Bronchodilating effects

The bronchodilating effect of caffeine has been recognized for hundreds of years. In the western world the first description of a caffeine preparation for asthma was made in 1859 (59) by a Scottish physician who recommended strong black coffee as a bronchodilator. In many parts of the world, however, use of xanthines is less frequent than in the United States. 

Beta adrenergic agonists also exert bronchodilating effects. These drugs are thus often used in conjunction with theophiline in asthma therapy. A drug that combines both moieties, reproterol (40), has interestingly proved... 

P2-Agonists cause airway smooth muscle relaxation by stimulating adenyl cyclase to increase the formation of cyclic adenosine monophosphate (cAMP). Other non-bronchodilator effects have been observed, such as improvement in mucociliary transport, but their significance is uncertain.11 P2-Agonists are available in inhalation, oral, and parenteral dosage forms the inhalation route is preferred because of fewer adverse effects. 

Isoproterenol (104) is an important agent for classification because of its selective p-receptor agonist activity. It is of special interest that its chronotropic (increase in heart rate) and inotropic (increase in force of contraction) effects exceed that of epinephrine it is also used in the management of mild to moderate asthma due to its bronchodilating effect, resulting in increased vital capacity of the lungs. 

Ipratropium bromide has a slower onset of action than short-acting /J2-agonists (15 to 20 minutes vs. 5 minutes for albuterol). For this reason, it may be less suitable for as-needed use, but it is often prescribed in this manner. Ipratropium has a more prolonged bronchodilator effect than short-acting /l2-agonists. Its peak effect occurs in 1.5 to 2 hours and its duration is 4 to 6 hours. The recommended dose via MDI is two puffs four times a day with upward titration often to 24 puffs/day. It is also available as a solution for nebulization. The most frequent patient complaints are dry mouth, nausea, and, occasionally, metallic taste. Because it is poorly absorbed systemically, anticholinergic side effects are uncommon (e.g., blurred vision, urinary retention, nausea, and tachycardia). 

Nogami-Itoh, M., I.Yakuo, D.M.Hammerbeck, R.I.Miller, and K.Takeyama. 1997. The equivalent bronchodilator effects of salbutamol formulated in chlorofluorocarbon and hydrofluoroalkane-134a metered dose inhalers on the histamine-induced pulmonary response in dogs. Pharmaceut. Res. 14 208-212. 

Methyixanthines relax smooth muscle, and have a bronchodilating effect in the lungs. Theophylline is used as a treatment for asthma. Methyixanthines dilate coronary arteries, increasing cardiac blood flow, but an opposite effect occurs on cerebral blood vessels (see below). 

This xanthine derivative is an only a modest bron-chodilator in COPD, and because of its narrow therapeutic range, frequently seen adverse effect and drug interactions, it is becoming less frequently used, some patients experience side effects even within the therapeutic range. The non-bronchodilator effects of theophylline such as systemic and pulmonary vascular dilatation, central nervous system stimulation, improvement of the strength and effectiveness of respiratory muscles and possibly anti-inflammatory effects are of disputed clinical significance at usual therapeutic levels. 

Ephedrine is a naturally occurring alkaloid that can cross the blood-brain barrier and thus exert a strong CNS-stim-ulating effect in addition to its peripheral actions. The latter effects are primarily due to its indirect actions and depend largely on the release of norepinephrine. However, ephedrine may cause some direct receptor stimulation, particularly in its bronchodilating effects. Because it resists metabolism by both COMT and MAO, its duration of action is longer than that of norepinephrine. As is the case with aU indirectly acting adrenomimetic amines,... 

Muscarinic antagonists inhibit secretions and relax smooth muscle in the respiratory system. The parasympathetic innervation of respiratory smooth muscle is most abundant in large airways, where it exerts a dominant constrictor action. In agreement with this innervation pattern, muscarinic antagonists produce their greatest bronchodilator effect at large-caliber airways. 

Mild bronchodilator effect Minimal biotransformation Inactive, non-toxic metabolites Easy... 

Desflurane does not have a marked bronchodilator effect and in cigarette smokers it is associated with significant bronchoconstriction. In clinical practice, both humidification of inspired gases and opioids are thought to reduce airway irritability but even at moderate concentrations (2 MAC), desflurane is more likely to cause coughing than sevoflurane. In common with other volatile agents, desflurane causes dose-related respiratory depression. Tidal volume is reduced and respiratory rate increases, initially. As inspired concentrations of desflurane increase, the trend is to hypoventilation and hypercardia and apnoea is to be expected at concentrations of 1.5 MAC or greater. 

Onset and duration of bronchodilation effects of inhaled adrenergic agonists. 

Hashimoto Y, Hirota K, Ohtomo N et al. (1996) In vivo direct measurement of the bronchodilating effect of sevoflurane using a superfine fiberoptic bronchoscope Comparison with enflurane and halothane. J Cardiothorac Vase Anesth 10 213-216... 

BETA-BLOCKERS BETA-2 AGONISTS Non-selective beta-blockers (e.g. propanolol) 1 or prevents the bronchodilator effect of beta-2 agonists Non-selective beta-blockers antagonize the effect of beta-2 agonists on bronchial smooth muscle Avoid co-administration... 

CALCIUM CHANNEL BLOCKERS Secondary drug BRONCHODILATORS Effect Mechanism Precautions... 

SALBUTAMOL BETAHISTINE 1 or prevents the bronchodilator effect Betahistine causes bronchoconstriction Avoid co-administration... 

Asthma. In severe asthma (given i.v.) when (5-adrenoceptor agonists fail to give adequate response and for chronic asthma (orally) to provide a background bronchodilator effect. 

An alternative hypothesis has been proposed to explain why beta2-agonists lose their bronchoprotective effect while retaining a bronchodilator effect. The beta2-agonists currently available for treating asthma consist of racemic mixtures of equal amounts of two stereoisomers, the i -isomer (or L-isomer), which is the beta-adrenoceptor agonist, and the 5-isomer (o-isomer) which is inactive. 

In another investigation, a single dose of 1.25 mg nebulized R-salbutamol, administered to asthmatics, produced equivalent bronchoprotection, bronchodilatation, tachycardia, and restlessness to that given by 2.5 mg of racemic salbutamol (26). In a further study, asthmatic patients were treated for 28 days with racemic or R-salbutamol administered by nebulizer three times a day. Improvement in FEVi was similar after R-salbutamol 0.63 mg and racemic salbutamol 2.5 mg and greatest with R-salbutamol 1.25 mg. Racemic salbutamol 1.25 mg had the least bronchodilator effect, especially after chronic dosing (27). 

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