Central nervous system stimulants theophylline

A naturally occurring substance (1,3,7-trimethytxan-thine) that competitively inhibits 3, 5 -cyclic AMP phosphodiesterase and acts as a powerful central nervous system stimulant. The inhibitory effect can be reversed at high cAMP concentrations. A related substance, theophylline (also known as aminophylhne) has a similar mode of action. 

This xanthine derivative is an only a modest bron-chodilator in COPD, and because of its narrow therapeutic range, frequently seen adverse effect and drug interactions, it is becoming less frequently used, some patients experience side effects even within the therapeutic range. The non-bronchodilator effects of theophylline such as systemic and pulmonary vascular dilatation, central nervous system stimulation, improvement of the strength and effectiveness of respiratory muscles and possibly anti-inflammatory effects are of disputed clinical significance at usual therapeutic levels. 

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 central nervous system 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 aminophylline is a less effective bronchodilator than beta-adrenergic agonists, it is particularly useful in preventing nocturnal asthma. 

However, the bronchodilation which is easily demonstrated in the asthmatic is not evident in CB. Nevertheless, the bronchitic with airways obstruction will report improvement of exercise capability with effective theophylline therapy. Theophylline is a phosphodiesterase inhibitor and results in a decreased breakdown of cAMP. This action in the bronchial tree has not been shown to be of benefit in the pathophysiologic mechanisms of CB. Although the mechanism of action in CB is not clear, benefit may be related to central nervous system stimulation, cardiac action, its modest diuretic activity, or to actions not... 

AH three of these materials are apparentiy central nervous system (CNS) stimulants. It is beheved that for most individuals caffeine causes greater stimulation than does theophylline. Theobromine apparentiy causes the least stimulation. There is some evidence that caffeine acts on the cortex and reduces drowsiness and fatigue, although habituation can reduce these effects. 

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. 

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see Box 14.3) and subsequent release of adrenaline. This leads to the major effects a stimulation of the central nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine. 

Caffeine and theophylline are more active on the central nervous system, while theobromine is much less active. Caffeine and theophylline also appear to stimulate the respiratory centers, making them useful in the treatment of infants who stop breathing for extended periods of time (sleep apnea), which can lead to sudden infant death. 

The principal xanthines of medical interest include caffeine, theophylline and aminophylline. Caffeine is synthesized by several plants and was originally isolated from tea in 1838. It is a methylxanthine (Figure 1.12) which stimulates the central nervous system, increasing mental alertness. It also acts as a diuretic and stimulates gastric acid secretion. It is absorbed upon oral administration and is frequently included in drugs containing an analgesic, such as aspirin or paracetamol. 

Smooth muscle relaxation, central nervous system (CNS) excitation, and cardiac stimulation are the principal pharmacological effects observed in patients treated with theophylline. The action of theophylline on the respiratory system is easily seen in the asthmatic by the resolution of obstruction and improvement in pulmonary function. Other mechanisms that may contribute to the action of theophylline in asthma include antagonism of adenosine, inhibition of mediator release, increased sympathetic activity, alteration in immune cell function, and reduction in respiratory muscle fatigue. Theophylline also may exert an antiinflammatory effect through its ability to modulate inflammatory mediator release and immune cell function. 

Thea assamica Mast T. bohea L. T. cantoniensis Lour. T. chinensis Sims. T. cochinchinensis Lour. T. sinensis L. T. viridis Link. Cha (Tea) (leaf) Caffeine, theophylline, tannic acid, theobromine, xanthine, polyphenols. 33-47.405,406,409 Diuretic effect, increase renal blood flow, stimulate central nervous system, antitumor, prevent lung cancer. 

Camellia sinensis (L.) Kuntze China Caffeine, theophylline, tannic acid, theobromine, xanthine.33,47 Diuretic effect, increases renal blood flow, stimulate central nervous system. 

These all resemble each other in most points of their pharmacological action, but they differ markedly in the relative intensity of their action on various functions. Thus, caffeine is the most potent central nervous system (CNS) stimulant of the group theobromine exerts the greatest action on the muscles and theophylline is the most effective diuretic and coronary dilator. Theobromine has comparatively little effect on the CNS, whereas theophylline has no action on the muscles. 

Caffeine, mp 263°C, sublimes on heating and is more soluble than dimethylxanthines. Caffeine has a stimulating effect on the central nervous system. It is extracted from green coffee beans with liquid CO2 [151]. Caffeine is synthesized by methylation of xanthine, theophylline or theobromine with methyl iodide or dimethyl sulphate [149]. 

The phosphodiesterase which cleaves cyclic AMP to adenylate is found in both particulate and soluble fractions of tissue homogenates, and it is inhibited by pyrophosphate and ATP, as well as by caffeine, theophylline, and theobromine. These three methylated xanthines cause central nervous system and respiratory stimulation, smooth muscle relaxation, diuresis, coronary dilatation, cardiac stimulation, and skeletal muscle stimulation these effects are believed to be due to increased tissue concentrations of cyclic AMP resulting from inhibition of phosphodiesterase activity. 

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