Pharmacology 6th B Chapter ppt.pptx . .

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1. Pharmacology-I Course code PMS-614 By Dr. Junaid Athar Chapter No. 6 (B) Thyroid and Anti-thyroid drugs Institute of paramedical sciences, Khyber Medical University Peshawar 1

2. Thyroid Gland and Parathyroid gland Thyroid is an endocrine gland. It has two lobes, which are connected in the middle by an isthmus. 2

3. Hormones of thyroid gland 3 Thyroid gland secretes three hormones: 1. Tetraiodothyronine or T4 (thyroxine) 2. Tri-iodothyronine or T3 3. Calcitonin T4 is otherwise known as thyroxine and it forms about 90% of the total secretion, whereas T3 is only 9% to 10%.

4. Synthesis of thyroid hormones Synthesis of thyroid hormones takes place in thyroglobulin ( protein) Substances needed for hormone: Iodine and tyrosine are essential for the formation of thyroid hormones. Iodine is consumed through diet. It is converted into iodide and absorbed from GI tract. Tyrosine is also consumed through diet and is absorbed from the GI tract. For the synthesis of normal quantities of thyroid hormones, approximately 1 mg of iodine is required per week or about 50 mg per year. 4

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6. CONT… Synthesis of thyroid hormones occurs in five stages : 1. Thyroglobulin synthesis 2. Iodide trapping 3. Oxidation of iodide 4. Transport of iodine into follicular cavity 5. Iodination of tyrosine 6. Coupling reactions. 6

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8. Functions of thyroid hormones 8 1. Action on basal metabolic rate (BMR) Thyroxine increases the metabolic activities in most of the body tissues, except brain, retina, spleen, testes and lungs. It increases BMR by increasing the oxygen consumption of the tissues. The action that increases the BMR is called calorigenic action. In hyperthyroidism, BMR increases by about 60% to 100%. 2. Action on protein metabolism: Thyroid hormone increases the synthesis of proteins in the cells. ﴾Basal Metabolic Rate  is the number of calories required to keep body functioning at rest﴿

9. CONT… 9 3. Action on carbohydrate metabolism: Enhances the glucose uptake by the cells Increases the breakdown of glycogen into glucose Accelerates gluconeogenesis 4. Action on blood: Thyroxine accelerates erythropoietic activity and increases blood volume. 5. Action on gastrointestinal tract : Generally, thyroxine increases the appetite and food intake. It also increases the secretions and movements of GI tract. So, hypersecretion of thyroxine may cause diarrhea and the lack of thyroxine constipation.

10. Thyroid Axis The thyroid gland is influenced by hormones produced by two other organs: The pituitary gland, located at the base of the brain, produces thyroid stimulating hormone (TSH) The hypothalamus, a small part of the brain above the pituitary, produces thyrotropin releasing hormone (TRH). Low levels of thyroid hormones in the blood are detected by the hypothalamus and the pituitary. TRH is released, stimulating the pituitary to release TSH. Increased levels of TSH, in turn, stimulate the thyroid to produce more thyroid hormone, thereby returning the level of thyroid hormone in the blood back to normal. The three glands and the hormones they produce make up the "Hypothalamic - Pituitary - Thyroid axis. 10

11. Thyroid Disorders Increased secretion of thyroid hormones is called Hyperthyroidism . Too little thyroid hormone production is known as Hypothyroidism . Graves'Disease Graves’ disease (thyrotoxicosis) is due to a unique antibody called "thyroid stimulating antibody" which stimulates the thyroid cells to grow larger and to produce excessive amounts of thyroid hormones. In this disease, the goiter is not due to TSH but to this unique antibody. Hashimoto'sThyroiditis Hashimoto’s thyroiditis: It is caused by an accumulation of white blood cells and fluid (inflammation) in the thyroid gland. This leads to destruction of the thyroid cells and, eventually, thyroid failure (hypothyroidism). 11

12. Drugs for Hypothyroidism 12 Hypothyroidism is usually treated by oral administration of L-thyroxine 75-200 micrograms daily. Others iodine, tyrosine

13. HYPERTHYROIDISM 1.Intolerance to heat as the body produces lot of heat due to increased basal metabolic rate caused by excess of thyroxine 2. Increased sweating due to vasodilatation 3. Decreased body weight due to fat mobilization 4. Diarrhea due to increased motility of GI tract 5. Muscular weakness because of excess protein catabolism 6. Nervousness, extreme fatigue, inability to sleep, mild tremor in the hands 7. Toxic goiter 8. Oligomenorrhea or amenorrhea 9. Polycythemia 11. Tachycardia 13

14. Reference Values for Thyroid Function Test (TFTs) 14

15. Anti-thyroid Drugs (Classification) 1. Thioamides Propylthiouracil Methylthiouracil Methimazole Carbimazole 2. β - adrenoreceptor blockers Propranolol: It is used in the management of hyperthyroid symptoms 15

16. Mechanism of action of Thioamides 16 The major action is to prevent hormone synthesis by inhibiting the thyroid peroxidase-catalyzed reactions.

17. Treatment of Hyperthyroidism Removal of part or all of the thyroid: This can be achieved either surgically or by destruction of the gland with radioactive iodine 131, which is selectively taken up by the thyroid follicular cells. Most patients become hypothyroid as a result of this drug and require treatment with levothyroxine. Blockade of hormone release”: Iodide inhibits the release of thyroid hormones from thyroglobulin by mechanisms not yet understood. Inhibition of thyroid hormone synthesis: The thioamides , propylthiouracil (PTU) inhibit both the oxidative processes required for iodination of tyrosyl groups and the condensation (coupling) of iodotyrosines to form T3 and T4. PTU also blocks the peripheral conversion of T4 to T3. Thyroid storm: Thyroid storm presents with extreme symptoms of hyperthyroidism. The treatment of thyroid storm is the same as that for hyperthyroidism, except that the drugs are given in higher doses and more frequently. β-blockers, such as metoprolol or propranolol, are effective in blunting the widespread sympathetic stimulation that occurs in hyperthyroidism. 17

18. Adverse effects of Thioamides Skin rashes Fever Hepatic abnormalities 18

19. Any Question?

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