英文版甲狀腺疾病治療藥課件

Chapter36ThyroidHormonesandAntithyroidDrugsDepartmentofpharmacologyLimingzhou2015.10Chapter36ContentsThyroidhormone

Thioureas(硫脲類）

IodineandIodide(碘及碘化物)

RadioactiveIodine

βadrenergicreceptorantagonistsContentsThyroidhormoneThyroidhormoneThethyroidglandisoneofthelargestendocrineorganandmainlyconsistsofthyroidfollicular,whichisthemainplacetogenerateandsecretethyroidhormone.ThyroidfollicularcolloidThyroglobulinT4T3hydrolysisT3ismorepotentT4ismorethanT3butweakThyroidhormoneThethyroidglaThyroidhormone

—synthesisandsecretionFollicleepithelialcellThyroidfollicleThyroidfollicleThyroidfollicleECSpace

FollicleLumenThyroidhormone

—synthesisandanteriorpituitaryparaventricularnucleusHypothalamusAnteriorPituitaryThyroidglandTRH++TSHThyroid-T4,T3-SRIFThyroidhormone—regulationanteriorpituitaryparaventricuThyroidhormone—intracorporalprocess

EasytoabsorbusingPoandtheoralabsorptionrateofT3andT4are50%~75%and75%~90%respectively.Therateofplasmaproteincombiningis99%,andtheproteinbindingofT3islessthantheT4,theroleofT3ismorepotentthanT4withahalf-lifefor2days,T4isslowandweakwithahalf-lifefor5days.Thyroidhormone—intracorporalThyroidhormone—intracorporalprocess

Theliveristhemajorsiteofnondeiodinativedegradation,T4andT3areconjugatedwithglucuronicandsulfuricacidsandexcretedintherenalAsitcangothroughtheplacentaandbreastmilk,pregnancyandlactationwomenshouldbecautious.Thyroidhormone—intracorporalThyroidhormone—intracorporalprocesskineticsT４T3dailyproduction(μg)70～9015～30fractionalturnoverperday(%)1060metabolicclearanceperday(L/d)1.124amountbound(％)99.9699.6volumeofdistribution(Ｌ)1040serumlevel(total)(μg/dL)4.5～1160～180serumlevel(free)(ng/dL)0.7～1.860.2～0.52half-life(biologic)(d)71biologicalpotency14oralabsorption(%)8095

Tab1SummaryofthyroidhormonekineticsThyroidhormone—intracorporalThyroid

hormone—Pharmacological

effects

GrowthandDevelopment

hypothyroidism：child

cretinism(呆小癥)

adult

myxedema(黏液水腫)

CalorigenicEffects

:

Increasethebasalmetabolicrateandexcessiveproductionofheat

Improvethesensitivityofsympathetic—Thesusceptibilityofadrenalsystem

Thyroidhormone—PharmacologicaThyroidhormone—PharmacologicalmechanismMediatedbyactivatingitsnuclearspecificityT3receptors.T4translatedintoT3bydeiodinationandcombinedwiththespecificityT3receptors,andregulategenetranscription,proteinsynthesisandplayfunctionsOtherfactorsleadtothedecreasinginT3receptorsThyroidhormone—PharmacologicaThyroidhormone—clinicalapplicationCretinism

Thehypofunctionbegininfetusorinfants,therapyisinstitutedwithinthefirstfewweeksoflife,normalphysicalandmentaldevelopmentisalmostalwaysachievedMyxedema

Generallytakethyroidtablet,fromlowdoesgraduallyincreasetothefulldoes.Thyroidhormone—clinicalappliThyroidhormone—clinicalapplicationSimplegoiter(單純性甲狀腺腫)

Usingtablesaltandfoodforprevention,

thyroidtabletsforasupplementarytreatment.T3suppressiontestAsadifferentialdiagnosisinpatientswithhighingestionrateofiodine.Thyroidhormone—clinicalappliThyroidhormone—untowardeffects

Toomuchdoesofthyroidhormonecancausetheclinicalmanifestationsof

hyperthyroidism,

anginaandmyocardialinfarctionmayoccurincardiopathandoldpatients,usingβadrenergicreceptorantagoniststoagainsttheadverseeffectsanddiscontinuingthyroidhormone.Diabetes,coronaryheartdisease,rapidarrhythmiapatientsshouldnotbeused.Thyroidhormone—untowardeffecClassifyThioureaIodineandiodide:βadrenergicreceptorantagonists:Thiouracils

硫脲嘧啶:PropylthiouracilImidazole

咪唑:Methimazole

AntithyroiddrugsCompoundIodineOralSolutionAtenololRadioactiveiodine125IClassifyThioureaIodineandioThiourea—【Mechanism】

IodideinthebloodIodinepassedintothethyroidcellsactivelyincorporationofiodineintotyrosylresiduesofthyroglobulinTSHPeroxidase2DITMIT+DIToxidationofiodideion(I+)

PeroxidaseT4

T3Thiourea

inhibitThiourea—【Mechanism】IodidePropylthiouracil

丙基硫氧嘧啶:Absorptionofpropylthiouracilfollowswithin20to30minutesofanoraldoseandpeakin2hours,plasmaproteinbindingwas75%,concentratedinthyroidandcouldcrosstheplacentaandalsocanbefoundinmilk,withthehalf-lifeabout2hours.Methimazole甲硫咪唑:Theroleslastforlongtimeandandpersistentwithplasmat1/2to4~9h；methimazole,derivedfromthemetabolismofcarbimazole,andnotusedin

ThyroidStormThiourea—pharmacokineticsPropylthiouracil

丙基硫氧嘧啶:Absor1.ResistancetothyroidfunctionHavingnoeffectson

thepreformedhormone,theclinicaleffectsbecomenoticeableafter2-3weeks,

basalmetabolicrateresumednormalafter1-3monthsbyinhibitingtheperipheraldeiodination脫碘ofT4toT3andcontrolingtheserumT3level.Asthefeedbackeffects,whichleadto

theincreasedsecretionofTSHandthegland

hyperplasia2.Immunosuppressive

effectsThiourea—pharmacologicaleffects1.ResistancetothyroidfunctThiourea—clinicalapplication

Treatmentofhyperthyroidism

Suitableformildpatientsandwhoareunfavorablesurgicalor131Itreatment,treatmentlastfor1~2years.

Tocontrolthedisorderinpreparationforsurgicaltreatment

Adjuvanttherapyofthethyroid

stormThiourea—clinicalapplicationThiourea—adverse

effectsTheincidenceofsideeffectsisrelativelylow1.Frequentcomplications:painandstiffnessn僵硬

inthejoints,headache,nausea2.Allergicreaction:

purpuric,urticarialpapularrash3.Agranulocytosis.粒性白血球缺乏癥:themostseriousreaction4.Goiterandhypothyroidism5.Patientswiththyroidcancerandnodulargoiteris

forbiddenThiourea—adverseeffectsTheinIodineandiodide—pharmacologicaleffects

Lowdosesofiodinepromotethesynthesisofthyroidhormones

Highconcentrationsofiodideinhibitthereleaseofthyroidhormone.

Thisactionisrapidandefficaciousanddiscerniblewithin24hours,withthemaximaleffectattainedafter10to15daysIodineandiodide—pharmacoloIodineandiodide—clinicalapplication

Simplegoiter

:1/105~1/104potassiumiodideorsodiumiodidejoinedintothetablesaltcanpreventthisdisease.

Preparationforthehyperthyroidismpreoperative:

TofacilitateoperationandreducebleedingThyroidcrisis:largedosesofiodinecanpreventthyroidhormonereleaseandcooperatewiththiourea..Iodineandiodide—clinicalIodineandiodide—adverseeffectsAllergicreaction:

Acutereactionmayoccurimmediatelyorseveralhoursafteradministration,angioedema(血管性水腫),laryngealedema(喉水腫)Chronicintoxicationwithiodide:unpleasantbrassytasteandburninginthemouthandthroat

Thyroiddysfunction:Iodinecanalsoenterintothemilkandcrosstheplacentaandcauseneonatalgoiter,pregnantwomenandlactatingwomenshouldbeusedwithcaution.Iodineandiodide—adverseefRadioactiveIodine—pharmacologicaleffects

131Iisgreatestusedinclinicalandhalf-lifeis8d

131Iisrapidlyandefficientlytrappedbythethyroid,andthedestructiveβparticlesoriginatewithinthefollicleandactexclusivelyupontheparenchymalcellsofthethyroid,withlittleornodamagetosurroundingtissue

Theγradiationcanbequantifiedbyexternaldetection,whichcanbeusedtomeasurementthyroidfunctionRadioactiveIodine—pharmacolog

Treatmentofhyperthyroidism:

131Iisappliedtothepatientswhocannotbetreatmentwithsurgey,recurrenceaftersurgeryorthioureatreatmentisinvalid.

Diagnosisofdisordersofthyroidfunction:

Lowdoesof131IcanbeusedtotestthethyroidfunctionRadioactiveIodine—clinicalapplicationTreatmentofhyperthyroidismHighincidenceofdelayedhypothyroidismwhichcanbetreatedwiththyroidhormone131Iisbannedforpregnancyhyperthyroidism,childrenhyperthyroidismandpatientswithseverehyperthyroidism.RadioactiveIodine—adverseeffectsHighincidenceofdelayedhypo

Mechanism

Mainlythroughblockingβreceptor,andrelievingthesymptomsinpatientswithhyperthyroidismcausedbyadrenalsystemexcitement.

itcaninhibitthyroidhormonesecretionandinhibittheperipheraldeiodinationofT4toT3βAdrenergicantagonistsMechanismβAdrenergicantagonApplication1.Controlthesymptomsofhyperthyroidism2.Preparationforthehyperthyroidismpreoperative3.Adjuvanttherapyofthyroidcrisis.TheeffectismuchbettersharedwiththioureaβAdrenergicantagonistsApplicationβAdrenergicantagoThioureasinhibitthesynthesisofthyroidhormones.PropythiouracilcanalsoblocktheconversionofT4toT3inperipheraltissues.KeyConceptsHighconcentrationsofiodideappeartoinfluencealmostallimportantaspectsofiodidemetaboli