藥理學(xué)教學(xué)課件：Chapter 32 Agents used to treat Thyroid diseases

Chapter32AgentsusedtotreatThyroiddiseasesContentstheactionofthyroidhormonesthepharmacologicaleffects,clinicalusesanduntowardreactionsofthioureasetheactionandusesofiodidesandradioiodineSection1ThyroidHormones1.IntroductionAhighlyvascularendocrineglandconsistingoftwolobes,oneoneithersideofthetrachea,joinedbyanarrowisthmus(峽);itproducesthethyroidhormoneswhichareconcernedinregulatingthemetabolicrateofthebody.Thethyroidhormones(TH)areproducedandreleasedbythyroidglands,whichinclude:T3

(3,5,3'-triiodothyronine,三碘甲狀腺原氨酸),

T4

(3,5,3’,5’-tetraiodothyronine,甲狀腺素).iodinatedformsoftheaminoacidthyronine(甲狀腺原氨酸).2.ChemcialStructure3.SynthesisofThyroidHormones(1)UptakeofIodide(2)OxidationandIodination(3)FormationofThyroxine(T4)andTriiodothronine(T3)fromIodotyrosines(碘化酪氨酸)(1)IodideTrappingIodineingested(攝入)inthedietreachesthecirculationintheformofiodideThethyroidactivelytransportstheiodideionviaaspecificmembrane-boundprotein.(2)OxidationandIodinationTheoxidationofiodidetoitsactiveformisaccomplishedbythyroidperoxidase.Thereactionresultsintheformationofmonoiodotyrosyl(MIT)anddiiodytyrosyl(DIT)residuesinthyroglobulin(TG).(3)FormationofT3andT4fromIodotyrosinesCouplingoftwoDITtoformThyroxine(T4);CouplingofoneMITandoneDITtoformTriiodothronine(T3).4.SecretionofThyroidhormonesSincethyroxineandtriiodothyroninearesynthesizedandstoredwithinthyroglobulin(TG),proteolysisisanimportantpartofthesecretionprocess.5.ReglationofThyroidSecretionHypothalamus→TRHPituitary→TSHThyroid→T3、T4

ThyroidHormomes:negativeeffectonHypothalamusandPituitary

6.ActionsofThyroidhormones(1)Thyroidhormonescanstimulatebasalmetabolicrate(BMR)andincreasethereactiontocatecholamine(兒茶酚胺）;(2)Thyroidhormonesareresponsibleforoptimal(最佳)growthanddevelopmentthroughcontrolofDNAtranscripionandproteinsynthesis;(3)Thyroidhormonesplayacriticalroleinbraindevelopment.TheabsenceofThyroidhormonesduringtheperoidofactiveneurogenesis(upto6monthspostpartum)leadstoirreversiblementalretardation（Cretinism,克汀病，呆小?。?WhatisCretinism?Cretinismisoftenencounteredinregionsofendemic(地方性)goiterandisusuallycausedbyextremedeficiencyofiodineThechildisdwarfed(矮小),withshortextremitiesandismentallyretarded.7.Clinicaluses

Hypothyroidism:Myxedema(黏液性水腫)Cretinism(克汀病)Endemic(地方性)Goiter8.AdverseReaction(1)Overdose(Hyperthyroidism):

Cardiopalmus(心悸),Colliquative(液化)sweating（多汗）,Handtremor,Hyperaesthesia(感覺過敏),Insomnia;(2)Gerontism(老年化)andheartdisease:

Angina,Myocardialinfarct,Myocardialfailure.Section2.AntithyroidDrugsthiouracils(硫氧嘧啶類)

methylthyioracil甲硫氧嘧啶

propylthiouracil丙硫氧嘧啶imidazoles(咪唑類)

methimazoletapazole甲巰咪唑（他巴唑）

carbimazloe卡比馬唑（甲亢平）1.PharmacologicaleffectInhibittheactivityofperoxydase:

preventthethyroidhormonesynthesisbyinhibitingthethyroidperoxidase-catalyzedreactionstoblockiodineorganification（有機(jī)化）.blockcouplingofiodotyrosine,mainlytheformationofDIT.Features:Sloweffect，1~2w；1~3m,thesymptomdisappear;Onlyactonsynthesis,butnotrelease;Can’tantagonizethyroidhormone;TSH↑(feedback)，thyroidhyperplasy.2.Therapeuticapplications(1)Hyperthyroidism:

Mildcase.Patientwhoisnotsuitableforsurgeryoperationorradioiodinetherapy.(2)Preparationforthyroidsurgery.(3)

Supplementarytreatmentofthyrotoxiccrisis

(甲狀腺危象).thyrotoxiccrisis:Themortalitymayapproach1in10.Severehyperthyroidismwith:Hyperpyrexia,dehydration.Increasingtachycardia,hypotension,atrialdysrhythmias,congestiveheartfailure.Nausea,vomiting,diarrhoea,abdominalpain.Confusion,agitation(焦慮不安),delirium,psychosis,seizuresorcoma.Death.3.AdverseReactionsSkinrash,headache,dizzy(頭暈),lymphadenectasis(淋巴結(jié)腫大),drugfeverandarthralgia(關(guān)節(jié)痛),Jaundice,toxichepatitis;Granulocytopenia（粒細(xì)胞減少癥）:seriousadversereaction.Hemogram(血象).Fetalhypothyroidism.4.DrugInteractionsEnhancetheeffectsofanticoagulantdrugs;Sulfanilamide,Oralhypoglycemicagents(sulfonylurea),PAS（對(duì)氨基水楊酸鈉）,PABA,phenylbutazone,barbiturates,phentolamine,VB12inhibitthyroidfunction.Section3.Iodides1.Pharmacologiceffect(Largedose)

Inhibitthyroidperoxidase-catalyzedreactions,Inhibitorganification;Inhibithormonerelease:thyroglobulinproteolysisDecreasethesizeandvascularity(血管供應(yīng))ofthehyperplasticgland.AntagonizeTSH

Smalldose？Features:Fastandstrongeffects,l-2d，2wstrongestDecreasethesizeandvascularityofthehyperplasticgland,convenientforsurgeryoperation2.Therapeuticapplications(1)Simplegoitre(單純性甲狀腺腫):

-Cookingsaltl/104～l/105,-Aqueousiodinesolution0.1～0.5ml

(2)Thyrotoxiccrisis(甲狀腺危象):conjunctionwiththioureas;(3)Preparationforthyroidectomy.3.AdverseReactions(1)hypersensitivereaction:

Acneiform(痤瘡樣)rash,drugfever,bleedingdisorders,migratory(遷移性)edema（血管神經(jīng)性水腫）,laryngeal(喉)edema;(2)Chroniciodism(碘中毒):

Metallictaste（金屬味）,swollensalivaryglands,mucousmembrnaeulcerations,mucoushyperemia(充血),conjunctivitis,rhinorrhea(流涕).(3)Neonatusthyroncus(新生兒甲狀腺腫)Section4.Radioiodine(131I)1.Pharmacologicproperties:Emit（發(fā)射）

bothbeta(99%)andgamma(1%)rays.(1)Thebetara