antithyroid drugs 2018.pptx.................

Antithyroid drugs

1. ANTITHYROID DRUGS

2. 2 Thyroid Gland Thyroid follicles are the structural & functional units of the thyroid gland . Each follicle is surround mainly by simple cuboidal epithelium and is filled with a colloid which mainly composed by thyroglobulin . Thyroid hormones are mainly synthesized in colloid while the simple cuboidal epithelium responsible for iodide intake & thyroid hormones release .

3. Synthesis & Release of thyroid hormone

4. Iodide trapping: Active transport of iodide ions into follicular cells of thyroid gland is known as iodide trapping.( Na,I symporter) (block by perchlorate & thiocynate ) B. Oxidation & Iodination: (iodine organification ) The iodide ion is oxidized to iodine by peroxidase enzyme. Iodine combines with the tyrosine residue of thyroglobulin molecule and forms mono & diiodotyrosine (MIT & DIT). The peroxidase enzyme is transiently blocked by high levels of iodide in the follicular cells and persistently blocked by thioamide drugs.

5. C. Coupling: Final step in the synthesis of thyroid hormone. MIT + DIT T3 (triiodothyronine) DIT + DIT T4 (thyroxine) D. Hormone Release: Release is under the control of TSH. The process involves the exocytosis and proteolysis of iodinated thyroglobulin and result in release of T4, T3, MIT and DIT. Thyroxine-binding globulin (TBG) binds thyroid hormone in circulation. The process of proteolysis is inhibited by high levels of iodide.

6. 6 Biosynthesis of thyroid hormones ,also showing various sites of anithyroid drug actions

7. 7 Thyroid Hormone Production and Metabolism per day

8. 8 ● Regulation of thyroid function TRH: thyrotropin-releasing hormone TSH: thyroid-stimulating hormone deiodinases

9. 9 Some of T4 are converted to T3 in kidney and liver T he actions of T3 on several organ systems are shown BMR : b asal metabolic rate; CNS : central nervous system Mechanism of action s of thyroid hormones T3 , via its nuclear receptor, induces new proteins generation which produce effects

10. 10 Physiological actions of thyroid hormones T o normalize growth and development , body temperature , and energy levels ▲ Insufficiency → cretinism (infant & child), and myxedema (adult); ▲ Excess → hyperthyroid To enhance CNS excitability & sensitivity of CVS to NA ＃ T3 is 3 to 4 times more potent than T4 in heat production; ＃ T4 in colloid is about 4 times more numerous than T3 ;

11. 12 cretinism myxedema hyperthyroid

12. CLASSIFICATION OF ANTI-THYROID DRUGS Thyroid hormone synthesis inhibitors ( thioamide derivitives ): Propylthiouracil Methimazole carbimazole Inhibitors of Iodide trapping (anion inhibitors ): Thiocynates perchlorates Hormone release inhibitors: Lugols Iodine iodides of Na and K D. Thyroid tissue- destroying agent: Radio active iodine E. Others : Propranolol atenolol diltiazem corticosteroids

13. A . Thioamides derivatives

14. Mechanism of action Inhibit thyroid peroxidase enzyme, which converts iodide to iodine. Inhibit iodination of tyrosine residue in thyroglobulin. Inhibit coupling of iodotyrosines (MIT & DIT) Propylthiouracil also inhibit the peripheral conversion of T4 to T3

15. PHARMACOKINETICS Well absorbed orally Get accumulated in thyroid Excreted in urine Propylthiouracil has short half life (6-8 h) Carbimazole i s converted to methamizole after absorption

16. USES For long term treatment of thyrotoxicosis For treatment of thyrotoxic crisis along with iodide and propranolol

17. Adverse effects Skin rashes Fever Joint pain Hepatitis Nephritis agranulocytosis

18. IODIDES High concentration of iodide appears to inhibit almost all steps in the synthesis of thyroid hormone and its release and also inhibit the organification of iodine.

19. Preparations and uses Lugols iodine (5% iodine in 10% KI): Ipodate sodium : (Used prior to surgery and in thyroid strom , make gland less vascular and decrease size)

20. Radioactive iodine Therapeutically used RA is I-131. It gets concentrated in the same way as stable iodine and emits gamma rays and beta particles. The beta particles cause destruction of follicular cells leading to fibrosis and correction of hyperthyroid state. Preparations: As solutions and capsule. Advantages: Treatment is simple and convenient. Inexpensive No risk of surgery and scar. Permanently cure hyperthyroidism.

21. Beta Blockers Improve thyrotoxicosis effects Also inhibit peripheral conversion of T4 to T3