Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Sex reassignment therapy wikipedia , lookup
Hormone replacement therapy (male-to-female) wikipedia , lookup
Hormone replacement therapy (menopause) wikipedia , lookup
Bioidentical hormone replacement therapy wikipedia , lookup
Growth hormone therapy wikipedia , lookup
Hypothalamus wikipedia , lookup
Thyroid Drugs Kaukab Azim, MBBS, PhD 1 Learning Outcomes By the end of the course the students should be able to discuss in detail • Physiology, synthesis and feed back control of thyroid hormone synthesis • Thyroid disorders: – Hypothyroidism • Cretinism, Myxedema coma – Hyperthyroidism • Thyroid storm • Drugs for the treatment of hypothyroidism and hyperthyroidism 2 Thyroid Hormones • Thyroid hormones: – Thyroxine T4 (90%) – Triiodothyronine T3 • Thyroid gland also secretes Calcitonin – serum calcium lowering hormone 3 Thyroid Hormones - Facts • Thyroid hormones are required for the growth and development of all tissues. • Thyroid hormone is critical for nervous, reproductive and skeletal growth. • Thyroid deprivation in early life results in irreversible mental retardation. • Thyroid hormones also augment sympathetic system function primarily by increasing the number of adrenergic receptors. 4 Hypothalamus-pituitary-thyroid axis • TSH secretion by anterior pituitary is stimulated by hypothalamic TRH • Feedback inhibition of TSH and TRH occurs with high levels of circulating thyroid hormones (T3 & T4) • Dopamine, Glucocorticoids and somatostatin can suppress TSH secretion (High dose) 5 Thyroid hormone synthesis • • • Uptake of iodide by thyroid gland Oxidation of iodide Organification – Iodination of tyrosine residues on thyroglobulin – MITs and DITs ● Coupling – formation of T4 and T3 ● Proteolysis of thyroglubulin and secretion of thyroid hormones ● Conversion of T4 to T3 in peripheral tissues 6 Thyroid hormone synthesis T4 TBP T3 & Free T4 & T3 (Iodide Organification) 4. Coupling 7 Metabolism of thyroid hormones Outer ring 5’-deiodinase Inner ring (T4) 8 (4X potent than T4) Metabolism of Thyroid hormones Drugs that inhibit deiodination: – Beta blockers – High dose propylthiouracil – Corticosteroids • They inhibit the 5’-deiodinase activity necessary for conversion of T4 to T3 resulting in low T3 and high reverse T3 (rT3) 9 Thyroid hormones Mechanism of action • T4 and T3 must dissociate from thyroxine binding globulin (TBG) in plasma before entering into the cells. • In the cells, T4 is deiodinated to T3 that enters nucleus and attaches to specific receptors which promotes mRNA and protein synthesis. 10 Hypothyroidism Clinical manifestations: – – – – – – Lethargy Wt. gain Bradycardia Constipation Cold intolerance Menstrual irregularities • Cretinism (congenital hypothyroidism) • Myxedema coma: most extreme manifestations of untreated hypothyroidism 11 Drugs for Hypothyroidism Levothyroxine (T4) • It is the treatment of choice for replacement therapy in hypothyroid patients • It has a long half life ~7 days; once a day dose. Triiodothyronine (T3) • Short half life (1 day) 12 Drugs for Hypothyroidism • • • • T4 and T3 given orally. T4 is better for long term replacement therapy I.V. administration in myxedema coma During pregnancy, hypothyroid woman require higher doses 13 Hyperthyroidism • Clinical manifestation – Weight loss and with increase in appetite. – Nervousness and irritability. – Palpitations. – Heat intolerance and increased sweating. – Tremors. – Thyroid enlargement – Menstrual irregularities 14 Hyperthyroidism Treatment options: • Surgical • Antithyroid drugs: – By inhibiting uptake of iodine – By inhibiting synthesis – By inhibiting release of hormones from thyroid • Medical destruction of thyroid tissue – Radioiodine (I131) 15 Drugs for hyperthyroidism Thioamides: Inhibit hormone synthesis Iodide salts: Blocks hormone release Propylthiouracil, Methimazole KI, Lugol’s solution Iodinated contrast media: Ipodate Anion inhibitors: Inhibition of peripheral T4 to T3 conversion; inhibits hormone release block uptake of iodide by thyroid Perchlorate, thiocyanate Radioactive iodine (131I) Beta-blocker: Propranolol, esmolol destruction of thyroid tissue Controls heart rate 16 (-) Anion Inhibitors 5’-deiodinase T4 T3 (-) Propylthiouracil, Ipodate, beta blockers, cortocosteroids 17 1. Thioamides Propylthiouracil, Methimazole • Inhibit hormone synthesis – Acts by inhibiting thyroid peroxidase to block iodine organification and coupling reactions • These are the major drugs for treatment of mild thyrotoxicosis and in preparation of patients for subtotal thyroidectomy 18 Thioamides • Slow onset of action (~ 4 weeks) • Propylthiouracil is relatively safe and preferred in pregnancy • Methimazole is more potent and longer acting than Propylthiouracil • Propylthiouracil also inhibits peripheral deiodination of T4 and T3 19 Thioamides: Adverse drug reactions • Common: Maculopapular Rash, Arthralgia, vasculitis • Serious side effect: Agranulocytosis 20 2. Iodides: Potassium iodide, Lugol’s solution • Mechanism of action – Inhibit hormone release – Inhibit organification – Decrease size and vascularity of the hyperplastic gland. • Effect is reversible and transient – not for long term as thyroid gland ‘escapes’ from its effect after 14 days • Contraindicated in pregnancy: fetal goiter 21 3. Iodinated contrast media Ipodate and Iopanoic acid – They inhibit the peripheral conversion of T4 into T3 in the liver, kidney and brain – Inhibition of hormone release is an additional mechanism • Adjunctive therapy in the treatment of thyroid storm 22 4. Anion Inhibitors Perchlorate (ClO4-), Pertechnetate (Tco4-), Thiocyanate (SCN-) • competitively block the uptake of iodide • Adverse effect: Aplastic anemia 23 5. Radioactive Iodine • 131I is the only isotope used in treatment of thyrotoxicosis while others are used in diagnosis. • Emission of beta particles – destroys the thyroid gland. • Patients can become hypothyroid – managed with thyroxine (T4) • Contraindications: – Pregnancy & lactation – Age <25 yrs 24 Thyroid storm • Clinical manifestation – High fever often above 40°C – Fast and often irregular heart beat – Vomiting, diarrhea and agitation. – Heart failure and myocardial infarction may occur. – Death may occur despite treatment. • Causes – Patients with known hyperthyroidism whose treatment has been stopped or become ineffective, – Untreated mild hyperthyroidism who have developed an intercurrent illness (such as an 25 infection). Thyroid storm Treatment • Propranolol /Esmolol / Diltiazem • Iodide/ipodate – ipodate also block the T4 to T3 conversion • Propylthiouracil • Hydrocortisone – blocks the T4 to T3 conversion 26 Qs 27