User:Matthew J Lowry/Sandbox 1: Difference between revisions
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== Function == | == Function == | ||
Montelukast is a cysteinyl leukotriene receptor antagonist that blocks production of leukotrienes and prevents them from binding to their receptors. Leukotrienes often cause many pulmonary dysfunctions and inflammatory illnesses such as asthma, peptic ulcers, and ischemia or reperfusion <ref name=“one”>Bentli, R., Ciftci, O., Cetin, A., and Otlu, A. (2016) Anti-inflammatory Montelukast prevents toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Oxidative stress, histological alterations in liver, and serum cytokine levels. Toxicology and Industrial Health, 32(5), 769-776. doi: 10.1177/0748233713505894</ref>. Montelukast is known for its effectiveness in the pathophysiological mechanisms of asthma and asthma associated allergic rhinitis<ref name=“two”>Cylllyl, A., Kara, A., Ozdemir, T., Ogus, C. , and Gulkesen K. (2003) Effects of oral montelukast on airway function in acute asthma. Respiratory Medicine, 97(5), 533-536. doi: 10.1053/rmed.2003.1479</ref>. Montelukast suppresses the activation of eosinophils, which are associated with increased asthma severity. It specifically targets and blocks the leukotriene cascade that is responsible for bronchoconstriction and sensory activation in the inflammatory pathway of asthma. Allergic rhinitis is often associated with asthma, this can lead to leukotrienes in the upper airway that act as inflammatory mediators producing the symptoms of allergic rhinitis <ref name=“three”>Nayak, A. (2004). A review of montelukast in the treatment of asthma and allergic rhinitis. Expert Opinion on Pharmacotherapy, 5:3, 679-686. doi:10.1517/14656566.5.3.679</ref>. Montelukast reduces the release of inflammatory cytokines from airway cells and concentration of exhaled nitric oxide, alleviating allergic symptoms by decreasing airway hyperresponsiveness and bronchoconstriction. Due to its efficacy and safety, it can work as a monotherapy for those who do not respond well to inhaled corticosteroids, but it can also be prescribed with other drugs such as inhaled or oral corticosteroids, antihistamines, and beta-2 agonists to maximize its effects<ref name=“four”>Paggiaro, P., Bacci, E. (2011) Montelukast in Asthma: A Review of its Efficacy and Place in Therapy. Therapeutic Advances in Chronic Disease, 2(1), 47-58. doi: 10.1177/ 2040622310383343</ref>. | Montelukast is a cysteinyl leukotriene receptor antagonist that blocks production of leukotrienes and prevents them from binding to their receptors. Leukotrienes often cause many pulmonary dysfunctions and inflammatory illnesses such as asthma, peptic ulcers, and ischemia or reperfusion <ref name=“one”>Bentli, R., Ciftci, O., Cetin, A., and Otlu, A. (2016) Anti-inflammatory Montelukast prevents toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Oxidative stress, histological alterations in liver, and serum cytokine levels. Toxicology and Industrial Health, 32(5), 769-776. doi: 10.1177/0748233713505894</ref>. Montelukast is known for its effectiveness in the pathophysiological mechanisms of asthma and asthma associated allergic rhinitis<ref name=“two”>Cylllyl, A., Kara, A., Ozdemir, T., Ogus, C. , and Gulkesen K. (2003) Effects of oral montelukast on airway function in acute asthma. Respiratory Medicine, 97(5), 533-536. doi: 10.1053/rmed.2003.1479</ref>. Montelukast suppresses the activation of eosinophils, which are associated with increased asthma severity. It specifically targets and blocks the leukotriene cascade that is responsible for bronchoconstriction and sensory activation in the inflammatory pathway of asthma. Allergic rhinitis is often associated with asthma, this can lead to leukotrienes in the upper airway that act as inflammatory mediators producing the symptoms of allergic rhinitis <ref name=“three”>Nayak, A. (2004). A review of montelukast in the treatment of asthma and allergic rhinitis. Expert Opinion on Pharmacotherapy, 5:3, 679-686. doi:10.1517/14656566.5.3.679</ref>. Montelukast reduces the release of inflammatory cytokines from airway cells and concentration of exhaled nitric oxide, alleviating allergic symptoms by decreasing airway hyperresponsiveness and bronchoconstriction. Due to its efficacy and safety, it can work as a monotherapy for those who do not respond well to inhaled corticosteroids, but it can also be prescribed with other drugs such as inhaled or oral corticosteroids, antihistamines, and beta-2 agonists to maximize its effects<ref name=“four”>Paggiaro, P., Bacci, E. (2011) Montelukast in Asthma: A Review of its Efficacy and Place in Therapy. Therapeutic Advances in Chronic Disease, 2(1), 47-58. doi: 10.1177/ 2040622310383343</ref>. | ||
== Structural highlights == | == Structural highlights == | ||
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Less information is known about the specifics of how Montelukast may affect the LTB4 pathway; once LTB4 is synthesized from arachidonic acid it is also carried to the extracellular space by a transmembrane transporter; once in the extracellular space it binds to the B leukotriene receptor, known as BLT <ref name=”seventeen”>Drazen, J., Elliot, I., & O’Byrne, P. (1999). Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. The New England Journal of Medicine, 340, 197-206. doi:10.1056/NEJM199901213400306</ref>.This leukotriene is a strong neutrophil-chemo-attracting compound that can cause neutrophilic adhesion, mucus generation, and can aid in increasing inflammation seen during asthma <ref name=”eighteen”>Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x</ref>.It is hypothesized that Montelukast may inhibit 5-lipooxygenase in neutrophils, monocytes, and macrophages possibly preventing the production of LTB4 <ref name=”nineteen”>Tintinger, G., Feldman, C., Theron, A., and Anderson, R. (2010) Montelukast:more than a cysteinyl leukotriene receptor antagonist? The Scientific World Journal, 10, 2403-2413. doi:10.1100/tsw.2010.229.</ref>.This mechanism for Montelukast would also be distinct from the mechanism used in the cascade involving leukotriene’s C4, D4, and E4. It is also thought that the amount of Montelukast needed to prevent production of LTB4 would need to be greater than that needed to prevent the CysLT cascade <ref name=”nineteen”>Tintinger, G., Feldman, C., Theron, A., and Anderson, R. (2010) Montelukast:more than a cysteinyl leukotriene receptor antagonist? The Scientific World Journal, 10, 2403-2413. doi:10.1100/tsw.2010.229.</ref>. | Less information is known about the specifics of how Montelukast may affect the LTB4 pathway; once LTB4 is synthesized from arachidonic acid it is also carried to the extracellular space by a transmembrane transporter; once in the extracellular space it binds to the B leukotriene receptor, known as BLT <ref name=”seventeen”>Drazen, J., Elliot, I., & O’Byrne, P. (1999). Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. The New England Journal of Medicine, 340, 197-206. doi:10.1056/NEJM199901213400306</ref>.This leukotriene is a strong neutrophil-chemo-attracting compound that can cause neutrophilic adhesion, mucus generation, and can aid in increasing inflammation seen during asthma <ref name=”eighteen”>Wenzel, S.E. (1997). Arachidonic Acid Metabolites: Mediators of Inflammation in Asthma. Pharmacotherapy, 17, 3S-12S. doi:10.1002/j.1875-9114.1997tbo3696.x</ref>.It is hypothesized that Montelukast may inhibit 5-lipooxygenase in neutrophils, monocytes, and macrophages possibly preventing the production of LTB4 <ref name=”nineteen”>Tintinger, G., Feldman, C., Theron, A., and Anderson, R. (2010) Montelukast:more than a cysteinyl leukotriene receptor antagonist? The Scientific World Journal, 10, 2403-2413. doi:10.1100/tsw.2010.229.</ref>.This mechanism for Montelukast would also be distinct from the mechanism used in the cascade involving leukotriene’s C4, D4, and E4. It is also thought that the amount of Montelukast needed to prevent production of LTB4 would need to be greater than that needed to prevent the CysLT cascade <ref name=”nineteen”>Tintinger, G., Feldman, C., Theron, A., and Anderson, R. (2010) Montelukast:more than a cysteinyl leukotriene receptor antagonist? The Scientific World Journal, 10, 2403-2413. doi:10.1100/tsw.2010.229.</ref>. | ||
== References == | == References == | ||
<references/> | <references/> | ||
