Diuretin

DIURETIN, Diuretinum (VII), a mixture of theobromine sodium and sodium salicylate in the form of a double compound - Theobrominna-trium cum Natrio salicylico, C₇H₇NaN₄O₂ + C₇H₆O₃(OH)(COONa), commonly called Theobrominum natrio-salicylicum; the drug was introduced for sale in 1890 by the firm Knoll under the trade name Diuretinum. A white, amorphous powder, with a saline-alkaline taste, odorless, very soluble in water; the aqueous solution reacts strongly alkaline; the addition of hydrochloric acid or carbon dioxide to the solution precipitates theobromine and salicylic acid. A solution of D. (1:5), acidified with acetic acid, turns violet with a few drops of iron chloride solution - a reaction for salicylic acid. D. contains about 45% theobromine, and its therapeutic application as a diuretic is due to the effect of this substance on the body. The pharmacological action of D. is characterized by (compared to caffeine, theobromine, and theophylline) very slight general excitation of the central nervous system. The acceleration of the heartbeat from D. occurs due to the direct irritant effect on the nerve apparatus of the heart (on the accelerantes) or, according to other authors, due to the direct influence on the muscular excitomotor apparatus of the heart. In humans, the acceleration of the pulse from D. is usually not marked (Hoffmann). The strength of heart contractions increases with small doses and with slight cardiac strain. The blood flow accelerates, while blood pressure decreases due to vasodilation from the effect of D. on the peripheral nerve apparatus of the vessels. Sometimes blood pressure remains at the previous level or even increases slightly if, due to the increased and strengthened heartbeat, the amount of blood in the arterial system becomes larger. The size of the dose plays a very significant role in this case. In severe poisonings, cardiac activity falls. D. has no effect on respiration. Urination is significantly increased by D. The mechanism of the diuretic action of diuretin is explained by the fact that this substance belongs to purine derivatives (the theory of urination under the influence of diuretin - see Caffeine). D. sometimes causes the temporary appearance of sugar in the urine (mostly in very small amounts), which was first pointed out by Jacoby, and Rose established that glycosuria is usually accompanied by hyperglycemia, reaching in some cases 0.33% sugar in the blood, and appears to be a hepatogenic phenomenon, while Pollak associates glycosuria with the glycogen content in the organs, and hyperglycemia with irritation of the corresponding brain center. Blood viscosity increases, the number of lymphocytes increases. The contractile ability of muscles is enhanced by D. if the dose used is small (Schmiedeberg); larger amounts of the substance cause prolonged convulsions or rigidity (Schmiedeberg, Jacoby and Golovinsky), and muscle rigidity from D. occurs with smaller doses than with caffeine; however, the cardiac muscle in this case has greater endurance than skeletal muscles. The rigidity reaction is more clearly obtained in Rana temporaria and weaker in Rana esculenta, which Jacoby and Golovinsky associate with the difference in the composition of the muscle sarcolemma in these frog species. The muscle contraction curve under the influence of D. is very similar in character to the curve from caffeine (see) and shows an increase in the maximum work and absolute strength of the muscles, but these phenomena with D. are expressed less than with caffeine; and since muscle fatigue occurs more easily with D., the total amount of work performed by the muscle under the influence of D. may be lower than normal. Metabolism and body temperature under the influence of D. do not change noticeably. According to Rost, the excretion of D. given orally in dogs occurs through the kidneys with breakdown into theobromine and probably into further products of its decomposition (methylxanthine), and the amount of theobromine in the urine varies in different animals. Thus, Rost determined in a dog that received 2.0 D. orally, within 43 hours of the experiment, 25% theobromine, in another within 50 hours - 10.5%; in a rabbit within a day 4-7.8% theobromine if 1.0 D. was given, and 12.5-17% if the rabbit received 2.0 D. per dose; in a person who took 3.0 D., the amount of theobromine excreted was 18-20%. The therapeutic use of diuretin is indicated as a diuretic and vasodilator in heart diseases accompanied by edema; in chronic and acute kidney and liver diseases; in arteriosclerosis; in angina pectoris; and in various other conditions arising from vascular constriction, e.g., in headaches, intermittent claudication; in pleurisy and pericarditis; in the latter, D. is usually combined with digitalis. Side effects from D. are very rarely observed and manifest as congestive catarrhal phenomena in the stomach area, nausea, vomiting, and headaches; some authors note damage to the kidneys from the salicylic acid released from D., but this question is controversial. - D. is taken orally in the form of tablets (0.5) or in mixtures. Prescribing D. in powders is irrational due to its easy decomposition in the presence of CO₂ in the air. For the same reason, acids, acid salts, acidic vegetable juices (fruit syrups, licorice juice, etc.), as well as ammonia alkalis cannot be added to D. solutions. Maximum doses of diuretin (VII): 1.0 per dose, 6.0 per day. The lethal dose of diuretin for animals is determined differently: from 0.7 to 1.25 per 1 kg of body weight. Literature.-Hoffman A., Über die therapeutische Anwendung des Diuretin, Archiv f. exp. Pathol. u. Pharmakol., B. XXVIII, 1890-91; Jacoby C., Über künstlichen Nierendiabetes, ibid., B. XXXV, 1895; Jacoby C. u. Golovinsky, Ein Beitrag zur Frage der verschiedenen Wirkung des Coffeins auf Rana esculenta u. Rana temporaria, ibid., B. LVI, 1908; Pollak L., Kritisches u. Experimentelles zur Klassifikation der Glykosurien, ibid., B. LXI, 1909; Rose U., Der Blutzuckergehalt des Kaninchens, seine Erhöhung durch den Aderlass, durch die Eröffnung der Bauchhöhle u. durch die Nierenausschaltung u. sein Verhalten im Diuretin-Diabetes, ibid., B. L, 1903. V. Nikolaev.