BACKGROUND
Leukotriene receptor antagonists are recommended to treat asthma and allergic rhinitis. Although they had been used for a long time, recent studies have reported neuropsychiatric adverse drug reactions are associated with montelukast.
OBJECTIVE
This study analyzed the adverse drug reactions of montelukast and pranlukast, which are the two most frequently prescribed leukotriene receptor antagonists, respectively in Korea.
METHODS
This study retrospectively reviewed ADRs of 5,426 montelukast and 1,146 pranlukast reported in the Korea Adverse Event Reporting System between January 2014 and December 2018.
RESULTS
When both drugs are classified by system organ class, the most adverse drug reactions were related to the gastro-intestinal system, followed by psychiatric events. The reported adverse drug reactions for both drugs were more common in women, and the ratio of adverse drug reactions to prescriptions was highest in the elderly. Women aged 19 to 64 years reported more than twice as many adverse drug reactions than men of the same age, and more than 5 times in insomnia.
CONCLUSIONS
When prescribing montelukast and pranlukast, attention would need to digestive and sleep disorders, especially women aged 19 to 64. After prescribing montelukast, physicians would need to pay more attention to agitation (5/396378 vs 0/82475), bad or vivid dreams (6/396378 vs 0/82475), anxiety (11/396378 vs 0/82475), depression (14/396378 vs 1/82475), tremor (53/396378 vs 7/82475), irritability (5/396378 vs 1/82475), insomnia (159/396378 vs 25/82475), and headache (68/396378 vs 10/82475), compared to when prescribing pranlukast. Further prospective research needs to elucidate the relationship between neuropsychiatric events and montelukast.
PubMed: 35278057
DOI: 10.12932/AP-030821-1202 -
Journal of Thoracic Disease Nov 2021Outcomes after lung transplantation are limited by chronic lung allograft dysfunction (CLAD). The incidence of CLAD is high, and its clinical course tends to be... (Review)
Review
Outcomes after lung transplantation are limited by chronic lung allograft dysfunction (CLAD). The incidence of CLAD is high, and its clinical course tends to be progressive over time, culminating in graft failure and death. Indeed, CLAD is the leading cause of death beyond the first year after lung transplantation. Therapy for CLAD has been limited by a lack of high-quality studies to guide management. In this review, we will discuss the diagnosis of CLAD in light of the recent changes to definitions and will discuss the current clinical evidence available for treatment. Recently, the diagnosis of CLAD has been subdivided into bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The current evidence for treatment of CLAD mainly revolves around treatment of BOS with more limited data existing for RAS. The best supported treatment to date for CLAD is the macrolide antibiotic azithromycin which has been associated with a small improvement in lung function in a minority of patients. Other therapies that have more limited data include switching immunosuppression from cyclosporine to tacrolimus, fundoplication for gastroesophageal reflux, montelukast, extracorporeal photopheresis (ECP), aerosolized cyclosporine, cytolytic anti-lymphocyte therapies, total lymphoid irradiation (TLI) and the antifibrotic agent pirfenidone. Most of these treatments are supported by case series and observational studies. Finally, we will discuss the role of retransplantation for CLAD.
PubMed: 34992842
DOI: 10.21037/jtd-2021-19 -
Toxicology Research Aug 2022Doxorubicin (DOX) is a powerful antitumor agent with a well-known cardiaotoxic side effects. In the current study, the ameliorative combined impacts of montelukast...
Doxorubicin (DOX) is a powerful antitumor agent with a well-known cardiaotoxic side effects. In the current study, the ameliorative combined impacts of montelukast (Mont) and Klotho against doxorubicin-induced cardiac toxicity were examined. Fifty-six adult male rats (2 months age and weighting 150-200 g) were grouped into 7 groups (8 rats per group). Animals received doxorubicin alone or in combination with either Mont or Klotho. After 2 weeks of treatments, serum samples were examined to assess the changes in cardiac activity biomarkers such as LDH, CK-MB, cardiac troponin-I (cTn-I), and heart fatty acid binding protein (H-FABP). Serum changes of IL-6, inducible nitric oxide synthase (iNOS), and caspase-3 levels were assayed. The oxidative stress biomarkers such as total antioxidant capacity (TAC) and inflammatory (rat IL-1β and rat TNF-α,) and anti-inflammatory (rat IL-10) cytokines were examined. Heart histology and transforming growth factor-β1 (TGF-β1) immunoreactivity were measured. DOX induced cardiomyopathy, which was reflected by the increases in all examined cardiac parameters. Real-time PCR confirmed that DOX upregulated the expression of TNF-α and IL-1β and decreased the expression of IL-10. Moreover, DOX showed marked elevation in the ST segment T wave complex, causing profound tachycardia. Heart histology assessments showed cardiac cell necrosis, inflammatory cell infiltration, interstitial congestion, and increased TGF-β1 immunoreactivity. Montelukast and Klotho administration ameliorated all the altered parameters when administered alone or in combination to DOX-intoxicated rats. Klotho was more effective compared with montelukast in terms of reductions in heart rate, ST segment T wave complex elevation, cardiac enzymes (lactate dehydrogenase; LDH, creatine kinase-MB; CK-MB, cardiac troponin I; cTn-I, heart fatty acid binding protein; H-FABP) cardiac histology, and caspase-3 levels and increases in TAC activity. Montelukast was more effective in reducing serum levels of IL6 and iNOS, expression of TNF-α and IL-1β, and the upregulation of IL-10 expression. The co-administration of both drugs led to significantly more synergistic results in terms of reducing cardiac toxicity. In conclusion, montelukast and Klotho either alone or in combination were confirmed to be effective in suppressing DOX-induced cardiac toxicity in rats.
PubMed: 36051669
DOI: 10.1093/toxres/tfac023 -
European Journal of Pharmacology Aug 2021Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction... (Review)
Review
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction with angiotensin converting enzyme 2 (ACE2) receptors, highly expressed in lung type II alveolar cells and other tissues, like heart, pancreas, brain, and vascular endothelium. This review aimed to elucidate the potential role of leukotrienes (LTs) in the pathogenesis and clinical presentation of SARS-CoV-2 infection, and to reveal the critical role of LT pathway receptor antagonists and inhibitors in Covid-19 management. A literature search was done in PubMed, Scopus, Web of Science and Google Scholar databases to find the potential role of montelukast and other LT inhibitors in the management of pulmonary and extra-pulmonary manifestations triggered by SARS-CoV-2. Data obtained so far underline that pulmonary and extra-pulmonary manifestations in Covid-19 are attributed to a direct effect of SARS-CoV-2 in expressed ACE2 receptors or indirectly through NF-κB dependent induction of a cytokine storm. Montelukast can ameliorate extra-pulmonary manifestations in Covid-19 either directly through blocking of Cys-LTRs in different organs or indirectly through inhibition of the NF-κB signaling pathway.
Topics: Acetates; COVID-19; Cyclopropanes; Cytokine Release Syndrome; Humans; Leukotriene Antagonists; Leukotrienes; Lung Diseases; Quinolines; Receptors, Leukotriene; Signal Transduction; Sulfides; COVID-19 Drug Treatment
PubMed: 34004207
DOI: 10.1016/j.ejphar.2021.174196 -
Children (Basel, Switzerland) Nov 2022Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies...
UNLABELLED
Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies have reported several adverse events, such as neuropsychiatric disorders and sleep disturbances, among children.
OBJECTIVE
To obtain more insight into the safety profile of montelukast for children with asthma, allergic rhinitis and sleep-related breathing disorders.
METHOD AND RESULTS
We retrospectively studied all adverse drug reactions to montelukast among 385 children 6 months or older in six tertiary centers over a two-year period. A total of 89.6% were asthmatic, 50% had allergic rhinitis and 13.6% had sleep-related breathing disorders; Singulair was the most common type of montelukast used (67.9%). This study reported a high prevalence of adverse drug reactions among 123 patients (31.9%), predominantly in those aged 4-9 years (52.8%), followed by adolescents (24.4%) and toddlers (22.8%). Two (ADRs) were reported in 9.8% of the children, while three or more were reported in 5.5%. Sleep disturbance was the most common (ADRs), affecting 15.1% of participants (overlap was common; 5.5% of children experienced sleep difficulties, 4.4% experienced sleep interruption and decreased sleep, and 1.82% experienced nightmares), followed by agitation (10.4%), pain (9.4%) and hyperactivity (6.8%). No serious (ADRs) were reported. Eleven percent of families faced difficulties in purchasing montelukast, and only 57% of families had insurance. Misconceptions were common (9.8% reported it to be a steroid, while 30.6% believed it to be a bronchodilator). Although 81% of the families believed it was an effective and preventive medication, 5.3% stopped the drug due to concern about side effects, especially agitation (3%) and nightmares (0.6%).
CONCLUSION
These data demonstrate that montelukast is effective, but the associated adverse neuropsychiatric drug reactions are more prevalent than those reported in the literature. In particular, sleep disturbance, agitation, pain and hyperactivity were observed. Pediatricians should be aware of such (ADRs). Misconceptions about montelukast are still common, and parental counseling and urgent epidemiological studies are needed to quantify the risk for management plans.
PubMed: 36421233
DOI: 10.3390/children9111783