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1、Chapter 36 Thyroid Hormones and Antithyroid Drugs Department of pharmacology,Contents,Thyroid hormone Thioureas (硫脲类） Iodine and Iodide (碘及碘化物) Radioactive Iodine adrenergic receptor antagonists,Thyroid hormone,The thyroid gland is one of the largest endocrine organ and mainly consists of thyroid fo
2、llicular , which is the main place to generate and secrete thyroid hormone.,Thyroid hormone synthesis and secretion,EC Space,Follicle Lumen,Thyroid hormoneregulation,Thyroid hormoneintracorporal process,Easy to absorb using Po and the oral absorption rate of T3 and T4 are 50% 75% and 75% 90% respect
3、ively. 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 hormoneintracorporal process,The liver is the major site of nondeiodinati
4、ve 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 hormoneintracorporal process,Tab 1 Summary of thyroid hormone kinetics,Thyroid hormonePha
5、rmacological 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 sympatheticThe susceptibility of adrenal system,Thyroid hormonePharmacological mec
6、hanism,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,Thyroid hormoneclinical
7、 application,Cretinism The hypofunction begin in fetus or infants, therapy is instituted within the first few weeks of life , normal physical and mental development is almost always achieved Myxedema Generally take thyroid tablet, from low does gradually increase to the full does.,Thyroid hormonecli
8、nical application,Simple goiter(单纯性甲状腺肿) Using table salt and food for prevention, thyroid tablets for a supplementary treatment. T3 suppression test As a differential diagnosis in patients with high ingestion rate of iodine.,Thyroid hormoneuntoward effects,Too much does of thyroid hormone can cause
9、 the clinical manifestations of hyperthyroidism, angina and myocardial infarction may occur in cardiopath and old patients, using adrenergic receptor antagonists to against the adverse effects and discontinuing thyroid hormone. Diabetes, coronary heart disease, rapid arrhythmia patients should not b
10、e used.,Classify,Thiourea,Iodine and iodide:, adrenergic receptor antagonists:,Thiouracils 硫脲嘧啶: Propylthiouracil,Imidazole 咪唑: Methimazole,Antithyroid drugs,Compound Iodine Oral Solution,Atenolol,Radioactive iodine 125I,Thiourea 【 Mechanism 】,Iodide in the blood,Iodine passed into the thyroid cells
11、 actively,incorporation of iodine into tyrosyl residues of thyroglobulin,TSH,Peroxidase,2DIT MIT+DIT,oxidation of iodide ion (I+),Peroxidase,T4 T3,Thiourea,inhibit,Propylthiouracil 丙基硫氧嘧啶: Absorption of propylthiouracil follows within 20 to 30 minutes of an oral dose and peak in 2 hours, plasma prot
12、ein binding was 75%, concentrated in thyroid and could cross the placenta and also can be found in milk, with the half-life about 2 hours. Methimazole甲硫咪唑:The roles last for long time and and persistent with plasma t1/2 to 4 9 h ； methimazole, derived from the metabolism of carbimazole, and not used
13、 in Thyroid Storm,Thioureapharmacokinetics,1. Resistance to thyroid function Having no effects on the preformed hormone, the clinical effects become noticeable after 2-3 weeks, basal metabolic rate resumed normal after 1-3 months by inhibiting the peripheral deiodination脱碘 of T4 to T3 and controling
14、 the serum T3 level. As the feedback effects, which lead to the increased secretion of TSH and the gland hyperplasia 2. Immunosuppressive effects,Thioureapharmacological effects,Thioureaclinical application,Treatment of hyperthyroidism Suitable for mild patients and who are unfavorable surgical or 1
15、31 I treatment, treatment last for 1 2 years. To control the disorder in preparation for surgical treatment Adjuvant therapy of the thyroid storm,Thioureaadverse effects,The incidence of side effects is relatively low 1. Frequent complications: pain and stiffnessn僵硬 in the joints, headache, nausea 2
16、. Allergic reaction: purpuric, urticarial papular rash 3.Agranulocytosis. 粒性白血球缺乏症:the most serious reaction 4. Goiter and hypothyroidism 5. Patients with thyroid cancer and nodular goiter is forbidden,Iodine and iodide pharmacological effects,Low doses of iodine promote the synthesis of thyroid hormones High concentrations of iodide inhibit the release of thyroid hormone. This action is rapid and efficacious and discernible with
