浙江大学医学院：《药理学 Pharmacology》课程教学资源（PPT讲稿）肾上腺皮质激素药物 Drugs affecting endocrine system

Drugs affecting endocrine system Weiwei Hu huwwoziu.edu. cn 88208227 Dept Pharmacology, Medical school Zhejiang University

Drugs affecting endocrine system Weiwei Hu huww@zju.edu.cn 88208227 Dept. Pharmacology, Medical School, Zhejiang University

o Drugs related to adrenocortical hormones n Thyroid hormones and antithyroid drugs D Insulin and oral hypoglycemic drugs

Drugs related to adrenocortical hormones Thyroid hormones and antithyroid drugs Insulin and oral hypoglycemic drugs

oduce ADH and oxytocin Neurosecretory cells produce These hormones move portal These hormones are secreted into a portal system Each type of hypothalamic hormone ether stimulates or When appropriate, ADH and The antenor pituitary secretes axon endings into the bloodstream its hormones into the bloodstream postenor pituitary homone(ADH (FSH and LH) Kidney tubules Ovanes, Testes hormone(GH) oxytocin prolactin(PAL) adrenocortical. tropin(ACTH Smooth muscleMammany in uterus gands 00 Mammary Bones, Tissues Adrenal cortex. Thyroid

Zona Glomerulosa P450 aldo AⅡ Aldosterone K medulla ACTH P450 Zonae Fasciculata/ P45017a Reticularis Cortisol Cortex: adrenocorticoid Androgens Glucocorticoids (Glucocorticosteroids Mineralocorticoids Sex hormones Medulla倒图的线 Medulla: epinephrine norepinepherine

Cortex: adrenocorticoid Glucocorticoids (Glucocorticosteroids) Mineralocorticoids Sex hormones Medulla:epinephrine norepinepherine

Adrenocorticoid n Glucocorticoids hydrocortisone(cortisol), cortisone a Mineralocorticoids: aldosterone, desoxycortone

Adrenocorticoid Glucocorticoids : hydrocortisone (cortisol), cortisone Mineralocorticoids： aldosterone, desoxycortone

Basic structure of adrenocorticoid drugs CH,OH 21CH3OH 20C=0 OH 甾核结构 oh 1:|∷…4… 21CH2OH 20C=0:0 Cortisone Hydrocortisone (可的松) (氢化可的松) A B HO CH-OH 2I CH-OH “:FQ 图301肾上腺皮质激素的基本结构 aldosterone 去氧皮质酮 desoxycortone) (醛固酮 rI ou

Basic structure of adrenocorticoid drugs Cortisone (可的松) Hydrocortisone (氢化可的松) 甾核结构 aldosterone (醛固酮)

Structure and Activity Relationship (1)1位和2位碳之间改成不饱和的双键 (抗炎↑水钠潴留!半衰期个: cortisone -> prednisone hydrocortisone ->prednisolone 21CH3OH C=0 20C=0 OH 基本结构 . oh Cortisone Prednisone 21CH,OH 0 (可的松) (泼尼松 CH2OH CH2OH D 0 HO H -OH Hydrocortisone Prednisolone 图30-1肾上腺皮质激素的基本结构 氢化可的松 (泼尼松龙) Cortisol)

Structure and Activity Relationship (1) 1位和2位碳之间改成不饱和的双键 (抗炎↑水钠潴留↓ 半衰期↑): cortisone → prednisone hydrocortisone → prednisolone 基本结构 Cortisone (可的松) Prednisone (泼尼松) Hydrocortisone (氢化可的松, Cortisol) Prednisolone (泼尼松龙)

Structure and Activity Relationship (2)9α引入氟原子(抗炎↑、水钠潴留↑) fludrocortisone (氟氢可的松 基本结构 21CHOH (3)引入甲基抗炎个水钠潴留!半衰期个) 20C=0 6a-methylprednisolone, dexamethasone (甲已龙地米松10倍他松飞 C13 D15 (4)16a引入羟基抗炎↑水钠潴留刂) 图30-1肾上腺皮质激素的基本结构 OH CH2OH H CH3 "OH Hc HO 2-OH Fludrocortisone Dexamethasone Triamcinolone (氟氢可的松 (地塞米松 (曲安西龙

Structure and Activity Relationship (2) 9引入氟原子(抗炎↑ 、水钠潴留↑): fludrocortosone (氟氢可的松). (3)引入甲基(抗炎↑水钠潴留↓ 半衰期↑): 6-methylprednisolone,dexamethasone (6甲泼尼龙, 地塞米松(16),倍他米松(16)). (4) 16引入羟基(抗炎↑水钠潴留↓): triamcinolone(曲安西龙). 基本结构 Triamcinolone (曲安西龙) (地塞米松) Fludrocortisone (氟氢可的松)

pillary apiary plasma membrane◇ hormone hormone (first messenger) pla asma membrane hormone receptor ATP ormone nuclear receptor cyclic AMP messenger) DNA nucleus Mnw inactive enzyme mRNA active enzyme bosoms on mRNA biochemical (enzymatic) effects protein synthesis Non-gene modulation Gene modulation(GCS, TH)

Non-gene modulation Gene modulation (GCS, TH)

0 1. Pharmacological effects o Mechanisms of glucocorticoid actions o(1Effects on metabolisms o(2) Permissive action o 3) Anti-inflammatory effects o(4 Effects on immune and allergy 0(5) Anti-shock o(6other effects antipyretic effects effects on blood and blood -forming organs skeletal system CNS effects

1. Pharmacological effects Mechanisms of glucocorticoid actions (1) Effects on metabolisms (2) Permissive action (3) Anti-inflammatory effects (4) Effects on immune and allergy (5) Anti-shock (6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects