Thyroid and Antithyroid Drugs



Thyroid and Antithyroid Drugs


Objectives


When you reach the end of this chapter, you will be able to do the following:



Drug Profiles



Key Terms


Euthyroid Referring to normal thyroid function. (p. 503)


Hyperthyroidism A condition characterized by excessive production of the thyroid hormones. A severe form of this disorder is called thyrotoxicosis. (p. 502)


Hypothyroidism A condition characterized by diminished production of the thyroid hormones. (p. 502)


Thyroid-stimulating hormone (TSH) An endogenous substance secreted by the pituitary gland that controls the release of thyroid gland hormones and is necessary for the growth and function of the thyroid gland (also called thyrotropin). (p. 502)


Thyroxine (T4) The principle thyroid hormone that influences the metabolic rate. (p. 502)


Triiodothyronine (T3) A secondary thyroid hormone that also affects body metabolism. (p. 502)


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Anatomy, Physiology, and Pathophysiology Overview


Thyroid Function


The thyroid gland lies across the larynx in front of the thyroid cartilage (“Adam’s apple”). Its lobes extend laterally on both sides of the front of the neck. It is responsible for the secretion of three hormones essential for the proper regulation of metabolism: thyroxine (T4), triiodothyronine (T3), and calcitonin (see Chapter 34). It is located close to and communicates with the parathyroid glands, which lie just above and behind it. The parathyroid glands are two pairs of bean-shaped glands. These glands are made up of encapsulated cells, which are responsible for maintaining adequate levels of calcium in the extracellular fluid, primarily by mobilizing calcium from bone.


Thyroxine (T4) and triiodothyronine (T3) are produced in the thyroid gland through the coupling of iodine and the amino acid tyrosine. The iodide (I–, which is the ionized form of iodine) needed for this process is acquired from the diet. One mg of iodide is needed per week. This iodide is absorbed from the blood and then sequestered by the thyroid gland, where it is concentrated to 20 times its blood level. Here it is also converted to iodine (I2), which is combined with tyrosine to make diiodotyrosine. The combination of two molecules of diiodotyrosine causes the formation of thyroxine, which therefore has four iodine molecules in its structure (T4). Triiodothyronine is formed by the coupling of one molecule of diiodotyrosine with one molecule of monoiodotyrosine; thus it has three iodine molecules in its structure (T3). The biologic potency of T3 is about four times greater than that of T4, but T4 is present in much greater quantities. After the synthesis of these two thyroid hormones, they are stored in the follicles in the thyroid gland in a complex with thyroglobulin (a protein that contains tyrosine and an amino acid) called the colloid. When the thyroid gland is signaled to do so, the thyroglobulin–thyroid hormone complex is enzymatically broken down to release T3 and T4 into the circulation. This entire process is triggered by thyroid-stimulating hormone (TSH), also called thyrotropin. Its release from the anterior pituitary gland is stimulated when blood levels of T3 and T4 are low.


The thyroid hormones are involved in a wide variety of bodily processes. They regulate the basal metabolic rate and lipid and carbohydrate metabolism, are essential for normal growth and development, control the heat-regulating system (thermoregulatory center in the brain), and have various effects on the cardiovascular, endocrine, and neuromuscular systems. Therefore, hyperfunction or hypofunction of the thyroid gland can lead to a wide range of serious consequences.


Pathophysiology of Hypothyroidism


There are three types of hypothyroidism. Primary hypothyroidism stems from an abnormality in the thyroid gland itself. It occurs when the thyroid gland is not able to perform one of its many functions, such as releasing the thyroid hormones from their storage sites, coupling iodine with tyrosine, trapping iodide, converting iodide to iodine, or any combination of these defects. Primary hypothyroidism is the most common of the three types of hypothyroidism. Secondary hypothyroidism begins at the level of the pituitary gland and results from reduced secretion of thyroid stimulating hormone (TSH). TSH is needed to trigger the release of the T3 and T4 stored in the thyroid gland. Tertiary hypothyroidism is caused by a reduced level of the thyrotropin-releasing hormone from the hypothalamus. This reduced level, in turn, reduces TSH and thyroid hormone levels. Symptoms of hypothyroidism include cold intolerance, unintentional weight gain, depression, dry brittle hair and nails, and fatigue.


Hypothyroidism can also be classified by when it occurs in the lifespan. Hyposecretion of thyroid hormone during youth may lead to cretinism. Cretinism is characterized by low metabolic rate, retarded growth and sexual development, and possible mental retardation. Hyposecretion of thyroid hormone as an adult may lead to myxedema. Myxedema is a condition manifested by decreased metabolic rate, but it also involves loss of mental and physical stamina, weight gain, hair loss, firm edema, and yellow dullness of the skin.


Some forms of hypothyroidism may result in the formation of a goiter, which is an enlargement of the thyroid gland resulting from its overstimulation by elevated levels of TSH. The TSH level is elevated because there is little or no thyroid hormone in the circulation. Certain drugs can cause hypothyroidism, with amiodarone (see Chapter 25) being the most common. Interestingly, amiodarone can also cause hyperthyroidism.


Pathophysiology of Hyperthyroidism


Excessive secretion of thyroid hormones, or hyperthyroidism, may be caused by several different diseases. Diseases known to cause hyperthyroidism include Graves’ disease, which is the most common cause; Plummer’s disease, also known as toxic nodular disease, which is the least common cause; multinodular disease; and thyroid storm, which is a severe and potentially life-threatening exacerbation of the symptoms of hyperthyroidism that is usually induced by stress or infection.


Hyperthyroidism can affect multiple body systems, resulting in an overall increase in metabolism. Commonly reported symptoms are diarrhea, flushing, increased appetite, muscle weakness, fatigue, palpitations, irritability, nervousness, sleep disorders, heat intolerance, and altered menstrual flow.


Pharmacology Overview


Thyroid Replacement Drugs


Hypothyroidism is treated with thyroid hormone replacement using various thyroid preparations. These drugs can be either natural or synthetic in origin. The natural thyroid preparations are derived from the thyroid glands of animals such as cattle and hogs. Currently only one natural preparation is available in the United States, and it is called simply thyroid or thyroid, desiccated. Desiccation is the term for the drying process used to prepare this drug form. All natural preparations are standardized for their iodine content. The synthetic thyroid preparations are levothyroxine (T4), liothyronine (T3), and liotrix (which contains a combination of T4 and T3 in a 4:1 ratio). The approximate clinically equivalent doses of the drugs are given in Table 31-1. This information is useful for guiding dosage adjustments when a patient is switched from one thyroid hormone to another. Monitoring of serum TSH and free thyroid hormone levels are required to determine the appropriate dose of thyroid replacement drugs.



Mechanism of Action and Drug Effects


Thyroid drugs work in the same manner as the endogenous thyroid hormones, affecting many body systems. At the cellular level, they work to induce changes in the metabolic rate, including the rate of protein, carbohydrate, and lipid metabolism, and to increase oxygen consumption, body temperature, blood volume, and overall cellular growth and differentiation. They also stimulate the cardiovascular system by increasing the number of myocardial beta-adrenergic receptors. This, in turn, increases the sensitivity of the heart to catecholamines and ultimately increases cardiac output. In addition, thyroid hormones increase renal blood flow and the glomerular filtration rate, which results in a diuretic effect.


Indications


Thyroid preparations are given to replace what the thyroid gland itself cannot produce to achieve normal thyroid hormone levels (euthyroid condition). Levothyroxine is the preferred thyroid drug because its hormonal content is standardized and its effect is predictable. Thyroid drugs can also be used for the diagnosis of suspected hyperthyroidism (as in a TSH-suppression test) and in the prevention or treatment of various types of goiters. They are also used for replacement hormonal therapy in patients whose thyroid glands have been surgically removed or destroyed by radioactive iodine in the treatment of thyroid cancer or hyperthyroidism. Hypothyroidism during pregnancy is treated with dosage adjustments every 4 weeks to maintain the TSH level at the lower end of the normal range. Fetal growth may be retarded if maternal hypothyroidism remains untreated during pregnancy.


Contraindications


Contraindications to thyroid preparations include known drug allergy, recent myocardial infarction, adrenal insufficiency, and hyperthyroidism.


Adverse Effects


The adverse effects of thyroid medications are usually the result of overdose. The most significant adverse effect is cardiac dysrhythmia with the risk for life-threatening or fatal irregularities. Other more common undesirable effects are listed in Table 31-2.



Interactions


Thyroid drugs may enhance the activity of oral anticoagulants, the dosages of which may need to be reduced. Taking thyroid preparations concurrently with digitalis glycosides may decrease serum digitalis levels. Cholestyramine binds to thyroid hormone in the gastrointestinal tract, which possibly reduces the absorption of both drugs. Diabetic patients taking a thyroid drug may require increased dosages of their hypoglycemic drugs. In addition, the use of thyroid preparations with epinephrine in patients with coronary disease may induce coronary insufficiency. See Table 31-3 for more drug interactions.



Dosages


For dosage information on the thyroid drugs, see the table on p. 504.


Drug Profile


The most commonly used thyroid replacement drugs are the synthetic drugs levothyroxine and liotrix. Some patients experience better results with the animal-derived products. Although the thyroid drugs differ chemically, their therapeutic actions are all the same. Factors to be considered before the initiation of drug therapy with a thyroid drug include the desired ratio


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May 9, 2017 | Posted by in NURSING | Comments Off on Thyroid and Antithyroid Drugs

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