Theophylline, consider

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. 

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... 

Albuterol is the preferred bronchodilator for treatment of acute exacerbations because of its rapid onset of action. Ipratropium can be added to allow for lower doses of albuterol, thus reducing dose-dependent adverse effects such as tachycardia and tremor. Delivery can be through metered-dose inhaler (MDI) and spacer or nebulizer. The nebulizer route is preferred in patients with severe dyspnea and/or cough that would limit delivery of medication through an MDI with spacer. If response is inadequate, theophylline can be considered however, clinical evidence supporting its use is lacking. 

While generally not of major concern, omeprazole may inhibit the metabolism of warfarin, diazepam, and phenytoin lansoprazole may decrease theophylline concentrations. Drug interactions with omeprazole are of particular concern in patients who are considered slow metabolizers, as are approximately 3% of the Caucasian population. Unfortunately, it is unclear which patients have the polymorphic gene variation that makes them slow metabolizers.17 The metabolism of esomeprazole may also be altered in patients with this polymorphic gene variation. Patients on potentially interacting drugs should be monitored for development of drug-related problems. 

The percentage of binding to plasma protein is low for caffeine (35%) and theobromine (15 to 25%), but fairly high for theophylline (55 to 67%). This higher binding of theophylline should be considered when it is used as a prescription drug. 

Cromolyn, leukotriene receptor antagonists, and theophylline are considered alternative agents, but they are not preferred. 

Methylxanthines are no longer considered first-line therapy for COPD. Inhaled bronchodilator therapy is preferred over theophylline for COPD because of theophylline s risk for drug interactions and the interpatient variability in dosage requirements. Theophylline may be considered in patients who are intolerant or unable to use an inhaled bronchodilator. A methylxanthine may also be added to the regimen of patients who have not achieved an optimal clinical response to an inhaled anticholinergic and [i2-agonist. 

Clinical evidence supporting theophylline use during exacerbations is lacking, and thus theophylline should generally be avoided. It may be considered for patients not responding to other therapies. 

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

Azithromycin Drugs that may interact with azithromycin include antacids, cyclosporine, HMG-CoA reductase inhibitors, pimozide, tacrolimus, theophyllines, and warfarin. Also consider all drug interactions with erythromycin. 

Many alkaloids are generally known to have stimulating properties, such as caffeine, cathine, theobromine and theophylline. These alkaloids are considered in many different medical applications. 

A variety of drugs in distinct pharmacological and chemical classes can be considered under the broad classification as stimulants. Xanthines and methylxan-thines constitute a weak class of stimulants that includes caffeine, theophylline (aminophylline),and theobromine. Caffeine is freely available in coffee, colas, and certain over-the-counter pills. A low degree of tolerance develops to some of their effects and a mild withdrawal syndrome is observed following immediate cessation of their repeated use. 

Natural antagonists for ARs, such as caffeine and theophylline show in general low affinity for the A3 AR subtype (Baraldi et al. 2003). In a recent work, the approach based on the annelation of xanthine derivatives for the development of adenosine receptors antagonists has been extensively considered (Drabczy ska et al. 2003). 

An example of diazepinone formation by lactamization is given by Da Settimo et al. <1999JHC639>. After reacting 8-aminotheophylline 50 with 2-carboxybenzaldehyde to form a Schiff base, reduction with NaBH4 forms precursor 51, which can be easily cyclized by heating at 300°C in a Pyrex tube to give 52 in 64% yield (Scheme 7). If the overall reaction is considered starting from theophylline, it could also be classified as a type eg bond formation. 

Poly(vinyl alcohol)-gel spheres with chitosan (PVA-GS/Ch) or without chitosan (PVA-GS) were prepared to control the GI transit time of drugs, and their particles were 5-10 pm [26]. PVA-GS/Ch displayed a longer small-intestinal transit time than PVA-GS. The transit rate was considered to decrease by the adhesion of chitosan to the intestinal mucus layer. PVA-GS/Ch and PVA-GS were loaded with theophylline and ampicillin. These released the drugs in a similar manner. The drugs were released almost completely at 4 h after the start of the release test. Both the gel spheres containing theophylline exhibited a bioavailability similar to that of the theophylline solution. Also, the bioavailability of ampicillin was greater in PVA-GS/Ch than in the PVA-GS and ampicillin solution the bioavailability of PVA-GS/Ch was approximately 150% of that of ampicillin solution (Table 3.2). As theophylline is rapidly absorbed in... 

Cromolyn or nedocromil may be considered as an alternative to inhaled corticosteroids in patients with symptoms occurring more than twice a week or who are wakened from sleep by asthma. They may also be useful in patients whose symptoms occur seasonally or after clear-cut inciting stimuli such as exercise or exposure to animal danders or irritants. In patients whose symptoms are continuous or occur without an obvious inciting stimulus, the value of these drugs can only be established with a therapeutic trial of inhaled drug four times a day for 4 weeks. If the patient responds to this therapy, the dose can be reduced. Maintenance therapy with cromolyn appears to be as effective as maintenance therapy with theophylline and, because of concerns over the possible long-term toxicity of systemic absorption of inhaled corticosteroids, has become widely used for treating children in the USA. 

Figure 6.8 shows the effect of the width of the confidence interval. We know that the interval width depends upon the variability (SD) of the data being considered and the number of observations available. Therefore, if the theophylline clearances are fairly consistent and large numbers of subjects have been studied,... 

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