EUFILLYN (Euphyllinum; synonym: Aminocardol, Aminophyllinum, Dia-phyllin, Genophyllin, Methaphyllin, Neophyllin, Novphyllin, Synthophyl-lin, Theophyllamin, Theophylline ethylendiamine, etc.; GFH, joint venture. B) — antispasmodic. Represents mix of 80% of theophylline (1,3 dimethylxantines) from 20% of ethylene diamine; C7H8N402 + C2H8N2:
Crystal powder, white or white with a yellowish shade, with a slight smell of ammonia, water soluble; pH of aqueous solution 9,0 — 9,7.
Has the myotropic spasmolytic effect on smooth muscles stimulating influence on a myocardium and c. the N of page, and also causes diuretic effect. Pharmakol. properties E. are defined by the theophylline which is its part (see). Contained in E. ethylene diamine increases solubility of drug in water (approximately by 20 times in comparison with theophylline). AA. weakens unstriated muscles of bronchial tubes and blood vessels, eliminating spasms of bronchial tubes; reduces resistance of coronary vessels (increases a coronary blood stream); reduces pulmonary pressure and expands peripheral blood vessels. Vessels of a brain E. usually narrows, reducing a blood stream; however at spasms of brain vessels E. can expand them. AA. strengthens and speeds up reductions of heart, shortening a systole and increasing stroke and minute output. Consumption by a myocardium of oxygen considerably increases. It is possible that at action E. coronary vessels extend substantially in response to stimulation of action of the heart. AA. increases venous return of blood to heart therefore cordial emission at the height of action of E. increases. AA. exerts the stimulating impact on c. N of page, similar to effect of caffeine (see). Due to stimulation of the centers of vagus nerves E. in small doses can cause bradycardia. Diuretic effect E. it is connected generally with oppression of processes of a reabsorption (in particular, ions of Na + and C1 ~) in renal tubules. Besides, E. increases glomerular filtering due to strengthening of a renal blood-groove. AA. slows down aggregation of thrombocytes, oppresses secretion of a histamine mast cells, strengthens effect of adrenaline and a glucagon, facilitates neuromuscular transmission. AA. stimulates release of adrenaline and noradrenaline from chromaffin cells of marrow of adrenal glands and other fabrics (activates a tiro-zingidroksilaza and increases the content of dopamine in adrenal glands). At the same time excretion with urine of catecholamines and their metabolites raises. It is possible that the broncholitic effect is partially connected with effect of the adrenaline which is released from adrenal glands under the influence of E. In recent years there is a hypothesis that the mechanism of action E. and other methylxanthines it is connected with oppression of adenosine receptors. It is confirmed by the fact that an Euphyllinum on influence on c. the N of page, on heart rate, a renal blood stream, release of adrenaline and a histamine is an antagonist of adenosine. Besides, E. blocks to tsAMF-fosfodieste-time, increasing the maintenance of intracellular tsAMF, promotes release of intracellular calcium from a sarcoplasmic reticulum, weakens effect of prostaglandins. However these effects are characteristic only for E. in high doses.
E. it is well soaked up from went. - kish. a path both at appointment inside, and at rectal administration. Bioavailability E. in these cases makes apprx. 90%; max. concentration in blood is reached in 2 hours, duration of action apprx. the 6th hour. Elimination half-life E.
at adults makes 8 — 9 hours, and children have 3 — 4 hours. Being a part E. theophylline approximately for 50% contacts proteins of a blood plasma. AA. well gets through fabric barriers, in particular through a placental barrier. To 90% of an Euphyllinum it is metabolized in a liver by oxidation and N-demeti-lirovaniya under the influence of microsomal enzymes of a liver. In urine find the following main metabolites of an Euphyllinum: 1,3-dime-
tilmochevy to - that (40 — 50%), 3-me-tilksantin (15 — 30%), to-ry has the same properties, as AA., but is approximately twice less active, 1-methyl-uric to - that (10%) and small amounts 1-metilksan-ooze. E is allocated. kidneys generally in the form of metabolites and partially in the form of not changed theophylline (10%).
AA. apply to stopping and prevention of attacks of bronchial asthma, to stopping of the asthmatic status, at treatment of bronchitis, to-rye are followed by increase in a tone of bronchial tubes, and also at cardiac asthma (especially at its combination to a bronchospasm), a thromboembolism of pulmonary arteries, a heart attack slight, brain vascular crises, for reduction of intracranial pressure in case of wet brain at strokes, at treatment of a vasomotor spasm of a retina of an eye.
Appoint inside 0,15 g 2 — 3 times a day, usually since a daily dose of 0,45 g and gradually increasing it to 0,9 g. If necessary enter intravenously on 5 — 10 ml 2,4% of solution from 10 — 20 ml of 20% or 40% of solution of glucose. For drop intravenous administration of 0,24 — 0,48 g of an Euphyllinum dissolve 5% of solution of glucose in 500 ml. Sometimes E. enter intramusculary or rektalno (in microclysters on 0,3 — 0,5 g into 20 — 25 ml of warm water). Under skin E. do not enter because of its irritant action. Children up to 14 years cannot enter an Euphyllinum intravenously in connection with possible development of a vascular collapse.
The highest doses for adults inside, intramusculary and rektalno: ra
zovy — 0,5 g, daily — 1,5 g; in a vein: one-time — 0,25 g, daily — 0,5 g.
Side effect E. it can be shown by nausea and vomiting (especially at appointment inside on an empty stomach). However these phenomena can arise as well at parenteral administration E. owing to stimulation of the emetic center. Also dizzinesses, a headache, irritability, nervousness, concern, sleeplessness, a tremor, paresthesias, heartbeat, decrease in the ABP (are possible especially at intravenous administration), increase of desires to an urination, allergic reactions (urticaria, an itch, thrombocytopenia, etc.). Against the background of a ftorotanovy anesthesia E. causes cardiac arrhythmias. At intramuscular introduction E. there is a long morbidity in the place of an injection, at rectal administration — irritation of a mucous membrane of a rectum. At overdose E. there are cardiac arrhythmias (hl. obr. ventricular extrasystoles, tachycardia); at a serious poisoning muscular twitchings and epileptiform or tonic spasms are observed. The spasms caused E., often are not stopped by usual anticonvulsants. Serious poisoning E. are followed by confusion of consciousness, a delirium, fever. Death comes from paralysis of a respiratory center and cardiovascular insufficiency. In case of poisoning E. at administration of drug inside the gastric lavage is carried out to early terms since in later terms the gastric lavage can provoke convulsive reactions. At a vascular collapse enter blood-substituting liquids. Adrenaline or ephedrine in such cases do not apply in connection with danger of increase in cardiotoxicity E. In case of development of spasms intravenously enter diazepam. At poisonings E. for reduction of its concentration in blood use disintoxication hemosorption or a hemodialysis (see). Clearance E. decreases at diseases of a liver (especially at cirrhosis), heart failure, a pulmonary heart, a fluid lungs, at low contents in food of proteins and high content of carbohydrates, at co-administration with E. erythromycin, Cimetidinum, Allopyrinolum, oral contraceptives, and also at persons 60 years are more senior. However at smokers and at reception of phenobarbital and dipheninum clearance E. raises. Children of 3 — 10 years have a clearance E. above, than at adults.
Contraindications to use E. hypotension, a Bouveret's disease and premature ventricular contraction, heart failure, a myocardial infarction are.
Form of release: powder, tablets on 0,15 g; ampoules on 1 ml of 24% of solution (for intramuscular introduction) and on 10 ml of 2,4% of solution (for intravenous injections). Storage: in well corked container protecting from effect of light.
Bibliography: Mashkovsky M. D.
Pharmaceuticals, t. 1, page 457, M., 1984; The pharmacological basis of therapeutics, ed. by A. G. Gilman and. lake, N. Y., 1980; Stirt J. A. a. SullivanS. F. Aminophylline, Anesth. Analg. Curr. Res., y. 60, p. 587, 1981. V. V. Maysky.