四川大学华西医学中心：《药理学》课程教学资源（PPT讲稿）Chapter 36 甲状腺激素与抗甲状腺药物 Thyroid Hormones and Antithyroid Drugs

Chapter 36 Thyroid Hormones and Antithyroid gs Department of pharmacology 2018.10

Chapter 36 Thyroid Hormones and Antithyroid Drugs Department of pharmacology Liming zhou 2018.10

Contents Thyroid hormone ■ Thioureas(硫脲类) Iodine and Iodide(碘及碘化物) Radioactive lodine p adrenergic receptor antagonists

Contents Thyroid hormone Thioureas (硫脲类） Iodine and Iodide (碘及碘化物) Radioactive Iodine β adrenergic receptor antagonists

Thyroid hormone T4 is more than T3 but weak Thyroid follicular Thyroglobulin hydrolysis TT colloid 3 s more potent The thyroid gland is one of the largest endocrine organ and mainly consists of thyroid follicular, which is the main place to genera secrete thyroid hormone

Thyroid hormone The thyroid gland is one of the largest endocrine organ and mainly consists of thyroid follicular , which is the main place to generate and secrete thyroid hormone. Thyroid follicular colloid Thyroglobulin T4 hydrolysis T3 T3 is more potent T4 is more than T3 but weak

Thyroid hormone -synthesis and secretion Thyroid a follicle.Thyroid Ya follicle Thyro follicle Follicle epithelial cell ECSDa Follicle lumen

Follicle epithelial cell Thyroid follicle Thyroid follicle Thyroid follicle EC Space Follicle Lumen

Thyroid hormone-requlation paraventricular nucleus Hypothalamus ↓↓ TRH SRIF ④ Anterior Pituitary TSH ④ Thyroid gland

anterior pituitary paraventricular nucleus Hypothalamus Anterior Pituitary Thyroid gland TRH + + TSH Thyroid - T4 , T3 - SRIF

Thyroid hormone-intracorporal process o easy to absorb using po and the oral absorption rate of T3 and Ta are 50%w 75% and 75%w 90% respectively oThe rate of plasma protein combining is 99%, and the protein binding of T3 is less than the T4, the role of t3 is more potent than Ta with a half-life for 2 days, T4 is slow and weak with a half-life for 5 days

Thyroid hormone—intracorporal process Easy to absorb using Po and the oral absorption rate of T3 and T4 are 50% ~ 75% and 75% ~ 90% respectively. The rate of plasma protein combining is 99%, and the protein binding of T3 is less than the T4 , the role of T3 is more potent than T4 with a half-life for 2 days, T4 is slow and weak with a half-life for 5 days

Thyroid hormone-intracorporal process o The liver is the major site of nondeiodinative degradation, T4 and T3 are conjugated with glucuronic and sulfuric acids and excreted in the rena OAs it can go through the placenta and breast milk pregnancy and lactation women should be cautious

Thyroid hormone—intracorporal process The liver is the major site of nondeiodinative degradation, T4 and T3 are conjugated with glucuronic and sulfuric acids and excreted in the renal As it can go through the placenta and breast milk, pregnancy and lactation women should be cautious

Thyroid hormone--intracorporal process Tab 1 Summary of thyroid hormone kinetics kinetics daily production(ug) 70≈90 15~30 fractional turnover per day ( % 10 60 metabolic clearance per day l/d 24 amount bound (%) 99.96 996 volume of distribution (l) 10 40 serum level (total)( ug/dL) 4.5~11 60~180 serum level(free)(ng/dL) 0.7~186 0.2~0.52 half-life(biologic)(d) 7 biological potency orarabaarption(% 80

kinetics T４ T3 daily production (µg) 70～90 15～30 fractional turnover per day (%) 10 60 metabolic clearance per day (L/d) 1.1 24 amount bound (％) 99.96 99.6 volume of distribution (Ｌ) 10 40 serum level(total) ( µg/dL) 4.5～11 60～180 serum level(free) (ng/dL) 0.7～1.86 0.2～0.52 half-life(biologic) (d) 7 1 biological potency 1 4 oral absorption (%) 80 95 Tab 1 Summary of thyroid hormone kinetics

Thyroid hormone--Pharmacological e斤 fects Growth and Development hypothyroidism: child→ cretinism(呆小症) adut→ myxedema(黏液水肿 o Calorigenic Effects Increase the basal metabolic rate and excessive production of heat Improve the sensitivity of sympathetic-The susceptibility of adrenal system

Thyroid hormone—Pharmacological effects Growth and Development hypothyroidism ：child cretinism(呆小症) adult myxedema(黏液水肿) Calorigenic Effects : Increase the basal metabolic rate and excessive production of heat Improve the sensitivity of sympathetic—The susceptibility of adrenal system

Thyroid hormone-Pharmacological mechanism o Mediated by activating its nuclear specificity T3 recepTors o T4 translated into T3 by deiodination and combined with the specificity T3 receptors, and regulate gene transcription, protein synthesis and play functions o Other factors lead to the decreasing in T3 receptors

Thyroid hormone—Pharmacological mechanism Mediated by activating its nuclear specificity T3 receptors. T4 translated into T3 by deiodination and combined with the specificity T3 receptors, and regulate gene transcription, protein synthesis and play functions Other factors lead to the decreasing in T3 receptors