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Antiasthma Agents during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Montelukast is a leukotriene inhibitor, which relieves inflammation and bronchospasm asthma symptoms. The drug is used to prevent asthma attacks in individuals as young as 12 months old, and to prevent exercise-induced bronchospasm in asthmatics as young as 6 years.
Respiratory Diseases
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Aref T. Senno, Ryan K. Brannon
Limited human data are available on the use of LTRA during pregnancy. Several small studies have not shown an increase in the rate of major malformations in offspring of women who took LTRA during pregnancy [30, 31]. Mean birth weight was lower, and risk of low birthweight and fetal distress was higher in the montelukast-exposed group, a difference that may have been related to asthma severity rather than drug effect. In nonpregnant individuals, these drugs are less effective than inhaled corticosteroids, and do not add much benefit to women already on inhaled steroids. They do not reduce the risk of exacerbation requiring systemic steroids, and are associated with modest improvement in PEF, with very modest decrease in use of rescue SABAs [32]. These drugs may be considered during pregnancy for women who had a good response to them prior to pregnancy, but they are not a preferred option when initiating therapy. Montelukast and zafirlukast are safe in pregnancy [33, 34]. Zileuton, a 5-lipoxygenase inhibitor, has been advised against in pregnancy based on animal data: Human data are lacking [19].
Answers
Published in Samar Razaq, Difficult Cases in Primary Care, 2021
Paradoxical bronchospasm can be a problem associated with inhaled corticosteroids. A trial of steroid by dry powder inhalation may be considered as an alternative to aerosol inhalers. Another useful way of preventing this is for the β2-agonist inhalation to precede steroid inhalation to counteract the bronchospasm. The risk of oral candidiasis can be minimised by washing the child’s mouth and brushing his or her teeth after steroid inhalation. This child has had two attempts and failed. Montelukast is a leukotriene receptor antagonist and is an effective, well-tolerated alternative where inhaled corticosteroids are not tolerated. This child remains poorly controlled and should be referred to a respiratory paediatrician.
Montelukast promotes mitochondrial biogenesis via CREB/PGC-1α in human bronchial epithelial cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Huan Wang, Yali Cheng, Ying Liu, Jiang Shi, Zhe Cheng
Montelukast, a selective antagonist of cysteinyl leukotriene (cysLT) receptor 1, is licenced for the therapy of bronchial asthma through blocking the action of leukotrienes [5]. A diversity of pharmacological capacities of montelukast has been reported. Montelukast has displayed antioxidant and anti-inflammatory effects in various diseases. Montelukast has been shown to improve motor recovery and reduce IL-6 levels in spinal cord ischemia-reperfusion (I/R) injury [6]. Another study demonstrated that administration of montelukast decreased respiratory syncytial virus-induced mucus hyperproduction in a rodent in vivo model [7]. Interestingly, montelukast treatment has been reported to increase concentrations of intracellular cyclic adenosine monophosphate (cAMP) through inhibiting the activity of cyclic nucleotide phosphodiesterases [5]. Consistently, another study reported that montelukast suppressed neutrophil-induced Ca2+-mediated pro-inflammatory activities of the cells in a cAMP dependent mechanism [8]. cAMP plays a critical role in mediating activation of CREB [9]. CREB has been shown to promote the expression of PGC-1α [10]. These results suggest that montelukast might possess an impact on PGC-1α signalling and mitochondrial biogenesis.
Advances in treating bronchopulmonary dysplasia
Published in Expert Review of Respiratory Medicine, 2019
Montelukast is a selective leukotriene receptor antagonist of cysteinyl leukotriene [34]. Cysteinyl leukotriene causes bronchoconstriction, mucus secretion, airway hyperactivity and increased vascular permeability [35]. The effect of daily montelukast therapy (1 mg/kg increasing to 1.5 mg/kg and finally 2 mg/kg) for at least three weeks administered to 11 preterm infants who required mechanical ventilatory support at twenty-eight days after birth was compared to eleven controls [36]. Seven controls died due to respiratory failure, whereas the one non-survivor in the montelukast group died post operatively from sepsis following necrotizing enterocolitis. There was also a significant decrease in the pulmonary severity score or the duration of ventilation between the groups [36]. No adverse effects related to montelukast therapy were reported. The study, however, was not randomised nor blinded, but the controls were matched for gestational age, birth weight and pulmonary severity score [36]. A subsequent study which was a prospective, multicentre, randomised controlled trial of 66 infants born at less than 32 weeks of gestational age with a postnatal age greater than 14 days, all ventilator or supplementary oxygen dependent demonstrated no significant difference in the incidence of moderate to severe BPD (43.4% versus 52.8%, p = 0.912) [37]. The long-term efficacy of montelukast needs to be determined in an appropriately randomised trial.
Montelukast attenuates radioactive I131-induced pulmonary damage on rats
Published in International Journal of Radiation Biology, 2018
Arif Osman Tokat, Aylin Akbulut, Deniz Billur, Gokhan Koca, Pinar Bayram, Serdar Kuru, Sezgin Karasu, Suheyla Aydogmus, Hüseyin Cakmak, Sengul Ozmert, Meliha Korkmaz
RAI-induced pulmonary damage is characterized by marked macrophage infiltration, interstitial edema and consequent fibrotic changes including alveolar septal wall thickening and perivascular fibrosis (Vergara et al. 1987), which usually presents as either radiation pneumonitis or radiation fibrosis, or both, and associated with proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), transforming growth factor beta (TGF-beta). Given that proinflammatory cytokines have an impact on response to radiation, inducing inflammation, cell invasiveness and fibrosis in irradiated tissues, the hypothesis of using specific inhibitors or drugs able to manipulate cytokine pathways (Di Maggio et al. 2015) such as montelukast, to improve radiation research and therapy have been the challenge. Montelukast, is a selective pharmacological antagonist of type 1 cysteinyl-leukotriene receptors (CysLT1R), with demonstrated clinical efficacy in the treatment of asthma, and has been used safely for many years, even in pediatric patients, with few side effects. Recently, the effects of montelukast administration at an early stage have been shown to prevent pulmonary fibrosis in a bleomycine-induced mouse model (Izumo et al. 2007).