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Abril 2016

ARTÍCULOS DE INVESTIGACIÓN 435 The effect of benzodiazepines on bronchoconstriction in asthma patients - M. Miric et al segundo día los pacientes se inhalaron con diazepam antes de hacer la prueba con metacolina. Resultados: En el primer día, el FEV1 bajo de 2,98 a 1,69 l con 6 mg/ml de metacolina. En el segundo día, la inhalación de diazepam redujo la respuesta a metacolina con una reducción de FEV1 de 2,48 a 2,21 L. Conclusiones: La benzodiacepinas reducen la respuesta de vasoconstricción a metacolina. Asthma is a chronic inflammatory disease of the airways characterized by attacks of reversible airflow obstruction that is clinically manifested by dyspnea, wheezing, chest tightness and cough. Asthma is characterized by pathological changes in the airway smooth muscle, which lead to obstruction and bronchial hyperreactivity1,2. The opposing actions of the parasympathetic and sympathetic divisions of the autonomic nervous system represent the primary mechanism for regulating airway function. It seems that the bronchial smooth muscle is normally under greater parasympathetic than sympathetic influence3. The role of the cholinergic nervous system in the regulation of muscle tone is in reflex bronchoconstriction and increased bronchial gland secretion. Acetylcholine is released from the intrapulmonary endings of vagus nerve branches and directly causes constriction of smooth muscles by stimulation of the muscarinic receptors4. Stimulation of the adrenergic sympathetic fibers causes dilation of bronchial and bronchiolar smooth muscle as well as inhibition of glandular secretion. This dilation of the airways smooth muscle is mediated by beta2 receptors1-3. Gamma-Aminobutyric acid (GABA), is the mostwidely distributed inhibitory neurotransmitter in the mammalian central nervous system5, it binds to postsynaptic receptors, GABAA, GABAB, and GABAC, which are localized in brain and peripheral tissues including the lung6,7. GABA receptors modulate cholinergic tone or flow to the airways8. Benzodiazepines increase the activity of GABA on the level of the postsynaptic receptors and at the level of all axons in CNS. Benzodiazepines are drugs which are used as muscle relaxants, anticonvulsants and anxiolytics9-13. Methacholine acts as a non-selective muscarinic receptor agonist to stimulate the parasympathetic nervous systemand administered in vivo or in vitro mimics the effects of parasympathetic innervation of the musculature of the respiratory tract, thus causing bronchoconstriction14-16. It is most commonly used for diagnosing bronchial hyperreactivity Rev Med Chile 2016; 144: 434-441 in asthma patients using the bronchial challenge test. Through this test, the drug causes bronchoconstriction and people with pre-existing airway hyperreactivity, such as asthmatics, will react to lower doses of drug. Methacholine inhalation test also helps in the assesment of disease severity15-17. With this research we expect to demonstrate that bronchoconstrictor effects of methacholine in patients with asthma are reduced if the patient has previously inhaled benzodiazepine. Therefore, the main purpose of our study was to examine the effect of benzodiazepines (diazepam) in modulating bronchoconstriction induced by methacholine, in patients with asthma. For this purpose, we tested: a) spirometric response of variables of lung function in bronchoconstrictor stimulus methacholine and; b) spirometric response variables on pulmonary function in methacholine after inhalation of diazepam. Patients and Methods Study was carried out in the period January- July 2011. The patients were contacted for permission to be included in the study and were asked to give their written informed consent. The clinical trial included 12 patients with well controlled asthma. Clinical evaluations were conducted at the Department of pathological physiology, Faculty of Medicine in Foca, with assistence of department of pneumophtisiology at University Hospital-Foca, Republic of Srpska, Bosnia and Herzegovina. The local Ethics Commitee revised and approved this protocol. Functional testing of respiratory system consisted of the determination of the vital capacity (VC), forced expiratory volume in first second (FEV1), Tiffeneaux index (100 x FEV1/VC), resistance to air flow in the airways (Rt) and intrathoracic gas volume (ITGV). From obtained values the specific resistance was calculated (SRt = Rt x ITGV). Obtained values for VC and FEV1 were compared with the expected table values of the European


Abril 2016
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