P.04.02 Thyroid & Antithyroid Drugs 2026 PDF

PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.04.02 THYROID AND ANTITHYROID DRUGS PHARMACOLOGY LECTURE LECTURER: DR. SHARON GAWIGAWEN DATE: JANUARY 22, 2024 TOPIC OUTLINE I. THYROID HORMONES II. THYROID DRUGS III. ANTI-THYROID DRUGS IV. DISORDER OF THE THYROID GLAND CASE STUDY JP is a 33-year-old wom...

PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.04.02 THYROID AND ANTITHYROID DRUGS PHARMACOLOGY LECTURE LECTURER: DR. SHARON GAWIGAWEN DATE: JANUARY 22, 2024 TOPIC OUTLINE I. THYROID HORMONES II. THYROID DRUGS III. ANTI-THYROID DRUGS IV. DISORDER OF THE THYROID GLAND CASE STUDY JP is a 33-year-old woman who presents with complaints of fatigue requiring daytime naps, weight gain, cold intolerance, and muscle weakness for the last few months. These complaints are new since she used to always feel “hot,” noted difficulty sleeping, and could eat anything that she wanted without gaining weight. She also would like to become pregnant in the near future. Because of poor medication adherence to methimazole and propranolol, she received radioactive iodine (RAI) therapy, developed hypothyroidism, and was started on levothyroxine 100 mcg daily. Other medications include calcium carbonate three times daily to “protect her bones” and omeprazole for “heartburn.” On physical examination, her blood pressure is 130/89 mm Hg with a pulse of 50 bpm. Her weight is 136 lb (61.8 kg), an increase of 10 lb. (4.5 kg) in the last year. Her thyroid gland is not palpable and her reflexes are delayed. Laboratory findings include a thyroid-stimulating hormone (TSH) level of 24.9 μIU/mL (normal 0.45–4.12 μIU/mL) and a free thyroxine level of 8 pmol/L (normal 10–18 pmol/L). o o Evaluate the management of her past history of hyperthyroidism and assess her current thyroid status. Identify your treatment recommendations to maximize control of her current thyroid status. THYROID HORMONES The hypothalamus produces TSH Releasing Hormone (TRH) that signals the pituitary to tell the thyroid gland to produce more or less of T3 and T4 by either increasing or decreasing the release of a hormone called thyroid-stimulating hormone (TSH). When T3 and T4 levels are low in the blood, the pituitary gland releases more TSH to tell the thyroid gland to produce more thyroid hormones. If T3 and T4 levels are high, the pituitary gland releases less TSH to the thyroid gland to slow the production of these hormones. THYROID GLAND - a butterfly-shaped organ located in the base of your neck. THYROID HORMONES - are critical determinants of brain and somatic development in infants; regulates metabolic activity such as: o Breathing o Central and peripheral nervous systems o Bodyweight o Muscle strength o Menstrual cycles o Body temperature o Cholesterol levels TWO PRINCIPAL THYROID HORMONES: THYROXINE TRIIODOTHYRONINE T4 or L-3,5,3',5'T3 or L-3,5,3'tetraiodothyronine triiodothyronine solely a product of the a product of the thyroid thyroid gland and of many other tissues, in which it is produced by deiodination of T4 IODINE: essential for normal thyroid function. The only known physiologic role of iodine (or iodide [I−] in its ionized form) is in the synthesis of thyroid hormones. There are two biologically active thyroid hormones: Thyroxine (T4) and Triiodothyronine (T3) - composed of a phenyl ring attached via an ether linkage to a tyrosine molecule. - Both have two iodine atoms on their tyrosine (inner) ring. - T4 has two iodine atoms on its phenyl (outer) ring, whereas T3 has only one. - The compound formed if an iodine atom is removed from the inner ring of T4 is the reverse T3 which has no biological activity. NOT E TAKE R: ABULENCIA| BACWADE N| BAL DO S| BAST IAN| CUTAY | FE RRE R| SANGDAA N Pa g e 1|5 PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.04.02 THYROID AND ANTITHYROID DRUGS THYROID HORMONE SYNTHESIS 1. 2. 3. 4. 5. 6. 7. 8. Iodide (I-) trapped by the thyroid follicular cells; Diffusion of iodide to the apex of the cells Transport of iodide into the colloid; Oxidation of inorganic iodide to iodine and incorporation of iodine into tyrosine residues within thyroglobulin molecules in the colloid; Combination of two DIT molecules to form tetraiodothyronine (T4) or of MIT with DIT to form T3; Uptake of thyroglobulin from the colloid into the follicular cell by endocytosis, fusion of the thyroglobulin with a lysosome, and proteolysis and release of T4, T3, DIT, and MIT; Release of T4 and T3 into the circulation; and Deiodination of DIT and MIT to yield tyrosine. T3 is also formed from monodeiodination TRANSPORT OF THYROID HORMONE - Thyroxine-binding globulin (TBG), transthyretin, albumin and lipoproteins - Only about 0.04% of total T4 and 0.4% of T3 exist in the free form (as FT4 and FT3) and it is the serum FT4 and FT3 concentrations that determine the hormones biological activity PERIPHERAL DEIODINATION: - T4 is converted to T3 by deiodinases in the peripheral tissues such as the kidneys and liver. Produces majority of T3. EVALUATION OF THYROID FUNCTION: - serum TSH, FT4, and FT3 ❖ EUTHYROIDISM (Normal thyroid function) o Normal levels of TSH, FT4, FT3 ❖ HYPERTHYROIDISM o Increased levels of FT4, FT3 o Decreased level of TSH ❖ HYPOTHYROIDISM o Decreased levels of FT4, FT3 o Increased level of TSH MECHANISM OF ACTION - T4 and T3 dissociate from the binding proteins → FT4 and FT3 THYROID DRUGS 1. LEVOTHYROXINE (T4) - Synthetic levothyroxine is the preparation of choice for thyroid replacement and suppression therapy because of its stability, content uniformity, low cost, lack of allergenic foreign protein, easy laboratory measurement of serum levels - T4 is converted to T3 intracellularly; thus, administration of T4 produces both hormones - Generic levothyroxine preparations provide comparable efficacy and are more cost-effective than branded preparations. - It is preferable that patients remain on a consistent levothyroxine preparation between refills to avoid changes in bioavailability. - Has interactions with certain foods (eg, bran, soy, coffee) and drugs can impair its absorption o Thyroxine should be administered on an empty stomach (eg, 60 minutes before meals, 4 hours after meals, or at bedtime) - Maintain TSH within an optimal range of 0.5–2.5 mIU/L. - Half-life: 7 days – permits once-daily dosing - Administration: Intravenous, oral - Children should be monitored for normal growth and development. - Serum TSH and free thyroxine should always be measured before a change in dosage to avoid transient serum alterations. It takes 6–8 weeks after starting a given dose of thyroxine to reach steady-state levels in the bloodstream. Thus, dosage changes should be made slowly. 2. LIOTHYRONINE (T3) – not available in the PH - 3-4x more potent than levothyroxine - Short half-life: 24 hours, hence not recommended because it will require multiple daily doses and difficulty in monitoring its adequacy of replacement by laboratory tests - Administration: intravenous, oral - Reserved for short-term TSH suppression CLINICAL INDICATIONS: 1. Thyroid hormone replacement therapy ❖ HYPOTHYROIDISM - defined as a low level or absence of thyroid hormones. It may be present at birth (congenital) or develop later in life (acquired). NOT E TAKE R: ABULENCIA| BACWADE N| BAL DO S| BAST IAN| CUTAY | FE RRE R| SANGDAA N Pa g e 2|5 PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.04.02 THYROID AND ANTITHYROID DRUGS Primary Hypothyroidism - Due to defects in the thyroid gland itself, is the most common cause of hypothyroidism. Congenital: Thyroid gland dysgenesis Acquired: Hashimoto’s thyroiditis Iodine deficiency After total thyroidectomy After radiation therapy of the head and neck area Medication - lithium, amiodarone, anti- epileptic drugs Secondary or Central Hypothyroidism - Secondary to defects at the level of the pituitary gland or hypothalamus (hypopituitarism) Congenital: Genetic mutations Acquired: Tumors, Hydrocephalus, Infiltrative diseases 2. TSH suppression - T4 dose taken is large enough to suppress blood levels of TSH below the normal TSH range - Part of the treatment protocol for differentiated thyroid cancer to prevent recurrence after total thyroidectomy +/- radioactive iodine therapy ANTI - THYROID HORMONES ❖ Reduce thyroid activity and hormone effects by interfering with the production of thyroid hormones, or by glandular destruction with radiation or surgery. 1. Thioamides (Methimazole, Carbimazole and Propylthiouracil) 2. Iodides 3. Radioactive iodine 1. THIOAMIDES (Methimazole, Carbimazole, Propylthiouracil) Propylthiouracil (PTU) Administration: Oral (every 6 – 8 hours) Half – life: 1.5 hours Use during pregnancy: YES Preferably given in the 1st trimester because it is strongly protein bound hence crosses the placenta less readily. Methimazole - The active metabolite of Carbimazole Administration: Oral (every 8 hours to once a day dosing) Half – life: 6 hours Use during pregnancy: YES PHARMACODYNAMIC ❖ Prevent hormone synthesis by: o Inhibiting the thyroid peroxidase-catalyzed reactions o Blocking iodine organification o Blocking coupling of iodotyrosine ❖ PTU inhibits peripheral deiodination of T4 to T3 ❖ Since the synthesis rather than the release of hormones is affected, the onset of these agents is slow, often requiring 3 - 4 weeks before stores of T4 are depleted. TOXICITY ❖ Adverse reactions: seen in 3 - 12% of treated patients o Maculopapular pruritis rash: most common o Severe hepatitis: reported in PTU o Cholestatic jaundice: more common with methimazole o Agranulocytosis: ▪ most dangerous complication (0.10.5% of patients) ▪ granulocyte count < 500 cells/mm3 ▪ rapidly reversible when the drug is discontinued 2. IODIDES - Prior to the introduction of the thioamides in the 1940s, iodides were the major antithyroid agents; today they are rarely used as sole therapy. - Inhibits organification and hormone release through inhibition of thyroglobulin proteolysis - Decreases the size and vascularity of hyperplastic thyroid gland - Given orally CLINICAL INDICATIONS 1. Thyroid storm: thyrotoxic crisis; acute lifethreatening, hypermetabolic state caused by excessive release of thyroid hormones. Improvement in thyrotoxic symptoms occurs rapidly with iodide— within 2–7 days NOT E TAKE R: ABULENCIA| BACWADE N| BAL DO S| BAST IAN| CUTAY | FE RRE R| SANGDAA N Pa g e 3|5 PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.04.02 THYROID AND ANTITHYROID DRUGS 2. Preoperative preparation for thyroid surgery: decrease the vascularity, size, and fragility of a hyperplastic gland DISADVANTAGES OF IODIDE THERAPY - include an increase in intraglandular stores of iodine, which may delay the onset of thioamide therapy or prevent use of radioactive iodine therapy for several weeks. It should be initiated after onset of thioamide therapy and avoided if treatment with radioactive iodine seems likely ❖ Chronic use of iodides in pregnancy should be avoided, since they cross the placenta and can cause fetal goiter. TOXICITY ❖ Adverse Reactions to iodine (IODISM) are uncommon and in most cases reversible upon discontinuance. ❖ They include acneiform rash, swollen salivary glands, mucous membrane, ulcerations, conjunctivitis, rhinorrhea, drug fever, metallic taste, bleeding disorders, and rarely, anaphylactoid reactions. 3. RADIOACTIVE IODINE - 131I is the only isotope used for treatment of thyrotoxicosis. - Administered orally in solution as sodium 131I, it is rapidly absorbed, concentrated by the thyroid, and incorporated into storage follicles. - Its therapeutic effect depends on emission of β rays with an effective half-life of 5 days and a penetration range of 400–2000 μm. - Within a few weeks after administration, destruction of the thyroid parenchyma is evidenced by epithelial swelling and necrosis, follicular disruption, edema, and leukocyte infiltration - Advantages of radioiodine: o Easy administration, o Effectiveness, o Low expense, and o Absence of pain - Fears of radiation-induced genetic damage, leukemia, and neoplasia have not been realized after more than 50 years of clinical experience with radioiodine therapy for hyperthyroidism. - Radioactive iodine should not be administered to pregnant women or nursing mothers, since it crosses the placenta to destroy the fetal thyroid gland and it is excreted in breast milk. CLINICAL INDICATIONS 1. Hyperthyroidism (thyrotoxicosis) - is the clinical syndrome that results when tissues are exposed to high levels of thyroid hormone a. Grave’s disease: most common form of hyperthyroidism; diffuse toxic goiter b. Toxic uni-/multinodular goiter c. Thyroid storm: thyrotoxic crisis d. Neonatal Grave’s disease: due to passage of maternal TSH-receptor antibody through the placenta, stimulate the thyroid gland of the neonate DISORDER OF THE THYROID GLAND NOT E TAKE R: ABULENCIA| BACWADE N| BAL DO S| BAST IAN| CUTAY | FE RRE R| SANGDAA N Pa g e 4|5 PCC SOM 2026 PHARMACOLOGY AND THERAPEUTICS P.04.02 THYROID AND ANTITHYROID DRUGS CHECKPOINT A. Thyroid Drug B. Antithyroid Drug ______ 1. Radioactive Iodine ______ 2. Liothyronine ______ 3. Carbimazole ______ 4. Iodides ______ 5. Levothyroxine A. Hypothyroidism B. Hyperthyroidism ______ 6. Weight loss ______ 7. Heat intolerance ______ 8. Dry hair ______ 9. Puffy face ______ 10. Diarrhea A. T3 B. T4 _____ 11. Solely a product of the thyroid gland _____ 12. Produced by deiodination of T4 A. Propylthiouracil B. Methimazole _____ 13. Half – life: 1.5 hours _____ 14. Active metabolite of Carbimazole _____ 15. Oral administration (every 6 – 8 hours) A. Levothyroxine CASE STUDY ANSWER The initial methimazole treatment was appropriate and preferable to propylthiouracil because of its longer duration of action allowing once daily dosing and its improved safety profile. JP presents with the typical signs and symptoms of hypothyroidism following RAI despite levothyroxine replacement. Either radioactive iodine or thyroidectomy are reasonable and effective strategies for definitive treatment of her hyperthyroidism, especially before becoming pregnant to avoid an acute hyperthyroid exacerbation during pregnancy or following delivery. Her hypothyroid symptoms should have been easily corrected by the addition of levothyroxine dosed correctly at 1.7 mcg/kg/ day or 100 mcg daily. Because she is young and has no cardiac disease, full replacement doses were appropriate to start. However, her elevated TSH level indicates inadequate levothyroxine replacement which may be related to nonadherence, or concomitant calcium and omeprazole co-administration. For optimal absorption, levothyroxine should be taken orally 60 minutes before meals on an empty stomach or at bedtime, and separated by 4 hours from her calcium administration. Lower thyroxine doses may also be sufficient if her omeprazole is stopped. Once weekly thyroxine injections may be effective in those with ongoing nonadherence. Thyroid function tests should be monitored after 6–8 weeks of therapy, obtained before thyroxine administration to avoid transient hormone alterations, and the dosage adjusted to achieve a normal TSH level and resolution of hypothyroid symptoms. BABBA|BBAAB|BA|ABA|BBAAA B. Liothyronine _____ 16. Reserved for short-term TSH suppression _____ 17. 3-4x more potent than the other drug _____ 18. Has interactions with bran, soy, and coffee _____ 19. Children should be monitored for normal growth and development _____ 20. Maintain TSH within an optimal range of 0.5–2.5 mIU/L NOT E TAKE R: ABULENCIA| BACWADE N| BAL DO S| BAST IAN| CUTAY | FE RRE R| SANGDAA N Pa g e 5|5