Additives aminophylline

An 8-month-old boy who had been given oral modifled-release theophylline and additional aminophylline suppositories developed convulsive status epilepticus [96 ]. A combination of diazepam, lidocaine, and thiopental was required to stop the convulsion. A pharmacokinetic study showed that the use of the mod-ified-release formula would have given a plasma concentration of no more than 15 mg/ 1, but that the addition of aminophylline would have increased it to over 20 mg/1. 

Xanthines such as caffeine (1)> theophylline (aminophylline) (2), and theobromine (3) are a class of alkaloids that occur in numerous plants. The CNS stimulant activity of aqueous infusions containing these compounds has been recognized since antiquity. This has, of course, led to widespread consumption of such well-known beverages as coffee (Coffea arabica), tea (Thea sinesis), mate, and cola beverages (in part Cola acuminata). The annual consumption of caffeine in the United States alone has been estimated to be in excess of a billion kilos. The pure compounds have found some use in the clinic as CNS stimulants. In addition, caffeine is widely used in conjunction with aspirin in various headache remedies. 

Examples of the xanthine derivatives (drag that stimulate the central nervous system [CNS] resulting in bronchodilation, also called methylxanthines) are theophylline and aminophylline. Additional information concerning the xanthine derivatives is found in the Summary Drag Table Bronchodilators. 

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 ... 

The commonest gastrointestinal adverse effects of aminophylline in adults are nausea and gastrointestinal irritation, which are primarily a function of serum theophylline concentrations, although some additional local irritation may be produced by oral administration. Nausea was reported in six of 20 asthmatic patients with serum theophylline concentrations of 20 pg/ml (SED-9, 4). In a survey of 2766 theophylline-treated patients with cardiac or pulmonary diseases, 11% had adverse effects, most of which were gastrointestinal disturbances (7.8%) (SED-9, 4). 

Certain issues of product instability may be resolved by formulation or careful selection of vehicle. Aminophylline injection, for example, is a solution of the drug in Water for Injections free from carbon dioxide, as the presence of this gas causes precipitation of the active. Similarly, promethazine injection is a solution of the active in Water for Injections free from dissolved air as the presence of oxygen would cause promethazine oxidation. Removal of these gases can be accomplished by prior boiling additionally the product may be packed under an atmosphere of nitrogen to eliminate oxygen from the head space in the ampoule. 

The Baboon Syndrome is an unusual presentation of a drug eruption with a characteristic intertriginous distribution pattern. Several drugs have been implicated, notably mercury, nickel, heparin, aminophylline, pseudoephedrine, terbinafine, IVIG, various antibiotics (amoxicillin, ampicillin), and food additives. 

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). 

Examples of die xanthine derivatives (dni diat stimulate die central nervous system [CNSl resulting in bronchodilation, also called mediylxandiines) are dieo-phylhiie and aminophylline. Additional information concerning die xandiine derivatives is found in die Summary Drug Table Bronchodilators. 

Caffeine 4 mg/kg intravenously (roughly equivalent to 2 to 3 cups of coffee), given before dipyridamole-thallium-201 myocardial scintigraphy, caused a false-negative test result in a patient. A further study in 8 healthy subjects confirmed that caffeine inhibits the haemodynamic response to an infusion of dipyridamole. Similarly, oral theophylline markedly reduced the diagnostic accuracy of myocardial imaging using dipyridamole. In addition, intravenous aminophylline accelerated the myocardial washout rate of thallium-201 after a dipyridamole infusion. ... 

The mean theophylline clearance, from a single intravenous dose of aminophylline, was increased hy 34% in healthy adult subjects given phenobarbital. In another study the clearance of theophylline was increased by 17% when phenoharhital was given for 2 weeks, although this was not significant. The eftects of phenoharhital can he additive with the effects of phenytoin and smoking one patient icquiicd 4 g of theophylline daily to maintain therapeutic serum levels and to control her asthma. ... 

In contrast, there are 2 case reports of patients who developed theophylline toxicity (theophylline levels raised to 30 mg/L and 41 mg/L), apparently due to the addition of nifedipine. In one case, the toxicity recurred on rechallenge, and resolved when the theophylline dosage was reduced by 60%. During a Swan Ganz catheter study of patient response to nifedipine for pulmonary hypertension, 2 patients developed serious nifedipine adverse effects, which responded to intravenous aminophylline. ... 

A patient taking theophylline developed elevated serum theophylline levels of 35.7 micrograms/mL while taking Quinamm for leg cramps (old formulation containing quinine 260 mg and aminophylline 195 mg). This case report highlights liie need to avoid the inadvertent intake of additional doses of theophylline if toxicity is to be avoided. The newer formulation of Quinamm does not contain theophylline. Note that non-prescription preparations containing theophylline are available in many countries. For... 

Protection of the pulmonary bronchi and bronchioles may be possible by the use of cytoprotective agents. Ongoing studies of pneumocytes, interstitial, and epithelial cells suggest that antiinflammatory agents, such as aminophylline, corticosteroids, and ibuprofen, may be useful. Further studies on the ability of N-acetylcysteine to limit the inflammatory cascade produced by effects ofphosgene and its metabolic byproducts are also justified, as are additional studies of its systemic antioxidant effects. 

Some examples of common additives are given which may be used as drugs themselves (such as benzoyl peroxide for acne), in the synthesis of drugs (dicyclohexyl carbodiimide) or as antioxidants in final products. Ethylene diamine is present in topical drugs and in aminophylline and is the allergen in the latter compound. Several cases of occupational contact dermatitis have been reported (Corazza et al. 

Compared to the widespread and long-term use of p-mimetic drugs, typically by nebulization, the few reports involving anti-asthmatic drugs indicate that they are weak allergens (Fung et al. 1996). Aminophyl-line is of importance, since it consists of ethylene diamine and theophylline therefore, positive patch tests to ethylendiamine are present in patients sensitized to aminophylline (see the section entitled Additives ) (Rudzki et al. 1989 Rudzki 1990). 

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