1、甲状腺激素(j s)和抗甲状腺药Thyroid hormones and antithyroid drugs,北京(bi jn)协和医学院基础医学院药理学系 叶菜英,第一页，共三十四页。,SummaryThyroid hormones Necessary to maintain normal metabolism,growth and development.Hypothyroidism Cause Cretinism if it happens in embryo or neonatal period.Cause myxedema if it happens in adults when t
2、he thyroid hormone could be used in replacement therapy.Hyperthyroidism A syndrom characterized by thyroid oversecretion and metabolic disorder caused by multiple reasons.It can be treated with radioactive iodine(131I)irradation,antithyroid drugs and operation.,第二页，共三十四页。,Thyroid hormones,Thyroxine,
3、T4Triiodothyreninum natricum,T3Synthesized and secreted by thyroid,第三页，共三十四页。,抗甲状腺药,分为4类：硫脲类 Thiourea碘和碘化物（复方碘溶液，lugols solution）放射性碘（131I）受体阻断(z dun)药（心得安等从略）,第四页，共三十四页。,硫脲类,硫氧嘧啶类（thiouracil）：甲基硫氧嘧啶（methykthiouracil）丙基硫氧嘧啶（propylthiouracil）咪唑类（imidazoles）他巴唑（Tapazole，甲巯咪唑(m zu)methimazole）甲亢平（卡比马唑C
4、arbimazole）,第五页，共三十四页。,Thyroid hormones are iodic amino acidsActive components Thyroxine,T4 Triiodothyreninum natricum,T3Chemical constitution,Thyroid hormones,第六页，共三十四页。,甲状腺激素(j s)的化学结构,第七页，共三十四页。,Physiological disposition of thyroid hormones,Absorbed rapidly when take orally,activity T3T4，maintain
5、ing time T4T3.T1/2 of T4 and T3 are 67 days and 12 days,respectively.Deiodination in mitochondria of liver and kidney,eliminated by kidney affer conjugated with glucuronic acid and sulfuric acid.T3,T4 can also pass the placenta and enter milk.Figure:the amount of normal adults thyroid hormones produ
6、ced and metabolized daily.,第八页，共三十四页。,Synthesis,storage and regulation of thyroid hormones,Iodine uptakeIodine activation and tyrosine iodationCondensation and storageDisintegration and releaseRegulation,第九页，共三十四页。,Steps of thyroid hormones synthesis,release and regulation(),Iodine uptake:I in blood
7、 can be uptaken into cells by iodine pump in the adenocyte membrane.The amino acids can be used to synthesize thyroid globulin in cells.Iodine activation and tyrosine iodation:I uptaken into cells can be oxydized to active iodine by peroxydase.Active iodine binds to tyrosine of TG and forms monoiodo
8、tyrosine(MIT)and diiodotyrosine(DTT).,第十页，共三十四页。,Condensation and storage:In the thyroid globulin molecule,two DTTs are condensed to T4,one DTT and one MIT are condensed to T3，which are all stored in gland alveolus colloid.Disintegration and release:T3 and T4 are released into blood after hydrolyzed
9、 by proteases.At the same time,some of them can be turned back to tyrosine and I by deiodinase in cells and reused.Regulation:By the positive and negative feedback regulation of hypothalamus-anterior lobe-thyroid axis.Hypothalamus secrets TRH,anterior lobe secrets TSH and thyroid synthesize T3,T4.,S
10、teps of thyroid hormones synthesis,release and regulation(),第十一页，共三十四页。,Synthesis,storage and release of thyroid hormone,Gastrointestinal I-,Blood I-,I-,Peroxidase,Io,TG,Tyr,Iodation,MIT,DIT,Con-den-sation,MIT+DIT,DIT+DIT,T3,T4,TG,Acinar lumina,Storage,Synthesis,Release,Activation,Protease,T3,T4,MIT
11、 一碘酪氨酸DIT 二碘酪氨酸TG 甲状腺球蛋白,blood,第十二页，共三十四页。,Thyroid hormones,Mechanism of actionThe binding of T3 and R increases the uptake of aa and glucose,resulting in the entrance to cytoplasm of T3.After reacting with CBP,T3 is educed.The free T3 can bind R in the mitochondria and make ADP to ATP.Besides,it ca
12、n enter the nuclear and bind R there,which can increase the transcription of DNA and the content of mRNA.Then the new proteins can be synthesized and play roles.,第十三页，共三十四页。,Mechanism of action（figure)It is believed now that the thermogenic action of T3 and T4 is due to the increase of sodium pumps
13、activity on the cell membrane.Na+,K+ATPase activity ATP utilization ADP concentration mitochondria respiration oxide consumption and heat production,Thyroid hormones,第十四页，共三十四页。,Physiological and pharmacological actions,Keep normal growth and development Promote synthesis of proteins as well as grow
14、th and development of skeleton and CNS.T3,T4 deficient secretion:causes cretinism in infants and young children and mucous edema in adults.Promote metabolism and increase heat production Promote oxidation,increase oxygen consumption,basal metabolic rate and heat production.Elevate sensitivity of sym
15、pathetic-adrenal system Nervousness,trembling,heartbeat speed up,blood pressure increase,第十五页，共三十四页。,Thyroid clinical application,Replacement therapy mainlyTherapy and diagnosis Application Cretinism Treating the infants and children as soon as possible could cure them to normal.If treating too late
16、,they need to be treated a lifetime.Mucous edema Increase the dosage of thyroid pallet gradually.Too large dosage may aggravate heart diseases.Patients in coma should be given a fist aid,which is infusion of T3（40-120g）intravenoiusly,reinjection 515g every 6h and oral administration when awake.Hypopituitarism patients should be given cortical hormone first and followed by thyroid hormone.Simple goiter Replacement therapy can inhibit TSH oversecretion and contract the glandular organ,3-6 months.T