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![Dr Umesh Kumar Maurya 21
NIS inhibitors
• Block uptake of iodide
• Highly toxic effects
• Cabbage is a rich source of Thiocyanate [Goitrogen]
20/05/2025](https://image.slidesharecdn.com/thyroid-1-250521125521-f742a130/85/thyroid-hormones-and-thyroid-inhibitors-21-320.jpg)
thyroid hormones and thyroid inhibitors
- 1. Dr Umesh KumarMaurya 1 Thyroid Hormones and Thyroid Inhibitors Presenter: Dr Umesh Kumar Maurya (JR-1) Moderator: Dr Ashish Dixit (SR) Peer support: Dr Naveen Maurya (JR-1) Department of Pharmacology and Therapeutics King George Medical University Lucknow (UP), India Email id - drumeshkgmu@gmail.com 20/05/2025
- 2. Dr Umesh KumarMaurya 2 Contents • Introduction • Thyroid hormones and their biosynthesis • Classification of thyroid inhibitors • Therapeutic uses of antithyroid drugs • Summary 20/05/2025
- 3. Dr Umesh KumarMaurya 3 Specific learning objectives By end of this teaching learning session co-learners will be able to: • Describe the synthesis of thyroid hormones • Explain clinical features of hypothyroidism and hyperthyroidism • Explain the classification of thyroid inhibitors • Enumerate uses of antithyroid drugs 20/05/2025
- 4. Dr Umesh KumarMaurya 4 Introduction • Thyroid gland is an endocrine gland • Located at the front of the neck, below the Adam's apple • Consists of two connected lobes • Lower two third of the lobes are connected by a thin band of tissue called the thyroid isthmus 20/05/2025
- 5. Dr Umesh KumarMaurya 5 Thyroid hormones Thyroid gland secretes 3 hormones 1. T4 - 3,5,3’,5’ tetra-iodothyronine or thyroxine 2. T3 - 3,5,3’ tri-iodothyronine 3. Calcitonin is produced by interfollicular ‘C’ cells Both T4 and T3 are iodine containing derivatives of thyronine which is a condensation product of 2 molecules of tyrosine produced by thyroid follicles 20/05/2025
- 6. Dr Umesh KumarMaurya 6 Biosynthesis Synthesis, storage and release of T4 and T3 involves the following processes: 1. Iodide uptake 2. Oxidation, Organification and Coupling 3. Storage and release 4. Peripheral conversion of T4 to T3 20/05/2025
- 7. Dr Umesh KumarMaurya 7 1. Iodide uptake • Thyroid cells have an active transport process • Na⁺- iodide symporter (NIS) 20/05/2025
- 8. Dr Umesh KumarMaurya 8 2. Oxidation and Organification • Iodide trapped by follicular cells is carried across the apical membrane by another transporter termed ‘pendrin’ and oxidized by the membrane-bound thyroid peroxidase enzyme to: • Iodonium ions (I+ ) or • Hypoiodous acid (HOI) or • Enzyme-linked hypoiodate (E-OI) via H₂O₂ Monoiodotyrosine (MIT) and Diiodotyrosine (DIT) combine with tyrosil residues of thyroglobulin 20/05/2025
- 9. Dr Umesh KumarMaurya 9 3. Coupling • Pair of iodinated tyrosil residues couple together to form T3 and T4 • Normally more T₄ is formed than T₃ • Oxidation of iodide and coupling are both stimulated by TSH 20/05/2025
- 10. Dr Umesh KumarMaurya 10 4. Storage and Release • MIT, DIT, T₃ and T₄ – all attached to thyroglobulin and stored in the colloid • Taken up by follicular cells by the process of endocytosis and broken down by lysosomal proteases • T₃ and T₄ so released is secreted into circulation • MIT and DIT residues are deiodinated and iodide released is reutilized • Normal human thyroid secretes 60–90 μg of T₄ and 10–30 μg of T₃ daily 20/05/2025
- 11. Dr Umesh KumarMaurya 11 5. Peripheral Conversion of T₄ to T₃ • Peripheral tissues (liver and kidney) convert T₄ to T₃ • T4 to T3 conversion is carried out by iodothyronine deiodinase • Target tissues take up T₃ from circulation for their metabolic need • Equal amounts of T₃ (3,5,3’ triiodothyronine, normal T3:active) and rT₃ (3,3’,5’ triiodothyronine, reverse T3: inactive)are produced in the peripheral tissues 20/05/2025
- 12. Dr Umesh KumarMaurya 12 • Types of iodothyronine deiodinase • Propylthiouracil inhibits D1 • Amiodarone inhibits both D1 and D2 Type 1 deiodinase (D1) Generates both T3 & rT3 Type 2 deiodinase (D2) Generates T3 Type 3 deiodinase(D3) Generates rT3 20/05/2025
- 13. Dr Umesh KumarMaurya 13 Synthesis, storage and secretion of thyroid hormones 20/05/2025
- 14. Dr Umesh KumarMaurya 14 Transport, metabolism and excretion • Only 0.03-0.08% of T₄ and 0.2-0.5% of T₃ are in free form • Main plasma proteins are – TBG (Thyroxine Binding Globulin), TBP (Thyroxine Binding Prealbumin) and Albumin • Metabolism: mainly in liver and kidneys by deiodination and conjugation • Conjugated products excreted by bile – enterohepatic circulation into urine • Plasma t½ of T₄ is 6-7 days, while that of T₃ is 1-2 days 20/05/2025
- 15. Dr Umesh KumarMaurya 15 Regulation of secretion 20/05/2025
- 16. Dr Umesh KumarMaurya 16 Actions of thyroid hormones Growth and Development Normal growth and Brain development Metabolism: • Lipid Induce lipolysis, ↑ free plasma FA • Carbohydrate glycogenolysis and gluconeogenesis • Protein Prolonged action – negative nitrogen balance & tissue wasting Nervous system Anxious, nervous, tremors and hyperreflexia Calorigenic effects Increase BMR & body temperature GIT Propulsive activity of gut Skeletal muscle Muscles are flabby and weak 20/05/2025
- 17. Dr Umesh KumarMaurya 17 Uses of thyroid hormone • Cretinism •Myxedema •Myxedema coma • Empirical uses: Refractory anemia Mental depression Menses disorders Chronic/non-healing ulcers Constipation 20/05/2025
- 18. Dr Umesh KumarMaurya 18 Clinical symptoms of hypothyroidism and hyperthyroidism Hypothyroidism Hyperthyroidism Hair loss, puffiness Hair loss, bulging eyes Goitre (enlarged thyroid) Goitre (enlarged thyroid) Reduced heart rate Heart palpitations Sensitivity to cold Heat intolerance, sweating Weight gain Weight loss Memory problems, depression, mood swings Anxiety, nervousness, depression, mood swings Constipation Diarrhoea 20/05/2025
- 19. Dr Umesh KumarMaurya 19 Classification of Thyroid inhibitors Classes of drugs Examples NIS inhibitors Thiocyanates (-SCN), Perchlorates (-ClO4), Nitrates (-N03) Thyroid peroxidase inhibitors Propylthiouracil (PTU), Methimazole, Carbimazole Secretion inhibitors NaI, KI, Lugol’s iodine Peripheral conversion inhibitors Propranolol, PTU, Prednisolone Thyroid destroying drug Radioactive iodine (¹³¹I) Adjuvant drug Propranolol 20/05/2025
- 20. Dr Umesh KumarMaurya 20 MOA of Antithyroid Drug 20/05/2025
- 21. Dr Umesh KumarMaurya 21 NIS inhibitors • Block uptake of iodide • Highly toxic effects • Cabbage is a rich source of Thiocyanate [Goitrogen] 20/05/2025
- 22. Dr Umesh KumarMaurya 22 Thyroid peroxidase inhibitors / Antithyroid drugs • Antithyroid drugs bind to the thyroid peroxidase and prevent oxidation of iodide/iodotyrosyl residues, thereby: (i) Inhibit iodination of tyrosine residues in thyroglobulin (ii) Inhibit coupling of iodotyrosine residues to form T3 and T4 • Propylthiouracil also inhibits peripheral conversion of T4 to T3 by D1 type of 5’ deiodinase 20/05/2025
- 23. Dr Umesh KumarMaurya 23 Differences between Propylthiouracil and Carbimazole Propylthiouracil (PTU) Carbimazole No active metabolites Active metabolite - methimazole Less potent 5 times more potent Less plasma t½ More plasma t½ Lesser transferred across placenta (DOC in 1st trimester of pregnancy) Transfer through placenta easily Decrease peripheral conversion No action on peripheral conversion Single dose acts for 4-8 hrs 12-24 hrs 20/05/2025
- 24. Dr Umesh KumarMaurya 24 Uses of antithyroid drugs • PTU is DOC in first trimester of pregnancy • Carbimazole/methimazole is used in second and third trimester • Long term treatment of thyrotoxicosis • Thyrotoxic crisis: Propylthiouracil is used along with iodide and propranolol 20/05/2025
- 25. Dr Umesh KumarMaurya 25 Secretion inhibitors • Fastest acting antithyroid drugs • Excess iodide inhibits its own transport into thyroid cells by inhibiting NIS and also inhibits iodination of tyrosine residues • Attenuates TSH stimulation 20/05/2025
- 26. Dr Umesh KumarMaurya 26 Uses • Preoperative preparation before thyroidectomy and thyroid storm • Prophylaxis of endemic goiter Adverse effects • Acute reaction: swelling of lips, eyelids, angioedema of larynx, fever joint pain, petechial hemorrhages, thrombocytopenia, lymphadenopathy • Chronic overdose (iodism): Inflammation of mucous membranes, salivation, blurring sensation in mouth, headache, rashes, GI symptoms etc. 20/05/2025
- 27. Dr Umesh KumarMaurya 27 Radioactive iodine • 131 I physical half life: 8 days • Emits s (penetrate only 0.5-2mm of tissues) • Radioactive iodine is administered as sodium salt of 131 I dissolved in water and taken orally • Slow acting, cause local soreness in neck • Incidence of hypothyroidism high 20/05/2025
- 28. Dr Umesh KumarMaurya 28 Advantages 1. Treatment with 131 I is simple, conventionally given on outpatient basis and inexpensive 2. No surgical risk, scar or injury to parathyroid glands & recurrent nerves 3. Once hyperthyroidism is controlled, cure is permanent Disadvantages 1. Hypothyroidism 2. Long latent period of response 3. Contraindicated during pregnancy 20/05/2025
- 29. Dr Umesh KumarMaurya 29 Thyrotoxic crisis (thyroid storm) Characterized by- • Hyperpyrexia • Cardiac arrythmias • Nausea, vomiting and diarrhea • Mental confusion • Precipitated by infection, trauma, surgery, DKA, myocardial infarction 20/05/2025
- 30. Dr Umesh KumarMaurya 30 Treatment • Hospitalization • Propranolol 1-2 mg slow I.V. followed by 40 -80 mg oral 6 hourly • Propylthiouracil 200-300 oral 6 hourly • Oral iodides to inhibit the release of thyroid hormones- sodium ipodate inhibits peripheral conversion of T4 to T3 • Hydrocortisone 100mg I.V. 8 hourly followed by oral prednisolone 20/05/2025
- 31. Dr Umesh KumarMaurya 31 Summary • Thyroid gland secretes 3 hormones T3, T4 and calcitonin • Biosynthesis includes Iodide uptake or trapping, oxidation, organification, coupling, storage, release and peripheral conversion of T4 to T3 • NIS inhibitors, Thyroid peroxidase inhibitors, Secretion inhibitors, Peripheral conversion inhibitors, Radioactive iodine 131 I are thyroid inhibitors • They are used to treat hyperthyroidism and prepare patients for thyroid surgery • Radioactive iodine (¹³¹I) treats hyperthyroidism by selectively destroying overactive thyroid tissue through localized beta radiation 20/05/2025
- 32. Dr Umesh KumarMaurya 32 References • Tripathi KD. Drugs for Cough and Bronchial Asthma. In: Essentials of Medical Pharmacology. 9th ed. New Delhi: Jaypee Brothers Medical Publishers; 2019 • Ritter, J. M., Flower, R. J., Henderson, G., Loke, Y. K., MacEwan, D., Robinson, E., & Fullerton, J. (2023). Rang & Dale’s Pharmacology E-Book: Rang & Dale’s Pharmacology E- Book. Elsevier Health Sciences • Goodman, L., Gilman, A., Brunton, L., Lazo, J. and Parker, K. Goodman & Gilman's the pharmacological basis of therapeutics, New York: McGraw-Hill. 2006 20/05/2025
- 33. Dr Umesh KumarMaurya 33 Specific learning objectives achieved By end of this teaching learning session co-learners are now able to: • Describe the synthesis of thyroid hormone • Explain clinical features of hypothyroidism and hyperthyroidism • Explain the classification of thyroid inhibitors • Enumerate uses of antithyroid drugs 20/05/2025
- 34. Dr Umesh KumarMaurya 34 Thank you 20/05/2025
- 35. Dr Umesh KumarMaurya 35 Questions 1. What are the steps of biosynthesis of thyroid hormones? 2. What are the clinical features of hypothyroidism? 3. What are the clinical features of hyperthyroidism? 4. Describe the classification of thyroid inhibitors 5. Differences between propylthiouracil and carbimazole 20/05/2025