SPIRONOLACTONUM (Spironolactonum; synonym: veroshpiron, Aldactonum etc.) — diuretic medicine from group of antagonists of Aldosteronum. Page it is synthesized by Kagawa (S. M. Kagawa) in 1959 after studying biol. activities of a series of compounds of the steroid nature (see. Steroids ), having at C 17 - atom an iropionkislotny γ-lactonic ring — so-called Spirolactonums (see. Lactones ). These connections showed properties of antagonists of Aldosteronum (see). S.'s advantage before other Spirolactonums is good absorbability from went. - kish. path and high biological activity. Thanks to these qualities Spironolactonum was implemented in medical practice in quality diuretic (see).
On a chemical structure of S. is a gamma lactone 3-(3-оксо-7-α-тиоацетил-17β-окси-4-андростен-17α-ил) - propionic to - you:
S.'s action is explained by its ability to compete with Aldosteronum and other steroids having mineralokortikoidny effect (see. Mineralokortikoidny hormones ),— cortexone (see), corticosterone (see), hydrocortisone (see), for receptors in target cells, without allowing those mineralokortikoidny hormones to have a promoting effect on transmembrane transfer of ions of Na + (see. Transport of ions ). In kidneys (see) S. blocks action of Aldosteronum in distal departments of nephron. Under the influence of S. the reabsorption of sodium decreases, than increase in allocation of ions of Na + and Cl-and reduction of allocation of ions of K+ speaks and urea (see). Thus, the diuretic effect of S. is connected with its natriuretic effect therefore at S.'s use the maintenance of ions of Na + in a blood plasma decreases, and the maintenance of ions of K+ increases.
Independent action on water salt metabolism (see) S. does not render. In an experiment on adrenalectomized rats for lack of mineralokortikoid of effect of S. did not observe. Diuretic action of S. is most expressed at hyper aldosteronism (see). Under the influence of S. there is also an increase in a ratio of Na+/K + in saliva, sweat, Calais. Reduction of intracellular maintenance of ions of Na + in vessels and the vasodepression connected with it is one of mechanisms of hypotensive action of S. V S.'s organism is metabolized with education 17 ketosteroids (see), to-rye are excreted with urine.
The clinic applies veroshpiron (Verospiron), coming to the USSR from VNR. As indications for S.'s use serve primary giperal-dosteronizm, and also the states which are followed by a secondary hyper aldosteronism such as steady physical stress, cirrhosis with ascites, a nephrotic syndrome, cardiovascular insufficiency in a stage of a decompensation, a hypertension, idiopathic hypostases, etc. S.'s use at primary hyper aldosteronism contributes to normalization of electrolytic balance, decrease in the ABP. With normo-and S.'s hypotonia of decrease in the ABP does not cause in patients. S.'s use in a combination with saluretics, hypothiazid, etc. strengthens their diuretic action, and also prevents development of a hypopotassemia and refrakternost to these drugs that is caused by distinctions in mechanisms of action of S. and these means.
The daily dose of S. can fluctuate from 0,075 to 0,3 g. The usual therapeutic dose makes 0,1 — 0,2 and (in 2 — 4 receptions), at approach of necessary effect it can be lowered to 0,075 — 0,025 g of drug a day. The maximum action of S. is usually shown in 2 — 3 days after the beginning of reception (sometimes in 5 days) and remains within 2 — 3 days after drug withdrawal.
By-effects, arising at overdose or long use of S., are a consequence of a hyperpotassemia and hyponatremia and are expressed by emergence of dizziness, the general weakness, drowsiness, nausea, skin rash.
Drug it is contraindicated at an acute renal failure, hron. nephrite, azotemia.
Form of release: tablets on 0,025 g (25 mg) of Spironolactonum in the microionized form. Storage in the dry place protected from light.
Bibliography: Komissarenko V. P. and Reznikov A. G. Inhibitors of function of epinephral glands, Kiev, 1972; G 1 ci z E. and. V e with s e i P. Aldosterone, Budapest, 1971; Kagawa C. M., Sturtevant F. M of a. Van Arman of Page G. Pharmacology of a new steroid that blocks salt activity of aldosterone and desoxycorticosterone, J. Pharmacol., exp. Ther., v. 126, p. 123, 1959.
V. S. Zelenetskaya.