thyroid and antithyriod drugs2012课件.ppt

Rich in thyroid glands Pass through placenta, milk Pharmacokinetics Pharmacological action: anti-thyroid Mechanism 1.Inhibiting synthesis of thyroid hormones Pathway: peroxidase 2.Inhibiting conversion from T4 to T3( PTU) Pathway: 5’-deiodinase 3.Immunosupressive effect Pathway: TSI (thyroid-stimulating immunoglobulins) Chapter 31 Thyroid hormones and antithyroid drugs Introduction Thyroid hormones: T3 and T4 Normal amount is essential Dysfunctions hypothyroidism hyperthyroidism cretinism(克汀病,呆小病) Hypothyroidism adult hypothyroidism: myxedema（粘液水肿） Hyperthyroidism Section 1 Thyroid hormones Characteristics: contain iodine Two major forms T3 (3,5,3’-triiodothyronine) T4 (3,5,3’5’-tetraiodothyronine , thyroxin) Synthesis, storage , release and regulation of thyroid hormones Synthesis: four steps 1. Iodine trapping: active transport 2. Oxidation of iodine: peroxidase (过氧化物酶) 3. Iodination of tyrosyl groups： productions: MIT and DIT 4. Formation of T4 and T3 from MIT and DIT : peroxidase Synthesis, storage and release and regulation Storage and release 1. Storage: thyroglobulin (TG,甲状腺球蛋白) 2. Release: thyroglobulin hydrolase Differences between T3 and T4 The amount of T4 is much more than that of T3 either in storage or release. The effect of T3 is much faster, stronger and shorter than that of T4. Conversion T4 can converse to T3 catalyzed by 5’-deiodinase (5’-脱碘酶) in peripheral tissues deiodinase Regulation TRH TSH T3,T4 Hypothalamus pituitary thyroid Controlled by HPT(hypothalamic-pituitary-thyroid) axis + + - - TRH (thyrotropin releasing hormone) TSH (thyroid stimulating hormone or thyrotropin) Regulation hyperplasy Synthesis, storage and release and regulation 1. High PPBR：T3 99.5% T4 99.95% 2. T3：fast、strong、short， T