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1、Chapter 36 Thyroid Hormones and Antithyroid DrugsDepartment of pharmacologyLiming zhou2015.10,Contents,Thyroid hormone Thioureas(硫脲类）Iodine and Iodide(碘及碘化物)Radioactive Iodine adrenergic receptor antagonists,Thyroid hormone,The thyroid gland is one of the largest endocrine organ and mainly consists
2、of thyroid follicular,which is the main place to generate and secrete thyroid hormone.,Thyroid hormonesynthesis and secretion,EC Space,Follicle Lumen,Thyroid hormoneregulation,Thyroid hormoneintracorporal process,Easy to absorb using Po and the oral absorption rate of T3 and T4 are 50%75%and 75%90%r
3、espectively.The rate of plasma protein combining is 99%,and the protein binding of T3 is less than the T4,the role of T3 is more potent than T4 with a half-life for 2 days,T4 is slow and weak with a half-life for 5 days.,Thyroid hormoneintracorporal process,The liver is the major site of nondeiodina
4、tive degradation,T4 and T3 are conjugated with glucuronic and sulfuric acids and excreted in the renalAs it can go through the placenta and breast milk,pregnancy and lactation women should be cautious.,Thyroid hormoneintracorporal process,Tab 1 Summary of thyroid hormone kinetics,Thyroid hormonePhar
5、macological effects,Growth and Development hypothyroidism：child cretinism(呆小症)adult myxedema(黏液水肿)Calorigenic Effects:Increase the basal metabolic rate and excessive production of heat Improve the sensitivity of sympatheticThe susceptibility of adrenal system,Thyroid hormonePharmacological mechanism
6、,Mediated by activating its nuclear specificity T3 receptors.T4 translated into T3 by deiodination and combined with the specificity T3 receptors,and regulate gene transcription,protein synthesis and play functions Other factors lead to the decreasing in T3 receptors,Thyroid hormoneclinical applicat
7、ion,CretinismThe hypofunction begin in fetus or infants,therapy is instituted within the first few weeks of life,normal physical and mental development is almost always achievedMyxedema Generally take thyroid tablet,from low does gradually increase to the full does.,Thyroid hormoneclinical applicati
8、on,Simple goiter(单纯性甲状腺肿)Using table salt and food for prevention,thyroid tablets for a supplementary treatment.T3 suppression test As a differential diagnosis in patients with high ingestion rate of iodine.,Thyroid hormoneuntoward effects,Too much does of thyroid hormone can cause the clinical mani
9、festations of hyperthyroidism,angina and myocardial infarction may occur in cardiopath and old patients,using adrenergic receptor antagonists to against the adverse effects and discontinuing thyroid hormone.Diabetes,coronary heart disease,rapid arrhythmia patients should not be used.,Classify,Thiour
10、ea,Iodine and iodide:,adrenergic receptor antagonists:,Thiouracils硫脲嘧啶:Propylthiouracil,Imidazole 咪唑:Methimazole,Antithyroid drugs,Compound Iodine Oral Solution,Atenolol,Radioactive iodine 125I,Thiourea【Mechanism】,Iodide in the blood,Iodine passed into the thyroid cells actively,incorporation of iod
11、ine into tyrosyl residues of thyroglobulin,TSH,Peroxidase,2DITMIT+DIT,oxidation of iodide ion(I+),Peroxidase,T4 T3,Thiourea,inhibit,Propylthiouracil丙基硫氧嘧啶:Absorption of propylthiouracil follows within 20 to 30 minutes of an oral dose and peak in 2 hours,plasma protein binding was 75%,concentrated in
12、 thyroid and could cross the placenta and also can be found in milk,with the half-life about 2 hours.Methimazole甲硫咪唑:The roles last for long time and and persistent with plasma t1/2 to 4 9 h；methimazole,derived from the metabolism of carbimazole,and not used in Thyroid Storm,Thioureapharmacokinetics
13、,1.Resistance to thyroid functionHaving no effects on the preformed hormone,the clinicaleffects become noticeable after 2-3 weeks,basal metabolic rate resumed normal after 1-3 months by inhibiting the peripheral deiodination脱碘 of T4 to T3 and controling the serum T3 level.As the feedback effects,whi
14、ch lead to the increased secretion of TSH and the gland hyperplasia2.Immunosuppressiveeffects,Thioureapharmacological effects,Thioureaclinical application,Treatment of hyperthyroidism Suitable for mild patients and who are unfavorable surgical or 131 I treatment,treatment last for 1 2 years.To contr
15、ol the disorder in preparation for surgical treatment Adjuvant therapy of the thyroidstorm,Thioureaadverse effects,The incidence of side effects is relatively low1.Frequent complications:pain and stiffnessn僵硬 in the joints,headache,nausea2.Allergic reaction:purpuric,urticarial papular rash3.Agranulo
16、cytosis.粒性白血球缺乏症:the most serious reaction4.Goiter and hypothyroidism5.Patients with thyroid cancer and nodular goiter is forbidden,Iodine and iodide pharmacological effects,Low doses of iodine promote the synthesis of thyroid hormones High concentrations of iodide inhibit the release of thyroid hor
17、mone.This action is rapid and efficacious and discernible within 24 hours,with the maximal effect attained after 10 to 15 days,Iodine and iodide clinical application,Simple goiter:1/105 1/104 potassium iodide or sodium iodide joined into the table salt can prevent this disease.Preparation for the hy
18、perthyroidism preoperative:To facilitate operation and reduce bleedingThyroid crisis:large doses of iodine can prevent thyroid hormone release and cooperate with thiourea.,Iodine and iodide adverse effects,Allergic reaction:Acute reaction may occur immediately or several hours after administration,a
19、ngioedema(血管性水肿),laryngeal edema(喉水肿)Chronic intoxication with iodide:unpleasant brassy taste and burning in the mouth and throat Thyroid dysfunction:Iodine can also enter into the milk and cross the placenta and cause neonatal goiter,pregnant women and lactating women should be used with caution.,R
20、adioactive Iodinepharmacological effects,131I is greatest used in clinical and half-life is 8 d,131I is rapidly and efficiently trapped by the thyroid,and the destructive particles originate within the follicle and act exclusively upon the parenchymal cells of the thyroid,with little or no damage to
21、 surrounding tissue The radiation can be quantified by external detection,which can be used to measurement thyroid function,Treatment of hyperthyroidism:131I is applied to the patients who can not be treatment with surgey,recurrence after surgery or thiourea treatment is invalid.Diagnosis of disorde
22、rs of thyroid function:Low does of 131I can be used to test the thyroid function,Radioactive Iodineclinical application,High incidence of delayed hypothyroidism which can be treated with thyroid hormone131 I is banned for pregnancy hyperthyroidism,children hyperthyroidism and patients with severe hy
23、perthyroidism.,Radioactive Iodineadverse effects,Mechanism Mainly through blocking receptor,and relieving the symptoms in patients with hyperthyroidism caused by adrenal system excitement.it can inhibit thyroid hormone secretion and inhibit the peripheral deiodination of T4 to T3,Adrenergic antagoni
24、sts,Application1.Control the symptoms of hyperthyroidism2.Preparation for the hyperthyroidism preoperative 3.Adjuvant therapy of thyroid crisis.The effect is much better shared with thiourea,Adrenergic antagonists,Thioureas inhibit the synthesis of thyroid hormones.Propythiouracil can also block the
25、 conversion of T4 to T3 in peripheral tissues.,Key Concepts,High concentrations of iodide appear to influence almost all important aspects of iodide metabolism by the thyroid gland,especially including an inhibition of the release of thyroid hormones.,131I exerts a destruction of thyroid gland by be
26、ta particles.The major indications for the therapeutic use of thyroid hormones are for hormone replacement therapy in patients with hypothyroidism or cretinism,and antithyroid drugs are for the treatment of hyperthyroid individual.,Key Concepts,131I exerts a destruction of thyroid gland by beta part
27、icles.The major indications for the therapeutic use of thyroid hormones are for hormone replacement therapy in patients with hypothyroidism or cretinism,and antithyroid drugs are for the treatment of hyperthyroid individual.,Key Concepts,1.Illustrate the influence of drug dose on the drug effects,take the effects of iodine on the thyroid function?2.Try to explain the purpose of thiourea and iodine used on the hyperthyroidism preoperative?,Review questions,
