Theophylline, consider Caffeine

The drug pentoxifylline, a 2-hexanoyl analog of such xanthines as theophylline and caffeine, has the ability to lower blood viscosity by increasing the flexibility of red blood cell membranes in patients. This is most probably due to PDE inhibition, which increases c-AMP levels. Unlike the vasodilators considered earlier, pentoxifylline is effective in claudication. 

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. 

The percentage of binding to plasma protein is low for caffeine (35%) and theobromine (15 to 25%), but fairly high for theophylline (55 to 67%). This higher binding of theophylline should be considered when it is used as a prescription drug. 

Many alkaloids are generally known to have stimulating properties, such as caffeine, cathine, theobromine and theophylline. These alkaloids are considered in many different medical applications. 

A variety of drugs in distinct pharmacological and chemical classes can be considered under the broad classification as stimulants. Xanthines and methylxan-thines constitute a weak class of stimulants that includes caffeine, theophylline (aminophylline),and theobromine. Caffeine is freely available in coffee, colas, and certain over-the-counter pills. A low degree of tolerance develops to some of their effects and a mild withdrawal syndrome is observed following immediate cessation of their repeated use. 

Natural antagonists for ARs, such as caffeine and theophylline show in general low affinity for the A3 AR subtype (Baraldi et al. 2003). In a recent work, the approach based on the annelation of xanthine derivatives for the development of adenosine receptors antagonists has been extensively considered (Drabczy ska et al. 2003). 

Drug interactions The effect of antacids and cations on the absorption of these agents was considered above. Ciprofloxacin, ofloxacin and enoxacin can increase the serum levels of theophylline by inhibiting its metabolism. They also may raise levels of warfarin, caffeine and cyclosporine. Cimetidine interferes with the... 

One of the most widely prescribed of these drugs — theophylline — has recently come under close scrutmy as a possible cause of bizarre and violent behavior. Theophylline is the active principle of tea, a near relative of caffeine. For many years most asthmatics have swallowed large daily doses of this stimulant, considered a safe and effective drug. Now, with increasing evidence that it can produce serious behavioral changes, its days of use as a medical treatment may be numbered. 

The purine group of alkaloids includes the vegetable alkaloids caffeine, theobromine, theophylline and the animal alkaloids xanthine, hypoxanthine, guanine and adenine. The most common substance which is a purine compound is uric acid, but, though directly related to the alkaloids given above, it is not itself usually considered as an alkaloid. The constitution of uric acid has been fully considered (Part I, p. 442). It is the tri-hydroxy derivative of a substance known as purine which is the mother substance of the purine alkaloids also. 

Estimates of efficiencies and resolution can be made by considering the chromatogram for 6.5% 2-methoxyethanol in carbon dioxide. The resolution between caffeine (k - 0.88) and theophylline (k = 1.24) is 2.17 and between theophylline (k s 1.24) and theobromine (k = 1.7) is 2.00, yielding an average effective number of plates (N) of 884 and an efflclency-per-unit-tlme parameter of 20 effective plates/s (theophylline). This is somewhat higher than expected for an LC system (Table I) and lower than the most efficient system. Compared to the values in Table I, the linear velocity is higher than optimum, the diffu-sivlty is different, and the analyte capacity factor (elution time) is lower. 

For the treatment of preterm neonatal apnea, theophylline serum concentrations of 5 to 10 pg/ml are being considered as effective in decreasing the number of apnea episodes. The pharmacodynamics of theophylline in this situation, however, have not well been studied, and theophylhne in neonates is converted to caffeine to varying degrees, which also is effective in suppressing apnea and thus confounds the concentration-effect relationship. 

IV. Diagnosis is suggested by the history of caffeine exposure or the constellation of nausea, vomiting, tremor, tachycardia, seizures, and hypokalemia (also consider theophylline see p 354). 

These three alkaloids are well-known compounds, as they are present in everyday foods and beverages, such as cocoa, drinking chocolate, tea, and cola, as well as in pharmaceutical products. In cocoa products, theobromine is the major alkaloid, followed by caffeine, which is found in small quantities. Slight traces of theophylline have been identified therefore, it is not considered relevant and is not reviewed in the cocoa products [22,23], The range of methylxanthines also depends on variables such as the origin of the cocoa beans, the fermentation process, and the cocoa production process. Thus, for instance, defatted cocoa beans may contain about 4% and 0.2% of theobromine and caffeine, respectively [24], Regarding their physiological effects in humans, methylxanthines have been related to various body systems, mainly the central nervous system, but also the cardiovascular, renal, and respiratory systems [25,26],... 

Mechanism of action. Meihybcanihines stimulate the certral nervous system (CNS) and cardiac muscle, promote diuresis and irMiucx smootii misde rdaxatkm. Theobromirte is considered a less potent CNS mubnt than either caffeine or theophylline. 

---