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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 58 Drugs for Thyroid Disorders
2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Physiology Chemistry and nomenclature Synthesis and fate of thyroid hormones Thyroid hormone actions Regulation of thyroid function by the hypothalamus and anterior pituitary Effect of iodine deficiency on thyroid function
3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormones Profound effect on: Metabolism Cardiac function Growth Promotes maturation in infancy and childhood Promotes maturation in infancy and childhood Development
4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormone Actions Stimulation of energy use Stimulation of the heart Promotion of growth and development
5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Produces two active hormones whose synthesis is stimulated by low plasma levels of iodine Triiodothyronine (T 3 ) Synthetic T 3 is liothyronine Synthetic T 3 is liothyronine Thyroxine (T 4, tetraiodothyronine) Synthetic T 4 is levothyroxine Synthetic T 4 is levothyroxine
6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Function Tests Serum thyroid-stimulating hormone (TSH) Screening and diagnosis of hypothyroidism Elevated TSH is indication of hypothyroidism Serum T 4 test Can measure total T 4 or free T 4 Serum T 3 test Can measure total T 3 or free T 3
7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism Severe deficiency of thyroid hormone Myxedema (adults) Cretinism (infancy)
8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism Clinical presentation (adults) Pale, puffy, and expressionless face Cold and dry skin Brittle hair or loss of hair Heart rate and temperature are lowered Lethargy and fatigue Intolerance to cold Impaired mentality
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism Causes Usually due to malfunction of the thyroid Hashimoto’s disease: chronic autoimmune thyroiditis Insufficient iodine in the diet Surgical removal of thyroid and destruction of thyroid with radioactive iodine Adults: insufficient secretion of TSH and thyrotropin-releasing hormone (TRH)
10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism Treatment Therapeutic strategy Lifelong replacement therapy Levothyroxine (T 4 ) Liothyronine (T 3 )
11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hypothyroidism: Life Span Issues During pregnancy In first trimester can result in permanent neuropsychologic deficits in the child In infants May be permanent or transient Can cause mental retardation and derangement of growth
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Two Forms of Hyperthyroidism Graves’ disease Most common form Affects women 20–40 years old Causes exophthalmos Toxic nodular goiter (Plummer’s disease)
13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hyperthyroidism Cause Thyroid-stimulating immunoglobulins (TSIs) Treatment Surgical removal of thyroid tissue Destruction of thyroid tissue Suppression of thyroid hormone synthesis
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyrotoxic Crisis (Thyroid Storm) Cause Patients with thyrotoxicosis who undergo significant stress (surgery, illness, etc.) Not triggered by a rise in thyroid hormones Cannot be identified by laboratory testing
15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyrotoxic Crisis (Thyroid Storm) Signs Hyperthermia (105°F or higher), severe tachycardia, restlessness, agitation, tremor, unconsciousness, coma, hypotension, heart failure Treatment Potassium iodide, propylthiouracil (PTU), and beta blocker Sedation, cooling, glucocorticoids, IV fluids
16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormone Preparations Levothyroxine (Synthroid) Synthetic preparation of thyroxine (T 4 ) and drug of choice for hypothyroidism Conversion to T 3 Half-life: 7 days Used for all forms of hypothyroidism
17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormone Preparations Levothyroxine (Synthroid) (cont’d) Should be taken in the morning at least 30 to 60 minutes before breakfast Adverse effects Tachycardia Tachycardia Angina Angina Tremors Tremors Can intensify effects of warfarin Can intensify effects of warfarin
18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Thyroid Hormone Preparations Levothyroxine (Synthroid) (cont’d) Drug interactions Drugs that reduce levothyroxine absorption Drugs that reduce levothyroxine absorption Drugs that accelerate levothyroxine metabolism Drugs that accelerate levothyroxine metabolism Warfarin Warfarin Catecholamines Catecholamines
19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Methimazole First-line drug for hyperthyroidism Prototype of the thionamides Does not cause the liver damage associated with PTU Does not destroy existing stores of thyroid hormone May take 3–12 weeks for euthyroid state More dangerous than PTU during lactation and during the first trimester of pregnancy
20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Methimazole Four applications in hyperthyroidism Sole form of therapy for Graves’ disease Adjunct to radiation therapy until the effects of radiation become manifest Suppress thyroid hormone synthesis in preparation for thyroid gland surgery (subtotal thyroidectomy) Patients experiencing thyrotoxic crisis (although PTU is preferred)
21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Propylthiouracil (PTU) Inhibits thyroid hormone synthesis Second-line drug for Graves’ disease Short half-life (about 90 minutes) Full benefits may take 6–12 months Therapeutic uses Graves’ disease Adjunct to radiation therapy Preparation for thyroid gland surgery Thyrotoxic crisis
22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Propylthiouracil (PTU) Adverse effects Agranulocytosis (most serious) Hypothyroidism Pregnancy and lactation Can cause severe liver damage
23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. PTU vs. Methimazole PTU can cause severe liver injury, whereas methimazole does not PTU has a shorter half-life than methimazole (90 minutes vs. 6 to 13 hours), hence it requires two or three daily doses rather than one. PTU crosses the placenta less readily than does methimazole and achieves lower concentrations in breast milk. PTU blocks conversion of T 4 to T 3 in the periphery, whereas methimazole does not.
24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Radioactive Iodine-131 ( 131 I) Radioactive isotope of stable iodine Emits gamma and beta rays Half-life: 8 days 2–3 months for full effect Used in Graves’ disease Effect on the thyroid Advantages and disadvantages of 131 I therapy
25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Radioactive Iodine-131 ( 131 I) Effect on thyroid Advantages and disadvantages of ( 131 I) therapy Who should be treated and who should not Use in thyroid cancer Diagnostic use Preparations
26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Nonradioactive Iodine Strong iodine solution (Lugol’s solution) Used to suppress thyroid function in preparation for thyroidectomy Adverse effects Brassy taste Brassy taste Burning sensation in the mouth and throat Burning sensation in the mouth and throat Soreness of the teeth and gums Soreness of the teeth and gums Frontal headache Frontal headache Coryza Coryza Salivation Salivation Various skin eruptions Various skin eruptions
27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Beta Blockers Can suppress tachycardia and other symptoms of Graves’ disease Benefits derive from beta-adrenergic blockade, not from reducing levels of T 3 or T 4 Beneficial in thyrotoxic crisis
Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Chapter 58 Drugs for Thyroid Disorders.
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 30 Thyroid and Antithyroid Drugs.
Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 31 Thyroid and Antithyroid Drugs.
Secretes three hormones essential for proper regulation of metabolism ◦ Thyroxine (T 4 ) ◦ Triiodothyronine (T 3 ) ◦ Calcitonin Located near the parathyroid.
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Copyright © 2013, 2010, 2006, 2002 by Saunders, an imprint of Elsevier Inc.
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