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1、甲状腺激素和抗甲状腺药 Thyroid hormones and antithyroid drugs 北京协和医学院基础医学院药理学系 叶菜英 Summary wThyroid hormones Necessary to maintain normal metabolism, growth and development. wHypothyroidism Cause Cretinism if it happens in embryo or neonatal period. Cause myxedema if it happens in adults when the thyroid hormo
2、ne could be used in replacement therapy. wHyperthyroidism A A syndromsyndrom characterized characterized by by thyroid thyroid oversecretionoversecretion and and metabolic disorder caused by multiple reasons.metabolic disorder caused by multiple reasons. It can be treated with radioactive iodine (13
3、1I) irradation, antithyroid drugs and operation. Thyroid hormones wThyroxine, T4 wTriiodothyreninum natricum, T3 Synthesized and secreted by thyroid 抗甲状腺药 分为4类： w硫脲类 Thiourea w碘和碘化物 （复方碘溶液， lugols solution） ） w放射性碘（131I） w受体阻断药（心得安等从略） 硫脲类 w硫氧嘧啶类（thiouracil）： 甲基硫氧嘧啶（methykthiouracil） 丙基硫氧嘧啶（propylth
4、iouracil） w咪唑类（imidazoles） 他巴唑（Tapazole，甲巯咪唑 methimazole） 甲亢平（卡比马唑Carbimazole） wThyroid hormones are iodic amino acids wActive components Thyroxine, T4 Triiodothyreninum natricum, T3 wChemical constitution Thyroid hormones 甲状腺激素的化学结构 Physiological disposition of thyroid hormones FAbsorbed rapidly wh
5、en take orally , activity T3T4， maintaining time T4T3. T1/2 of T4 and T3 are 67 days and 12 days, respectively. FDeiodination in mitochondria of liver and kidney, eliminated by kidney affer conjugated with glucuronic acid and sulfuric acid. FT3, T4 can also pass the placenta and enter milk. FFigure:
6、 the amount of normal adults thyroid hormones produced and metabolized daily. Synthesis, storage and regulation of thyroid hormones wIodine uptake wIodine activation and tyrosine iodation wCondensation and storage wDisintegration and release wRegulation Steps of thyroid hormones synthesis, release a
7、nd regulation () wIodine uptake: I in blood can be uptaken into cells by iodine pump in the adenocyte membrane . The amino acids can be used to synthesize thyroid globulin in cells. wIodine activation and tyrosine iodation: I uptaken into cells can be oxydized to active iodine by peroxydase. Active
8、iodine binds to tyrosine of TG and forms monoiodotyrosine (MIT) and diiodotyrosine (DTT). wCondensation and storage: In the thyroid globulin molecule , two DTTs are condensed to T4 , one DTT and one MIT are condensed to T3，which are all stored in gland alveolus colloid . wDisintegration and release:
9、 T3 and T4 are released into blood after hydrolyzed by proteases .At the same time , some of them can be turned back to tyrosine and I by deiodinase in cells and reused. wRegulation: By the positive and negative feedback regulation of hypothalamus-anterior lobe-thyroid axis. Hypothalamus secrets sec
10、rets TRH TRH ,anterior ,anterior lobe lobe secrets secrets TSH TSH and and thyroid synthesize Tthyroid synthesize T3 , 3 , T T4. 4. Steps of thyroid hormones synthesis, release and regulation () Synthesis, storage and release of thyroid hormone Gastrointestinal I- Blood I- I- Peroxidase Io TGTyr Iod
11、ation MIT DIT Con- den- sation MIT+DIT DIT+DIT T3 T4 TG Acinar lumina StorageSynthesisReleaseActivation Protease T3 T4 MIT 一碘酪氨酸 DIT 二碘酪氨酸 TG 甲状腺球蛋白 bloodblood Thyroid hormones Mechanism of action wThe binding of T3 and R increases the uptake of aa and glucose, resulting in the entrance to cytoplasm
12、 of T3 . After reacting with CBP, T3 is educed. The free T3 can bind R in the mitochondria and make ADP to ATP. Besides, it can enter the nuclear and bind R there, which can increase the transcription of DNA and the content of mRNA. Then the new proteins can be synthesized and play roles. wMechanism
13、 of action（figure) wIt is believed now that the thermogenic action of T3 and T4 is due to the increase of sodium pumps activity on the cell membrane . Na+,K+ATPase activity ATP utilization ADP concentration mitochondria respiration oxide consumption and heat production Thyroid hormones Physiological
14、 and pharmacological actions w Keep normal growth and development Promote synthesis of proteins as well as growth and development of skeleton and CNS. T3, T4 deficient secretion: causes cretinism in infants and young children and mucous edema in adults. w w Promote metabolism and increase heat produ
15、ctionPromote metabolism and increase heat production Promote oxidation, increase oxygen consumption, basal metabolic rate and heat production. w w Elevate sensitivity of sympathetic - adrenal systemElevate sensitivity of sympathetic - adrenal system Nervousness, trembling, heartbeat speed up, blood pressure increase Thyroid clinical application Replacement therapy mainly Therapy and diagnosis Application wCretinism Treating the infants and children as soon as possible could cure them to normal . If treating too late, they need to be treated a lifetime. wMucous edema Increase the dosage of
