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Chapter 58

Chapter 58. Drugs for Thyroid Disorders. 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.

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Chapter 58

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  1. Chapter 58 Drugs for Thyroid Disorders

  2. 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

  3. Thyroid Hormones • Profound effect on: • Metabolism • Cardiac function • Growth • Promotes maturation in infancy and childhood • Development

  4. Thyroid Hormone Actions • Stimulation of energy use • Stimulation of the heart • Promotion of growth and development

  5. Thyroid • Produces two active hormones whose synthesis is stimulated by low plasma levels of iodine • Triiodothyronine (T3) • Synthetic T3 is liothyronine • Thyroxine (T4, tetraiodothyronine) • Synthetic T4 is levothyroxine

  6. Thyroid Function Tests • Serum thyroid-stimulating hormone (TSH) • Screening and diagnosis of hypothyroidism • Elevated TSH is indication of hypothyroidism • Serum T4 test • Can measure total T4 or free T4 • Serum T3 test • Can measure total T3 or free T3

  7. Hypothyroidism • Severe deficiency of thyroid hormone • Myxedema (adults) • Cretinism (infancy)

  8. 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

  9. 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)

  10. Hypothyroidism Treatment • Therapeutic strategy • Lifelong replacement therapy • Levothyroxine (T4) • Liothyronine (T3)

  11. 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

  12. Two Forms of Hyperthyroidism • Graves’ disease • Most common form • Affects women 20–40 years old • Causes exophthalmos • Toxic nodular goiter (Plummer’s disease)

  13. Hyperthyroidism • Cause • Thyroid-stimulating immunoglobulins (TSIs) • Treatment • Surgical removal of thyroid tissue • Destruction of thyroid tissue • Suppression of thyroid hormone synthesis

  14. 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

  15. 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

  16. Thyroid Hormone Preparations • Levothyroxine (Synthroid) • Synthetic preparation of thyroxine (T4) and drug of choice for hypothyroidism • Conversion to T3 • Half-life: 7 days • Used for all forms of hypothyroidism

  17. Thyroid Hormone Preparations • Levothyroxine (Synthroid) (cont’d) • Should be taken in the morning at least 30 to 60 minutes before breakfast • Adverse effects • Tachycardia • Angina • Tremors • Can intensify effects of warfarin

  18. Thyroid Hormone Preparations • Levothyroxine (Synthroid) (cont’d) • Drug interactions • Drugs that reduce levothyroxine absorption • Drugs that accelerate levothyroxine metabolism • Warfarin • Catecholamines

  19. 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

  20. 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)

  21. 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

  22. Propylthiouracil (PTU) • Adverse effects • Agranulocytosis (most serious) • Hypothyroidism • Pregnancy and lactation • Can cause severe liver damage

  23. 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 T4 to T3 in the periphery, whereas methimazole does not.

  24. Radioactive Iodine-131 (131I) • 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 131I therapy

  25. Radioactive Iodine-131 (131I) • Effect on thyroid • Advantages and disadvantages of (131I) therapy • Who should be treated and who should not • Use in thyroid cancer • Diagnostic use • Preparations

  26. Nonradioactive Iodine • Strong iodine solution (Lugol’s solution) • Used to suppress thyroid function in preparation for thyroidectomy • Adverse effects • Brassy taste • Burning sensation in the mouth and throat • Soreness of the teeth and gums • Frontal headache • Coryza • Salivation • Various skin eruptions

  27. Beta Blockers • Can suppress tachycardia and other symptoms of Graves’ disease • Benefits derive from beta-adrenergic blockade, not from reducing levels of T3 or T4 • Beneficial in thyrotoxic crisis

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