Pharmacologic Therapy PDF

11/7/23, 1:54 PM Realizeit for Student Pharmacologic Therapy Two forms of pharmacotherapy are available for treating hyperthyroidism and controlling excessive thyroid activity: (1) the use of irradiation by administration of the radioisotope 131I for destructive effects on the thyroid gland and (2...

11/7/23, 1:54 PM Realizeit for Student Pharmacologic Therapy Two forms of pharmacotherapy are available for treating hyperthyroidism and controlling excessive thyroid activity: (1) the use of irradiation by administration of the radioisotope 131I for destructive effects on the thyroid gland and (2) antithyroid medications that interfere with the synthesis of thyroid hormones and other agents that control manifestations of hyperthyroidism. Radioactive Iodine Therapy Radioactive iodine has been used to treat toxic adenomas, toxic multinodular goiter, and most varieties of thyrotoxicosis and is considered the treatment of choice because a single dose is effective in treating 80% to 90% of cases (Bauerle & Clutter, 2019). Radioactive iodine is contraindicated during pregnancy because it crosses the placenta. Women of childbearing age should be given a pregnancy test 48 hours before administration of radioactive iodine. They should also be instructed to not conceive for at least 6 months following treatment. In addition, breast-feeding for up to 6 weeks prior to radioactive iodine treatment is contraindicated (Lee & Khardori, 2018). The goal of radioactive iodine therapy (131I) is to eliminate the hyperthyroid state with the administration of sufficient radiation in a single dose (Lee & Khardori, 2018). Almost all of the iodine that enters and is retained in the body becomes concentrated in the thyroid gland. Therefore, the radioactive isotope of iodine is concentrated in the thyroid gland, where it destroys thyroid cells without jeopardizing other radiosensitive tissues. Over a period of several weeks, thyroid cells exposed to the radioactive iodine are destroyed, resulting in reduction of the hyperthyroid state and inevitably hypothyroidism. The use of an ablative dose of radioactive iodine initially causes an acute release of thyroid hormone from the thyroid gland and may cause increased symptoms. The patient is observed for signs of thyroid storm, a life-threatening condition manifested by cardiac arrhythmias, fever, and neurologic impairment (Norris, 2019) which may lead to heart failure, circulatory collapse and dangerous elevation of body temperature, all related to the increase in metabolism. Beta-blockers are used to control these symptoms. Thyroid hormone replacement is started 4 to 18 weeks after the antithyroid medications have been stopped based on the results of thyroid function tests. TSH measurements can be misleading in the early months following treatment with radioactive iodine. Therefore, serum free T4 is the principal test measured at 3 to 6 weeks following administration of radioactive iodine and then every 1 to 2 months until normal thyroid function is established. If TSH and free T4 are both persistently low, the total T3 then must be measured to differentiate between persistent hyperthyroidism (T3 elevated) or transient hypothyroidism (T3 normal or low). Once a normal thyroid state has been established, TSH should be measured every 6 to 12 months for life (Fischbach & Fischbach, 2018). A major advantage of treatment with radioactive iodine is that it avoids many of the side effects associated with antithyroid medications. However, some patients may elect to be treated with antithyroid medications rather than radioactive iodine for a variety of reasons, including fear of radiation. Patients who receive radioactive iodine should be informed that they can contaminate their household and other people through saliva, urine, or radiation emitting from their body. They should avoid sexual contact, sleeping in the same bed with other people, having close contact with children and pregnant women, and sharing utensils and cups. The patient should follow the instructions provided regarding the time restrictions for these cautions because they are dose related (Fischbach & Fischbach, 2018). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IZMyySaAjt8dTx3FnIrt15HOKniKu5nqplgCFS7%2bEIEJ2a… 1/5 11/7/23, 1:54 PM Realizeit for Student Antithyroid Medications Antithyroid medications (thionamides) are summarized in Table 45-1. The objective of pharmacotherapy is to inhibit one or more stages in thyroid hormone synthesis or hormone release. Antithyroid agents block the utilization of iodine by interfering with the iodination of tyrosine and the coupling of iodotyrosines in the synthesis of thyroid hormones. This prevents the synthesis of thyroid hormone. The most commonly used antithyroid drugs in the United States are methimazole or propylthiouracil. The medications are used until the patient is euthyroid (i.e., neither hyperthyroid nor hypothyroid). These medications block extrathyroidal conversion of T4 to T3 (Bauerle & Clutter, 2019). Prior to initiating therapy with these drugs, baseline blood tests are performed, including complete blood count (white blood cell [WBC] count with differential) and liver profile (transaminases and bilirubin) (Bauerle & Clutter, 2019). The therapeutic dose is determined on the basis of clinical criteria, including changes in pulse rate, pulse pressure, body weight, size of the goiter, and results of laboratory studies. The patient should be instructed to take the medication in the morning on an empty stomach 30 minutes before eating to avoid decrease in absorption associated with some foods such as walnuts, soybean flour, cottonseed meal, and dietary fiber. Because antithyroid medications do not interfere with release or activity of previously formed thyroid hormones, it may take several weeks until symptom relief occurs. At that time, the maintenance dose is established, and the medication is gradually tapered over several months. Toxic complications of antithyroid medications are relatively uncommon; nevertheless, the importance of periodic follow-up is emphasized, because medication sensitization, fever, rash, urticaria, or even agranulocytosis and thrombocytopenia (decrease in granulocytes and platelets) may develop (Bauerle & Clutter, 2019). With any sign of infection, especially pharyngitis and fever or the occurrence of mouth ulcers, the patient is advised to stop the medication, notify the primary provider immediately, and undergo hematologic studies (Bauerle & Clutter, 2019). Propylthiouracil is recommended during the first trimester of pregnancy rather than methimazole due to the teratogenic effects of methimazole. Due to risk of hepatotoxicity, propylthiouracil should be discontinued after the first trimester and the patient should be switched to methimazole for the remainder of the pregnancy and when breast-feeding (Bauerle & Clutter, 2019). Discontinuation of antithyroid medications before therapy is complete usually results in relapse within 6 months. It is important that the possibility of relapse be discussed so that a treatment strategy will be in place if relapse occurs. Adjunctive Therapy Additional medications may be necessary. Potassium iodide (SSKI) may be used in combination with antithyroid agents or beta-adrenergic blockers to prepare the patient with hyperthyroidism for surgery. The drugs reduce the effects of hyperthyroidism quickly and help to prevent the onset of thyroid storm. The usual dosage for SSKI is 5 drops every 6 hours. The usual dose of propylthiouracil is 200 mg every 6 hours and the usual dose of propranolol is 60 to 80 mg orally every 6 hours to prevent tachycardia. The patient will need to continue to take the propylthiouracil and any cardiac medication until the free T4 and T3 levels are near normal (Bauerle & Clutter, 2019). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IZMyySaAjt8dTx3FnIrt15HOKniKu5nqplgCFS7%2bEIEJ2a… 2/5 11/7/23, 1:54 PM Realizeit for Student Antithyroid Drugs Propylthiouracil and Related Drugs Propylthiouracil is the prototype of the thioamide antithyroid drugs. The U.S. Food and Drug Administration (FDA) approved it for the treatment of hyperthyroidism more than 60 years ago. Pharmacokinetics Propylthiouracil is well absorbed with oral administration, and peak plasma levels occur within 30 minutes. The drug's plasma half-life is 1 to 2 hours. However, its duration of action depends on the half-life within the thyroid gland rather than the plasma half-life. Because this time is relatively short, the drug must be given every 8 hours. It is metabolized in the liver and excreted in urine. Action Propylthiouracil acts by inhibiting production of thyroid hormones and peripheral conversion of T4 to the more active T3. The drug does not interfere with release of thyroid hormones previously produced and stored. Thus, therapeutic effects do not occur for several days or weeks until the stored hormones have been used. Use Health care providers may use propylthiouracil alone to treat hyperthyroidism, as part of the preoperative preparation for thyroidectomy, before or after radioactive iodine therapy, and in the treatment of thyroid storm. Treatment of hyperthyroidism changes the rate of body metabolism, including the rate of metabolism of many drugs. In the hyperthyroid state, drug metabolism may be very rapid, and higher doses of most drugs may be necessary to achieve therapeutic results. When the patient becomes euthyroid, the rate of drug metabolism decreases. Consequently, it is necessary to evaluate and likely reduce doses of all medications to avoid severe adverse effects. Use in Older Adults Propylthiouracil (or methimazole) may be useful. However, radioactive iodine is often preferable because it is associated with fewer adverse effects than other antithyroid drugs or surgery. It is necessary that patients be monitored closely for hypothyroidism, which usually develops within 1 year after receiving treatment for hyperthyroidism. Use in Patients With Hepatic Impairment The FDA has issued a BLACK BOX WARNING ♦ for propylthiouracil stating that severe liver injury resulting in death or acute liver failure may occur within 6 months of treatment. Routine liver function testing to assess for liver failure is important. Adverse Effects Administration of propylthiouracil may have several adverse effects, including the following: Signs and symptoms of hypothyroidism: bradycardia, heart failure, anemia, coronary artery disease, peripheral vascular disease, slow speech and body movements, emotional and mental dullness, excessive sleeping, increased weight, constipation, and skin changes Hematologic effects: leukopenia, agranulocytosis (puts patient at risk for sepsis, rare but severe, earliest symptoms likely to be sore throat and fever), and hypoprothrombinemia Dermatologic effects: rash, pruritus, and alopecia CNS effects: headache, dizziness, loss of taste, drowsiness, and paresthesias Gastrointestinal (GI) effects: nausea, vomiting, abdominal discomfort, gastric irritation, and cholestatic hepatitis Other reported effects: lymphadenopathy, edema, joint pain, and drug fever Contraindications The only contraindication to propylthiouracil is a known hypersensitivity reaction to the medication. QSEN Alert: Evidence-Based Practice Wall, Weaver, Litt, and Rae (2017) conducted a case report and review of literature to provide evidence of the clinical symptoms, diagnosis, prevent associated vasculitis in the intensive care setting. The case reports described the onset of rashes in patients taking propylthiouracil. Of the 128 cas vasculitis, the majority were women who presented with a rash, fever, and arthralgia. The patients were treated with steroids. Eight of the patients p required intubation, and five died of multiple organ failure that was related to the vasculitis. The result of the analysis is screening with myeloperoxid Patients who screen positive should be evaluated for skin manifestations, and aggressive wound care should be implemented. Nursing Implications Preventing Interactions https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IZMyySaAjt8dTx3FnIrt15HOKniKu5nqplgCFS7%2bEIEJ2a… 3/5 11/7/23, 1:54 PM Realizeit for Student Propylthiouracil may increase the effect of anticoagulants, which may put patients at risk for bleeding. Also, use with amiodarone, potassium iodide, and sodium iodide reverses thyroid hormone efficacy. Lithium acts synergistically with propylthiouracil to produce hypothyroidism. Administering the Drug Patients should take propylthiouracil around the clock in evenly divided doses. If they choose to take one dose of the medication without food, they should take all doses without food. (The same is true if they take it with food.) Assessing for Therapeutic Effects The nurse assesses for a slower pulse rate, slow speech, normal level of activity without the signs of hyperactivity, decreased nervousness and tremors, increased sleep patterns, and weight gain. The therapeutic effects should be apparent in 1 to 2 weeks, but a euthyroid state may not occur for 6 to 8 weeks. Assessing for Adverse Effects The nurse assesses the patient’s heart rate and peripheral pulses for increases, the lung sounds for crackles, and the heart sounds for an audible S3; these are all indicative of heart failure. It is also necessary to assess for slow speech and emotional status (dullness). In addition, the nurse checks for increased periods of rest, increased weight, constipation, and skin changes. Finally, he or she assesses for CNS depression and gastric irritation, as well as for fever or sore throat, the first signs of agranulocytosis. It is important to assess the white blood count for leukopenia. Patient Teaching All patients should receive instructions about the signs and symptoms of acute liver failure and seeking immediate medical treatment should those symptoms occur. Box 42.1 identifies additional patient teaching guidelines for propylthiouracil. BOX 42.1 Patient Teaching Guidelines for Propylthiouracil To decrease the production of thyroid hormone by an overactive thyroid gland, it is necessary to take antithyroid drugs for 1 year or longer to retu Have periodic tests of thyroid function. Dosage adjustments may be necessary. Have periodic tests of liver function tests during the first 6 months of treatment. Ask the prescriber if it is necessary to avoid or restrict amounts of seafood or iodized salt. It may be necessary to reduce or omit these sources o Take this drug at regular intervals around the clock, usually every 8 hours. Report fever, sore throat, unusual bleeding or bruising, headache, skin rash, yellowing of the skin, or vomiting to the prescriber. If these adverse e drug dosage or have you stop taking the drug. Consult a health care provider before taking over-the-counter drugs. Some drugs contain iodide, which can increase the likelihood of goiter and doses of iodide. For example, some cough syrups, asthma medications, and multivitamins may contain iodide. Take your pulse daily and report rates above 100 and below 60 beats/min to the prescriber. Check your weight two to three times per week, and if it increases suddenly, call your health care provider. Consult a health care provider if signs or symptoms of a rash occur. Other Drugs in the Class Methimazole (Tapazole) is similar to propylthiouracil in terms of action, use, and adverse effects. It is also well absorbed with oral administration and rapidly reaches peak plasma levels. QSEN Alert: Safety Because of the risk of fetal abnormalities associated with methimazole, women of childbearing age should have a pregnancy test before beginning methimazole during the first trimester; it is safe to use in the second and third trimesters. Strong iodine solution (Lugol solution) and saturated solution of potassium iodide (SSKI) are iodine preparations sometimes used in shortterm treatment of hyperthyroidism. These drugs inhibit release of thyroid hormones, causing them to accumulate in the thyroid gland. Lugol solution is usually used to treat thyrotoxic crisis and to decrease the size and vascularity of the thyroid gland before thyroidectomy. SSKI is more often used as an expectorant but may be given as preparation for thyroidectomy. Iodine preparations should not be followed by propylthiouracil, methimazole, or radioactive iodine because the latter drugs cause release of stored thyroid hormone and may precipitate acute hyperthyroidism. Sodium iodide 131I (Hicon) is a radioactive isotope of iodine. The thyroid gland cannot differentiate between regular iodide and radioactive iodide, so it picks up the radioactive iodide from the circulating blood. As a result, small amounts of radioactive iodide can be used as a diagnostic test of thyroid function, and larger doses are used therapeutically to treat hyperthyroidism. Therapeutic doses act by emitting beta and gamma rays, which destroy thyroid tissue and thereby decrease production of thyroid hormones. The drug is also used to treat thyroid cancer. It is safe, effective, inexpensive, and convenient. One disadvantage is hypothyroidism, which usually develops within a few https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IZMyySaAjt8dTx3FnIrt15HOKniKu5nqplgCFS7%2bEIEJ2a… 4/5 11/7/23, 1:54 PM Realizeit for Student months and requires lifelong thyroid hormone replacement therapy. Another disadvantage is the delay in therapeutic benefits. Results may not be apparent for 3 months or longer, during which time it is necessary to bring severe hyperthyroidism under control with one of the thioamide antithyroid drugs. Note that after radioactive iodine therapy, patients should not expectorate or cough freely because their saliva will be radioactive for 24 hours. Adjuvant Medication Used To Treat Hyperthyroidism The drug propranolol (Inderal) is a beta-adrenergic–blocking agent that is recommended in all patients with symptomatic hyperthyroidism. It is particularly useful in older adults who have resting heart rates greater than 90 beats/min or have a history of cardiovascular conditions, such as dysrhythmias, angina pectoris, and hypertension. When given to patients with hyperthyroidism, propranolol blocks beta-adrenergic receptors in various organs and thereby controls symptoms of hyperthyroidism resulting from excessive stimulation of the sympathetic nervous system. These symptoms include tachycardia, palpitations, excessive sweating, tremors, and nervousness. Propranolol is useful for controlling symptoms during the delayed response to thioamide drugs and radioactive iodine, before thyroidectomy, and in treating thyrotoxic crisis. When patients become euthyroid and definitive treatment has controlled hyperthyroid symptoms, it is necessary to taper propranolol and discontinue it. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IZMyySaAjt8dTx3FnIrt15HOKniKu5nqplgCFS7%2bEIEJ2a… 5/5