REPLY
Therapeutic Theophylline Levels and Adverse Cardiac Events
Michael Shannon, MD, MPH
15 May 1994 | Volume 120 Issue 10 | Page 891
IN RESPONSE:
We appreciate Dr. Raggi's comments on the potential for normally therapeutic theophylline levels to produce significant cardiac disturbances. This risk has been reported by many investigators. In a separate study, Bittar and colleagues [1] reported that among elderly patients receiving theophylline, those with serum concentrations between 10 and 20 mg/L had an 3.7-fold greater risk for cardiac disturbances than did patients of similar age with nondetectable serum theophylline concentrations. In an in vitro study, Lin and coworkers [2] found that theophylline has specific arrhythmogenic effects on human atrial tissue. Although their data suggest that theophylline has direct actions on cardiac membrane depolarization, other theories of theophylline-induced cardiotoxicity include the drug's ability to antagonize the cardioprotective effects of endogenous adenosine (for example, coronary artery dilation) as well as its ability to stimulate plasma catecholamine activity and to increase myocardial oxygen demand. These findings provide consistent evidence that adverse cardiac events may occur not only in patients with theophylline intoxication [3] but also in patients whose levels are within the therapeutic range.
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Author and Article Information
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Children's Hospital; Harvard Medical School; Boston, MA 02115
1. Bittar G, Friedman HS. The arrhythmogenicity of theophylline. A multivariate analysis of clinical determinants. Chest. 1991; 99:1415-20.
2. Lin CI, Chuang IN, Cheng KK, Chiang BN. Arrhythmogenic effects of theophylline in human atrial tissue. Int J Cardiol. 1987; 17:289-97.
3. Sessler CN, Cohen MD. Cardiac arrhythmias during theophylline toxicity. A prospective continuous electrocardiographic study. Chest. 1990; 98:672-8.
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