Theophylline, asthma prevention

Theophylline reduces contractile activity of smooth musculature, widens bronchi and blood vessels, reduces pulmonary vascular resistance, stimulates the respiratory center, and increases the frequency and power of cardiac contractions. It is used for bronchial asthma, preventing attacks, and systematic treatment. Theophylline is also used for symptomatic treatment of bronchospastic syndrome of a different etiology (chronic obstructive pulmonary disease, chronic bronchitis, and pulmonary emphysema). A large number of combined drags are based on theophylline. Synonyms of theophylline are adophyllin, asthmophyllin, theocin, and many others. 

In persistent asthma, inhaled corticosteroids provide the most comprehensive control of the inflammatory process and are the cornerstone of therapy.2 Inhaled corticosteroids are more effective than cromolyn, leukotriene modifiers, nedocromil, and theophylline in reducing markers of inflammation and AHR, improving lung function, and preventing emergency department visits and hospitalizations due to asthma exacerbations.2,25 The primary... 

Pirbuterol Prevention and reversal of bronchospasm in patients with reversible bronchospasm including asthma. Use with or without concurrent theophylline or steroid therapy. 

Based on the concept that asthma is an inflammatory disease that leads to airway obstruction, inhaled glucocorticoids are the first-line treatment for moderate to severe asthma. Inhaled preparations are particularly effective when used to prevent recurrent attacks. This therapy is often combined with an inhaled bron-chodUator such as a p-adrenergic agonist. The use of p-adrenergic agonists or theophylline enables use of a lower dose of glucocorticoid, especially in patients relatively resistant to therapy (see Chapter 39). 

THEOPHYLLINE CORTICOSTEROIDS Risk of hypokalaemia Additive effect. The CSM notes that this effect occurs with beta-2 agonists, theophyllines and corticosteroids, all of which may be given during severe asthma hypoxia exacerbates this effect Monitor blood potassium levels prior to concomitant administration and during therapy (monitor 1—2-hourly during parenteral administration). Administer potassium supplements to prevent hypokalaemia, which may also be worsened by hypoxia during severe attacks of asthma... 

Theophylline, available under many proprietary names, relaxes bronchial smooth muscles to relieve or prevent asthma. The therapeutic effect of theophyUine is likely due to antagonism of adenosine receptors in smooth muscle, whereas the toxic effects are due to inhibition of cyclic nucleotide phosphodiesterase. With increased use of p-adrenergic agonists, and because of the considerable toxicity associated with it, theophylline is now considered... 

The bronchodilation effect of theophyllines has been well known for many years, and recent data indicate an additive anti-inflammatory effect of this drug and that they can prevent exacerbations of asthma [131, 141],... 

The principal asthma therapies have all been in clinical practice since the early 1970s and before, yet their mechanisms and potential hazards in many cases remain obscure. The trend towards inhaled corticosteroids continues to raise concerns about their long-term side-effects. This has fuelled efforts to develop safer anti-inflammatory therapies, despite the advent of fluticasone, which is 100 per cent first-pass metabolized in the liver and has fewer systemic effects (Harding, 1990). Suggestions that the long-actingy 2-agonists (salmeterol, formoterol) may be anti-inflammatory appear to be unfounded, but the possibility of an antiinflammatory effect of theophylline (Ward et al., 1993) has accelerated development of selective phosphodiesterase (PDE IV) inhibitors, which may have reduced side-effects and a better therapeutic index than theophylline itself. The immunosuppressants, such as cyclosporin A which prevents expression of IL-2 and IL-2R in T cells, are limited by toxicity to a small minority of very severe corticosteroid-dependent asthmatics. 

The methylxanthines consist of aminophylline, dyphyl-line, enprofylline, and pentoxifylline. Aminophylline (theophylline ethylenediamine) is the most widely used of the soluble theophyllines. Its main therapeutic effect is bronchodilation. In addition, it causes CNS stimulation, cardiac acceleration, diuresis, and gastric secretion. Aminophylline is available in an oral, rectal (pediatric), or intravenous solution, which is used in the treatment of status asthmaticus. Although it is a less effective bronchodilator than beta-adrenergic agonists, it is particularly useful in preventing nocturnal asthma (see also Figure 94). 

Some clinical benefits of theophylline, including anti-inflammatory, immun-emodulatory, and bronchodilatory effects, already occur at serum concentrations above 5 ag/ml. Thus, these concentrations may be adequate for some patients. In patients receiving theophylline as monotherapy for chronic asthma, however, doses resulting in serum concentrations beyond 10 pg/ml have clearly been shown as most likely to prevent asthma symptoms and decrease the occurrence and severity of exacerbations. 

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