Asthma aminophylline

Xanthines Direct relaxation of bronchial smooth muscle Aminophylline Asthma Chronic bronchitis... 

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. 

Drugs (and, therefore, test chemicals) are occasionally administered by rectum, but most are not as well absorbed here as they are from the upper intestine. Aminophylline, used in suppository form for the management of asthma, is one of the few drugs routinely given in this way. Inert vehicles employed for suppository... 

For a one-year-old child weighing 5.5 kg and suffering from a serious asthma problem, a physician prescribed 0.85 mg/kg/min of aminophyl-line. The instruction was to add 50 mg of aminophylline in 500 mL of D5W and administer at a rate of 40 mL per hour. The available drug is aminophyllme 2.5% w/v. Check if the dilution factor is accurate. 

Theophilline is also a minor constituent of tea, but is prepared by direct chemical synthesis for medical use. It functions to relax smooth muscle and, therefore, can be used as a bronchodilator in the treatment of asthma and bronchitis. Aminophylline is a derivative of theophilline (theophylline ethylenediamine), which is often used in place of theophilline due to its greater aqueous solubility. 

Twenty years ago theophylline (Theo-Dur, Slo-bid, Uniphyl, Theo-24) and its more soluble ethylenedi-amine salt, aminophylline, were the bronchodilators of choice in the United States. Although the p2-adreno-ceptor agonists now fill this primary role, theophylline continues to have an important place in the therapy of asthma because it appears to have antiinflammatory as well as bronchodilator activity. 

Among the methylxanthines, aminophylline is most commonly used drug in the treatment of bronchial asthma. It is a stable mixture of theophylline and ethylenediamine. These drugs inhibit the enzyme phosphodiesterase, this inhibition results in higher concentration of intracellular cyclic AMP. 

Nakano J et al Aminophylline suppresses the release of chemical mediators in treatment of acute asthma. Respir Med 2006 100 542. [PMID 16337368]... 

Mitra A, Bassler D, Goodman K, et al. Intravenous aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators. Cochrane Database Syst Rev. 2005 CD001276. 

Aminophylline (theophylline ethylenediamine), given intravenously, is used in patients with status asthmaticus who do not respond to epinephrine. In addition, epinephrine may be administered subcutaneously for acute asthma attacks. Epinephrine may also be given along with theophylline. It is thought that the bronchodilation is associated with me enhanced concentration of cyclic AMP, which is metabolized according to the following sequence ... 

In low and moderate doses, the methylxanthines—especially caffeine—cause mild cortical arousal with increased alertness and deferral of fatigue. The caffeine contained in beverages—eg, 100 mg in a cup of coffee—is sufficient to cause nervousness and insomnia in unusually sensitive individuals and slight bronchodilation in patients with asthma. At very high doses, medullary stimulation and convulsions may occur and can lead to death theophylline has been used successfully in suicide attempts. Nervousness and tremor are primary side effects in patients taking large doses of aminophylline for asthma. 

The treatment of acute attacks of asthma in patients reporting to the hospital requires more continuous assessment and repeated objective measurement of lung function. For patients with mild attacks, inhalation of a -receptor agonist is as effective as subcutaneous injection of epinephrine. Both of these treatments are more effective than intravenous administration of aminophylline. 

Aminophylline is used in the treatment of asthma (as a bronchodilator) and in chronic obstructive pulmonary disease. In acute bronchospasm, aminophylline should not be given by the intravenous route the oral route is preferred. Parenteral administration can cause pain and is not recommended. Aminophylline is used as a cosmetic to remove fat from the thigh.45... 

A 3-year-old boy comes into A E with a severe asthma attack. This is his third in the last three months. He is started on nebulised salbutamol, intravenous aminophylline and oral prednisolone. The presenting symptoms include ... 

Mode of action. Caffeine and theophylline have complex and incompletely elucidated actions, which include inhibition of phosphodiesterase (the enzyme that breaks down cyclic AMP, see p. 191), effects on intracellular calcium distribution, and noradrenergic function. When theophylline (as aminophylline) is used alongside salbutamol in asthma its action adds up to increased benefit to the bronchi, but increased risk to the heart. 

Theophylline is relatively insoluble and it is formulated either as a salt with choline (choline theophyllinate) or complexed with EDTA (amino-phylline). Aminophylline is sufficiently soluble to permit i.v. use of theophylline in status asthmaticus. There are numerous sustained-release oral forms for use in chronic asthma. These are not bioequivalent and patients should not switch between them once they are stabilised on a particular preparation. It has also been used in the past for the emergency treatment of left ventricular failure (see p. 518). At high therapeutic doses some patients... 

A 43-year-old male non-smoker, with a history of asthma, hypertension, and angina pectoris, was admitted to an intensive care unit for mechanical ventilation for acute severe asthma (50). He was given an inhaled bronchodilator, aminophylline, and prednisolone. His condition improved slowly but he became hypovolemic. Within 60 seconds of a fluid challenge with pentastarch 200 ml he had a severe anaphylactoid reaction. 

Aminophylline sometimes aggravates bronchial asthma sensitization to the ethylenediamine component is considered to be responsible (SEDA-6, 5). 

The emergency department use of aminophylline, a moderate bron-chodUator, for acute asthma has not been recommended for a number of years. Clinical trials of aminophylline in adults and children hospitalized with acute asthma have not reported sufficient evidence of efficacy (improvement in lung function and reduced hospital stay) but have reported an increased risk of adverse effects. However, two smdies of aminophylline in children with severe disease suggested a possible small benefit in reducing intensive care unit admissions. Adverse effects of theophylline include nausea and vomiting and potentiation of the cardiac effects of the inhaled /32-agonists. 

Theophylline occurs in such a low concentration in all xanthine drugs that extraction is not profitable. Theophylline can be produced by demethylation of caffeine or by total synthesis. Theophylline has a spasmolytic effect on smooth muscles, which is apparent in a pronounced bronchodilating action, hence it is used in asthma either on its own or combined with ethylenediamine to produce aminophylline. Furthermore, theophylline has a diuretic action. 

Although asthma is considered to be a reversible condition, severe acute attacks can cause obstruction that can take days to reverse and in some cases is not reversible at all. Such attacks need to be treated as a medical emergency requiring hospital treatment. Treatment includes oxygen, inhalation of salbutamol in oxygen, intravenous hydrocortisone and oral prednisolone. Sometimes inhaled antimuscarinics are also used and intravenous salbutamol and aminophylline plus antibiotics if there is infection as well. 

Aminophylline - bronchodilator asthma, chronic bronchitis Amiodarone - anti-arrhythmic Amisulpiride - antipsychotic Amitriptyline - antidepressant... 

The methylxanthines consist of aminophylline, dyphyl-line, enprofylline, and pentoxifylline. Aminophylline (theophylline ethylenediamine) is the most widely used of the soluble theophyllines. Its main therapeutic effect is bronchodilation. In addition, it causes CNS stimulation, cardiac acceleration, diuresis, and gastric secretion. Aminophylline is available in an oral, rectal (pediatric), or intravenous solution, which is used in the treatment of status asthmaticus. Although it is a less effective bronchodilator than beta-adrenergic agonists, it is particularly useful in preventing nocturnal asthma (see also Figure 94). 

Methylxanthines have a few valid therapeutic uses, including treatment of asthma and relief of dyspnea (see Antiasthmatic agents). The CNS stimulatory effects are also utilized for the treatment of the prolonged apnea that may be observed in premature infants. Theophylline may be combined with doxapram (13) for this use (20). The methylxanthine most widely used therapeutically is theophylline, although caffeine may also be used. For parenteral administration, a salt of theophylline is employed. There are several salts available, including theophylline ethylenediamine (aminophylline [317-34-0]) and oxtriphylline (choline theophyllinate). Other synthetic xanthines that are used include dyphylline [479-18-5] and enprofylline [410784)2-8] (21). Caffeine is obtained in pure form from tea waste, from the manufacture of caffeine coffee, and by total synthesis (22,23). 

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