Intravenous Montelukast Research Articles

Psychiatrc symptoms induced by montelukast: A case report

Introduction Montelukast is a leukotrienes receptor antagonist, which is used, in chronic asthma, exercise induced broncoconstriction and allergic rhinitis treatment. Montelukast inhibates the proinflammatory cytokines and leukotriene is released from the specific cells. Leukotrienes cause mucus secretion, vasodilatation, broncoconstriction and eosinophilia. This case is about an asthma-diagnosed child who had acute disturbing behaviour and sleeping problems after using montelukast treatment. Case A 5 year-old boy assessed because of symptoms like breaking the rules, disturbing friends, self-harming, hyperactivity, distractability, insomnia and nightmares. In his history, when he was 9months old acute hyperactivity, yelling, naughtiness, insomnia, disturbing and self-harming behaviours occurred suddenly 24hours after intravenous montelukast treatment due to asthma crisis. While he was still using oral montelukast, his parents had cut off the treatment. After about 2months, there was decrease in the symptoms. After using montelukast, these kinds of misbehaviour occurred again in a week. The montelukast treatment was terminated controlled way under a pediatrician consultation. Turgay DSM-IV Based Distruptive Behaviour Disorders Screening and Rating Scale were completed by both of the parents in the first interview and after 2months of cutting off montelukast treatment. While comparing 2 scales and parents' anamnesis, we found that impulsivity, oppositional defiant, hyperactivity, distractability, breaking off the rules, irritability, insomnia and having nightmares reduced. Conclusion Montelukast can cause many psychiatric symptoms. In that case we found sleeping problems and disturbing behaviour caused or induced by montelukast treatment. As in that case, other drugs also can cause or enhance psychiatric symptoms. So it is important to assess the other drugs while assessing the diagnosis and the treatment.

Evaluation and Treatment of Critical Asthma Syndrome in Children

The heterogeneity of asthma is illustrated by the significantly different features of pediatric asthma compared to adult asthma. One phenotype of severe asthma in pediatrics includes atopy, lack of reduction in lung function, and absence of gender bias as the main characteristics. Included in the NIH NAEPP EPR-3 are recommendations for the treatment and management of severe pediatric asthma and critical asthma syndrome, such as continuous nebulization treatments, intubation and mechanical ventilation, heliox, and magnesium sulfate. In addition, epinephrine, intravenous immunoglobulin, intravenous montelukast, extracorporeal membrane oxygenation, and many biological modulators currently under investigation are additional current and/or future treatment modalities for the severe pediatric asthmatic. But, perhaps the most important strategy for managing the severe asthmatic is preventative treatment, which can significantly decrease impairment and risk, particularly for severe acute exacerbations requiring emergency care and/or hospitalization. In order for preventative therapy to be successful, several challenges must be met, including selecting the correct therapy for each patient and then ensuring compliance or adherence to a treatment plan. The heterogeneity of asthma renders the former difficult in that not all patients will respond equally to the same treatment; the latter is only helpful if the correct treatment is employed. Strategies to ensure compliance include education of caregivers and patients and their families. As newer medications are introduced, options for individualized or customized medicine increase, and this may pave the way for significant decreases in morbidity and mortality in severe pediatric asthma.

The Efficacy and Tolerability of Intravenous Montelukast in Acute Asthma Exacerbations in Japanese Patients

Objectives. In Japan, the Asthma Prevention and Management Guidelines recommend nebulized β-agonists, IV (intravenous) drip corticosteroids, as well as IV drip aminophylline for acute asthma treatment. However, current treatment for acute asthma provides inadequate benefit for some patients. We evaluated the efficacy and safety of IV montelukast added to standard therapy in Japanese patients with acute asthma exacerbations. Methods. This multicenter, randomized, double-blind, parallel-group study compared IV montelukast 7 mg, 14 mg, and placebo in Japanese patients with acute asthma exacerbations (N = 242). Fifteen- to sixty-five-year-old patients with acute asthma were treated with standard care during a screening period that lasted ≤60 minutes. Patients with FEV1 (forced expiratory volume in 1 second) ≤70 predicted were randomly allocated to one of three treatment groups. The primary end point was the time-weighted average change in FEV1 from baseline over 60 minutes [ΔFEV1 (0–60 minutes)] after study drug administration. Secondary end points included the time-weighted average change in FEV1 over 20, 40, and 120 minutes [ΔFEV1 (0–T min)]. Results. IV montelukast 7 mg was significantly more effective than placebo for the time-weighted average ΔFEV1 (0–60 minutes) [least squares (LS) mean 0.09 L vs. 0.01 L; p < .05]. IV montelukast 14 mg was also more effective than placebo (LS mean 0.17 L; p < .001). Similar improvements in time-weighted average [ΔFEV1 (0–T min)] were seen at all time points (all p < .05). Both doses of IV montelukast demonstrated a significant increase in average ΔFEV1 compared with placebo within 10 minutes of administration (p < .001 to p < .01). The tolerability of IV montelukast was similar to that of placebo. Conclusion. IV montelukast was significantly more effective than placebo in the improvement of ΔFEV1 in Japanese patients, suggesting its role as an adjunctive therapy to existing guideline recommendations.

A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma

A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma

A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma

A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma

A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma

Current treatments for acute asthma provide inadequate benefit for some patients. Intravenous montelukast may complement existent therapies. To evaluate efficacy of intravenous montelukast as adjunctive therapy for acute asthma. A total of 583 adults with acute asthma were treated with standard care during a < or = 60-minute screening period. Patients with FEV(1) < or =50% predicted were randomly allocated to intravenous montelukast 7 mg (n = 291) or placebo (n = 292) in addition to standard care. This double-blind treatment period lasted until a decision for discharge, hospital admission, or discontinuation from the study. The primary efficacy endpoint was the time-weighted average change in FEV(1) during 60 minutes after drug administration. Secondary endpoints included the time-weighted average change in FEV(1) at various intervals (10-120 minutes) and percentage of patients with treatment failure (defined as hospitalization or lack of decision to discharge by 3 hours postadministration). Montelukast significantly increased FEV(1) at 60 minutes postdose; the difference between change from baseline for placebo (least-squares mean of 0.22 L; 95% CI, 0.17, 0.27) and montelukast (0.32 L; 95% CI, 0.27, 0.37) was 0.10 L (95% CI, 0.04, 0.16). Similar improvements in FEV(1)-related variables were seen at all time points (all P <.05). Although treatment failure did not differ between groups (OR 0.92; 95% CI, 0.63, 1.34), a prespecified subgroup analysis suggests likely benefit for intravenous montelukast at US sites. Intravenous montelukast added to standard care in adults with acute asthma produced significant relief of airway obstruction throughout the 2 hours after administration, with an onset of action as early as 10 minutes.

A randomized, placebo-controlled study of intravenous montelukast in children with acute asthma

Up to 30% of patients require hospitalization for acute asthma despite standard therapy in the emergency department. In adults, intravenous montelukast added to standard therapy significantly improved forced expiratory volume in 1 second (FEV1) and reduced hospital admissions compared with standard therapy alone. To evaluate the efficacy of intravenous montelukast added to standard therapy in children with acute asthma. This was a randomized, double-blind, placebo-controlled, multicenter study of children aged 6 to 14 years conducted from August 25, 2005 to March 17, 2008. Patients with an FEV1 of 75% or less of the predicted value after up to 120 minutes of standard therapy (e.g., oxygen, albuterol, inhaled anticholinergics, and systemic oral corticosteroids) were randomized to intravenous montelukast, 5.25 mg (n=145), or placebo (n=131) added to standard therapy. The primary end point was the time-weighted average change in FEV1 during 60 minutes (deltaFEV1[0-60 min]). Secondary end points included the percentage of patients in whom treatment failed (patients who required hospitalization or for whom a decision to discharge was not reached within 2 hours after drug administration) and the change from baseline in modified pulmonary index score after 60 minutes of treatment. Montelukast was not significantly more effective than placebo for deltaFEV1[0-60 min] when added to standard therapy (0.08 vs. 0.07 L; least squares mean, 0.01; 95% confidence interval, -0.06 to 0.08; P = .78). No significant differences were found in the percentages of patients in whom treatment failed or the modified pulmonary index score after 60 minutes. Both treatments were well tolerated. In this study of children with acute asthma, intravenous montelukast was not significantly better than placebo in improving FEV1, symptoms, or overall hospital course.

Pharmacological profile and clinical effects of montelukast sodium (Singulair chewable tablet), an antiasthmatic agent

Montelukast (Singulair) is an antiasthmatic agent that has the chemical structure of a quinoline. Montelukast has a high affinity for the CysLT1 receptor and a potency that is not influenced by human serum protein. Montelukast antagonizes contractions of guinea-pig trachea induced by LTD4 in a competitive manner. Intravenous montelukast inhibited bronchoconstriction induced by LTD4 in guinea pigs. Oral montelukast inhibited increased airway resistance induced by antigen in squirrel monkeys. Montelukast also inhibited both inflammatory and immunologic responses induced by either LTD4 or antigen in guinea pigs and rats. Plasma concentrations of montelukast after oral administration of 10 mg in humans were shown to be over the effective level for at least 24 h. These lines of evidence support the effectiveness of a regimen of 10 mg/day for asthmatic symptoms in humans. In a number of clinical experiments, montelukast not only improved asthmatic symptoms and respiratory indices, but also inhibited airway inflammation and exercise-induced bronchoconstriction. These effects persisted during extended treatment. Montelukast produced an additive effect to basic therapy with an inhaled steroid. There were no differences in the incidence and magnitude of adverse effects between montelukast and placebo groups in clinical experiments. Montelukast is expected to serve as a first line of asthmatic therapy because of its consistent efficacy and good safety profile and it is associated with good compliance in patients because of its simple regimen of one 10 mg tablet/day.

Comparison of the effects of intravenous and oral montelukast on airway function: a double blind, placebo controlled, three period, crossover study in asthmatic patients

BACKGROUNDMontelukast, a leukotriene receptor antagonist, improves parameters of asthma control including forced expiratory volume in one second (FEV1) when given orally to patients aged six years or older. This study...

Pharmacology of montelukast sodium (Singulair™), a potent and selective leukotriene D4receptor antagonist

Montelukast sodium (Singulair), also known as MK-0476 (1-(((1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)-ethenyl)phenyl)(3-2-(1- hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropane) acetic acid sodium salt, is a potent and selective inhibitor of [3H]leukotriene D4 specific binding in guinea pig lung (Ki 0.18 +/- 0.03 nM), sheep lung (Ki 4 nM), and dimethylsulfoxide-differentiated U937 cell plasma membrane preparations (Ki 0.52 +/- 0.23 nM), but it was essentially inactive versus [3H]leukotriene C4 specific binding in dimethylsulfoxide-differentiated U937 cell membranes (IC50 10 microM) and [3H]leukotriene B4 specific binding in THP-1 cell membranes (IC50 40 microM). Montelukast also inhibited specific binding of [3H]leukotriene D4 to guinea pig lung in the presence of human serum albumin, human plasma, and squirrel monkey plasma with Ki values of 0.21 +/- 0.08, 0.19 +/- 0.02, and 0.26 +/- 0.02 nM, respectively. Functionally, montelukast antagonized contractions of guinea pig trachea induced by leukotriene D4 (pA2 value 9.3; slope 0.8). In contrast, montelukast (16 microM) failed to antagonize contractions of guinea pig trachea induced by leukotriene C4 (45 mM serine-borate), serotonin, acetylcholine, histamine, prostaglandin D2, or U-44069. Intravenous montelukast antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. leukotriene D4 but did not block bronchoconstriction to arachidonic acid, histamine, serotonin, or acetylcholine. Oral administration of montelukast blocked leukotriene D4 induced bronchoconstriction in conscious squirrel monkeys, ovalbumin-induced bronchoconstriction in conscious sensitized rats (ED50 0.03 +/- 0.001 mg/kg; 4 h pretreatment), and also ascaris-induced early and late phase bronchoconstriction in conscious squirrel monkeys (0.03-0.1 mg/kg; 4 h pretreatment). A continuous i.v. infusion of montelukast (8 micrograms.kg-1.min-1) resulted in a 70% decrease in the peak early response and a 75% reduction of the late response to ascaris aerosol in allergic conscious sheep. Montelukast, a potent and selective leukotriene D4 receptor antagonist with excellent in vivo activity is currently in clinical development for the treatment of asthma and related diseases.