Part 2 Thyroid hormones and antithyroid drugs. A. Thyroid hormones.

Part 2Part 2

Thyroid hormones and Thyroid hormones and antithyroid drugsantithyroid drugs

A.A. Thyroid hormones Thyroid hormones

Metabolism of thyroid hormonesMetabolism of thyroid hormones

1.1. Uptake of iodideUptake of iodide

2.2. Activation of iodide (peroxidase), and iodination Activation of iodide (peroxidase), and iodination and coupling of tyrosineand coupling of tyrosine

3.3. Formation of thyroxine Formation of thyroxine (T(T44)) and triiodothyronine and triiodothyronine

(T(T33)) from iodotyrosine from iodotyrosine

4.4. Secretion of thyroid hormones (proteolytic enzymSecretion of thyroid hormones (proteolytic enzymes)es)

5.5. Regulation by thyroid stimulating hormone (TSRegulation by thyroid stimulating hormone (TSH),H), T T44, T, T33

Metabolism of thyroid hormonesMetabolism of thyroid hormones

Formation of thyroxiFormation of thyroxine (Tne (T44) and triiodoth) and triiodoth

yronine (Tyronine (T33) from iod) from iod

otyrosineotyrosine

Formation of thyroxine (TFormation of thyroxine (T44) and triiodothyronine (T) and triiodothyronine (T33) from io) from io

dotyrosinedotyrosine

Secretion of thyroid horSecretion of thyroid hormones mones ( lysosomal prote( lysosomal proteolytic enzymes )olytic enzymes )

Regulation of the Regulation of the secretion of thyroid secretion of thyroid hormones hormones (feedback (feedback inhibition)inhibition)

1. Normalizing growth and development1. Normalizing growth and development

2. Promoting body metabolism2. Promoting body metabolism Body temperature; energy levels, Body temperature; energy levels, ect.ect.

3. Enhancing sympathetic activity3. Enhancing sympathetic activity

Pharmacology of thyroid hormonesPharmacology of thyroid hormones

Action of thyroid hormones:Action of thyroid hormones: interaction with their interaction with their receptors in the nucleireceptors in the nuclei

Action of thyroid Action of thyroid hormones:hormones: interaction with their interaction with their receptors in the receptors in the nucleinuclei

1. Treatment of hypothyroidism1. Treatment of hypothyroidism (1) cretinism ((1) cretinism ( 呆小病呆小病 )) (2) myxoedema ((2) myxoedema ( 黏液性水肿黏液性水肿 ))

2. Simple goiter (2. Simple goiter ( 单纯性甲状腺肿单纯性甲状腺肿 ))

Clinical uses of thyroid hormonesClinical uses of thyroid hormones

B.B. Antithyroid d Antithyroid drugsrugs

Symptoms of the patient with Symptoms of the patient with hyperthyroidismhyperthyroidism

Therapeutic drugs for Therapeutic drugs for HypothyroidismHypothyroidism

antithyroid drugs:antithyroid drugs: thiourea derivativesthiourea derivatives iodine and iodidesiodine and iodides receptor antagonistsreceptor antagonists surgerysurgery

radioiodines:radioiodines: 131131I, I, 125125II

Thiourea derivativesThiourea derivatives Propylthiouracil Propylthiouracil 丙硫氧嘧啶丙硫氧嘧啶 Methimazole (tapazole) Methimazole (tapazole) 甲巯咪唑甲巯咪唑 Carbimazole Carbimazole 卡比马唑卡比马唑

Iodine and iodidesIodine and iodides Receptor antagonistsReceptor antagonistsRadioiodideRadioiodide ((131131I)I)

B.B. Antithyroid drugs Antithyroid drugs

Thiourea derivativesThiourea derivatives


丙硫氧嘧啶丙硫氧嘧啶甲巯咪唑甲巯咪唑 ThiaThiamazolemazole

卡比马唑卡比马唑

Thiourea derivativesThiourea derivatives

1. 1. Pharmacological effectsPharmacological effects

(1) Inhibiting the formation of thyroid hormones by i(1) Inhibiting the formation of thyroid hormones by interfering with iodination:nterfering with iodination: inhibiting peroxidation, tinhibiting peroxidation, then the iodination and couplinghen the iodination and coupling

Symptom relieving: 2~3 weeksSymptom relieving: 2~3 weeks Basic metabolic rate returning: 1~2 months Basic metabolic rate returning: 1~2 months

(2) Inibiting peripheral deiodination of T(2) Inibiting peripheral deiodination of T44: : TT44 T T33 (propylthiouracil)(propylthiouracil)

(3) Goitrogenic action (3) Goitrogenic action (goiter)(goiter) : TSH : TSH ↑↑


Mechanism of inhibition of thyroid hormone Mechanism of inhibition of thyroid hormone synthesis by thiaureas:synthesis by thiaureas:

Thiaureas are oxidized by thyroid peroxidase (TPO)Thiaureas are oxidized by thyroid peroxidase (TPO)

Mechanism of inhibition of thyroid hormone synthesis by thiaureasMechanism of inhibition of thyroid hormone synthesis by thiaureas

Mechanism of inhibition of thyroid hormone synthesis Mechanism of inhibition of thyroid hormone synthesis by thiaureasby thiaureas

2.2. Clinical uses Clinical uses (1) Non-operative therapy of hyperthyroidism:(1) Non-operative therapy of hyperthyroidism: 11

~3 month~3 month latent periodlatent period (2) Preoperative therapy of hyperthyroidism:(2) Preoperative therapy of hyperthyroidism: coco

mbined with larger dose of iodidembined with larger dose of iodide (3) Thyrotoxic crisis:(3) Thyrotoxic crisis: combined with larger dose combined with larger dose

of iodide, of iodide, propylthiouracilpropylthiouracil

3.3. Adverse effects Adverse effects (1) Agranulocytosis (1) Agranulocytosis (0.3%~0.6%)(0.3%~0.6%) (2) Hypersensitivity (3) GI reactions(2) Hypersensitivity (3) GI reactions


Iodine and iodidesIodine and iodides

1.1. Pharmacological effects Pharmacological effects

(1) Small doses:(1) Small doses: simple goitersimple goiter

(2) Larger doses:(2) Larger doses: inhibiting the release of thyroid hinhibiting the release of thyroid hormones (proteolysis ormones (proteolysis ) and synthesis) and synthesis

After iodide use, the thyroid vascularity is reduced, After iodide use, the thyroid vascularity is reduced, and the gland becomes much firmer, the cells becomand the gland becomes much firmer, the cells become smaller (e smaller (inhibiting TSH releaseinhibiting TSH release).).


Mechanism of iodidesMechanism of iodides

Mechanism of Mechanism of iodidesiodides

2.2. Clinical uses Clinical uses (1) Preoperative therapy of hyperthyroidism:(1) Preoperative therapy of hyperthyroidism: cc

ombined with thiourea derivatives (for 2 weeks)ombined with thiourea derivatives (for 2 weeks) (2) Thyrotoxic crisis:(2) Thyrotoxic crisis: combined with thiourea dcombined with thiourea d

erivatives (propylthiouracil)erivatives (propylthiouracil) Lugol’s solution:Lugol’s solution: 5% iodine and 10% potasium 5% iodine and 10% potasium

iodideiodide


3.3. Adverse effects Adverse effects (1) Acute effects:(1) Acute effects: hypersensitivity, angioedema, hypersensitivity, angioedema,

swelling of the larynxswelling of the larynx (2) Chronic intoxication (iodism)(2) Chronic intoxication (iodism) (3) Thyroid dysfunction:(3) Thyroid dysfunction: exacerbation of hypertexacerbation of hypert

hyroidism, goiterhyroidism, goiter


Receptor antagonistsReceptor antagonists

1. 1. Pharmacological effectsPharmacological effects (1) Heart: (1) Heart: 11 block block (2) CNS: (2) CNS: relieving anxietyrelieving anxiety (3) Presynaptic (3) Presynaptic 22 receptor: receptor: NE release NE release (4) Inhibiting the conversion of T(4) Inhibiting the conversion of T44 to T to T33

2. 2. Clinical usesClinical usesAdjuvant therapeutic drugAdjuvant therapeutic drug


RadioiodineRadioiodine

131131I, I, 125125I, I, 123123II

Destroying thyroid tissueDestroying thyroid tissue DiagnosisDiagnosis Careful useCareful use


Part 2 Thyroid hormones and antithyroid drugs. A. Thyroid hormones.

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Transcript of Part 2 Thyroid hormones and antithyroid drugs. A. Thyroid hormones.