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Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
Thyroid & antithyroid drugs
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Thyroid & antithyroid drugs

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  • Regulation of thyroid hormone synthesis. Left. Thyroid hormones T4 and T3 feed back to inhibit hypothalamic production of thyrotropin-releasing hormone (TRH) and pituitary production of thyroid-stimulating hormone (TSH). TSH stimulates thyroid gland production of T4 and T3. Right. Thyroid follicles are formed by thyroid epithelial cells surrounding proteinaceous colloid, which contains thyroglobulin. Follicular cells, which are polarized, synthesize thyroglobulin and carry out thyroid hormone biosynthesis (see text for details). TSH-R, thyroid-stimulating hormone receptor; Tg, thyroglobulin; NIS, sodium-iodide symporter; TPO, thyroid peroxidase; DIT, diiodotyrosine; MIT, monoiodotyrosine
  • hyroid cellular mechanisms for iodine transport, thyroxine and triiodothyronine formation, and thyroxine and triiodothyronine release into the blood. MIT, onoiodotyrosine; DIT, diiodotyrosine; T3, triiodothyronine; T4, thyroxine; TG, thyroglobulin.
  • Biosynthesis of thyroid hormones. The sites of action of various drugs that interfere with thyroid hormone biosynthesis are shown
  • Worldwide iodine nutrition.Data are from the WHO and the International Council for the Control of Iodine Deficiency Disorders (http://indorgs.virginia.edu/iccidd/mi/cidds.html).
  • Thyroid hormone activation of target cells. Thyroxine (T4) and triiodothyronine (T3) readily diffuse through the cell membrane. Much of the T4 is deiodinated to form T3, which interacts with the thyroid hormone receptor, bound as a heterodimer with a retinoid X receptor, of the thyroid hormone response element of the gene. This causes either increases or decreases in transcription of genes that lead to formation of proteins, thus producing the thyroid hormone response of the cell. The actions of thyroid hormone on cells of several different systems are shown. mRNA, messenger ribonucleic acid.
  • Model of the interaction of T3 with the T3 receptor. A:  Inactive phase —the unliganded T3 receptor dimer bound to the thyroid hormone response element (TRE) along with corepressors acts as a suppressor of gene transcription. B:  Active phase — T3 and T4 circulate bound to thyroid-binding proteins (TBPs). The free hormones are transported into the cell by a specific transport system. Within the cytoplasm, T4 is converted to T3 by 5'-deiodinase; T3 then moves into the nucleus. There it binds to the ligand-binding domain of the thyroid receptor (TR) monomer. This promotes disruption of the TR homodimer and heterodimerization with retinoid X receptor (RXR) on the TRE, displacement of corepressors, and binding of coactivators. The TR-coactivator complex activates gene transcription, which leads to alteration in protein synthesis and cellular phenotype. TR-LBD, T3 receptor ligand-binding domain; TR-DBD, T3 receptor DNA-binding domain; RXR-LBD, retinoid X receptor ligand-binding domain; RXR-DBD, retinoid X receptor DNA-binding domain; T3, triiodothyronine; T4, tetraiodothyronine, L-thyroxine; 5'DI, 5'deiodinase.
  • Structure of thioamides. The thiocarbamide moiety is shaded in color
  • Approximate prolonged effect on the basal metabolic rate caused by administering a single large dose of thyroxine.
  • Activating mutations of the TSH-R. Mutations (*) that activate the thyroid-stimulating hormone receptor (TSH-R) reside mainly in transmembrane 5 and intracellular loop 3, though mutations have occurred in a variety of different locations. The effect of these mutations is to induce conformational changes that mimic TSH binding, thereby leading to coupling to stimulatory G protein (Gs) and activation of adenylatecyclase (AC), an enzyme that generates cyclic AMP.
  • Graves diseases
  • The hypothalamic-pituitary-thyroid axis. Acute psychosis or prolonged exposure to cold may activate the axis. Hypothalamic TRH stimulates pituitary TSH release, while somatostatin and dopamine inhibit it. TSH stimulates T4 and T3 synthesis and release from the thyroid, and they in turn inhibit both TRH and TSH synthesis and release. Small amounts of iodide are necessary for hormone production, but large amounts inhibit T3 and T4 production and release. (Solid arrows, stimulatory influence; dashed arrows, inhibitory influence. H, hypothalamus, AP, anterior pituitary.)
  • Clinical course of subacutethyroiditis. The release of thyroid hormones is initially associated with a thyrotoxic phase and suppressed thyroid-stimulating hormone (TSH). A hypothyroid phase then ensues, with low T4 and TSH levels that are initially low but gradually increase. During the recovery phase, increased TSH levels combined with resolution of thyroid follicular injury leads to normalization of thyroid function, often several months after the beginning of the illness. ESR, erythrocyte sedimentation rate; UT4, unbound T4.
  • Drugs Used in the Management of Thyroid Disease
  • Transcript

    • 1. Thyroid & Antithyroid Drugs By M. H. Farjoo M.D, Ph.D.Shahid Beheshti University of Medical Science
    • 2. Thyroid & Antithyroid Drugs Introduction Drugs in Hypothyroidism Drugs in Hyperthyroidism Adjuncts to Antithyroid Therapy Thyroid malfunction and Pregnancy Neonatal Graves Disease Drug Pictures
    • 3. Introduction Thyroid releases T3 & T4 The ratio of T4 to T3 is 5:1, so most of the hormone released is thyroxine Most of the T3 in the blood is derived from thyroxine T3 is three to four times more potent than T4 The affinity of the receptor site for T3 is about ten times higher than that for T4
    • 4. Drugs in Hypothyroidism Levothyroxine is the choice drug for hypothyroidism T4 is converted to T3 intracellularly so levothyroxine produces both hormones If angina pectoris or cardiac arrhythmia develops, it is essential to stop thyroxine immediately
    • 5. Drugs in Hyperthyroidism The antithyroid compounds include: Thioamides  Methimazole  Propylthiouracil Iodides Radioactive iodine
    • 6. Thioamides Their major action is blocking iodine organification Since the synthesis of hormones is affected, their effect requires 4 weeks Propylthiouracil is preferable in pregnancy:  It crosses the placenta less readily  Is not secreted in breast milk The most common adverse effect is a maculopapular pruritic rash The most dangerous complication is reversible agranulocytosis
    • 7. Iodide Iodides can induce hyperthyroidism (jodbasedow phenomenon) or precipitate hypothyroidism In pharmacologic doses the major action is to inhibit hormone release Improvement in thyrotoxic symptoms occurs within 2–7 days (iodide therapy in thyroid storm) Iodides in pregnancy should be avoided, since they cross the placenta and can cause fetal goiter
    • 8. Radioactive Iodine Women in the childbearing period should be treated with I131 or subtotal thyroidectomy prior to pregnancy I131 should NOT be administered to pregnant or nursing women I131 is the preferred treatment for patients over 21 years Hypothyroidism occurs in 80% of patients by radioiodine
    • 9. 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
    • 10. Thyroid malfunction and Pregnancy In a pregnant hypothyroid patient, it is extremely important that the dose of thyroxine be adequate. This is because early development of the fetal brain depends on maternal thyroxine If thyrotoxicosis occurs, propylthiouracil is used and an elective subtotal thyroidectomy performed
    • 11. Neonatal Graves Disease Is either due to passage of TSH-R Ab [stim], or to genetic transmission of the trait If caused by maternal TSH-R Ab [stim], the disease is self-limited and subsides over 4–12 weeks, Treatment is necessary because of the severe metabolic stress of the infant Therapy includes : propylthiouracil, Lugols solution, propranolol and careful supportive therapy
    • 12. Iodinates Contrast Media Gastrografin
    • 13. Iodinates Contrast Media iodixanol
    • 14. Iodinates Contrast Media iodixanol
    • 15. Iodinates Contrast Media iodixanol
    • 16. Iodinates Contrast Media iohexol
    • 17. Iodinates Contrast Media iohexol
    • 18. Iodinates Contrast Media iohexol
    • 19. Iodinates Contrast Media iohexol
    • 20. Iodinates Contrast Media iohexol
    • 21. Iodinates Contrast Media iopromide
    • 22. Iodinates Contrast Media iopromide
    • 23. Iodinates Contrast Media iopromide
    • 24. Iodinates Contrast Media Urografin
    • 25. Summary In English
    • 26. Thank you Any question?
    • 27. Hypothyroidism Hypothyroidism can occur with or without thyroid enlargement (goiter). The laboratory diagnosis of hypothyroidism in the adult is easily made by the combination of a low free thyroxine (or low free thyroxine index) and elevated serum TSH Infants and children require more T4 per kilogram of body weight than adults Chronic overtreatment with T4, particularly in elderly patients, can increase the risk of atrial fibrillation and accelerated osteoporosis
    • 28. Myxedema Correction of myxedema must be done cautiously to avoid provoking arrhythmia, angina, or acute myocardial infarction. myxedema coma:  It is associated with progressive weakness, stupor, hypothermia, hypoventilation, hypoglyce mia, hyponatremia, water intoxication, shock, and death  It is important to give all preparations intravenously  The treatment of choice in myxedema coma is to give a loading dose of levothyroxine intravenously— usually 300–400 µg initially, followed by 50 µg daily  Opioids and sedatives must be used with extreme caution
    • 29. Hyperthyroidism The most common form of hyperthyroidism is Graves disease, or diffuse toxic goiter The three primary methods for controlling hyperthyroidism are antithyroid drug therapy, surgical thyroidectomy, and destruction of the gland with radioactive iodine Antithyroid Drug Therapy  the more severe reaction of agranulocytosis is often heralded by sore throat or high fever Thyroidectomy  A near-total thyroidectomy is the treatment of choice for patients with very large glands or multinodular goiters
    • 30. Hyperthyroidism Toxic Uninodular Goiter & Toxic Multinodular Goiter  These forms of hyperthyroidism occur often in older women with nodular goiters. FT4 is moderately elevated or occasionally normal, but T3 by RIA is strikingly elevated Subacute Thyroiditis episodes of transient thyrotoxicosis have been termed "spontaneously resolving hyperthyroidism." Supportive therapy is usually all that is necessary, such as propranolol for tachycardia and aspirin or nonsteroidal anti-inflammatory drugs to control local pain and fever
    • 31. Special Problems Ophthalmopathy  elevation of the head to diminish periorbital edema and artificial tears to relieve corneal drying. Smoking cessation should be advised to prevent progression of the ophthalmopathy  If steroid therapy fails or is contraindicated, irradiation of the posterior orbit, using well-collimated high-energy x-ray therapy, will frequently result in marked improvement of the acute process
    • 32. Special Problems Nontoxic Goiter  The most common cause of nontoxic goiter worldwide is iodide deficiency, but in the USA, it is Hashimotos thyroiditis. Less common causes include dietary goitrogens, dyshormonogenesis, and neoplasms
    • 33. Thyroid Neoplasms Some adenomas will regress following thyroxine therapy; those that do not should be rebiopsied or surgically removed. Management of thyroid carcinoma requires a total thyroidectomy, postoperative radioiodine therapy in selected instances, and lifetime replacement with levothyroxine.
    • 34. Class Mechanism of Action Indications Pharmacokine and Effects tics, Toxicities, InteractionsThyroid Preparations Levothyroxine (T4 ) Activation of nuclear Hypothyroidism maximum Liothyronine (T3) receptors results in effect seen gene expression with after 6–8 RNA formation and weeks of protein synthesis therapy
    • 35. Class Mechanism of Action and Indications Pharmacokinetics, Effects Toxicities, InteractionsAntithyroid AgentsThioamides Propylthiouracil (PTU) Inhibit thyroid peroxidase Hyperthyroidism Oral duration of action: 6– reactions block iodine 8 h delayed onset of organification inhibit peripheral action Toxicity: Nausea, deiodination of T4 and T3 gastrointestinal distress, rash, agranulocytosis, hepatitis,hypothyroidismIodides Lugol solution Inhibit organification and Preparation for surgical Oral acute onset within 2– Potassium iodide hormone release reduce the thyroidectomy 7 days Toxicity: Rare (see size and vascularity of the text) glandBeta blockers Propranolol Inhibition of adrenoreceptors Hyperthyroidism, Onset within hours inhibit T4 to T3 conversion especially thyroid storm duration of 4–6 h (oral (only propranolol) adjunct to control propranolol) Toxicity: tachycardia, Asthma, AV blockade, hypertension, and atrial hypotension, bradycardia fibrillationRadioactive iodine 131I (RAI) Radiation destruction of Hyperthyroidism patients Oral half-life 5 days onset thyroid parenchyma should be euthyroid or on of 6–12 weeks maximum blockers before RAI avoid effect in 3–6 months in pregnancy or in nursing Toxicity: Sore throat, mothers sialitis, hypothyroidism

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