Part 2 Thyroid hormones and antithyroid drugs

A. Thyroid hormones

Metabolism of thyroid hormones 1. Uptake of iodide 2. Activation of iodide (peroxidase), and iodination and coupling of tyrosine 3. Formation of thyroxine (T 4 ) and triiodothyronine (T 3 ) from iodotyrosine 4. Secretion of thyroid hormones (proteolytic enzymes) 5. Regulation by thyroid stimulating hormone (TSH), T 4, T 3

Metabolism of thyroid hormones

Formation of thyroxine (T 4 ) and triiodothyronine (T 3 ) from iodotyrosine

Secretion of thyroid hormones ( lysosomal proteolytic enzymes )

Regulation of the secretion of thyroid hormones (feedback inhibition)

§1. Normalizing growth and development §2. Promoting body metabolism § Body temperature; energy levels, ect. §3. Enhancing sympathetic activity Pharmacology of thyroid hormones

Action of thyroid hormones: interaction with their receptors in the nuclei

§1. Treatment of hypothyroidism § (1) cretinism ( 呆小病 ) § (2) myxoedema ( 黏液性水肿 ) §2. Simple goiter ( 单纯性甲状腺肿 ) Clinical uses of thyroid hormones

B. Antithyroid drugs

Symptoms of the patient with hyperthyroidism

§Therapeutic drugs for Hypothyroidism § antithyroid drugs: thiourea derivatives § iodine and iodides §  receptor antagonists § surgery § radioiodines: 131 I, 125 I

§Thiourea derivatives § Propylthiouracil 丙硫氧嘧啶 § Methimazole (tapazole) 甲巯咪唑 § Carbimazole 卡比马唑 §Iodine and iodides §  Receptor antagonists §Radioiodide( 131 I) §Radioiodide ( 131 I) B. Antithyroid drugs

§Thiourea derivatives B. Antithyroid drugs 丙硫氧嘧啶 甲巯咪唑 Thiamazole 卡比马唑

§Thiourea derivatives §1. Pharmacological effects §(1) Inhibiting the formation of thyroid hormones by interfering with iodination:inhibiting peroxidation, then the iodination and coupling §(1) Inhibiting the formation of thyroid hormones by interfering with iodination: inhibiting peroxidation, then the iodination and coupling § Symptom relieving: 2~3 weeks § Basic metabolic rate returning: 1~2 months §(2) Inibiting peripheral deiodination of T 4 : T 4  T 3  (propylthiouracil) §(3) Goitrogenic action (goiter) : TSH ↑ B. Antithyroid drugs

Mechanism of inhibition of thyroid hormone synthesis by thiaureas: Thiaureas are oxidized by thyroid peroxidase (TPO)

Mechanism of inhibition of thyroid hormone synthesis by thiaureas

§2. Clinical uses §(1) Non-operative therapy of hyperthyroidism: 1~3 monthlatent period §(1) Non-operative therapy of hyperthyroidism: 1~3 month latent period §(2) Preoperative therapy of hyperthyroidism: combined with larger dose of iodide §(3) Thyrotoxic crisis:combined with larger dose of iodide, propylthiouracil §(3) Thyrotoxic crisis: combined with larger dose of iodide, propylthiouracil §3. Adverse effects §(1) Agranulocytosis (0.3%~0.6%) §(2) Hypersensitivity (3) GI reactions B. Antithyroid drugs

§Iodine and iodides §1. Pharmacological effects §(1) Small doses:simple goiter §(1) Small doses: simple goiter §(2) Larger doses:inhibiting the release of thyroid hormones (proteolysis  ) and synthesis §(2) Larger doses: inhibiting the release of thyroid hormones (proteolysis  ) and synthesis §After iodide use, the thyroid vascularity is reduced, and the gland becomes much firmer, the cells become smaller (inhibiting TSH release). B. Antithyroid drugs

Mechanism of iodides

§2. Clinical uses §(1) Preoperative therapy of hyperthyroidism: combined with thiourea derivatives (for 2 weeks) §(2) Thyrotoxic crisis:combined with thiourea derivatives (propylthiouracil) §(2) Thyrotoxic crisis: combined with thiourea derivatives (propylthiouracil) §Lugol’s solution: 5% iodine and 10% potasium iodide B. Antithyroid drugs

§3. Adverse effects §(1) Acute effects:hypersensitivity, angioedema, swelling of the larynx §(1) Acute effects: hypersensitivity, angioedema, swelling of the larynx §(2) Chronic intoxication (iodism) §(3) Thyroid dysfunction:exacerbation of hyperthyroidism, goiter §(3) Thyroid dysfunction: exacerbation of hyperthyroidism, goiter B. Antithyroid drugs

§  Receptor antagonists §1. Pharmacological effects §(1) Heart:  1 block §(2) CNS: relieving anxiety §(3) Presynaptic  2 receptor: NE release  §(4) Inhibiting the conversion of T 4 to T 3 §2. Clinical uses §Adjuvant therapeutic drug B. Antithyroid drugs

§Radioiodine § 131 I, 125 I, 123 I § Destroying thyroid tissue § Diagnosis § Careful use B. Antithyroid drugs