Physical Properties
Iodine-131 is a radioactive isotope of stable iodine that emits a combination of beta particles and gamma rays. Radioactive decay of 131I takes place rapidly, with a half-life of 8 days.
CHAPTER 58 Drugs for Thyroid Disorders
The doses of 131I used to treat cancer are large, ranging from 50 to 150 mCi.
These doses are much higher than those used in Graves’ disease. Because high amounts of radioactivity are involved, body wastes must be disposed of properly. In addition, adverse effects from large doses of 131I can be severe:
radiation sickness may occur; leukemia may be produced; and bone marrow function may be depressed, resulting in leukopenia, thrombocytopenia, and anemia. Fortunately, these severe effects are rare.
Diagnostic Use
Iodine-131 is employed to diagnose a variety of thyroid disorders, including hyperthyroidism, hypothyroidism, and goiter. Following 131I administration, the thyroid is scanned for uptake of radioactivity; the amount and location of
131I uptake reveal the extent of thyroid activity. Doses for diagnosis are minuscule (less than 1 mCi for children and less than 10 mCi for adults). These tracer doses pose virtually no threat to health. Please note that although 131I can be used for diagnosis, the preferred isotope is 123I.
Preparations
Iodine-131 is supplied in capsules and solution for oral administration. Both preparations are odorless and tasteless. Capsules contain between 0.75 and 100 mCi of 131I. Vials of oral solution contain between 3.5 and 150 mCi of 131I.
Nonradioactive Iodine: Lugol’s Solution
Description
Lugol’s solution, also known as strong iodine solution, is a mixture containing 5% elemental iodine and 10% potassium iodide. The iodine undergoes reduction to iodide within the GI tract before absorption.
Mechanism of Action
When present in high concentrations, iodide has a paradoxical suppressant effect on the thyroid. Three mechanisms are involved. First, high concentrations of iodide decrease iodine uptake by the thyroid. Second, high concentrations of iodide inhibit thyroid hormone synthesis by suppressing both the iodination of tyrosine and the coupling of iodinated tyrosine residues. Third, high concentrations of iodine inhibit release of thyroid hormone into the blood.
All three actions combine to decrease circulating levels of T3 and T4. Unfortunately, the effects of iodide on thyroid function cannot be sustained indefinitely. With long-term iodide administration, suppressant effects become weaker. Accordingly, iodide is rarely used alone for thyroid suppression.
Therapeutic Use
Strong iodine solution can be given to hyperthyroid individuals to suppress thyroid function in preparation for thyroidectomy. Initial effects develop within 24 hours. Peak effects develop in 10 to 15 days. In most cases, plasma levels of thyroid hormone are reduced with methimazole before initiating strong iodine solution. Then strong iodine solution (along with more PTU) is administered for the last 10 days before surgery. In addition to its use before thyroidectomy, strong iodine solution is employed in thyrotoxic crisis and as an antiseptic (see Chapter 96).
Adverse Effects
Chronic ingestion of iodine can produce iodism. Signs and symptoms include a brassy taste, a burning sensation in the mouth and throat, soreness of the teeth and gums, frontal headache, coryza (nasal inflammation and sneezing), salivation, and various skin eruptions. All of these fade rapidly after iodine use stops.
Overdose
Iodine is corrosive, so overdose will injure the GI tract. Symptoms include abdominal pain, vomiting, and diarrhea. Swelling of the glottis may cause asphyxiation. Treatment consists of gastric lavage (to remove iodine from the stomach) and giving sodium thiosulfate (to reduce iodine to iodide).
Dosage and Administration
When employed to prepare hyperthyroid patients for thyroidectomy, strong iodine solution is administered in a dosage of 5 to 7 drops 3 times daily for 10 days immediately preceding surgery. Iodine solution should be mixed with juice or some other beverage to mask its unpleasant taste. The dosage for thyrotoxic crisis is 10 drops every 8 hours.
Beta Blockers
Propranolol [Inderal LA, InnoPran XL] and other beta blockers can suppress tachycardia and other symptoms of Graves’ disease. Benefits derive from
Hence, after 56 days (seven half-lives), less than 1% of the radioactivity in a dose of 131I remains.
Use in Graves’ Disease
Iodine-131 can be used to destroy thyroid tissue in patients with hyperthyroidism. The objective is to produce clinical remission without causing complete destruction of the gland.
Unfortunately, delayed hypothyroidism, due to excessive thyroid damage, is a frequent complication.
Effect on the Thyroid. Like stable iodine, 131I is concen-trated in the thyroid gland. Destruction of thyroid tissue is produced primarily by emission of beta particles. (The gamma rays from 131I are relatively harmless.) Because beta particles have a very limited ability to penetrate any type of physical barrier, they do not travel outside the thyroid. Hence, damage to surrounding tissue is minimal.
Reduction of thyroid function is gradual. Initial effects become apparent in days or weeks. Full effects develop in 2 to 3 months.
Not all patients respond satisfactorily to a single treatment.
About 66% of patients with Graves’ disease are cured with a single exposure to 131I. Others require two or more treatments.
Advantages and Disadvantages of 131I Therapy. The advantages of 131I treatment are considerable: (1) low cost; (2) patients are spared the risks, discomfort, and expense of thyroid surgery; (3) death from 131I treatment is extremely rare; and (4) no tissue other than the thyroid is injured (patients should be reassured of this).
Treatment with 131I is not without drawbacks. First, the effect of treatment is delayed, taking several months to become maximal. Second, and more important, treatment is associ-ated with a significant incidence of delayed hypothyroidism.
Hypothyroidism results from excessive dosage and occurs in up to 90% of patients within the first year following 131I exposure.
Who Should Be Treated and Who Should Not. Iodine-131 is indicated for adults with hyperthyroidism, as well as in patients who have not responded adequately to antithyroid drugs or to subtotal thyroidectomy.
As a rule, very young children are considered inappropriate candidates. The likelihood of delayed hypothyroidism is higher than in adults. Also, there is concern that administration of
131I to young patients may carry a slight risk of cancer. It should be noted, however, that there is no evidence that the use of
131I in Graves’ disease has ever caused cancer of the thyroid or any other tissue. Although 131I is generally avoided in young children, it is commonly used in postpubertal adolescents and young adults.
Iodine-131 is contraindicated in pregnancy and lactation.
Exposure of the fetus to 131I after the first trimester may damage the immature thyroid, and exposure to radiation at any point in fetal life carries a risk of generalized developmental harm.
Accordingly, a negative pregnancy test is required before giving
131I. Because 131I enters breast milk, women receiving this agent should not breast-feed.
Dosage. Dosage of 131I is determined by thyroid size and by the rate of thyroidal iodine uptake. For Graves’ disease, the dosage usually ranges between 4 and 10 millicuries (mCi).
Use in Thyroid Cancer
Iodine-131 can be used to destroy malignant thyroid cells. However, since most forms of thyroid cancer do not accumulate iodine, only a small percentage of patients are candidates for 131I therapy.
immediately. Administration may be oral or IV. The dosage for propranolol is 10 to 40 mg PO every 6 to 8 hours, or 0.5 to 1 mg IV repeated every four hours until effects are observed.
The basic pharmacology of beta blockers is discussed in Chapter 18.
beta-adrenergic blockade, not from reducing levels of T3 or T4. One advantage of beta blockers is that they work quickly, unlike PTU, methimazole, and 131I.
Dosages for hyperthyroidism are highly individualized.
Beta blockers are also beneficial in thyrotoxic crisis. In the absence of contraindications (e.g., asthma, heart failure), all patients should receive one
KEY POINTS
■ The thyroid gland produces two active hormones: triiodo-thyronine (T3), which is highly active, and thyroxine (T4, tetraiodothyronine), which appears inactive.
■ Thyroid hormones have three principal actions: stimulation of energy use, stimulation of the heart, and promotion of growth and development.
■ Hormonal regulation of thyroid function occurs as follows:
TRH from the hypothalamus causes the pituitary to release TSH, which causes the thyroid to make and release T3 and T4, which then act on the pituitary to suppress further release of TSH.
■ The four steps in thyroid hormone synthesis are (1) uptake of iodide by the thyroid, (2) conversion of iodide to iodine, (3) linking of iodine to tyrosine, and (4) coupling of two iodinated tyrosines to form T3 or T4.
■ Much of the T4 released by the thyroid is converted to T3
in the periphery.
■ Low plasma levels of iodine stimulate synthesis of T3 and T4.
■ In iodine-sufficient countries, the major cause of hypothy-roidism is chronic autoimmune thyroiditis (Hashimoto’s thyroiditis).
■ A goiter is an enlargement of the thyroid.
■ Testing serum for elevated levels of TSH is the most sensitive way to diagnose hypothyroidism.
■ Most patients with hypothyroidism require lifelong replace-ment therapy with thyroid hormones.
■ Maternal hypothyroidism during the first trimester of pregnancy can result in permanent neuropsychologic deficits in the child.
■ Levothyroxine (synthetic T4) is the drug of choice for most patients who require thyroid hormone replacement.
■ There is debate as to whether certain levothyroxine prepara-tions are interchangeable. Until the debate is resolved, it would seem best for patients to use only one product, unless the switch is approved of and monitored by the prescriber.
■ Levothyroxine should be taken on an empty stomach in the morning, at least 30 to 60 minutes before eating.
■ Chronic overtreatment with levothyroxine can cause atrial fibrillation and bone loss, especially in older adults.
■ Many drugs—including cholestyramine [Questran], colestipol [Colestid], sucralfate [Carafate], H2 receptor blockers, proton pump inhibitors, aluminum-containing antacids, iron supplements, and calcium supplements—can significantly reduce levothyroxine absorption. At least 4 hours should separate administration of levothyroxine and these drugs.
■ Levothyroxine can intensify the anticoagulant effects of warfarin.
■ Graves’ disease is the most common cause of excessive thyroid hormone secretion.
■ Graves’ disease can be treated by surgical removal of thyroid tissue, destruction of thyroid tissue with radioactive iodine (131I), or treatment with antithyroid drugs (methimazole or propylthiouracil).
■ Methimazole, an antithyroid drug, benefits patients with hyperthyroidism by suppressing thyroid hormone synthesis.
■ Full benefits of methimazole may take 3 to 12 weeks to develop.
■ The most serious adverse effect of methimazole is agranulocytosis.
■ Methimazole should be avoided during the first trimester of pregnancy.
■ Methimazole is on the NIOSH hazardous drug list and should be handled with caution by healthcare workers of childbearing age
■ Full effects of 131I require 2 to 3 months to develop.
■ Iodine-131 is contraindicated during pregnancy and lactation.
■ Strong iodine solution (Lugol’s solution) can be used to suppress thyroid hormone synthesis.
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CHAPTER 58 Drugs for Thyroid Disorders
Summary of Major Nursing Implications
aLEVOTHYROXINE (T4) Preadministration Assessment Therapeutic Goal
Resolution of signs and symptoms of hypothyroidism and restoration of normal laboratory values for serum TSH and free T4.
Baseline Data
Obtain serum levels of TSH and free T4. Implementation: Administration Routes
Oral, IV.
Administration
Oral. Instruct the patient to take levothyroxine on an empty stomach in the morning, at least 30 to 60 minutes before breakfast.
Make certain the patient understands that replacement therapy must continue for life. Caution patients against discontinuing treatment without consulting the prescriber.
Intravenous. Intravenous administration is reserved for treating myxedema coma and for patients who cannot take levothyroxine orally.
Ongoing Evaluation and Interventions Evaluating Therapeutic Effects
Adults. Clinical evaluation should reveal reversal of signs of thyroid deficiency and an absence of signs of thyroid excess (e.g., tachycardia). Laboratory tests should indicate normal plasma levels of TSH and T4.
Infants. Clinical evaluation should reveal normalization of intellectual function, growth, and development. Monthly measurements of height provide a good index of thyroid sufficiency. Laboratory tests should show normal plasma levels of TSH and T4. (Note: TSH levels may remain high in some children, despite adequate dosing.)
Minimizing Adverse Effects
Thyrotoxicosis. Overdose may cause thyrotoxicosis.
Inform patients about symptoms of thyrotoxicosis (tachycardia, angina, tremor, nervousness, insomnia, hyperthermia, heat intolerance, sweating), and instruct them to notify the pre-scriber if these develop.
Atrial Fibrillation and Bone Loss. Chronic overtreatment with levothyroxine can cause atrial fibrillation and fractures (from bone loss), especially in older adults. To prevent overtreatment, measure TSH levels at least once a year.
Minimizing Adverse Interactions
Drugs That Reduce Levothyroxine Absorption. Absorp-tion of levothyroxine can be reduced by multiple drugs, including H2 receptor blockers, proton pump inhibitors,
cholestyramine, colestipol, sucralfate, aluminum-containing antacids, iron supplements, calcium supplements, magnesium salts, and orlistat. Instruct patients to separate administration of levothyroxine and these drugs by 4 hours.
Drugs That Accelerate Levothyroxine Metabo-lism. Several drugs, including carbamazepine, rifampin, phenytoin, phenobarbital, and sertraline, can accelerate metabolism of levothyroxine and can thereby reduce its effects.
An increase in levothyroxine dosage may be needed.
Warfarin. Levothyroxine can intensify the effects of warfarin. Warfarin dosage may need to be reduced.
Catecholamines. Thyroid hormones sensitize the heart to catecholamines (epinephrine, dopamine, dobutamine) and may promote dysrhythmias. Exercise caution when catechol-amines and levothyroxine are used together.
LIOTHYRONINE (T3)
With the exceptions noted below, the nursing implications for liothyronine are the same as those for levothyroxine.
Evaluating Therapeutic Effects
Success is indicated by resolution of the signs and symptoms of hypothyroidism and by normalization of plasma T3 and TSH levels. T4 levels cannot be used to evaluate therapy.
METHIMAZOLE
Preadministration Assessment Therapeutic Goals
Methimazole has four indications: (1) reduction of thyroid hormone production in Graves’ disease, (2) control of hyperthyroidism until the effects of radiation on the thyroid become manifest, (3) suppression of thyroid hormone produc-tion before subtotal thyroidectomy, and (4) treatment of thyrotoxic crisis.
Baseline Data
Obtain serum levels of free T3 and free T4. Identifying High-Risk Patients
Methimazole should be avoided during the first trimester of pregnancy.
Implementation: Administration Route
Oral.
Administration
Instruct the patient to take methimazole once daily, at the same time every day.
Ongoing Evaluation and Interventions Summary of Monitoring
Evaluate treatment by monitoring for weight gain, decreased heart rate, and other indications that levels of thyroid hormone
Continued
aPatient education information is highlighted as blue text.
have declined. Laboratory tests should indicate a decrease in serum free T3 and free T4.
Minimizing Adverse Effects
Agranulocytosis. Inform patients about early signs of agranulocytosis (fever, sore throat), and instruct them to notify the prescriber if these develop. If follow-up blood tests reveal leukopenia, methimazole should be withdrawn.
Giving granulocyte colony-stimulating factor may accelerate recovery.
Hypothyroidism. Methimazole may cause excessive reductions in thyroid hormone synthesis. If signs of hypo-thyroidism develop or if plasma levels of T3 and T4 become subnormal, methimazole dosage should be reduced. Supple-mental thyroid hormone may be needed.
Effects in Pregnancy. When used during the first tri-mester, methimazole can cause neonatal hypothyroidism, goiter, and even congenital hypothyroidism. Use in the second and third trimesters is considered safe. If a thionamide is needed during the first trimester of pregnancy, PTU should be selected.
RADIOACTIVE IODINE (131I) Use in Graves’ Disease Therapeutic Goal
Suppression of thyroid hormone production.
Identifying High-Risk Patients
Iodine-131 is contraindicated during pregnancy and lactation.
Dosage and Administration
Iodine-131 is administered in capsules or an oral liquid. The dosing objective is to reduce thyroid hormone production without causing complete thyroid destruction. The dosage for Graves’ disease is 4 to 10 mCi.
Promoting Therapeutic Effects
Responses take 2 to 3 months to develop fully. Methimazole or propylthiouracil may be required during this interval.
Minimizing Adverse Effects
Excessive thyroid destruction can cause hypothyroidism.
Patients who develop thyroid insufficiency need thyroid hormone supplements.
Use in Thyroid Cancer
High doses (50 to 150 mCi) are required. These doses can cause radiation sickness, leukemia, and bone marrow depres-sion. Monitor for these effects. Body wastes will be con-taminated with radioactivity and must be disposed of appropriately.
Diagnostic Use
Iodine-131 is used to diagnose hyperthyroidism, hypothyroid-ism, and goiter. Diagnostic doses are so small (less than 10 mCi) as to be virtually harmless.
STRONG IODINE SOLUTION (LUGOL’S SOLUTION)
Preadministration Assessment Therapeutic Goal
Suppression of thyroid hormone production in preparation for subtotal thyroidectomy. Also used to suppress thyroid hormone release in patients experiencing thyroid storm.
Baseline Data
Obtain tests of thyroid function.
Implementation: Administration Route
Oral.
Administration
Advise patients to dilute strong iodine solution with fruit juice or another beverage to increase palatability.
Ongoing Evaluation and Interventions Minimizing Adverse Effects
Mild Toxicity. Inform patients about symptoms of iodism (brassy taste, burning sensations in the mouth, soreness of gums and teeth), and instruct them to discontinue treatment and notify the prescriber if these occur. Symptoms fade upon drug withdrawal.
Severe Toxicity. Iodine solution can cause corrosive injury to the GI tract. Instruct patients to discontinue the drug and notify the prescriber immediately if severe abdominal distress develops. Treatment includes gastric lavage and giving sodium thiosulfate.
Summary of Major Nursing Implications
a—cont’d
C H A P T E R
59 Drugs Related to Hypothalamic and Pituitary Function
Overview of Hypothalamic and Pituitary Endocrinology, p. 723
Anatomic Considerations, p. 723
Hormones of the Anterior Pituitary, p. 723 Hormones of the Posterior Pituitary, p. 723 Hypothalamic Release-Regulating Factors, p. 724 Feedback Regulation of the Hypothalamus and
Anterior Pituitary, p. 724 Growth Hormone, p. 724
Physiology, p. 724 Pathophysiology, p. 725 Clinical Pharmacology, p. 725
Mecasermin (Insulin-like Growth Factor-1), p. 726 Prolactin, p. 726
Regulation of Release, p. 726 Prolactin Hypersecretion, p. 727
Suppressing Prolactin Release With Dopamine Agonists, p. 727
Antidiuretic Hormone (Vasopressin), p. 727 Physiology, p. 728
Pathophysiology: Hypothalamic Diabetes Insipidus, p. 728
Antidiuretic Hormone Preparations, p. 728 Clinical Pharmacology, p. 728
Antidiuretic Hormone (Vasopressin) Antagonists, p. 729
Conivaptan, p. 729
Drugs for Acromegaly, p. 729 Somatostatin Analogs, p. 729
Pegvisomant, a Growth Hormone Receptor Antagonist, p. 730
Key Points, p. 730
Summary of Major Nursing Implications, p. 730