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ARTÍCULOS DE INVESTIGACIÓN The effect of benzodiazepines on bronchoconstriction in asthma patients - M. Miric et al to the Gi protein, known to impair relaxation of airway smooth muscle28-31. Many laboratory examinations 440 proved that except diazepam, many other derivates of GABA for example baclofen effects on spinal respiratory neurons depending on doses. Low doses of baclofen from (0,5-2 mg/kg) increases frequency action potentials on phrenic and intercostal neurons. Middle dose of 2-4 mg/ kg increases the lasting of inspiration. Higher dose 4-10 mg/kg paralyses the inspiration. The common things about these two medicines are that their effect on central neurons is dose dependent and muscle relaxant30-32. From previous experience, it can be concluded that increased parasympathetic innervation, which leads to constriction of bronchi, becomes blocked or reduced by giving GABA or medicines that are GABA’s derivates. GABA has relaxing effect by inhibiting muscle conduction, by decreasing resistance in airway breathing channels and by decreasing contractility of trachea muscle. The same effect produce benzodiazepines by increasing GABA secretion indirectly13,23-25. Our research shows that benzodiazepines have bronchodilatory effect on the smooth muscle of the airways. Methacholine is a synthetic choline ester that mimics the effects of parasympathetic innervation of the musculature of the respiratory tract, thus causing constriction of the bronchi. For this reason, methacholine may be used as a pharmaceutical in broncho provocation tests for the detection of bronchial reactivity3,10,15 and also for this reason we used it in this clinical trial, as a drug that provokes bronchoconstriction. Based on this research results in patients with asthma, we conclud that the bronchoconstrictor effects of methacholine in patients with asthma is significantly reduced if the patient has previously inhaled diazepam. References 1. Kaicker J, Dang W, D’Urzo A. The challenge of objective confirmation of asthma diagnosis in primary care. NPJ Prim Care Respir Med 2014; 24: 14032. 2. Dekkers BG, Maarsingh H, Meurs H, Gosens R. Airway structural components drive airway smooth muscle remodeling in asthma. Proc Am Thorac Soc 2009; 6 (8): 683-92. 3. An SS, Bai TR, Bates JH, Black JL, Brown RH. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma. Eur Respir J 2007; 29 (5): 834- 60. 4. Haxhiu MA, Erokwu B, Bhardwaj V, Dreshaj IA. The role of the medullary raphe nuclei in regulation of cholinergic outflow to the airways. J Auton Nerv Syst 1998; 69 (1): 64-71. 5. Chapman RW, Danko G, Rizzo C, Egan RW, Mauser PJ, Kreutner W. Prejunctional GABA-B inhibition of cholinergic, neurally-mediated airway contractions in guinea-pigs. Pulm Pharmacol 1991; 4 (4): 218-24. 6. Bolser DC, DeGennaro FC, O’Reilly S. Peripheral and central sites of action of GABA-B agonists to inhibit the cough reflex in the cat and guinea pig. Br J Pharmacol 1994; 113 (4): 1344-8. 7. Chapman RW, Hey JA, Rizzo CA, Bolser DC. GABA-B receptors in the lung. Trends Pharmacol Sci 1993; 14 (1): 26-9. 8. Moore CT, Wilson CG, Mayer CA, Acquah SS, Massari VJ, Haxhiu MA. GABAergic inhibitory microcircuit controlling cholinergic outflow to the airways. J Appl Physiol 2004; 96 (1): 260-70. 9. Advenier C, Devillier P, Blanc M, Gnassounou JP. Peripheral type benzodiazepine receptors and response to adenosine on the guinea-pig isolated trachea. Pulm Pharmacol 1990; 3 (3): 137-44. 10. Galleguillos T, Risco L, Garay JL, González M, Vogel M. Benzodiazepine use in primary care patients. Rev Med Chile 2003; 131 (5): 535-40. 11. Candenas ML, Devillier P, Naline E, Advenier C. Influence of diazepam, alpidem, zolpidem and zopiclone, on the response to adenosine of the guinea pig isolated trachea.Fundam Clin Pharmacol 1991; 5 (1): 1-10. 12. Vinkers CH, Tijdink JK, Luykx JJ, Vis R. Choosing the correct benzodiazepine: mechanism of action and pharmacokinetics. Ned Tijdschr Geneeskd 2012; 155 (35): A4900. 13. Formiga F, Duaso E, Ruiz D, San José A, Urrutia A, López-Soto A. Use of benzodiazepines according to the admission diagnosis. Med Clin (Barc) 2012; 139 (12): 531-4. 14. Matera MG, D’Agostino B, Costantino M, Mangrella M, Calderaro V, Rossi F. K+ channels and guinea-pig trachea: a possible functional modulation by GABA-B receptors. Pulm Pharmacol 1994; 7 (4): 259-63. 15. Kim MH, Song WJ, Kim TW, Jin HJ, Sin YS, Ye YM, et al. Diagnostic properties of the methacholine and mannitol bronchial challenge tests: a comparison study. Respirology 2014; 19 (6): 852-6. 16. Singh D, Corradi M, Bindi E, Baronio R, Petruzzelli S, Paggiaro P. Relief of methacholine-induced bronchos- Rev Med Chile 2016; 144: 434-441


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