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硫代酰胺硫脲类丙硫氧嘧啶PTU卡比马唑.ppt

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Biosynthesisofthyroidhormones三碘甲状腺原氨酸甲状腺素的生理及药理作用HypothyroidismHyperthyroidism Hypothyroidism:iodineandiodides(smalldoses);thyroidhormone Hypothyroidism: thyroidhormones iodineandiodides(小剂量) Hyperthyroidism: antithyroiddrugs: thioureaderivatives硫脲类 iodineandiodides碘和碘化物（大剂量） receptorantagonists Radioiodines放射性碘:131I(硫代酰胺；硫脲类)丙硫氧嘧啶PTUThioureaderivatives 1.Pharmacologicaleffects (1)Inhibittheformationofthyroidhormonesbyinterferingwithiodination:competingperoxidation,thentheiodinationandcoupling Symptomrelieving:2-3weeks Basicmetabolicratereturning:1-2months (2)InhibitperipheraldeiodinationofT4:T4T3(propylthiouracil丙硫氧嘧啶),rapidremissionofhyperthyroidismduetoT3upregulation.Thioureaderivatives 1.Pharmacologicaleffects (3)Inhibitglucosemetabolismbydown-regulatingβreceptor (4)Immunosuppression:TSI↓ 2.Clinicaluses (1)Non-operativetherapyofhyperthyroidism:longduration(1-2y) (2)Preoperativetherapyofhyperthyroidism:combinedwithlargedoseofiodide (3)Thyrotoxiccrisis:propylthiouracil,combinedwithlargedoseofiodide, 3.Adverseeffects Hypersensitivity Agranulocytosis(0.2%ormore) (3)GIreactions (4)Goitrogenicaction(goiter):TSH↑Iodineandiodides 1.Pharmacologicaleffects (1)Smalldoses:simplegoiter (2)Largedosesforshorttermuse:inhibitthesynthesisandreleaseofthyroidhormone(proteolysis)byinhibitingperoxidaseandGSHreductase. Afteriodideuse,thethyroidvascularityisreduced,andtheglandbecomesmuchfirmer,thecellsbecomesmaller.2.Clinicaluses (1)Simplegoiter(smalldoses) (2)Preoperativetherapyofhyperthyroidism:combinedwiththioureaderivatives (3)Thyrotoxiccrisis:combinedwiththioureaderivatives(propylthiouracil) Lugol’ssolution卢戈氏液:5%iodineand10%potassiumiodide3.Adverseeffects (1)Acuteeffects:hypersensitivity,angioedema,swellingofthelarynx (2)Chronicintoxication(iodism) (3)Thyroiddysfunction:exacerbationofhyperthyroidism,goiter20receptorantagonists 1.Pharmacologicaleffects (1)Heart:1block (2)CNS:relievinganxiety (3)Presynaptic2receptor:NErelease (4)DecreaseT3:inhibitdeiodinationofT4 2.Clini