Hypothyroidism medications Notes

NOTES NOTES HYPOTHYROIDISM MEDICATIONS Figure 1.1 Hypothyroidism medications: mechanism of action. WHAT ARE THEY? Basic information ▪ Drugs used to supply the body with normal levels of thyroid hormones (triiodothyronine/T3 and thyroxine/T4) Key points ▪ Thyroid hormone synthesis ▫ Iodide trap: inorganic iodide ions + 2Na+ ions via sodium-iodide symporters taken by follicular cells ▫ Oxidation: oxidation of iodide ions by thyroid peroxidase (TPO) to iodine atoms ▫ Iodination: attachment of iodine to tyrosine amino acid residues on thyroglobulin → monoiodotyrosine (MIT) and diiodotyrosine (DIT) OSMOSIS.ORG 1

▫ Coupling by TPO: MIT + DIT → T3 (↑ active); DIT + DIT → T4 (↓ active; converted to T3 at peripheral sites by 5’deiodinase) ▪ Thyroid hormone secretion ▫ Hypothalamus secretes thyrotropinreleasing hormone (TRH) ▫ TRH stimulate anterior pituitary gland to secrete thyroid-stimulating hormone (TSH) ▫ TSH binds TSH receptors on follicular cells in thyroid gland → ↑ synthesis and release of T4 and T3 ▪ Two fractions of thyroid hormones in blood ▫ Majority bound to thyroxine binding globulins (TBG)—physiologically inactive ▫ Small amounts unbound (“free”)— physiologically active Mechanism of action ▪ Synthetic and natural thyroid hormones exert effects on cells primarily in T3 form → T3 binds thyroid hormone receptors (TRs) in nucleus → TRs bind specific DNA sequences → promotes DNA transcription, protein synthesis → ↑ basal metabolic rate and heat production; ↑ sympathetic nervous system, myocardial function, respiratory rate, mental alertness; ↑ GI motility; normal growth & development of nervous system TYPES ▪ Liothyronine (Cytomel, Triostat): PO, IV ▫ Synthetic T3 ▪ Levothyroxine (Levoxyl, Synthroid): PO, IV ▫ Synthetic T4 ▪ Liotrix (Thyrolar): PO ▫ Synthetic T4, T3 mix (4:1) ▪ Desiccated thyroid/thyroid extract (Armour Thyroid): PO ▫ Natural T3, T4 (derived from pigs) Common indications ▪ Hypothyroidism (primary/thyroidal, secondary/pituitary, tertiary/hypothalamic; congenital) ▪ Myxedema coma (hypothermia, bradycardia, hypotension, hypoventilation, confusion, coma) 2 OSMOSIS.ORG ▪ TSH suppressive therapy (eg. thyroid nodules, thyroid cancer) CLINICAL CONCERNS ADVERSE EFFECTS ▪ Clinical hyperthyroidism manifestations from overdose (e.g. heat intolerance, anxiety, tremors; diarrhea; tachycardia, arrhythmia) ▪ Osteoporosis: long-term therapy → ↑ bone resorption, remodeling → ↓ bone density Boxed warning ▪ Thyroid hormones should not be used for weight loss, obesity treatment DISEASE-RELATED CONCERNS ▪ Cardiovascular disease: may worsen cardiac symptoms ▪ Diabetes: may worsen glycemic control ADMINISTRATION ▪ Elderly / cardiovascular patients / patients with longstanding hypothyroidism: ↓ initial dose, gradually ↑ to prevent cardiovascular adverse effects Dietary ▪ Food interactions (↓ absorption): grapefruit juice, espresso coffee, calcium salts, iron/ iron supplements, magnesium salts, multivitamins (vitamins ADEK, iron, folate), fiber CONTRAINDICATIONS ▪ Uncorrected adrenal insufficiency: treat adrenal insufficiency before hypothyroidism to prevent adrenal crisis PREGNANCY/BREASTFEEDING IMPLICATIONS ▪ Pregnancy: levothyroxine (treatment of choice) ▪ Once pregnancy confirmed, ↑ levothyroxine doses due to increased demand (↑ estrogen levels, normal fetal development)

Endocrine Hypothyroidism Medications Figure 1.2 Hypothyroidism medications: common drug-drug interactions. Figure 1.3 Major drug interactions of levothyroxine. OSMOSIS.ORG 3

Figure 1.4 Hypothyroidism medications: general adult dosing guidelines. *Dosage varies depending on dosing interval, individual characteristics 4 OSMOSIS.ORG