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Pathway Description
Ipratropium M3 Bronchodilation Action Pathway
Homo sapiens
Drug Action Pathway
Ipratropium is an anticholinergic drug used to control and prevent symptoms of chronic obstructive pulmonary disease (COPD) such as wheezing and shortness of breath. It can also be used for asthma or any pulmonary disease that can be relieved by opening of the bronchial airway. It is inhaled where it can immediately enter the lungs and act on the smooth muscles. Ipratropium inhibits the M1, M2, and M3 muscarinic acetylcholine receptors. These receptors are coupled to the Gq cascade which is being prevented by Ipratropium. The inhibition of the Gq cascade prevents the acitvation of phospholipase C, which would convert Phosphatidylinositol (3,4,5)-trisphosphate to inositol (3,4,5)-trisphosphate (IP3) and diacylglycerol (DAG). IP3 would then activate IP3 receptors on the sarcoplasmic reticulum leading to the release of stored calcium into the cytosol. the muscarinic acetylcholine receptors being inhibited prevents calcium from entering the cell which means calcium does not readily bind to calmodulin, and calmodulin isn't present to activate myosin light chain kinase. Since myosine light chain kinase is not activated, Serine/threonine-protein phosphatase continues to dephosphorylate myosin LC-P, and more cannot be synthesized so myosin remains unbound from actin causing muscle relaxation. This relaxation of the smooth muscles in the lungs causes the bronchial airways to relax which causes bronchodialation, making it easier to breathe.
References
Ipratropium M3 Bronchodilation Pathway References
Osmond MH, Klassen TP: Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis. Acad Emerg Med. 1995 Jul;2(7):651-6.
George R., Light R., Matthay M. and Matthay R. (2005). Chest Medicine. Essentials of pulmonary and critical care medicine. (5th ed.). Lippincott Williams & Wilkins.
Barnes P., Drazen J., Rennard S. and Thomson N. (2002). Asthma and COPD. Elsevier Science Ltd.
Wellington K: Ipratropium bromide HFA. Treat Respir Med. 2005;4(3):215-20; discussion 221-2.
Rehder KJ: Adjunct Therapies for Refractory Status Asthmaticus in Children. Respir Care. 2017 Jun;62(6):849-865. doi: 10.4187/respcare.05174.
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
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