Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,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,*,*,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,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。,Summary,Thyroid 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 the 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(,131,I)irradation,antithyroid drugs and operation.,第二页，共三十四页。,Thyroid hormones,Thyroxine,T4,Triiodothyreninum natricum,T3,Synthesized 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,（,131,I）,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Carbimazole）,第五页，共三十四页。,Thyroid hormones are iodic amino acids,Active components,Thyroxine,T4,Triiodothyreninum natricum,T3,Chemical 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,，maintaining time,T4T3,.,T,1/2,of T4 and T3,are,6,7,days and,1,2,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 produced and metabolized daily.,第八页，共三十四页。,Synthesis,storage and regulation of thyroid hormones,Iodine uptake,Iodine activation and tyrosine iodation,Condensation and storage,Disintegration and release,Regulation,第九页，共三十四页。,Steps of thyroid hormones synthesis,release and regulation(),Iodine uptake:,I,in blood 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 monoiodotyrosine(MIT)and,diiodotyrosine,(,DTT).,第十页，共三十四页。,Condensationandstorage,:,In the thyroid globulinmolecule,two DTTsarecondensed toT4,one DTT and one MIT are condensedto T3，whichareallstored in glandalveoluscolloid.,Disintegration and release:,T3 and T4 are released intoblood afterhydrolyzed by proteases.Atthesametime,someofthemcanbeturned backto tyrosineand,I,bydeiodinaseincellsandreused.,Regulation:,Bythepositiveandnegativefeedbackregulationofhypothalamus-anteriorlobe-thyroidaxis.Hypothalamus,secretsTRH,anteriorlobesecretsTSHandthyroidsynthesizeT,3,T,4.,Stepsofthyroidhormonessynthesis,releaseandregulation(,),第,十,十,一,一,页,页,，,，,共,共,三,三,十,十,四,四,页,页,。,。,Synthesis,storageandreleaseofthyroidhormone,Gastrointestinal,I,-,Blood,I,-,I,-,Peroxidase,I,o,TG,Tyr,Iodation,MIT,DIT,Con-den-sation,MIT+DIT,DIT+DIT,T,3,T,4,TG,Acinarlumina,Storage,Synthesis,Release,Activation,Protease,T,3,T,4,MIT,一,碘,碘,酪,酪,氨,氨,酸,酸,DIT,二,碘,碘,酪,酪,氨,氨,酸,酸,TG,甲,状,状,腺,腺,球,球,蛋,蛋,白,白,blood,第,十,十,二,二,页,页,，,，,共,共,三,三,十,十,四,四,页,页,。,。,Thyroidhormones,Mechanismofaction,ThebindingofT3andRincreasestheuptakeofaaandglucose,resultingintheentrancetocytoplasmofT3.,AfterreactingwithCBP,T3 iseduced.The free T3canbindR inthe mitochondria andmakeADPto ATP.,Besides,it canenter thenuclear and bind Rthere,which can increasethetranscription of DNAand,the content ofmRNA.Thenthenew proteins can,be synthesizedand play roles.,第十三页，,共,共三十四页,。,。,Mechanismof action,（figure),It isbelievednow that the thermogenicaction ofT3 and T4is due tothe increase ofsodium pumps activity onthecellmembrane.Na+,K+ATPaseactivityATP utilizationADPconcentration,mitochondria respirationoxideconsumption and heat production,Thyroid hormones,第十四页，,共,共三十四页,。,。,Physiological and pharmacological actions,Keepnormal growth and development,Promote synthesis ofproteinsas well asgrowth and development of skeletonandCNS.T3,T4 deficient secretion:causes cretinism ininfants and young,children and mucousedemain adults.,Promote metabolism and increase heat production,Promote oxidation,increase oxygenconsumption,basalmetabolicrateand heat production.,Elevate sensitivityof sympathetic-adrenalsystem,Nervousness,trembling,heartbeat speedup,bloodpressure increase,第十五页，,共,共三十四页,。,。,Thyroid clinical application,Replacement therapymainly,Therapy and diagnosisApplication,Cretinism,Treating the infantsandchildren,as soon aspossiblecouldcurethemto,normal.If treatingtoolate,theyneedto betreated alifetime.,Mucous edemaIncreasethe dosageof thyroid pallet gradually.,Too largedosage mayaggravateheart diseases.,Patients in coma should be given afistaid,whichis infusion ofT3（40-120g）intravenoiusly,reinjection