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This medical talks about thyroid and anti-thyroid drugs.

The thyroid gland is a small, butterfly-shaped gland located in the front of the neck, just below the Adams apple. It produces hormones that regulate the bodys metabolism, including heart rate, body temperature, and energy levels.

Sometimes the thyroid gland produces too much or too little hormone, which can lead to a variety of health problems. In these cases, drugs are often used to help regulate thyroid hormone levels.

Anti-thyroid drugs are used to treat an overactive thyroid (hyperthyroidism), where the thyroid gland produces too much hormone. These drugs work by blocking the production of thyroid hormone in the thyroid gland. Examples of anti-thyroid drugs include methimazole and propylthiouracil.

On the other hand, thyroid hormone replacement therapy is used to treat an underactive thyroid (hypothyroidism), where the thyroid gland doesnt produce enough hormone. In this case, synthetic thyroid hormone is given to replace the missing hormone. The most commonly used synthetic hormone is levothyroxine (also known as T4), which is converted into the active form of thyroid hormone (T3) in the body.

It is important to note that thyroid disorders are complex and often require a multidisciplinary approach, involving endocrinologists, primary care physicians, and other healthcare providers. Treatment decisions should be individualized based on each patients unique circumstances, and patients should be monitored regularly to ensure that their thyroid hormone levels are within the appropriate range.

Tags : thyroid, anti-thyroid drugs, endocrinology, endocrinology

Published on : Apr 21, 2023 | Views : 2032 | Downloads : 10

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Slide 1-

Thyroid and Anti-Thyroid Drugs
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Anatomy and Physiology of the Thyroid Gland
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www.medscape.com; http://ae.medseek.com/
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Evaluating Hoarseness: Keeping Your Patient's Voice Healthy - June 1998 - American Academy of Family Physicians; http://www.aafp.org/afp/980600ap/rosen.html
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Anatomy and Physiology of the Thyroid Gland Member of the Endocrine System Secretes thyroid hormones, thyroxine and calcitonin, which regulate metabolism and growth. Located in neck adjacent to the 5th cervical vertebra (C5). Composed of epithelial cells which specialize in the absorption of iodine and, of course, secretion of thyroid hormones. Follicles surround a protein core, the colloid, where thyroglobulin, a substrate in thyroid hormone synthesis, and thyroid hormones are stored.
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Synthesis of Thyroid Hormones Thyroid hormones are synthesized by iodination of tyrosine residues on thyroglobulin within the lumen of the thyroid follicle. The thyroglobulin is endocytosed and thyroxin (T4) and triiodothyronine (T3) are secreted. Synthesis and secretion of T3 and T4 are regulated by thyroid-stimulating hormone (TSH; thyrotrophin) and influenced by plasma iodide. .
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Synthesis of Thyroid Hormones There is a large pool of T4 in the body; it has a low turnover rate and is found mainly in the circulation. There is a small pool of T3 in the body; it has a fast turnover rate and is found mainly intracellular.
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Detail of Synthesis: The oxidation of iodide and its incorporation into thyroglobulin (termed the organification of iodide) is catalysed by thyroperoxidase TPO, an enzyme situated at the inner surface of the cell at the interface with the colloid. The reaction requires the presence of hydrogen peroxide (H2O2) as an oxidising agent
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Tyrosine residues are iodinated first at position 3 on the ring, forming monoiodotyrosine (MIT) and then, in some molecules, on position 5 as well, forming di-iodotyrosine (DIT). While still incorporated into thyroglobulin, these molecules are then coupled in pairs, either MIT with DIT to form T3, or two DIT molecules to form T4. The mechanism for coupling is believed to involve a peroxidase system similar to that involved in iodination. About one-fifth of the tyrosine residues in thyroglobulin are iodinated in this way.
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SECRETION OF THYROID HORMONE The thyroglobulin molecule is taken up into the follicle cell by endocytosis. The endocytotic vesicles then fuse with lysosomes, and proteolytic enzymes act on thyroglobulin, releasing T4 and T3 to be secreted into the plasma. The surplus MIT and DIT, which are released at the same time, are scavenged by the cell, where the iodide is removed enzymatically and reused.
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The effect of thyroid hormones on metabolism Stimulate metabolism generally causing - increased oxygen consumption -increased metabolic rate -Influence growth and development. Within cells, the T4 is converted to T3, which interacts with a nuclear receptor; the receptor represses basal transcription when not bound to T3, and activates transcription when bound.
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Hormone Loop ↓Metabolic rate  Detected by hypothalamus  Stimulates anterior pituitary  Secretes TSH  Blood stream  target organ  thyroid Stimulate Thyroid to secrete T3/T4  Blood stream  target organs  adrenal medulla  Secretes Epinephrine & Norepinephrine  ↑Metabolic rate
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Regulation of thyroid hormone synthesis Regulation: The hypothalamus in the brain secretes thyroid releasing hormone, TRH, that target the pituitary gland which, in turn, secretes thyroid stimulating hormone, TSH. The pituitary gland’s sensitivity toward TRH varies with the body’s need for thyroid hormones. Protirelin is a synthetic TRH causes increase secretion of TSH used for diagnostic purpose
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TSH is absorbed into the thyroid, stimulating the thyroid to absorb iodine and synthesize hormones. Thyroid hormones provide negative feedback for TSH production via a “homeostatic feedback loop.”
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Regulation of thyroid hormone synthesis
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Detail of thyroid hormones effects on Metabolism TH serves as a nuclear transcription factor, regulating gene expression in targeted cells to increase metabolism. Increase size and number of mitochondria in the cell. Synthesizes cytochromes which feed into the electron transfer chain of cellular respiration, stimulating metabolism through increasing ATP production. Increase ATPase concentration, the enzyme which cleaves a phosphate group from ATP forming ADP and inorganic phosphate. Increased K+ and Na+ concentrations in the cell. Increase the body’s basal metabolic rate, BMR, to maintain electrochemical gradient in cell. Stimulate carbohydrate metabolism and lipolysis Affects protein synthesis. Increase the body’s sensitivity to catecholamine, i.e. adrenaline
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Abnormalities of thyroid function include Hyperthyroidism (thyrotoxicosis), either diffuse toxic goiter or toxic nodular goiter Hypothyroidism; in adults this causes myxoedema, in infants, cretinism Simple non-toxic goiter, caused by dietary iodine deficiency, usually with normal thyroid function
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Hypothyroidism cretinism simple goiter
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Hypothyroidism Insufficient amount of thyroid hormone synthesized causing lethargy and weight gain, among other symptoms. Primary hypothyroidism is typically caused by Hashimoto’s Disease, an auto-immune disorder in which the thyroid is destroyed by antibodies. Impaired hypothalamus and pituitary function, typically due to a tumor, can inhibit the secretion of THS, causing secondary hypothyroidism. A diet insufficient in iodine causes hypothyroidism as well.
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Symptoms of Thyroid Dysfunction: Goiter Enlarged thyroid, symptom of hypothyroidism. Goiters form for different reasons depending on the cause of hypothyroidism Hashimoto’s disease, also known as chronic lymphocytic thyroiditis, causes goiters due to the accumulation of lymphocytes. The decreased amount of thyroid hormones in the body, due to Hashimoto’s or other thyroid disorders including infection, signals the increased production of TSH which accumulates in the thyroid causing a characteristic goiter. Goiters form due to an insufficient amount of ingested iodine and serve to increase the surface area of the thyroid and aid in its absorption of iodine.
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Treatment for Hypothyroidism Thyroxine is the standard replacement therapy for hypothyroidism. Thyroxine has all the actions of endogenous thyroxine; it is given orally. Liothyronine (T3) is the treatment of choice for myxoedema coma. Liothyronine has all the actions of endogenous triiodothyronine; it is given intravenously
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Treatment for Hypothyroidism Hormone replacement therapy Administered orally with a bioavailability ranging from 48%-80%. Levothyroxine—Synthetic T4 Liothyronine—Synthetic T3 Liotrix—Combination of synthetic T4 and T3 Natural Thyroid Hormones—Thyroid hormones derived from pigs, contains T4 and T3 Armour Thyroid Dosage specific to individual and is determined by their TSH serum levels. Typically 1.5μg T4 per kg body weight.
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Because thyroid hormones serve to increase heart rate, T4, the inactive form, is typically administered to older patients who have an increased risk for heart attack on account of their age. Synthetic T3 is reserved for younger patients, who do not have a history of heart problems and individuals non-responsive to T4 treatment. Dosage for individuals suffering from secondary hypothyroidism determined by the amount of free T4 and T3 circulating in their system. Administering too high of a dosage leads to hyperthyroid symptoms
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Hyperthyroidism The over production of thyroid hormones. Symptoms include fatigue, weight lose, rapid heart beat, anxiety, swollen eyes, and sensitivity to hot temperatures. Causes: Grave’s disease, and autoimmune disorder in which antibodies serve as agonists to the THS receptors on the thyroid’s surface, causing thyroid growth and activation of hormone synthesis and secretion. Thyroid tumors which cause the uncontrolled synthesis and secretion of thyroid hormones. Thyroiditis, inflammation of the thyroid typically caused by infection.
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Treatment of Hyperthyroidism Drugs thioureylenes iodides radioactive iodine beta adrenoceptor blocking agents 'Lugol's iodine Surgical Subtotal Thyroidectomy
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Drugs Treatment for Hyperthyroidism 1-Anti-thyroid drugs—Thioureylenes Inhibits thyroid hormone synthesis by irreversibly binding to TPO inhibiting its ability to break down iodine (I2→I-) and covalently attach it to the tyrosine residue of thyroglobulin. Three thioureylenes available: Propylthiouracil Methimazole Carbamizole─Degraded to methimazole in the body. Best indicated for children ,adolescents ,young adults and pregnant women.
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Methimazole 5mg; Propylthiouracil (PTU) 50mg; Carbimazole 5mg, 20mg MOA: contain a sulfhydryl group and a thiourea moiety within a heterocyclic structure inhibit synthesis by acting against iodide organification (both) coupling of iodotyrosines (both) blocks conversion of T4 to T3 (PTU)
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Clinical uses Carbimazole (or propylthiouracil) 1-Hyperthyroidism (diffuse toxic goitre), at least 1 year of treatment being necessary; recurrence occurs eventually in over half the patients but can be managed by a repeat course of treatment. 2-Propylthiouracil can be used in patients who suffer sensitivity reactions to carbimazole. 3-Preliminary to surgery for toxic goitre. 4-Part of the treatment of thyroid storm (very severe hyperthyroidism); propylthiouracil is preferred because of its action in decreasing the conversion of T4 to T3 in the tissues
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β-blockers β-blockers are effective in treatment of thyrotoxicosis to treat symptoms Propranolol is the most widely studied and used.
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Radioactive Iodine 131I As first-line treatment for hyperthyroidism; recurrence is rare provided the dose is adequate. For treatment of relapse of hyperthyroidism after carbimazole therapy or surgery. Radioiodine, given orally, is selectively taken up by thyroid and damages cells; it emits short-range β radiation, which affects only thyroid follicle cells of. Hypothyroidism will eventually occur. Woman in pregnancy or lactation is forbidden
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131I cytotoxic action is restricted to the cells of the thyroid follicles, resulting in significant destruction of the tissue. 131I has a half-life of 8 days, so by 2 months its radioactivity has effectively disappeared. It is given as one single dose, but its cytotoxic effect on the gland is delayed for 1-2 months and does not reach its maximum for a further 2 months.
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Iodine dissolved in aqueous potassium iodide ('Lugol's iodine') is used short-term to control thyrotoxicosis preoperatively. It reduces the vascularity of the gland. Iodine, given orally in high doses, transiently reduces thyroid hormone secretion and decreases vascularity of the gland.