Theophylline, asthma

Theophylline, asthma, 17.2, 18.1, 18.2 Thiazides, see Diuretics Thiazolidinediones cardiovascular reactions, 31.697 musculoskeletal reactions, 32.779 peripheral edema, 29.531 Thiomersal, in vaccines, 28.357 Thiopurines, genetic susceptibility, 31.634 Thyroid hormones, 29.464 Thyroxine, drug interactions, 24.484 Tiaprofenic acid, cystitis, 18.106 TNF, see tumor necrosis factor Tolcapone, 32.289... 

This experiment describes the quantitative analysis of the asthma medication Quadrinal for the active ingredients theophylline, salicylic acid, phenobarbital, ephedrine HGl, and potassium iodide. Separations are carried out using a Gi8 column with a mobile phase of 19% v/v acetonitrile, 80% v/v water, and 1% acetic acid. A small amount of triethylamine (0.03% v/v) is included to ensure the elution of ephedrine HGl. A UV detector set to 254 nm is used to record the chromatogram. 

For many years oral xanthines, shown in Table 2, were the preferred first-line treatment for asthma in the United States, and if the aerosol and oral formulations of P2" go sts are considered separately, as they are in Table 1, this was still the case in 1989. Within this class of compounds theophylline (8), or one of its various salt forms, such as aminophylline [317-34-0] (theophylline ethylenediamine 2 l), have been the predominant agents. Theophylline, 1,3-dimethylxanthine [58-55-9], is but one member of a class of naturally occurring alkaloids. Two more common alkaloids are theobromine (9), isomeric with theophylline and the principal alkaloid in cacao beans, and caffeine, (10), 1,3,7-Trimethylxanthine [58-08-2], found in coffee and tea. 

Common side effects of theophylline therapy include headache, dyspepsia, and nausea. More serious side effects such as lethal seizures or cardiac arrythmias can occur if blood levels are too high. Many derivatives of theophylline have been prepared in an effort to discover an analogue without these limitations (60,61). However, the most universal solution has resulted from the development of reHable sustained release formulations. This technology limits the peaks and valleys in semm blood levels that occur with frequent dosing of immediate release formulations. ControUed release addresses the problems inherent in a dmg which is rapidly metabolized but which is toxic at levels ( >20 7g/mL) that are only slightly higher than the therapeutically efficacious ones (10—20 p.g/mL). Furthermore, such once-a-day formulations taken just before bedtime have proven especially beneficial in the control of nocturnal asthma (27,50,62). 

The effectiveness of theophylline in the treatment of asthma seems to result from a combination of biological properties which are not clearly understood (63). Detailed discussions of the possible role of xanthines in asthma may be found in references 64—66. 

Theophylline s predominant mode of action appears to be bronchocHlation. However, it has also been shown that prophylactic acHriinistration of theophylline provides some protection from asthma attacks and suppresses the late-phase response (67,68). Some researchers beHeve that at therapeutic semm concentrations theophylline may inhibit the development of airway inflammation (69). There are conflicting reports on the effect of theophylline on allergen-induced bronchial hyperresponsiveness some clinical stucHes report a reduction in hyper-responsiveness, others do not (69,70). Theophylline clearly does not reverse the general bronchial hyperresponsiveness over the course of long-term therapy (71). Because of the relationship between... 

In the USA, LTRAs have largely replaced theophylline as the incremental drug for the treatment of moderate and severe asthma, where LABA plus ICS alone do not provide adequate control. For patients with mild persistent asthma, LTRAs have been designated as a suitable substitute for low dose ICS by the National Asthma Education Panel Program (NAEPP) of the National Heart and Lung Institute (National Institutes of Health). However, inhaled ICS are more efficacious. 

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... 

Patients receiving these agents may notice improvement in 1 to 2 weeks, but maximal benefit may not be seen for 4 to 6 weeks. Cromolyn and nedocromil appear to be similar in efficacy to the leukotriene antagonists and theophylline for persistent asthma.18 Both agents are well tolerated with adverse effects limited to cough and wheezing. Bad taste and headache have also been reported with nedocromil. One dose of cromolyn or nedocromil prior to exercise or allergen exposure will provide effective prophylaxis for 1 to 2 hours. Cromolyn and nedocromil are not as effective as albuterol for prophylaxis of exercise-induced asthma. 

Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use. Theophylline causes bronchodilation through inhibition of phosphodiesterase and antagonism of adenosine and appears to have anti-inflammatory and immunomodulatory properties as well.36... 

Theophylline is not recommended for treatment of acute asthma.2 It provides no additional benefit when optimal inhaled bronchodilators are used and increases the risk of adverse events. Similarly, although magnesium has bron-chodilator activity, it offers no significant benefits when optimal bronchodilator therapy is used.12,40... 

In the clinical area, the largest share of analytical methods development and publication has centered on the determination of theophylline in various body fluids, since theophylline is used as a bronchodilator in asthma. Monitoring serum theophylline levels is much more helpful than monitoring dosage levels.44 Interest in the assay of other methylxanthines and their metabolites has been on the increase, as evidenced by the citations in the literature with a focus on the analysis of various xanthines and methylxanthines. 

Theophylline is used pharmacologically to manage asthma. Therapeutic effect is seen at concentrations in plasma above 10 mg/L. At 20 mg/ L, adverse effects limit the usefulness of theophylline. 

In nocturnal asthma, long-acting inhaled /T-agonists are preferred over oral sustained-release / -agonists or sustained-release theophylline. However, nocturnal asthma may be an indicator of inadequate antiinflammatory treatment. 

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). 

Asthma prophylaxis 600 mg qid, not for acute attacks inhibition of theophylline and warfarin metabolism. Hepatotoxic. 

Theophylline (Fig. 20) is structurally very similar to caffeine and present at a low concentration in tea. It is also known as dimethyl xanthine. It is used for the treatments of asthma and COPD, for more than 50 years despite its many side effects. The mechanism of beneficial effect of theophylline is through HD AC activation. 

Bronchodilators. Narrowing of bronchioles raises airway resistance, e.g in bronchial or bronchitic asthma Several substances that are employed as bronchodilators are described elsewhere in more detail P2-sympathomimetics (p. 84, given by pulmonary, parenteral, or oral route), the methylxanthine theophylline (p. 326, given parenterally or orally), as well as the parasympatholytic ipratropium (pp. 104, 107, given by inhalation). 

Severe cases may, however, require an intensified bronchodilator treatment with systemic jk-mimetics or theophylline (systemic use only low therapeutic index monitoring of plasma levels needed). Salmeterol is a long-acting in-halative P2-mimetic (duration 12 h onset -20 min) that offers the advantage of a lower systemic exposure. It is used prophylactically at bedtime for nocturnal asthma. 

A plant-derived compound used in the treatment of asthma and COPD is the methylxanthine-type alkaloid, theophylline (50), found naturally in tea Camellia sinensis Kuntze). This compound demonstrated higher activity when complexed with bases, as in its semisynthetic analogue amino-phylline (51). 5... 

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. 

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