Theophylline diuretic action

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. 

The general properties of the methylxanthines (theophylline, caffeine) are discussed elsewhere (see p. 194). Their mild diuretic action probably depends in part on smooth muscle relaxation in the afferent arteriolar bed increasing renal blood flow, and in part on a direct inhibitory effect on salt reabsorption in the proximal tubule. Their uses in medicine depend on other properties. 

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. 

Pharmacological actions - 5-Alkyl derivatives of (LXVI) are also cited as having diuretic activity [431]. Certain 1,3-dimethyl-6-alkylaminouracils are reported to have diuretic activity similar to that of theophylline [432]. 1,3-Dimethyl-5-ethyl-6-(methylamino)uracil (LXVII) was found to be among the most active of the compounds tested. Diuretic and hypotensive activity are also claimed with anils of 5-amino derivatives, such as (LXVIII) [433]. 

Theophylline, a dimethylxanthine, causes broncho-dilation, possibly by inhibiting the enzyme phosphodiesterase in smooth muscle of the bronchioli. An other proposed mechanism of action is that of adenosine receptor antagonism. It has positive chronotropic and inotropic, CNS stimulant and weak diuretic properties. In obstructive lung disease sustained release tablets are to be preferred. Theophy-line has a narrow therapeutic index. Therapeutic plasma concentrations are between 7-15 mg/1. Theophylline undergoes N-demethylation via CYPl A2 in the liver and is eliminated in the urine as metabolites... 

Theophylline. The prototypic xanthine, theophylline.h known to promote a weak diuresis by. stimulation of cardiac function and by a direct action on the nephrtrn. Although ii is infircquently used as a diuretic, diuresis may be an ub-served side effect when it is used as a bronchodilator. 

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. 

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