Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of ipratropium bromide are reviewed. Ipratropium bromide, a synthetic quaternary isopropyl derivative of atropine, interrupts vagally mediated bronchoconstriction by inhibiting the cyclic guanosine 3',5'-monophosphate system at parasympathetic nerve endings. Ipratropium bromide is poorly absorbed after oral and inhaled administration but diffuses rapidly into tissue after i.v. or i.m. administration. The elimination half-life is 3.2-3.8 hours. After inhalation, the drug is eliminated in the urine and feces. The bronchodilatory effect of ipratropium bromide in stable chronic obstructive pulmonary disease appears to be comparable, and may be superior, to that of the beta-sympathomimetic agents. In acute exacerbations, ipratropium bromide is useful but may not be the preferred agent because of a delayed onset of action (within 15 minutes; mean dose-dependent duration of effect, three to five hours). Combination therapy with other bronchodilating drugs has proved useful. Ipratropium bromide may be a useful adjunctive agent in the treatment of asthma. Since the onset of action is delayed, ipratropium bromide should not be used as single-drug therapy in an acute asthmatic exacerbation. Reported adverse effects, including cough, nausea, palpitations, dry mouth, nervousness, gastrointestinal distress, and dizziness, have been mild. The usual dosage is two inhalations (36 micrograms) four times daily, and the maximum number of doses per day should not exceed 12. Although ipratropium bromide is currently indicated only for maintenance therapy in stable chronic bronchitis and emphysema, it may be useful as adjunctive therapy in asthma and in the management of acute exacerbations of chronic bronchitis and asthma. Additional experience in a variety of chronic obstructive pulmonary disorders will help to clarify the role of ipratropium bromide in the treatment of obstructive pulmonary disease.
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PMID:Use of ipratropium bromide in obstructive lung disease. 297 9

The effect of elastin peptides (Kappa-elastin) was investigated on human monocytes. The data presented here indicate that elastin peptides increase the intracellular Ca2+ level measured by Quin 2 fluorescence and mediate the release of beta glucuronidase and elastase. The O2 consumption and H2O2 release were stimulated in a dose-dependent manner. The early rise of cAMP was followed by a return to the original level at 30 min and by a concomitant increase of cGMP level. The action of elastin peptides on intracellular calcium level and cGMP levels may well be related to its previously demonstrated chemotactic activity. These activities may well play a role in the modifications of the extracellular matrix following elastin degradation as observed in atherosclerosis, emphysema and aging.
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PMID:Effect of elastin peptides on human monocytes: Ca2+ mobilization, stimulation of respiratory burst and enzyme secretion. 364 24

In 11 normal subjects (mean age = 22.8 years) and 8 patients with pulmonary emphysema (mean age = 70.4 years), the role of chemosensitivity in determining ventilation, cardiac output, lactic acid, and cyclic AMP and GMP was evaluated quantitatively during 150 or 30 W exercise and simulated exercise. Simulated exercise was done while the subjects took a rest by regulating arterial blood gases at exercise levels in patients and at PaO2 = 65 mm Hg and PaCO2 = 48 mm Hg in normal subjects. In normal subjects, the role of arterial blood gases in determining exercise ventilation, cardiac output, cyclic AMP and GMP are large, while those contributed much less to lactic acid. In patients, PaO2 contributed only half of the exercise ventilation. It accounted for a negligibly small portion of exercise cardiac output, lactic acid, and cyclic GMP. These results indicate, by deduction, that either augmentation of chemosensitivity, pH, or humoral factors is responsible for about half of the changes of exercise ventilation in patients with pulmonary emphysema. These factors seem to influence cardiac output, lactic acid, and cyclic AMP and GMP more strongly than PaO2 alone in exercising patients.
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PMID:Role of chemosensitivity during exercise in normal subjects and patients with pulmonary emphysema. 626 58

We previously reported the clinical role of plasma immunoreactive atrial natriuretic polypeptide (ANP) and cyclic GMP in patients with respiratory diseases, bronchial asthma (BA), chronic pulmonary emphysema (CPE) and pulmonary insufficiency induced by pulmonary tuberculosis (TBC). In this study, moreover, we divided patients with respiratory failure induced by tuberculosis sequelae into two groups, patients with oxygen therapy group [O2 (+) group] or ordinary practical treatment group [O2 (-) group], and we evaluated the difference of the roles of ANP in two groups and the correlation of ANP and c-GMP with clinical findings, blood gas analysis, electrocardiogram, chest roentogen photography and spirogram in two groups. In conclusion, the respiratory failure in patients with tuberculosis sequelae is compensated by increased cardiac output, and that causes the rising of right atrial pressure. These results show, addition to the basic effects of ANP, the concentration of plasma ANP is released with relating the degree of respiratory failure.
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PMID:[Clinical evaluation of plasma atrial natriuretic polypeptide in patients with respiratory failure in pulmonary tuberculosis]. 826 22

We have analyzed the effect of the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 in a therapeutic intervention in guinea pigs chronically exposed to cigarette smoke (CS). The effects of sGC stimulation on respiratory function, pulmonary hemodynamics, airspace size, vessel remodeling, and inflammatory cell recruitment to the lungs were evaluated in animals that had been exposed to CS for 3 mo. CS exposure was continued for an additional 3 mo in half of the animals and withdrawn in the other half. Animals that stopped CS exposure had slightly lower pulmonary artery pressure (PAP) and right ventricle (RV) hypertrophy than those who continued CS exposure, but they did not recover from the emphysema and the inflammatory cell infiltrate. Conversely, oral BAY 41-2272 administration stopped progression or even reversed the CS-induced emphysema in both current and former smokers, respectively. Furthermore, BAY 41-2272 produced a reduction in the RV hypertrophy, which correlated with a decrease in the PAP values. By contrast, the degree of vessel remodeling induced by CS remained unchanged in the treated animals. Functional network analysis suggested perforin/granzyme pathway downregulation as an action mechanism capable of stopping the progression of emphysema after sGC stimulation. The pathway analysis also showed normalization of the expression of cGMP-dependent serine/kinases. In conclusion, in guinea pigs chronically exposed to CS, sGC stimulation exerts beneficial effects on the lung parenchyma and the pulmonary vasculature, suggesting that sGC stimulators might be a potential alternative for chronic obstructive pulmonary disease treatment that deserves further evaluation.
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PMID:Therapeutic effects of soluble guanylate cyclase stimulation on pulmonary hemodynamics and emphysema development in guinea pigs chronically exposed to cigarette smoke. 3116 28

Cigarette smoke exposure is a leading cause of chronic obstructive pulmonary disease (COPD), a major health issue characterized by airway inflammation with fibrosis and emphysema. Here we demonstrate that acute exposure to cigarette smoke causes respiratory barrier damage with the release of self-dsDNA in mice. This triggers the DNA sensor cGAS (cyclic GMP-AMP synthase) and stimulator of interferon genes (STING), driving type I interferon (IFN I) dependent lung inflammation, which are attenuated in cGAS, STING or type I interferon receptor (IFNAR) deficient mice. Therefore, we demonstrate a critical role of self-dsDNA release and of the cGAS-STING-type I interferon pathway upon cigarette smoke-induced damage, which may lead to therapeutic targets in COPD.
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PMID:Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice. 3161 33