Aminophylline is a bronchodilator and vasodilator. It is used primarily as an antiasthmatic agent in bronchial asthma and chronic obstructive pulmonary disease (COPD).
What is aminophylline?
Aminophylline is used primarily as an antiasthmatic agent for bronchial asthma and chronic obstructive pulmonary disease (COPD). As a drug combination of theophylline and ethylenediamine (ratio 2:1), aminophylline belongs to the methylxanthine derivatives group of active ingredients. Theophylline is the physiologically active component, while ethylenediamine primarily increases solubility. The combination of active ingredients is less potent than pure theophylline and has a shorter duration of action. Aminophylline is used primarily as an antiasthmatic or bronchospasmolytic agent in airway obstruction due to bronchial asthma or COPD. In the blood, aminophylline is present bound to proteins at a rate of approximately 60%. The plasma half-life is between 7 and 9 hours.
Pharmacologic effects
Once aminophylline enters the organism, theophylline is released from the drug combination and conditions the mechanisms of action characteristic of methylxanthine derivatives. These include, in particular, its action as a phosphodiesterase (PDE) inhibitor and adenosine receptor blocker. Phosphodiesterase inhibitors inhibit the enzymes belonging to phosphodiesterase. Aminophylline is a non-selective PDE inhibitor that inhibits several different phosphodiesterases simultaneously rather than specific types of enzymes. The effect is due in particular to the theophylline contained in aminophylline. This causes vascular dilation (widening) via PDE inhibition in the airways and blood vessels. At the same time, aminophylline stimulates diuresis (urine excretion via the kidneys), gastric acid secretion and the central nervous system. In this context, aminophylline increases the intracellular cAMP (cyclic adenosine monosphate) concentration, which activates protein kinase A (PKA), which regulates energy metabolism. The increased cAMP concentration in the tissue further activates the energy metabolism controlled via catecholamine and causes the release of epinephrine. In addition, the synthesis of leukotrienes involved in inflammatory processes in bronchial asthma and thus the innate immune response is inhibited. Aminophylline, as an adenosine antagonist, blocks its action at the cell surface receptors of the heart, resulting in increased heart rate and contractility.
Medical application and use
Aminophylline, analogous to other theophylline-containing drugs, is used primarily for the treatment of bronchial asthma, chronic bronchitis, and COPD (chronic obstructive pulmonary disease). It has a relaxing effect on the smooth muscles of the bronchi and pulmonary vessels. In addition, aminophylline causes bronchial dilation, stimulates the respiratory muscles and inhibits the release of endogenous inflammatory substances. By dilating the bronchi (bronchodilation), the active ingredient leads to a reduction in the bronchial spasms characteristic of bronchial asthma and COPD, which cause shortness of breath and coughing. Accordingly, aminophylline is used primarily in the treatment and prophylaxis of respiratory distress caused by bronchoconstriction (narrowed airways). In this context, it is particularly suitable for the treatment and prophylaxis of nocturnal asthma symptoms. Aminophylline can also be used in acute asthma attacks. In moderate to severe bronchial asthma, the active substance is generally used in combination with beta-2-adrenoceptor agonists and glucocorticoids. In the presence of COPD, however, aminophylline is combined with beta-2-adrenoceptor agonists and anticholinergics. Because children and smokers excrete the active ingredient more quickly, aminophylline shows a shortened duration of action in these patients. In heart failure, impaired liver or kidney function, pneumonia, viral infections and severe oxygen deficiency, on the other hand, aminophylline excretion is slower. In both cases, dosage should be adjusted accordingly.
Risks and side effects
During drug therapy with aminophylline, insomnia, diarrhea, nausea, heartburn, headache, agitation, increased urination, cardiac arrhythmias, increased blood glucose, and limb tremors may often be observed.In addition, blood uric acid and creatinine levels are often elevated, while blood calcium concentrations are decreased. Overdose may lead to seizures, acute hypotension, severe cardiac arrhythmias, as well as gastrointestinal complaints. In case of hypersensitivity to the active substance, after acute myocardial (fresh myocardial infarction) as well as acute cardiac arrhythmia, therapy with aminophylline is contraindicated. Theophylline contained in aminophylline is metabolized (metabolized) primarily via CYP1A2 – an endogenous enzyme important for drug biotransformation. Plasma levels may therefore vary between individual sufferers. Numerous interactions with other active ingredients are also possible. The active ingredient is therefore generally administered with restraint. To avoid overdoses-especially dangerous theophylline intoxication with convulsions and cardiac arrhythmias-close monitoring by the physician is recommended.