Thyroid Drugs

Iodides (Thyro-Block®)

Inhibitors of Thyroid Hormone Synthesis Oldest therapy for hyperthyroidism Mechanism of Action: Excess iodide will decrease synthesis of T3 and T4 Causes a rapid decrease in the release of thyroid hormone Indications/Therapeutic Effects: Often used prior to thyroid surgery because it decreases the vascularity of the gland o It is not used prior to radioactive iodine treatment, as it will compete with its uptake Thioamide treatment should be initiated first, as iodide will prevent response to thioamides Iodide can also be used to prevent uptake of radioactive iodine in the event of an accident (e.g. nuclear power plant) where large quantities of the radioactive compound might be released. Pharmacokinetics: Iodide alone not a good treatment for hyperthyroidism, as effect wears off after 2-8 weeks, resulting in thryotoxicosis.

Propylthiouracil (PTU)

Inhibitors of Thyroid Hormone Synthesis Thioamide derivatives Mechanism of Action: Inhibit the synthesis of thyroid hormone in the thyroid gland Decrease incorporation of iodine, decrease synthesis, and prevent coupling T3 and T4 that is already circulating in the blood will still affect the receptors Cause a gradual decrease (3-4 weeks) in the symptoms of thyrotoxicosis. Propylthiouracil (PTU) decreases the peripheral conversion of T3 from circulating T4, which may produce a slightly more rapid effect Indications/Therapeutic Effects: First line of treatment for Graves' disease Used in conjunction with radioactive iodine (decrease likelihood of thyroid storm if given beforehand), for thyrotoxic crisis, and to prepare patients for subtotal thyroidectomy. Adverse Effects: Propylthiouracil has a Black Box Warning for severe liver injury and acute liver failure, so methimazole is now the drug of choice for anti-thyroid medicines o PTU should only be used in those who cannot tolerate methimazole o PTU may be the drug of choice for early pregnancy (1sttrimester only), as birth defects have been observed with methimazole therapy, but not PTU Most common side effects are itching and skin rash The most serious side effect is granulocytopenia and agranulocytosis, which is reversible when the drug is stopped. o These are often heralded by a sore throat; patients should be advised to have blood counts done whenever they get a sore throat. Headaches Nausea, jaundice Myalgia, arthralgia Lupus-like syndrome Lymphadenopathy Psychosis Prolonged administration may result in formation of goiter, due to increased TSH. Thyroxine is often administered concurrently to prevent this. o In pregnancy, dose is kept low to decrease the chance of inducing goiter and cretinism in the fetus.

Radioactive iodine (131I)

Inhibitors of Thyroid Hormone Synthesis Mechanism of Action: Radioactive iodine becomes trapped in the gland and beta rays destroy the tissue Indications/Therapeutic Effects: The principal indication for radioactive iodine is hyperthyroidism in elderly patients and in those with heart disease Low dose (microcuries) used for diagnostic procedures Large doses (millicuries) used for thyroid ablation in the management of thryotoxicosis due to toxic adenoma or toxic multinodular goiter o Also used to remove remaining thyroid tissue after thyroidectomy because of thyroid cancer Adverse Effects: Although the dose can be titrated to produce partial destruction of the thyroid, hypothyroidism usually develops after radioactive iodine

Methimazole (Tapazole®)

Inhibitors of Thyroid Hormone Synthesis ~Propylthiouracil (PTU) Methimazole is more potent and longer-acting than PTU, but does not inhibit the conversion of T4 to T3 drug of choice for anti-thyroid medicines birth defects have been observed with methimazole therapy, but not PTU

Liotrix (Euthroid®, Thyrolar®)

Thyroid Hormone Replacement 4:1 mixture of T4 to T3 No advantage over T4 alone, since T4 is converted in the body to T3.

Thyroid, USP (Thyrar®, Armour Thyroid®)

Thyroid Hormone Replacement Derived from thyroid glands of sheep, cows, or pigs Although standardized, potency can vary greatly from one batch to another, making it very difficult to maintain patients on a stable level Adverse effects of thyroid hormone therapy Side effects are symptoms of hyperthyroidism. Hyperthyroidism resembles excess sympathetic stimulation. Effects include: o Cardiac palpitation and a predisposition to arrhythmias o Tachycardia o Angina pectoris o Tremor o Weight loss o Insomnia o Heat intolerance o Increased appetite Decrease dose or stop medication for a few days and resume at a lower dose. Drug Interactions with thyroid hormones Estrogen and tamoxifen o Can increase levels of thyroxine-binding globulin (TBG), which will reduce the clinical response to levothyroxine. o Hypothyroid patients may require larger doses of levothyroxine if an estrogen is added. o Free T4 is measured in women on thyroid treatment and estrogens. o Glucocorticoids and androgens decrease levels of TBG, so have the opposite effect. Salicylates o Displace thyroxine from binding sites. o Dose may have to be adjusted. Sympathetic stimulants o Given together with large doses of thyroxine (this has been done to promote weight loss), can produce serious and life-threatening cardiotoxicity. Iodides and lithium o Inhibit release or synthesis of thyroid hormones. o Amiodarone (antiarrythmic drug) contains iodide. Antacids, sucralfate, cholestyramine, or ferrous sulfate o May interfere with absorption of levothyroxine, which should be taken on an empty stomach. Phenytoin, carbemazepine, or rifampin o Induce hepatic enzymes, and can increase the metabolism of levothyroxine o This necessitates an increased dose. Warfarin o Hyperthyroidism accelerates the metabolic degradation of vitamin K-dependent clotting factors, and augments the response to warfarin. Antidiabetic agents o Dose may need to be adjusted if levothyroxine is added or deleted, since thyroid hormones can affect the diabetic state. o This represents a pharmacodynamic interaction, not necessarily pharmacokinetic. Corticosteroid o Metabolism can be decreased in hypothyroid patients and increased in hyperthyroid states o Dose alterations may be required when initiating, changing, or discontinuing thyroid therapy.

Liothyronine sodium (Cytomel®)

Thyroid Hormone Replacement Sodium salt of T3; short half life and duration of action Indications/Therapeutic Effects: Sometimes used for initial therapy of myxedema (hypothyroidism) and myxedema coma o To achieve normal thyroid activity faster. o But not for maintenance treatment

Levothyroxine sodium (Levothroid®, Synthroid®)

Thyroid Hormone Replacement This is the drug of choice for treating hypothyroidism. Mechanism of Action: Sodium salt of T4, may produce normal levels of both T3 and T4 Indications/Therapeutic Effects: Levothyroxine can also be used to treat simple nonendemic goiter, Hashimoto's disease, and thryrotropin-dependent thyroid carcinoma. It can also be used to prevent goiter resulting from drugs that interfere with thyroid function, such as lithium, aminosalicylic acid, and some sulfonamides. Pharmacokinetics: Dose should be sufficient to keep TSH levels in the normal range. Changes in the functional amount of T4 and TSH occur slowly. TSH levels should be measured four to six weeks after adjusting the dose of T4

Propranolol (Inderal®)

b-Adrenergic Blocking Agents Mechanism of Action: Decreases many of the signs and symptoms of hyperthyroidism, particularly tremor, tachycardia, anxiety, heat intolerance, and sweating It also decreases the peripheral conversion of T4 to T3 by the liver, reducing the potency of the circulating thyroid hormone o This is not a large enough antithyroid effect to be used independently of other antithyroid medication, but can help when combined with other drugs o This is specific to propranolol, it is not seen with other b-blockers Indications/Therapeutic Effects: Used to prepare for surgery and while waiting for the thioamide derivatives or radioactive iodine to take effect Generally combined with the thioamides; rarely given alone Contraindications/Precautions: Contraindicated in patients with obstructive airway disease or asthma o It may cause bronchoconstriction. Use caution in diabetics o It can prolong or enhance hypoglycemia by interfering with glycogenolysis o It can mask signs of hypoglycemia, especially tachycardia, palpitations, and tremors. Calcium channel blockers such as verapamil may be used if propranolol is contraindicated