ANTI-THYROID MEANS (grech, anti-against + thyreoeides thyroid) — the connections of various chemical nature reducing function of a thyroid gland. On chemical constitution of Ampere-second. classify as follows:
1) drugs of iodine (inorganic and organic);
5) potassium perchlorate.
Mechanism of action of Ampere-second. it is various and depends on their chemical structure.
Drugs of iodine
Drugs of iodine exert direct impact on a thyroid epithelium, specific feature to-rogo is capture and concentration of iodine for biosynthesis of thyroid hormones — thyroxine and triiodothyronine. Already in 10 — 15 sec. after introduction to an organism iodine selectively collects in an apical part of a thyroid epithelium and in a colloid. Accumulation of iodine above norm causes decrease in synthesis of thyroid hormones. Ability of a thyroid gland to take iodine of blood, quantity organic (connected with protein) iodine in a thyroid gland is broken transition of thyroid hormones from gland in blood goes down, at a loss.
At the same time drugs of iodine suppress secretion of thyritropic hormone that in turn leads to reduction of synthesis of hormones of a thyroid gland. The drugs of iodine administered with the medical purpose cause reduction of the sizes of a thyroid gland, suppression of its function and corresponding changes in a clinical picture of a disease.
Drugs of inorganic iodine are applied in the form of «Microiodum» appointed in pills (0,0005 g of pure iodine and 0,005 g of potassium iodide), or solution of Lugol (1 part of iodine, 2 parts of potassium iodide and 17 parts of water). Microiodum is appointed courses for 20 days with 10-day breaks at the rate of 2 pills a day or on 10 drops of solution of Lugol pass 2 times. The number of courses of treatment depends on clinical effect and usually does not exceed 3 — 4.
Organic drugs of iodine — diiodotyrosine (see. Yodtirozina ) and its isomer Betazinum (see) — are applied at a diffusion toxic craw and hyper thyroid forms of a local and sporadic craw on 0,05 g in tablets 2 — 3 times a day, courses for 20 days with 10 — 20-day breaks. They are appointed for preoperative training of patients with a diffusion toxic craw and by preventions of thyrocardiac crises in the postoperative period.
Side effect: at hypersensitivity to iodine and at prolonged use of drugs of iodine the phenomena of an iodism (cold, urticaria, an itch of skin, a Quincke's disease, nausea, vomiting, a diarrhea, bronchitis, conjunctivitis) are possible. At patients with a local craw at overdose of drugs of iodine the hyperthyroidism («iodine-bazedov»), and at patients with a diffusion toxic craw — strengthening of the phenomena of a thyrotoxicosis is sometimes observed.
To contraindications and to use of drugs of iodine are: an idiosyncrasy to iodine, «iodine-bazedov».
Drugs of thiourea and its derivatives
Are offered in 1943 by E. Astwood. Most in clinic 6 methylthiouracil, propylthiouracil, and also a 1-methyl-2-mercaptoimidazole, 2-karboetoksimerkapto-1-methylimidazole were widely used. The thyreostatic effect of these drugs is explained by suppression of activity of the enzymes (cytochrome oxydase, peroxidase) participating in oxidation of iodides in atomic iodine and processes of transformation of iodtyrosines into yodtironina. At the same time the thyroid gland takes iodine, but does not use it in biosynthesis of thyroid hormones. Iodine is quickly removed from gland. In it more predecessors, than hormones are found (content of monoiodtyrosine in comparison with the content of diiodotyrosine and triiodothyronine in comparison with thyroxine increases). In most cases at use of these drugs in a thyroid gland decrease in exchange of iodine is noted. 2 days later since the beginning of use of Ampere-second. groups of thiourea at experimental animals in a thyroid gland are marked out histologic changes: the colloid disappears, cells of an epithelium increase, vascularization of gland amplifies. In 2 weeks increase in gland is observed. Exhaustion of hormonal reserves of gland, decrease in content of hormonal iodine in blood serum, and then and in fabrics leads to increase in secretion of thyritropic hormone (the principle of a feed-back). In an adenohypophysis at the same time there are «cells of a thyroidectomy» containing glycoproteins and which are degranulated under the influence of drugs of thiourea. Simultaneous use together with drugs of thiourea of hormones of a thyroid gland (thyroxine and triiodothyronine) prevents emergence of these cells and an enlargement of the thyroid gland. Accurate dosing of Ampere-second. in clinic prevents these changes.
Ampere-second. like thiourea pass through a placenta, and also in milk of mother. They are easily soaked up in intestines and quickly come to fabrics. During the day 40% of the received dose of Ampere-second. this group are removed with urine. After cancellation of drugs function of a thyroid gland is quickly recovered.
Activity of various Ampere-second. on thyreostatic action it is various (tab.).
Drugs of thiourea and mercaptoimidazole are shown for treatment of patients with a diffusion toxic craw, for preoperative training of such patients, and also for the purpose of specification of the diagnosis of a diffusion toxic craw (therapy of ex juvantibus).
In clinic mercazolil (see), Methothyrinum and methylthiouracil (see), abroad — propylthiouracil are applied.
Treatment of a diffusion toxic craw is carried out by drugs of thiourea and drugs of a mercaptoimidazole, applying shock doses. For mercazolil the shock (initial) dose is in limits of 50 — 80 mg. The dose of drugs decreases gradually, according to clinical effect. Criteria of a dose decline of drugs of thiourea are pulse rate and weight of the patient. In the absence of sufficient effect the dose of drug shall be increased by the short period again. After achievement of a condition of remission pass to maintenance doses. If the condition of remission remains at these doses within 4 months, drugs are cancelled. Permanent remission terminates in considerable reduction of the sizes of a thyroid gland [V. R. Klyachko, D. D. Solomon et al.]. Reduction of a thyroid gland to the normal sizes is the main indicator for the termination of treatment by maintenance doses on. background of remission. The average duration of treatment of a diffusion toxic craw drugs of thiourea and a mercaptoimidazole makes 12 — 18 months [Oberdisse, Klein (K. Oberdisse, E. Klein)]. The long-term favorable effect of therapy remains at 60 — 80% of patients.
Complications and side effects. At treatment of Ampere-second. this group toksiko-allergic reactions, goitrogenic effect and a medicamentous hypothyroidism can appear. Toksiko-allergichesky reactions are shown by a leukopenia and a granulocytopenia and sometimes lead to an agranulocytosis. Constant control behind a condition of white blood at treatment is necessary these drugs. Except changes from white blood, fever, skin reactions, sometimes nausea can be noted.
The goitrogenic effect is connected with increase in thyritropic activity of a hypophysis. The medicamentous hypothyroidism has, as a rule, tranzitorny character and is a consequence of overdose.
In case of toksiko-allergic reactions (change of white blood) purpose of antihistaminic drugs (Dimedrol, Pipolphenum), the means stimulating a hemopoiesis (pentoxyl, leucogenum, methacil, nukleinovokisly sodium, etc.), glucocorticoid hormones is recommended.
At repeated decrease in number of leukocytes, including granulocytes, it is necessary to cancel drugs. For elimination of goitrogenic effect sometimes it is enough to replace one drug with another or to appoint thyroid hormones.
A contraindication to use of Ampere-second. this group diseases of white blood, a retrosternal craw, the craw of the big sizes causing a prelum of a gullet and respiratory tracts, pregnancy are.
Drugs of group of derivatives of aniline did not find application in clinic because of their small efficiency and considerable toxicity.
Thiocyanates also in clinic do not apply because of their toxicity.
Potassium perchlorate suppresses selective capture of iodine a thyroid gland and by that reduces process of a gormonoobrazovaniye. In clinic it is applied seldom that is connected with its small efficiency and side effects (see. Potassium perchlorate ). Indications to use the same, as for drugs of thiourea.
Table. Relative activity of separate anti-thyroid means
Bibliography: Astvud E. B. and Solomon X. Mechanisms of effect of anti-thyroid substances, iodides and other inhibitors of a thyroid gland, in book: A thyroid gland, under the editorship of S. Verner, the lane with English, page 31, L., 1963, bibliogr.; Voytkevich A. A. Anti-thyroid effect of streptocides and tioureat, M., 1957; The Multivolume guide to internal diseases, under the editorship of E. M. Ta-reeva, t. 7, page 62, L., 1966; The Drugs used in endocrinology under the editorship of H. T. Starkova, page 5, etc., M., 1969, bibliogr.; Turakulov Ya. X. The biochemistry of hormones of a thyroid gland is normal also at thyroid pathology, page 66, Tashkent, 1962, bibliogr.; Astwood E. Century of Chemical nature of compounds which inhibit function of thyroid gland, J. Pharmacol, exp. Ther., v. 78, p. 79, 1943; it, Mechanisms of action of various antithyroid compounds, Ann. N. Y. Acad. · Sci., v. 50, p. 419, 1949. bibliogr.; Crooks J. Wayne E. J. A comparison of potassium perchlorate, methylthiouracil and carbimazole in the treatment of thyrotoxicosis, Lancet, v. 1, p. 401, 1960, bibliogr.; pberdisse K. u. Klein K. Die Krankheiten der Schilddrüse, Stuttgart, 1967; Solomon D. H. a. o. Prognosis of hyperthyroidism treated by antithyroid drugs, J. Amer. med. Ass., v. 152, p. 201, 1953.
P. K. Islambekov.