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,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Chapter 36,Thyroid Hormones and Antithyroid Drugs,Department of pharmacology,Liming zhou,2015.10,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 follicular , which is the main place to generate and secrete thyroid hormone.,Thyroid follicular,colloid,Thyroglobulin,T,4,T,3,hydrolysis,T,3,is,more potent,T4 is more than T3,but weak,Thyroid hormone,synthesis and secretion,Follicle epithelial cell,Thyroid follicle,Thyroid follicle,Thyroid follicle,EC Space,Follicle Lumen,anterior pituitary,paraventricular nucleus,Hypothalamus,Anterior Pituitary,Thyroid gland,TRH,+,+,TSH,Thyroid,-,T,4, T,3,-,SRIF,Thyroid hormone,regulation,Thyroid hormone,intracorporal process,Easy to absorb using Po and the oral absorption rate of T,3,and T,4,are 50% 75% and 75% 90% respectively.,The rate of plasma protein combining is 99%, and the protein binding of T,3,is less than the T,4, the role of T,3,is more potent than T,4,with a half-life for 2 days, T,4,is slow and weak with a half-life for 5 days.,Thyroid hormone,intracorporal process,The liver is the major site of nondeiodinative degradation, T,4,and T,3,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,kinetics,T,T,3,daily production (,g),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 (,),10,40,serum level(total) (,g/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,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,Mediated by activating its nuclear specificity T,3,receptors.,T,4,translated into T,3,by deiodination and combined with the specificity T,3,receptors, and regulate gene transcription, protein synthesis and play functions,Other factors lead to the decreasing in T,3,receptors,Thyroid,hormone,clinical 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,hormone,clinical application,Simple goiter,(,单纯性甲状腺肿,),Using table salt and food for prevention,thyroid tablets for a supplementary treatment.,T,3,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 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 be 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,125,I,Thiourea 【,Mechanism,】,Iodide in,the blood,Iodine passed,into the thyroid,cells actively,incorporation of iodine,into tyrosyl residues,of thyroglobulin,TSH,Peroxidase,2DIT,MIT+DIT,oxidation of,iodide ion,(I,+,),Peroxidase,T,4,T,3,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 protein 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 t,1/2,to 4 9 h,；,methimazole, derived from the metabolism of carbimazole, and not used in,Thyroid Storm,Thiourea,pharmacokinetics,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 T,4,to T,3,and controling the,serum T,3,level. As the feedback effects, which lead to the increased secretion of TSH and the gland hyperplasia,2.,Immunosuppressiveeffects,Thiourea,pharmacological effects,Thiourea,clinical application,Treatment of hyperthyroidism,Suitable for mild patients and who are unfavorable surgical or,131,I treatment, treatment last for 1 2 years.,To control the disorder in preparation for surgical treatment,Adjuvant therapy of the thyroidstorm,Thiourea,adverse,effects,The incidence of side effects is relatively low,1,.,Frequent complications,:,pain and stiffness,n,僵硬,in the joints, headache, nausea,2.,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 within 24 hours, with the maximal effect attained after 10 to 15 days,Iodine and iodide,clinical application,Simple goiter,:,1/10,5, 1/10,4,potassium iodide or sodium iodide joined into the table salt can prevent this disease.,Preparation for the hyperthyroidism preoperative,:,To facilitate operation and reduce bleeding,Thyroid crisis,:,large doses of iodine can prevent thyroid hormone release and cooperate with thiourea.,.,Iodine and iodide ,adverse effects,Allergic reaction,:,Acute reaction may occur immediately or several hours after administration, angioedema(,血管性水肿,), laryngeal edema(,喉水肿,),Chronic intoxication with iodide,: unpleasant brassy taste and burning in the mouth and throat,Thyroid dysfunction,:,Iodine can also enter into the milk and cross the placenta and cause neonatal goiter, pregnant women and lactating women should be used with caution,.,Radioactive Iodine,pharmacological effects,131,I is greatest used in clinical and half-life is 8 d,131,I is rapidly and efficiently trapped by the thyroid , and the destructive particles originate within the follicle and act exclusively upon the parenchymal cells of the thyroid, with little or no damage to surrounding tissue,The radiation can be quantified by external detection, which can be used to measurement thyroid function,Treatment of hyperthyroidism,:,131,I,is applied to the patients who can not be treatment with surgey, recurrence after surgery or thiourea treatment is invalid.,Diagnosis of disorders of thyroid function,:,Low does of,131,I can be used to test the thyroid function,Radioactive Iodine,clinical application,High incidence of delayed hypothyroidism which can be treated with thyroid hormone,131,I is banned for pregnancy hyperthyroidism, children hyperthyroidism and patients with severe hyperthyroidism.,Radioactive Iodine,adverse effects,Mechanism,Mainly through blocking receptor, and relieving the symptoms in patients with hyperthyroidism caused by adrenal system excitement.,it can inhibit thyroid hormone secretion and inhibit,the peripheral deiodination of T,4,to T,3, Adrenergic antagonists,Application,1. Control the symptoms of hyperthyroidism,2. Preparation for the hyperthyroidism preoperative,3. Adjuvant therapy of thyroid crisis.,The effect is much better shared with thiourea, Adrenergic antagonists,Thioureas inhibit the synthesis of thyroid hormones. Propythiouracil can also block the conversion of T,4,to T,3,in peripheral tissues,.,Key Concepts,High concentrations of iodide appear to influence,almost all important aspects of iodide metabolism,by the thyroid gland, especially including an,inhibition of the release of thyroid hormones,.,131,I exerts a destruction of thyroid gland by beta particles.,The major indications for the therapeutic use of thyroid hormones are for hormone replacement therapy in patients with hypothyroidism or cretinism, and antithyroid drugs are for the treatment of hyperthyroid individual.,Key Concepts,131,I exerts a destruction of thyroid gland by beta particles.,The major indications for the therapeutic use of thyroid hormones are for hormone replacement therapy in patients with hypothyroidism or cretinism, and antithyroid drugs are for the treatment of hyperthyroid individual.,Key Concepts,1,.,Illustrate the influence of drug dose on the drug effects, take the effects of iodine on the thyroid function?,2. Try to explain the purpose of thiourea and iodine used on the hyperthyroidism preoperative?,Review questions,
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