Thyroid drugs Flashcards
Levothyroxine sodium (Synthroid)
Class: Synthetic thyroid hormone (T4)
Mech: Converted to T3 in liver; T3 binds toTR complex to influence gene expression
Thera: Drug of choice for hypothyroidism (longer half-life than T3)
Important SE’s: Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss
Misc: “Start low, go slow” in patients with angina pectoris, CAD, and elderly; requires periodic monitoring and adjustment (especially during pregnancy); not effective in Chronic Fatigue Syndrome; kids need more T4/kg of body weight than adult
half-life of 6-7 days and time to peak therapeutic effect: 3-4 wks
Liothyronine sodium (Cytomel)
Class: Synthetic thyroid hormone (T3)
Mech: T3 binds to TR complex in nucleus to influence gene expression
Thera: Acute management of hypothyroidism (rapid effect); can use in combo with levothyroxine; myxedema coma (IV formulation)
Important SE’s: Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss, frequent bowel movements, insomnia
Misc: 4X as potent as T4, but not desirable for chronic replacement (less stable, more costly, transient high levels);
more rapidly effective and reaches peak levels 2-4 hrs after oral administration
Liotrix (Thyrolar)
Class: Synthetic thyroid hormone (T4 & T3)
Mech: Converted to T3 in liver; T3 binds toTR complex to influence gene expression
Thera: Thyroid hormone replacement therapy (4:1 mix of T4:T3; not used much)
Important SE’s: Hyperthyroidism: heart palpitations, nervousness, shaking, heat intolerance, weight loss
Propylthiouracil
Class: Thioamide (thyroid peroxidase inhibitors)
Mech: Inhibit organification of iodide and coupling of iodotyrosine; also reduces peripheral deiodination of T4 to T3
Thera: Hyperthyroidism; thyrotoxicosis (high dose); drug of choice for hyperthyroidism during pregnancy
Important SE’s: Rare side effects: hepatitis, agranulocytosis (higher than methimazole), lupus-like syndrome
Misc: Discontinue and use radio-iodine if patient develops agranulocytosis or drug-induced lupus;
75 min half life, excreted in less than 24 hrs, less transplacental passage, lower concentration in breast milk, higher risk of agranulocytosis
Methimazole (Tapazole)
Class: Thioamide (thyroid peroxidase inhibitors)
Mech: Inhibit organification of iodide and coupling of iodotyrosine; active metabolite of carbimazole; less effect on T4 to T3 conversion
Thera: Hyperthyroidism; thyrotoxicosis (high dose)
Important SE’s: Rare side effects: hepatitis, agranulocytosis (less than propylthiouracil), lupus-like syndrome
Misc: Discontinue and use radio-iodine if patient develops agranulocytosis or drug-induced lupus;
4-6 hr half life, excreted in greater than 48 hrs, more transplacental passage, higher concentration in breast milk, lower risk of agranulocytosis (too much of this could lead to hypothyroidism in pregnant women or birth defects in new-born infants)
Carbimazole (Neomercazole)
Class: Thioamide (thyroid peroxidase inhibitors)
Mech: Prodrug converted to methimazole; Inhibits organification of iodide and coupling of iodotyrosine; less effect on T4 to T3 conversion
Thera: Hyperthyroidism; thyrotoxicosis (high dose)
Important SE’s: Rare side effects: hepatitis, agranulocytosis, lupus-like syndrome
Misc: Discontinue and use radio-iodine if patient develops agranulocytosis or drug-induced lupus; not available in US
Radioactive Iodine
Class: Radioactive isotope
Mech: Radioactive agent that emits beta particles and gamma rays that destroy thyroid cells; half-life of 5 days and wait for 4 weeks before activity
Thera: Treatment of choice for hyperthyroidism after antithyroid drug therapy; ablation after cancer
Important SE’s: Transient or permanent hypothyroidism; increases cancer risk
Misc: Contraindicated in pregnant/breast feeding, patients under 10 (use antithyroid drugs); monitor serum thyroid hormones post-treatment every 2-3 months for first year with risk of permanent hypothyroidism in some pts
β-blockers
Class: β-blockers
Mech: Reduce sympathetic tone
Thera: Symptomatic treatment of hyperthyroidism (no effect on T3 synthesis) like tremor, anxiety, palpitations (TAP)
Misc: Do not use on patient’s at risk of heart failure! Discontinue use when patient returns to euthyuroid.
For the three thyroid hormones, list something about their chemistry:
- Thyroxine (T4) has 4 I’s
- Active T3 has I’s in a 353 pattern
- Reverse/inactive T3 has I’s in a 335 pattern
How does I get into the follicular cell?
- Uses a Na-I symporter to get I into the follicular cell
2. Use a Na-K pump to get Na back into EC space
Diseases caused by defective Na-I symporter:
- symporter gene mutation (congenital hypothyroidism)
2. Autoimmune thyroiditis (autoAb’s against symporter affecting iodide transport)
How is thyroid hormone synthesized?
- Thyroid peroxidase first to get I’s onto tyrosine residues on thyroglobulin
- Thyroid peroxidase to move two tyrosine residues together
Moving thyroid hormone from colloid into the blood involves:
- Endocytosis of the iodinated TG
- Fusion of the endosome with a lysosome to separate iodinated tyrosines from TG
- Free thyroid hormone moved into the blood to bind to TBG (thyroxin-binding globulin)
T4 is converted to _____ in ___ and other cells; T3 is a
T3; liver;
ligand for thyroid hormone receptor (heterodimer with TR monomer and retinoic acid receptor monomer; TR-RXR heterodimer binds to thyroid hormone response element or TRE)
Hypothyroid conditions:
- Hashimoto’s thyroiditis: autoimmune disorder with Ab’s against thyroid peroxidase, Na-I symporter, TG, or TSH receptor
- Myxedema: think older women
- Iodine deficiency
- Thyroid ablation (e.g. cancer)
- Cretinism: infancy/childhood hypothyroidism; think mental retardation and Dwarfism
