Content area
Full Text
Key words: Doxolline -- Theophylline -- Bronchodilators -- Arrhythmogenic -- Asthma -- Chronic obstruclive pulmonary disease
Summary
Doxofylline (7-(1,3-dioxa Ian-2-ylmethyl) theophylline) is a novel xanthine bronchodilator which differs from theophylline in that it contains a dioxalane group in position 7. Similarly to theophylline, its mechanism of action is related to the inhibition of phosphodiesterase activities, but in contrast it appears to have decreased affinities towards adenosine A^sub 1^ and A^sub 2^ receptors, which may account for its better safety profile. The bronchodilating activities of doxofylline have been demonstrated in clinical trials involving patients with either bronchial asthma or chronic obstructive pulmonary disease. In contrast to other bronchodilators, experimental and clinical studies have shown that the drug is devoid of direct stimulatory effects. This may be of importance because the arrhythmogenic actions of bronchodilators may have a negative impact on the survival of patients with respiratory diseases.
Introduction
Methylxanthines are a group of structurally related compounds that are widely used in the treatment of patients with asthma, chronic obstructive pulmonary disease (COPD) and chronic cor pulmonale. Their effect is a generalised reduction of airway obstruction that decreases the overall resistance of the airways, improves blood gas exchange and reduces the dyspnoea1,2. It has been recognised that these drugs may provide benefits above and beyond the usual bronchodilation3. Unfortunately, therapy with xanthines is generally associated with a number of adverse events, affecting the cardiovascular system, the central nervous system and the gastrointestinal system. Serious ventricular arrhythmias, arrhythmia aggravation and cardiac arrest are of major concern in patients treated with methylxanthines intravenously4.
Cardiac Rhythm Disturbances in Respiratory Disease
It is well known that cardiac rhythm disturbances are frequent findings in patients with chronic bronchitis and emphysema. The type of arrhythmias found may be supraventricular (premature atrial beats, paroxysmal supraventricular tachycardia, multifocal supraventricular tachycardia, atrial flutter and atrial fibrillation) or ventricular (premature ventricular beats, couplets, non-sustained or sustained ventricular tachycardia). The pathogenesis of arrhythmias is complex and many factors may be involved, such as hypoxaemia, hypercapnia, respiratory acidosis, hypokalaemia, concomitant ischaemic heart disease, chronic cor pulmonale, left ventricular dysfunction (Table 1)5.
In the absence of structural heart disease, mild increases in spontaneous supraventricular and ventricular ectopy are not considered life-threatening. However, cardiac rhythm disturbances may adversely...