Lecture 17Thyroid Pharmacology

Pharmacology

Lecture 17Thyroid Pharmacology

1)What are the different forms of thyroid hormone available for replacement therapy and how do they compare with the normal secretion and metabolism of thyroid hormone? Thyroxine is the major hormone secreted from the thyroid gland.

Thyroxine - given orally as replacement therapy when thyroid hormone levels are low. Taken once a day, thyroxine has a six-day half-life.

Triiodothyronine - is the active form of thyroid hormone formed from thyroxine in peripheral tissues. Triiodothyronine has a shorter half-life and greater potency than thyroxine, and therefore, is subject to greater fluctuations in hormone levels. It is useful in cessation of replacement therapy due to its feedback inhibition of TSH. This induces temporary hypothyroidism to enhance uptake of radiolabeled iodine.

2)What drugs raise the total serum T4 concentration without raising the free hormone concentration? Do any drugs lower the total T4? Total T4 concentration can be increased without increasing the free hormone concentration by increasing the thyroxine binding globulin (TBG), which binds more T4 in the blood stream, but maintains a stable level of free T4 through dissociation and cell uptake. Drugs that increase TBG include: estrogens, tamoxifen, heroine, methadone, and mitotane. Drugs that lower the total T4 concentration include: androgens and glucocorticoids. They do this by lowering the blood concentration of TBG.

3)How do Thiourea drugs decrease thyroid hormone levels?The thiouracil agents, propylthiouracil and methimazol, decreased the synthesis of thyroid hormone in the thyroid gland by blocking the organification of iodide. Propylthiouracil also decreases the peripheral conversion of T4 to T3.

4)How is radioiodide 131 used to treat hyperthyroidism? Any contraindications?In patients with persistent hyperthyroidism, radioiodide 131 can be given orally to destroy overactive thyroid tissue. The radioactive iodide is taken up by the thyroid tissue and induces radiation injury to the cells, causing loss of function over the next weeks to months. Achieving the appropriate amount of destruction is difficult and patients often end up with hypothyroidism and must be treated with thyroxine. Radioiodide is contraindicated in pregnant women or nursing mothers, because it will also destroy the thyroid gland of the fetus.

5)Why are adrenergic blocking agents used to treat hyperthyroidism?A beta adrenergic receptor antagonist, such as propranolol may be used to relieve the symptoms of hyperthyroidism. It suppresses tachycardia and other catecholamine affects and prevents thyroid storm.

6)What are the three calcium-regulating hormones and how are they used as drugs?

Parathyroid hormone - can be used as a diagnostic test to distinguish pseudohypoparathyroidism from hypoparathyroidism wherein patients with pseudohypoparathyroidism fail to respond to injection of parathyroid hormone by elevation of urinary cAMP. Recombinant human parathyroid hormone (teriparatide) has been shown to increase bone density in patients with osteoporosis.

Calcitonin - used to treat patients with hypercalcemia, because it decreases calcium and phosphorus resorption from bone. It also treats Paget's disease and osteoporosis.

Vitamin D - used as a supplement in the treatment of rickets or osteomalacia. The most potent form, 1, 25-dihydroxyvitamin D, promotes calcium absorption from the intestine and to a lesser extent, mobilizes calcium resorption from bone. It is also given in large. "Supraphysiologic" doses in the treatment of hypoparathyroidism.

7)What drugs are available to treat hypercalcemia?Treatment of hypercalcemia includes intravenous hydration with saline, often combined with a diuretic furosemide to increase renal excretion of calcium. Glucocorticoids are often effective in patients in whom the hypercalcemia is due to excessive vitamin D (including granulomatous diseases such as sarcoidosis). Calcitonin infusions are also used to decrease serum calcium. In severe cases, mithramycin, a cytotoxic anabiotic the decreases osteoclast activity, is given in low IV doses.

8)What are diphosphonates and how are they used?Diphosphonates are analogues of pyrophosphate in which the P-O-P bond has been replaced with a non-hydrolyzable P-C-P bond. Retard formation and dissolution of hydroxyapatite crystals within and outside the skeletal system. However, the exact mechanism by which they selectively inhibit bone resorption is not clear. Sodium etidronate, Alendonate, and Risedronate are drugs currently in use for treatment of patients with Paget's disease and osteoporosis.