Abstract

The use of theophylline and its derivatives is becoming more general as the application of these drugs to disease states is more clearly understood. Their importance in the therapeutic armamentarium is such that we have felt it advisable to attempt a general review of the literature and to discuss the conditions in which the xanthines may have definite value in the relief of distressing symptoms. For the benefit of those less familiar with their uses, the concluding portion of this presentation will attempt to show the effect of aminophyllin, one of the derivatives of theophylline, on the electrocardiogram.The available combinations of theophylline are loose chemical mixtures which break down in the stomach to release free purine and the substance that has been used to increase solubility. Those most commonly used are theophylline ethylene diamine or aminophyllin, theophylline with sodium acetate, theophylline with calcium acetate, theophylline monoethanolamine and theophylline with methyl glucamine.The degree of solubility of these derivatives determines the mode of administration and the rapidity of action, while the clinical effectiveness of the combinations depends to a great extent upon the amount of theophylline present. Theophylline itself is insoluble. Theophylline sodium acetate, containing 60 per cent of theophylline, is soluble one part in twenty parts of water and theophylline ethylene diamine, containing 78 to 83 per cent of theophylline, will dissolve in water to 40 per cent. It is the greater solubility of the last named derivative that increases the extent of its clinical use and renders it suitable for multiple modes of administration.Theophylline and all of its derivatives may be administered orally in capsules or tablets. Theophylline ethylene diamine may be administered by rectum in a suppository and also by the intramuscular or intravenous routes. The dosage of the drugs varies slightly, but all should be given in sufficient quantity to produce physiologic effects. Gastric irritation frequently occurs in patients unduly sensitive to the drugs, or in those in whom larger doses have been used. The gastric symptoms most commonly expressed are distention, nausea and vomiting, and a burning epigastric or substernal pain. They may be avoided by frequently changing the derivative used or by using the drugs intensively for short periods of time, discontinuing with the onset of gastric irritability and resuming after a brief interval of rest.These drugs in larger doses or in sensitive individuals often produce other symptoms disturbing to the patients. The most important among these, according to Gilbert and Kerr,1 are a throbbing type of headache, a sensation of fulness in the head, vertigo or lightheadedness, nervousness of a subjective type and cardiac palpitation with precordial pain or a sensation of oppression. The rapid intravenous administration of aminophyllin may be followed by the above symptoms in an exaggerated and distressing form. Mild syncopal attacks may appear in some sensitive patients or in those who are highly neurotic. These symptoms may be avoided by slow administration of the drug extending over a period of three to five minutes.Theophylline and its derivatives may be used as: (1) diuretics, in the relief of the edema of congestive heart failure; (2) respiratory stimulants, in the abnormalities of respiration associated with congestive heart failure and in bronchial asthma; (3) vasodilators, in coronary artery disease associated with arteriosclerotic and hypertensive heart disease; and (4) myocardial stimulants, through their action on the coronary arteries with the resultant improvement of coronary circulation and myocardial nutrition.