Page 33

Abril 2016

ARTÍCULOS DE INVESTIGACIÓN The effect of benzodiazepines on bronchoconstriction in asthma patients - M. Miric et al Figure 4. The effect of benzodiazepines on the change in FEV1, caused by methacholine in patients with asthma. Given methacholine resulted in the decrease of FEV1 (p < 0.05, n = 12). On the second day of study, the changes in FEV1 after inhalation of methacholine were not significant, if benzodiazepines were previously inhaled in 5 minutes. (p > 0.5). Values are given as mean values of X ± SE. 439 FEV1 data, wherein the patients were only treated with methacholine and methacholine with previous administration of diazepam, FEV1 was given as a function of changes in the dynamic parameter of lung function. In Figure 4 a significant decline in FEV1 is noticeable after the administration of methacholine from 2.8 L to 1.9 L (p < 0.005). In this case, also, the FEV1 curve was normalized even after 30 min (2.2 L). The previous administration of diazepam showed no significant changes at FEV1 curve to the provocation, which means that diazepam diminished the effects of methacholine. Discussion and Conclusions The smooth muscle of the airways from the trachea down to the alveolar ducts is under the control of efferent fibers of the autonomic nervous system. Different typical transmitters and peptides participate in regulation of contractility of airway smooth muscle (opioid, GABA, serotonin, tachykinin and glutamat). Airway preganglionic nerve activity is regulated by subsets of pulmonary and extrapulmonary afferent nerve fibers, which continuously provide polysynaptic input to brain stem preganglionic nuclei22-24. On the basis of our present knowledge, clinical tests and experimental studies, the hypothesis that increased cholinergic activity leads to bronchoconstriction and that it may be blocked or reduced by administering inhaled diazepam, is confirmed. Airway effector cells (bronchial and vascularsmooth muscle and glands) are densely, albeit differentially,innervated by fibers derived from both the parasympathetic and sympathetic nervous system which regulate airway smooth-muscle tone, glandular secretion and blood-vessel diameter. Autonomic innervation of the airways is derived primarily from the parasympathetic nervous system1,3,24. Benzodiazepines are drugs that have direct and indirect bronchodilatory effect on the smooth muscle of the airways, directly by inhibiting a voltage-dependent Ca²+ channels, and indirectly by increasing neurotransmision role of GABA at postsynaptic receptors, resulting in an increase in the number of open channels for chloride10-12. Benzodiazepine receptor agonists increase the affinity of GABA to its receptor. The bronchodilatory effect of diazepam indicates its potential application in the treatment of acute exacerbation of asthma25-27. It is known that GABA-B-specific agonists decrease airway responsiveness to various bronchoconstricting agents by modulating presynaptic acetylcholine release from parasympathetic nerves. On the other hand, a GABA-B receptor agonist, baclofen, can worsen airway responses following the administration of methacholine to asthmatic patients. This paradoxical enhancement by baclofen of airway responsiveness led us to hypothesize that there may be postganglionic (i.e., smooth muscle) GABA-B functional receptors that couple Rev Med Chile 2016; 144: 434-441


Abril 2016
To see the actual publication please follow the link above