Inhaled bronchodilator effect

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. 

Theophylline is a non-specific phosphodiesterase inhibitor that increases intracellular cAMP within airway smooth muscle resulting in bronchodilation. It has a modest bronchodila-tor effect in patients with COPD, and its use is limited due to a narrow therapeutic index, multiple drug interactions, and adverse effects. Theophylline should be reserved for patients who cannot use inhaled medications or who remain symptomatic despite appropriate use of inhaled bronchodilators. 

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. 

Onset and duration of bronchodilation effects of inhaled adrenergic agonists. 

Salmeterol 42 micrograms bd has been compared with inhaled ipratropium bromide 36 micrograms/day and inhaled placebo in a randomized, double-blind study for 12 weeks in 405 patients with chronic obstructive pulmonary disease (6). Both salmeterol and ipratropium bromide significantly increased the peak expiratory flow rate compared with placebo. Non-specific ear, nose, and throat symptoms (for example sore throat and upper respiratory tract infections) were more common with salmeterol and ipratropium than placebo. There were no significant differences between the groups in the total number of ventricular and supraventricular extra beats. There was no tolerance to the bronchodilating effects of salmeterol. 

Experimental studies continue to show that regular treatment with either formoterol or salmeterol in patients with asthma can produce subsensitivity to the bronchodilator effects of salbutamol (19,20). This bronchodilator subsensitivity can be partly reversed by a bolus dose of inhaled or systemic corticosteroids. The clinical relevance of these experimental findings is unclear. 

These structural features allow the Ipratropium molecule to attain a relatively selective bronchodilator effect on the cholinergi-cally innervated airways. By the inhalation route of application, this poorly absorbable quaternary ammonium derivative becomes selective to primarily affect the airway smooth muscle. Another advantage of ipratropium over atropine is that, in contract to the latter, it does not suppress mucociliary function. 

Ikeda A, Nishimura K, Koyama H, et al. Comparison of the bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease. Respiration 1999 66 119-123. 

As noted in Section II, a bronchodilator effect of inhaled NO was demonstrated in guinea pigs (Dupuy et al., 1992) and later in anesthetized rabbits (Hogman et al., 1993b). However, the bronchodilator effect in humans with stable asthma or chronic bronchitis was less dramatic, or absent, in several patients inhaling 80 ppm NO for 10 min (Hogman etal., 1993c). Similar weak bronchodilatory effects of inhaled NO were reported by Kacm-arek et al. (1993). 

Improvements in asthma treatment include the development of more effective, safer formulations of known drugs. The aerosol administration of p2-agonists or corticosteroids results in a decrease in side effects. Also, the use of reliable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index (see Controu d release technology). For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilators do not usually last through an entire night s sleep (26,27). 

The most commonly used bronchodUators are the beta-adrenoceptor agonists. In some patients, a muscarinic blocking drug (eg, ipratropium) has a useful bronchodilating effect. Cromolyn and nedocromil inhibit the degranulation of mast cells and are useful as prophylactic agents in some patients. They are not useful in an acute attack. Systemic corticosteroids are reserved for patients with severe asthma who do not respond adequately to other agents, but inhaled steroids (eg, beclomethasone) are standard prophylactic therapy for aU individuals with moderate or severe recurrent asthma... 

The most common source of these xanthines is in the beverages coffee, tea, and cocoa, which are universally consumed mainly for their stimulant properties. A cup of coffee or tea contains between 60 and 85 mg of caffeine, and a cup of cocoa can have as much as 250 mg of theobromine. Caffeine frequently is added to cola drinks as well as to over-the-counter analgesics and stimulants. Theophylline is used for its bronchodilating effects in the treatment of asthma. Its importance has declined greatly since the development of the inhaled P2-adrenergic agonists and inhaled steroids and because its narrow therapeutic window requires close patient monitoring and periodic blood level determination to avoid serious side effects. 

Mast cells release histamines, leukotrienes and other mediators of the inflammatory process. Mast cell stabilizer drugs inhibit the early asthmatic response and the late asthmatic response. They have no bronchodilator effect nor do they have any effect on any inflammatory mediators already released in the body. They are indicated for the prevention of bronchospasms and bronchial asthma attacks. They are administered by aerosol inhalation. The exact action of the drugs have not been determined. However, they are believed to have a modest effect in lowering the required dose of corticosteroids. The most common mast stabilizer dmgs are cromolyn (Intal) and nedocromil (Tilade). 

The client is prescribed albuterol (Ventolin), a sympathomimetic bronchodilator, metered-dose inhaler. Which behavior indicates the teaching concerning the inhaler is effective ... 

Inappropriate use of inhalers or mistakes in inhalation technique reduces the dose delivered and compromises the efhcacy of the treatment. For example, it was demonstrated that the increase in FEVj was 80% of maximum achievable after inhalation from the unprimed pMDl, compared to 92% after inhalation from the primed one (69). In one study with plastic spacers, priming of the spacer by actuating the pMDI a few times increased pulmonary deposition of glucocorticosteroids in asthmatic patients by 40-50% (70), whereas in another study, pulmonary deposition of salbutamol was doubled if the spacer was coated with benzalkonium chloride (71). For Turbuhaler, pulmonary deposition decreased by 50% if the flow applied to inhale was reduced from a normal flow of 60 F/min to a suboptimal flow of 30 L/min (72), whereas in others studies, the bronchodilating effect was similar at 30 and 60 L/min in both children and adults (73,74). 

At appropriate doses, a twofold increase in dose of an inhaled pj-agonist has been shown to result in a statistically significant increase in bronchodilating effect (11). Conversely, it appears to be much more difficult to assess this relationship for inhaled glucocorticosteroids, as an at least fourfold increase in dose is necessary to obtain a statistically significant difference in effect (36). The next paragraphs of this section therefore focus mainly on the relationship between pulmonary deposition and clinical effects of Pj-agonists. 

Although, in one study with children, a significantly greater increase in FEVj was obtained when salbutamol was inhaled via Rotahaler at a higher flow of 90 to 120 L/min that at an inhalation flow of 30 to 50 L/min (31), most studies in which the effects of terbutaline inhaled via Turbuhaler were assessed showed that at a low inhalation flow of 30 L/min, a less pronounced improvement of expiratory flow was obtained than at a higher inhalation flow (60 L/min) (88). In another study, it could be shown in children who inhaled terbutaline via Turbuhaler at flows of 13, 22, 31, and 60 L/min that the bronchodilating action was flow-dependent once the inhalation flow was below the critical value of 30 L/min (74). It should, however, be underlined that even an extranely low flow, 13 L/min, resulted in a bronchodilating effect. 

Derom EY, Pauwels RA. Time course of bronchodilating effect of inhaled formoterol, a potent and long acting sympathomimetic. Thorax 1992 47 30-33. 

Borgstrom L, Derom E, Stahl E, Wahlin-Boll E, Pauwels R. The inhalation device influences lung deposition and bronchodilating effect of terbutaline. Am J Respir Crit Care Med 1996 153 1636-1640. 

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