ANTI-THYROID DRUG.pptx

Hello there!
This is Jayhind Bharti from M-Pharmacy 1st year pharmacology,
the above uploaded ppt is on the topic anti-thyroid drug from "advance pharmacology - 2" of m pharm 2nd semister
initially i have discussed about the basics of thyroid gland, its synthesis procedure, what are its pharmacological action and all
further our main topic starts in which i have listed the class of drug which are used to treat hyper- thyroidism with their examples and have explained the moa of each class wit their possible adverse effect, side effect, advantages and disadvantages
lastly i have added some recent advancements in the field of anti- thyroid drug

1. ANTI-THYROID DRUG Jayhind l Bharti M pharmacy(pharmacology) Sem 2

2. CONTENT 1) BASIC INTRODUCTION 2) ANTI-THYROID DRUGS + RECENT ADVANCEMENTS

3. 1) BASIC INTRODUCTION

4. THYROID GLAND The thyroid gland is an endocrine gland . The thyroid gland's location is in the front or anterior part of the neck, below Adam's apple.

5. HORMONES SECRETED? Tri- iodo -thyronine (T3) Tetra- iodo -thyronine (T4, thyroxine) Calcitonin

6. SYNTHESIS OF THYROID HORMONE  STEP 1 . Transport of iodide into the thyroid gland by sodium-iodide symporter STEP 2. Iodide is oxidized by thyroidal peroxidase to iodine STEP 3. Tyrosine in thyroglobulin is iodinated and forms MIT & DIT- iodide organification ( MIT- monoiodotyrosine , DIT- Diiodotyrosine) STEP 4. Iodotyrosines condensation within thyroglobulin molecule MIT+DIT→T3; DIT+DIT→T4 STEP 5. T4, T3, MIT & DIT - released from thyroglobulin by exocytosis & proteolysis of thyroglobulin .

7. RELATION BETWEEN T3 AND T4 T4 & T3 ratio within thyroglobulin - 5:1 Most of the T3 circulating in the blood is derived from peripheral metabolism of thyroxine. T3 is three to four times more potent than T4 R eceptor affinity of T3 about ten times higher than T4 

8. PHARMACOLOGICAL ACTION OF THYROID HORMONE 1) Growth & Development 2) Intermediary metabolism carbohydrate metabolism protein metabolism 3) Cardiovascular system 4 ) Nervous system 5 ) Skeletal muscle 6 ) Haemopoiesis 7) On GIT

9. DISEASE OF THYROID GLAND A) Hyperthyroidism/Thyrotoxicosis Grave’s disease Thyroid Nodules

10. 2) ANTI-THYROID DRUGS + RECENT ADVANCEMENTS

11. Anti-thyroid drugs/ Thyroid inhibitors Definition: “ These are the pharmacological agents which are used to lower the functional capacity of hyperactive thyroid gland” These are the agents used in treatment of thyrotoxicosis ( It is excess secretion of thyroid hormone due to disorders; like Graves disease( auto immune disease) Toxic nodular goiter.

12. CLASSIFICATION A) Thioamide derivatives Ex:- Carbimazole , Methimazole , Propylthiouracil B) Ionic inhibitors Ex:- Thiocyanate (-SCN) , Perchlorates (-ClO4) , Nitrates (NO3) C) Iodinated contrast media Ex:- Oral ipodate , Ipanoic acid , Diatrizoate (I.V) D) Inhibitor of hormone release Ex:- Iodine , Iodides of Na, k Organic iodides E) Radioactive iodine Ex:- 131I (Radioactive iodine)

13. A) Thioamide derivatives Ex:- Methimazole (carbimazole) Propyl thiouracil (PTU) These 2 are the major drugs used in the treatment of thyrotoxicosis (Carbimazoles converted to methimazole in vivo).

14. MOA Thioamide derivatives These drug inhibit thyroid hormone production by inhibiting thyroid peroxidase which is required in intrathyroidal oxidation of Iodide. by inhibiting the iodination of tyrosine by inhibiting coupling of MIT and DIT to form thyroid hormones propylthiouracil also inhibits peripheral conversion of T4 to T3 by inhibiting DID -1 enzyme

15. Adverse drug reaction The most common adverse effect Hypothyroidism and goiter maculopapular pruritic rash Other side effects: GI intolerance, Skin rashes, joint pain. Graying or loss of hair, loss of taste, fever & liver damage. Agranulocytosis & Jaundice may occurs.

16.   Uses: 1) Control thyrotoxicosis in graves disease & toxic nodular goiter. 2) Preoperatively 3) Treatment along with I131

17.   Advantages of Antithyroid drug over surgery / I131 treatment  side effect like hypothyroidism can be reversed by stopping the treatment Can be used for children as well as young adults   Disadvantage: Prolonged (often life long) treatment is needed Not practicable in uncooperative/unintelligent patient.

18. Preparation:  Propylthiouracil (50mg-150mg ) Methimazole (5-10mg) Carbimazole (5-15mg)

19. B) Ionic inhibitors Ex:- Perchlorate, Thiocyanate  MOA:- block uptake of iodide by the gland through competitive inhibition of the iodide transport mechanism.  They inhibit organification  Hormone release Decrease  the size & vascularity of the hyperplastic gland decreases

20. Other drug Potassium iodide- B lock thyroidal reuptake of I- in patients with iodide-induced hyperthyroidism.

21. Use:  Thyrotoxic crisis – Preparation for thyroidectomy (decrease the size & vascularity of the hyperplastic gland) Prophylaxis in endemic goiter

22. Adverse effect: Acute : swelling of lip, eye lid, face, fever, joint pain, lymphadenopathy, thrombocytopenia Chronic : ulceration of mucous membrane of mouth, salivation, lacrimation, burning sensation in the mouth, rhinorrhoea, GI intolerance

23. C) Iodinated contrast media Ex:- Oral ipodate , Ipanoic acid , Diatrizoate (I.V) MOA:- These drugs rapidly inhibit the conversion of T4 to T3 in the liver, kidney, pituitary gland, & brain.

24. Uses Ipodate has proved very useful in rapidly reducing T3 concentration in thyrotoxicosis (in thyroid storm) as alternatives when iodides or thioamides are contraindicated. Their toxicity is similar to that of iodides. safety in pregnancy is undocumented.

25. D) Inhibitor of hormone release Ex:- Iodine , Iodides of Na, k Organic iodides Even if the iodine is one of the constitute of thyroid hormone but still it acts as faster acting thyroid inhibitor due to negative feedback mechanism iodide inhibit release of thyroid hormone.

26. Preparation Lugols solution: 5% iodine in 10% KI solution : 5- 10drops/day Iodide salts (sod/pot) 100-300 mg/day Within 1-2 days of starting of treatment causes inhibition of secretion of thyroid hormone while 10-14 days causes marked reduction in vascularity of gland & which decreases the size of gland.

27. MOA Actual mechanism is unknown; It inhibits own transport in to thyroid cell ( Step 1 in thyroid synthesis) by acting on NIS (Sodium Iodide symporter) It attenuates TSH & cAMP & causes thyroid inhibition. Also excess iodide rapidly interferes with tyrosine ( Iodination step2)

28. Uses: 1) Preoperative preparation : For thyroidectomy in graves disease; iodine for 10 days before surgery will given which makes gland less vascular & easier to remove by operation. 2) Thyroid storm 3) Prophylaxis of endemic goiter: It is used as "iodized salt“. Other use Antiseptic: The tincture of iodine, povidone iodine is used as antiseptic.

29. Adverse drug reaction: 1) Acute (It occurs in sensitive people). Shows symptoms like swelling of lips, eyelids, angio- edema of larynx (may be dangerous), fever, joint pain, petechial haemorrhages. 2) Chronic overdose (iodism): Inflammation of mucous membranes, salivation, rhinorrhoea, sneezing, lacrimation, burning sensation in mouth, headache, rashes. 3) Long-term use of high doses can cause hypothyroidism & goiter . 4) If high dose given to pregnant women chance to hypothyroidism & goiter in foetus.

30. E) Radioactive iodine Ex- I131, I123 I125. The stable form of isotope of iodine is I127 but medically useful isotope is I 131 But one of the advantage of radioactive iodine is it produce necrosis of cell (affected thyroid follicular cell) without damaging neighboring tissue.

31. MOA  Administered orally in solution as sodium 131I, it is rapidly absorbed, concentrated by the thyroid, & incorporated into storage follicles emits β particles & X rays β particles damage the thyroid cells thyroid tissue destroyed replaced by fibrosis

32. Advantages: Treatment with I 131 is inexpensive. No surgical risk, scar after treatment with I 131 Once hyperthyroidism is controlled, cure is permanent. Disadvantages: Hypothyroidism: About 5-10% patients of Graves' disease treated with 1311 become hypothyroid. Very slow response was observed for treatment with I131. during pregnancy drug is Contraindicated because it causes foetal thyroid destruction. I131 not suitable for young patients more likely to develop hypothyroidism & genetic damage/cancer 

33. Adjuncts to Antithyroid Therapy Hyperthyroidism resembles sympathetic overactivity Propranolol , will control tachycardia, hypertension, and atrial fibrillation Diltiazem , can control tachycardia in patients in whom beta-blockers are contraindicated Barbiturates accelerate T4 breakdown (by enzyme induction) and are also sedative

34. RECENT ADVANCMENTS NOVEL THERAPIES MECHANISM STAGE OF DEVELOPMENT Rituximab ( Anti-CD20 mAb ) B-cell depletion Phase 2 trials Iscalimab (CFZ533) ( Anti-CD40 mAb ) Blocking CD40 receptor interactions  Phase 2 trial RVT-1401 Rozanolixizumab Efgartigimod Blocking FcRn -IgG interactions Phase 2 trial Belimumab ( Anti-BAFF mAb ) Blocking BAFF interaction Phase 2 trial ANTAG-3 VA-K-14 S37a Small molecule TSHR antagonists Preclinical ATX-GD-59 ( TSHR peptide ) TSHR-specific immunotherapy Phase I trial 

35. REFERENCE https://assignmentpoint.com/structure-and-function-of-thyroid-gland/ http://basicmedicalkey.com/wp-content/uploads/2016/06/image02625.jpeg https://www.slideshare.net/JannatulFerdous2/thyroid-antithyroid-drug?from_m_app=android https://www.slideshare.net/SnehalChakorkar/thyroid-antithyroid-drug-179413572?from_m_app=android https://www.slideshare.net/asifsuraiya/thyroid-antithyroid-drugs-43059141?from_m_app=android https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567404/

36. THANK YOU