Bronchodilatation

Abstract: The anticholinergic, antimuscarinic compounds are potent and hitherto neglected bronchodilators. Although atropine itself has drawbacks, principally related to its rapid absorption and consequent systemic side effects, its quaternary ammonium congeners, atropine methonitrate and ipratropium bromide, are poorly absorbed. When given by inhalation, they are as effective bronchodilators as atropine is, but longer acting and much less prone to side effects. They act predominantly at a site that is different from adrenergic agents and thus afford an alternative, complementary approach to the treatment of airways obstruction. In stable asthmatic subjects, ipratropium is almost as potent a bronchodilator as beta 2-adrenergic agents are. In patients with chronic bronchitis and emphysema, it is more potent than beta 2-adrenergic agents are. In both conditions, its combination with other bronchodilators adds significantly to the level and duration of bronchodilatation. It may also be occasionally useful in counteracting bronchospasm caused by specific stimuli, such as cold air and exercise, and particularly that caused by inadvertent beta-adrenergic blockade. By inhalation, ipratropium is relatively free of side effects, even in doses as much as 20 times those that produce maximal bronchodilatation. It does not significantly affect mucus production, viscosity, or clearance, problems for which atropine is suspect. Nor does it produce tremor and tachycardia, as do adrenergic agents. It can also probably be safely used in patients with glaucoma and bladder neck obstruction, unlike atropine. Ipratropium will probably find its major application in the long-term management of chronic bronchitis and emphysema, and in asthmatic patients who are poorly controlled by, or who experience troublesome side effects from, adrenergic agents.

Abstract: BACKGROUND: Asthma death rates are rising, with the greatest rise and highest death rates in old age. A reduced cardiovascular response in the elderly may lead to the underestimation by physicians of the severity of acute asthma attacks. This would be compounded if elderly patients had reduced awareness of bronchoconstriction. METHODS: Methacholine provoked bronchoconstriction was compared in 34 elderly (17 asthmatic, 17 normal; age 60-83, mean 68 years) and 33 young subjects (16 asthmatic, 17 normal; 20-46, mean 30 years). None were smokers. All underwent inhaled methacholine challenge by the Newcastle dosimeter method, monitored by maximal expiratory flow-volume loops (MEFVL). The endpoints were a 35% fall in forced expiratory flow at 50% vital capacity or cumulative inhalation of 6.4 mg methacholine. The one second forced expiratory volume (FEV1) was derived from MEFVL. After challenge and before bronchodilatation subjects graded awareness of respiratory discomfort from 1 (no symptoms) to 4 (pronounced symptoms needing immediate treatment). RESULTS: Despite a greater fall in FEV1 in elderly asthmatic patients (mean (SE) 27.4% (2.2%)) than in young asthmatic patients (21.5% (1.7%)) elderly patients were less aware of bronchoconstriction (awareness score 2.00 (SE 0.15) than young patients (3.06 (0.11)). Similar differences in awareness score were seen between elderly normal subjects (1.53 (0.17)) and young normal subjects (2.76 (0.22)), despite no difference in degree of bronchoconstriction. CONCLUSIONS: Reduced awareness of moderate acute bronchoconstriction in old age may delay self referral in acute asthma and contribute to higher asthma mortality in the elderly.

Abstract: To study the relative contributions of parasympathetic and sympathetic mechanisms in airway obstruction in patients with emphysema, we gave supramaximal doses of anticholinergic and adrenergic agents in sequence and in combination. Serial doses of one agent were administered to achieve a plateau of bronchodilatation; after that the other agent was administered. The plateau achieved with the anticholinergic agent (atropine methonitrate) was significantly higher than that achieved with the adrenergic agent (salbutamol). When the adrenergic agent was given first, additional bronchodilatation was achieved with subsequent use of the anticholinergic agent. When the anticholinergic agent was given first, no additional bronchodilatation was achieved with subsequent administration of the adrenergic agent. When both agents were given simultaneously, the degree of bronchodilatation was virtually identical to that obtained with the anticholinergic agent alone. Tests sensitive to small-airway and large-airway...