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Similar to Thyroid and Antithyroid drugs, Medicinal Chemistry,Mr.Jimmy Alexander ,Associate Professor,Dept.of.Medicinal Chemistry,Dr.MGR Medical Universit
Similar to Thyroid and Antithyroid drugs, Medicinal Chemistry,Mr.Jimmy Alexander ,Associate Professor,Dept.of.Medicinal Chemistry,Dr.MGR Medical Universit (20)
10. Normal functions of Thyroid hormones
• Increases the basal metabolic rate
• Depending on the metabolic status it can induce lipolysis or lipid synthesis
• Stimulate the metabolism of carbohydrates
• Anabolism of proteins. Thyroid hormones can also induce catabolism of proteins in
high doses
• Permissive effect on catecholamines
• In children, thyroid hormones act synergistically with growth hormone to stimulate
bone growth
• The impact of thyroid hormone in CNS is important. During the prenatal period, it
is needed for the maturation of the brain. In adults, it can affect mood.
Hyperthyroidism can lead to hyperexcitability and irritability. Hypothyroidism can
cause impaired memory, slowed speech, and sleepiness.
• Thyroid hormone affects fertility, ovulation, and menstruation
11. Biosynthesis of Thyroid hormones
i. Active uptake of iodide by follicular cells
ii. Oxidation of iodide and formation of iodotyrosine
iii. Coupling of iodotyrosine residue
iv. Proteolysis of thyroglobulin and release of iodothyronines
Iodide is oxidized to iodine by thyroid peroxidase, which in turn iodinates
tyrosine residues of the thyroglobulin (TG) to form monoiodotyrosine (MIT)
and diiodotyrosine (DIT) , The coupling of two DIT forms T4 and the coupling
of one MIT and DIT forms T3. The process of coupling is also catalysed by
thyroid peroxidase , T4 and T3 are released by Proteolysis.
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18. • Iodide is actively transported to thyroid gland through NaI symporter.
• Iodide is secreted into the lumen of thyroid follicle by pendrin which is a sodium
independent iodide transporter.
• Once the iodide is in the lumen, it is converted to iodine by thyroid peroxidase
enzyme.
• Then iodine is attached to thyroglobulin in a process called organification forming MIT
and DIT.
• MIT and DIT are then coupled together by peroxidase leading to the formation of T3
and T4 while it remain attached to the thyroglobulin.
• This complex is then taken up by the follicular cells by endocytosis where thyroglobulin
is cleaved away by lysosomes freeing T3 and T4 and is released into the blood stream.
• Some of the T4 is converted to the more active T3.
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23. Hypothyroidism is a condition in which thyroid gland fails to produce
enough thyroid hormone.
27. Treatment
Anti thyroid drugs
• Anti-thyroid drugs (ATDs) are compounds that interfere with the body’s
production of thyroid hormone, thereby reducing symptoms of
hyperthyroidism.
• ATDs were discovered accidentally in the mid-1940’s when thiocyanate
compounds used for heart disease were found to cause hypothyroidism.
• This led to the development of a number of compounds specifically
tailored to reduce thyroid hormone production.
28. Classification of antithyroid drugs
1. Thiourylene Derivatives
a. Thiouracils: Methylthiouracil, Propylthiouracil
b. Imidazoles: Methimazole, Carbimazole, Centimizone
2. Ion Inhibitors
- Thiocyanates, Perchlorates, Pertechnetates
3. Radioactive Iodine
- 131I
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30. MOA
Propyl thiouracil and Methimazole
PTU and methimazole inhibit the enzyme thyroperoxidase, which normally
acts in thyroid hormone synthesis by oxidizing the anion iodide (I−) to
iodine (I0), facilitating iodine's addition to tyrosine residues on the
hormone precursor thyroglobulin. This is one of the essential steps in the
formation of thyroxine (T4).
31. Goiter
It is the most common disorder of the thyroid gland.
It is a condition where there is visible enlargement of the neck due to the
swelling of thyroid gland.
It can be caused by both hypo- and hyperthyroidism.
Treatment:
Medications of hypo- and hyperthyroidism
Corticosteroids to reduce inflammation
Surgery
Radioactive iodine