甲状腺激素及抗甲状腺药ThyroidhormonesandantithyroidVIP免费

甲状腺激素和抗甲状腺药Thyroidhormonesandantithyroiddrugs北京协和医学院基础医学院药理学系叶菜英SummaryThyroidhormonesNecessarytomaintainnormalmetabolism,growthanddevelopment.HypothyroidismCauseCretinismifithappensinembryoorneonatalperiod.Causemyxedemaifithappensinadultswhenthethyroidhormonecouldbeusedinreplacementtherapy.HyperthyroidismAsyndromcharacterizedbythyroidoversecretionandmetAsyndromcharacterizedbythyroidoversecretionandmetabolicdisordercausedbymultiplereasons.abolicdisordercausedbymultiplereasons.Itcanbetreatedwithradioactiveiodine(131I)irradation,antithyroiddrugsandoperation.ThyroidhormonesThyroxine,T4Triiodothyreninumnatricum,T3Synthesizedandsecretedbythyroid抗甲状腺药分为4类：硫脲类Thiourea碘和碘化物（复方碘溶液，lugol’ssolution））放射性碘（131I）β受体阻断药（心得安等从略）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methimazole）•甲亢平（卡比马唑Carbimazole）ThyroidhormonesareiodicaminoacidsActivecomponentsThyroxine,T4Triiodothyreninumnatricum,T3ChemicalconstitutionThyroidhormones甲状腺激素的化学结构PhysiologicaldispositionofthyroidhormonesAbsorbedrapidlywhentakeorally,activityT3>T4，maintainingtimeT4>T3.T1/2ofT4andT3are6－7daysand1－2days,respectively.Deiodinationinmitochondriaofliverandkidney,eliminatedbykidneyafferconjugatedwithglucuronicacidandsulfuricacid.T3,T4canalsopasstheplacentaandentermilk.Figure:theamountofnormaladults’thyroidhormonesproducedandmetabolizeddaily.Synthesis,storageandregulationofthyroidhormonesIodineuptakeIodineactivationandtyrosineiodationCondensationandstorageDisintegrationandreleaseRegulationStepsofthyroidhormonessynthesis,releaseandregulation()ⅠIodineuptake:I－inbloodcanbeuptakenintocellsbyiodinepumpintheadenocytemembrane.Theaminoacidscanbeusedtosynthesizethyroidglobulinincells.Iodineactivationandtyrosineiodation:I－uptakenintocellscanbeoxydizedtoactiveiodinebyperoxydase.ActiveiodinebindstotyrosineofTGandformsmonoiodotyrosine(MIT)anddiiodotyrosine(DTT).Condensationandstorage:Inthethyroidglobulinmolecule,twoDTTsarecondensedtoT4,oneDTTandoneMITarecondensedtoT3，whichareallstoredinglandalveoluscolloid.Disintegrationandrelease:T3andT4arereleasedintobloodafterhydrolyzedbyproteases.Atthesametime,someofthemcanbeturnedbacktotyrosineandI－bydeiodinaseincellsandreused.Regulation:Bythepositiveandnegativefeedbackregulationofhypothalamus-anteriorlobe-thyroidaxis.HypothalamussecretsTRH,anteriorlobesecretsTSHandthyroidsynthesecretsTRH,anteriorlobesecretsTSHandthyroidsynthesizeTsizeT3,3,TT4.4.Stepsofthyroidhormonessynthesis,releaseandregulation()ⅡSynthesis,storageandreleaseofthyroidhormoneGastrointestinalI-GastrointestinalI-BloodI-BloodI-I-I-PeroxidaseIoIoTGTGTyrIodationMITMITDITDITCon-den-sationMIT+DITDIT+DITT3T3T4T4TGTGAcinarluminaStorageSynthesisReleaseActivationProteaseT3T3T4T4MIT一碘酪氨酸DIT二碘酪氨酸TG甲状腺球蛋白bloodbloodThyroidhormonesMechanismofactionThebindingofT3andRincreasestheuptakeofaaandglucose,resultingintheentrancetocytoplasmofT3.AfterreactingwithCBP,T3iseduced.ThefreeT3canbindRinthemitochondriaandmakeADPtoATP.Besides,itcanenterthenuclearandbindRthere,whichcanincreasethetranscriptionofDNAandthecontentofmRNA.Thenthenewproteinscanbesynthesizedandplayroles.Mechanismofaction（figure)Itisbelievednowthatthethermogen...