浙江大学医学院：《药理学 Pharmacology》课程教学资源（PPT课件）甲状腺激素和抗甲状腺药物 Thyroid hormones and antithyroid drugs

Thyroid hormones and antithyroid drugs CEAN KAYA其 Dept of Pharmacology Shi-Hong Zhang(张世红 shzhang713@zju.edu.cn

Thyroid hormones and antithyroid drugs Dept of Pharmacology Shi-Hong Zhang (张世红) shzhang713@zju.edu.cn

Thyroid gland Thyroid gland Parathyroid glands Back view Front view

Front view Thyroid gland

Thyroid hormones 1. Uptake of iodide 2. Oxidation of iodide(peroxidase) and iodination and coupling of tyrosine 3. Formation of thyroxine(t4) and triiodothyronine (T3) from iodotyrosine 4. Secretion of thyroid hormones(proteolytic enzymes) 5. Regulation by thyroid stimulating hormone(TSH), T4s

Thyroid hormones 1. Uptake of iodide 2. Oxidation of iodide (peroxidase) and iodination and coupling of tyrosine 3. Formation of thyroxine (T4 ) and triiodothyronine (T3 ) from iodotyrosine 4. Secretion of thyroid hormones (proteolytic enzymes) 5. Regulation by thyroid stimulating hormone (TSH), T4 , T3

NH CH -CH-COOH L-tyrosine CH.-CH-COOH HO >CH2-CH-COOH monoiodo tyrosine(MIT) diiodotyrosine(DIT) NH 2 HO CH2-CH-COOH 3, 5. 3'-triodothyronine (T3) NH CH2-CH-COOH 3, 5, 3, 5, tetraiodothyronine(Ta) thyroxine)

Acute Circadian and psychosis pulsatile rhythms Severe Cold H Hypothalamus Somato /(Statin Corticoids 打TRH dopamine AP T4,T3 TSH Thyroid

Hyperthyroidism 颤抖 心慌,心脏肥大 甲状腺肿大,突眼,情绪激动 腱反射亢进多食、腹泻、消瘦

Hyperthyroidism 颤抖 腱反射亢进 心慌，心脏肥大 甲状腺肿大，突眼，情绪激动 多食、腹泻、消瘦

Hypothyroidism sImple goIter cretinism(呆小症) (单纯性甲状腺肿) 瘿

Hypothyroidism cretinism (呆小症) 瘿 simple goiter (单纯性甲状腺肿)

System Thyrotoxicosis Hypothyroidism Skin and Warm, moist skin; sweating: heat Pale, cool, puffy skin: dry and brittle engages intolerance: fine, thin hair: Plummer's hair: brittle nails nails: pretibial dermopathy( graves disease) Eyes. face Retraction of upper lid with wide Drooping of eyelids; periorbital edema stare: periorbital edema loss of temporal aspects of eyebrows exophthalmos;diplopia(Graves' puffy, nonpitting facies; large tongue disease Cardiovascular Decreased peripheral vascular Increased peripheral vascular resistance system resistance, increased heart rate, stroke decreased heart rate, stroke volume volume, cardiac output, pulse cardiac output, pulse pressure; low pressure; high-output heart failure; output heart failure; ECG: bradycardia, increased inotropic and chronotropic prolonged PR interval, flat T wave, low eIfects, aRrhythmias angina voltage:pericardial effusion Respirator Dyspnea; decreased vital capacity Pleural effusions; hypoventilation and system CO, retention Gastrointestinal Increased appetite: increased Decreased appetite: decreased frequency system frequency of bowel movements of bowel movements: ascites ypoproteinemia

Central nervousNervousness: hyperkinesia; emotional Lethargy: general slowing of mental system lability processes: neuropathies Musculoskeletal Weakness and muscle fatigue Stiffness and muscle fatigue decreased system Increased deep tendon reflexes deep tendon reflexes: increased alkaline hypercalcemia: osteoporosis phosphatase LDH. AST Renal system Mild polyuria: increased renal blood Impaired water excretion:decreased flow increased glomerular filtration renal blood flow decreased glomerular rate filtration rate Hematopoietic Increased erythropoiesis: anemia Decreased erythropoiesis; anemia' Reproductive Menstrual iregularities; decreasedHypermenorrhea: infertility: decreased system fertility; increased gonadal steroid libido; impotence; oligospermia metabolism decreased gonadal steroid metabolism Metabolic Increased basal metabolic rate Decreased basal metabolic rate: slight system negative nitrogen balance positive nitrogen balance; delayed hyperglycemia: increased free fatty degradation of insulin, with increased acids; decreased cholesterol and sensitivity; increased cholesterol and triglycerides: increased hormone triglycerides: decreased hormone degradation: increased requirements degradation: decreased requirements for for fat- and water-soluble vitamins: fat- and water-soluble vitamins increased drug metabolism decreased drug metabolism

Therapeutic drugs on thyroid dysfunction ° Hyperthyroidism antithyroid drugs thiourea derivatives硫脲类 iodine and iodides碘和碘化物 β receptor antagonists Radioiodine放射性碘:131 Hypothyroidism thyroid hormones iodine and iodides

• Hyperthyroidism: – antithyroid drugs: thiourea derivatives 硫脲类 iodine and iodides 碘和碘化物  receptor antagonists Radioiodines 放射性碘: 131I • Hypothyroidism: – thyroid hormones – iodine and iodides Therapeutic drugs on thyroid dysfunction