Nursing Pharmacology:  Chapter 30:  Thyroid and Antithyroid Drugs

• Overview

  • Purpose

    • Reduction of thyroid activity

    • Reduction of hormone effects

  • Approach

    • Use drugs that change tissue response to thyroid hormones

    • Destroy the the thyroid with surgical or radiation interventions

  • Definition

    • "Goitrogens" represent

      1. Compounds that suppress T₃ and T₄ secretion

      2. Thereby increasing TSH

      3. Increased TSH levels produces thyroid gland enlargement (goiter)

  • Antithyroid drugs include

    • Thioamides

    • Iodides

    • Radioactive iodine

• Thioamides

  • Major drugs for thyrotoxicosis:

    • Propylthiouracil

      • Rapidly absorbed

      • Bbioavailability: 50 -- 80% (incomplete absorption/large first-pass effect)

      • Metabolism: glucuronidation by the liver; excreted by the kidney

      • Sort half-life (1.5 hours) but accumulated by the thyroid

      • Crosses placental barrier (increased protein binding compared to methimazole makes propylthiouracil preferable for use in pregnancy since less free drug is available to cross into the fetus)

    • Methimazole

      • About 10 times more active than propylthiouracil

      • Well absorbed

      • Accumulated by the thyroid

      • Crosses the placental barrier

    • Mechanism of Action: thioamides

      1. Major action: inhibits thyroidal peroxidase-catalyzed reactions, blocking iodine organification which prevents hormone synthesis.

      2. Propylthiouracil and methimazole (too a much reduced degree) inhibit peripheral deiodination of T₄ and T₃ .

      3. Slow onset of pharmacological effect

    •  Toxicity

      • Frequency of adverse effects: 3-12%.

      • Most common: maculopapular pruritic rash

      • Most serious potential reaction: agranulocytosis -- risk 0.3% - 0.6 % of patients; reversible upon discontinuation; cross sensitivity between propylthiouracil and methimazole

      • possibly increased risk in:

        • Elderly

        • Patients receiving high-dose methimazole

• Anion Inhibitors

  • Anion inhibitors act by competitive inhibition

    • Perchlorate

    • Pertechnetate

    • Thiocyanate

  • Major clinical use: 

    • Blockade of thyroid gland reuptake of I^- in patients with iodide-induced hyperthyroidism

    • Potassium perchlorate ( not often used because of the possibility of causing aplastic anemia)

• Iodides

  • Rarely used now as monotherapy

  • Actions on the thyroid

    • Inhibit organification

    • Inhibition of hormone release represents iodide major action.

      • Mechanism: perhaps inhibition of thyroglobulin proteolysis

    • Decreased thyroidal size and vascularity

    • May induce hyperthyroidism

    • May precipitate hypothyroidism

  • Clinical Considerations

    • May be useful in short-term management of thyroid storm

    • Maybe helpful in preoperative preparation for surgery (due to reduction in gland vascularity, size, and fragility)

    •   Major disadvantages

      1.  Iodide therapy increases intraglandular iodine concentration

         • May delay initiation of thioamides treatment

         • May delay use of radioactive iodine treatment

      2.   Chronic iodide used in pregnancy: avoid -- iodide crosses the placenta and may cause fetal goiter

      3.   Iodide as monotherapy: not appropriate; iodide block lasts only 2-8 weeks; withdrawal at this time may exacerbate thyrotoxicosis

    • Iodide use, if at all, should be initiated only after thioamide treatment and not used if radioactive iodine therapy is planned

• Iodinated Radiographic Contrast Media

  • Useful in management of hyperthyroidism (off label use)

  • Ipodate and iopanoic acid inhibit T₄ to T₃ conversion in:

    • Kidney

    • Liver

    • Pituitary gland

    • Brain

  • Additional mechanism: iodine release-mediated inhibition of hormone release

  • Clinical Use:

    1. Adjunctive treatment of thyroid storm

    2. Alternatives if thioamides and iodides are contraindicated

  •  Toxicity:  similar to iodides; relatively nontoxic.

• Radioactive Iodine

  • ¹³¹I is the radioactive isotope used for treating thyrotoxicosis.

  • Mechanism of Action:

    • Rapidly absorbed, concentrated in the thyroid

    • Incorporated into thyroid follicles

    • Beta emission is the basis for therapeutic efficacy

    • Thyroid parenchymal destruction occurs within a few weeks.

  • Therapeutic Advantages for radioiodine

    1. Good efficacy

    2. Easy to administer

    3. Low expense

    4. Pain free treatment

  •   Contraindication

    • ¹³¹I should not be not administered to pregnant women or nursing mother given that ¹³¹I crosses placental barrier and excreted in breast milk.

• Adrenergic receptor blocking drugs

  • Rationale for adrenergic receptor blockade is reduction of sympathetic manifestations in thyrotoxicosis.

    • Applicable drugs:

      • β-adrenoceptor blockers

      • Guanethidine

    • Agent of choice:  propranolol (Inderal, nonselective beta-receptor antagonist)

Greenspan, F.S., and Dong, B. J.. Histamine, Thyroid and Antithyroid Drugs, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 619-633.

Wartofsky, L., Diseases of the Thyroid, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2012-2034