Chapter 8 Adrenoceptor agonists (adrenomimetic drugs, Sy.pptVIP

Chapter 8 Adrenoceptor agonists (adrenomimetic drugs, Sympathomimetic amines) α, β-R agonists α-R agonists, β-R agonists  Section 1 Structure-activity relationship and classification Chemistry structure-activity relationship (1) Catecholamine (CA,儿茶酚胺) (2) ?-C： block MAO (3) N- ：? or ? selective classifications α, β-R agonists: AD,ephedrine（麻黄碱） α-R agonists α1、α2-R agonists ：NA α1-R agonists: phenylephrine(去氧肾上腺素) α2-R agonists：oxymetazoline(羟甲唑啉）apraclonidine(阿可乐定) β-R agonists, β1、 β 2-R agonists : Isoprenaline β1-R agonists ：dobutamine(多巴酚丁胺) β2-R agonists: salbutamol（沙丁胺醇） section 2 α、 β -R agonists Adrenaline (AD,肾上腺素) Ephedrine（麻黄碱） Dopamine (DA，多巴胺) Adrenaline (epinephrine,AD,肾上腺素) Source and Chemistry 1. adrenal medulla: pheochromocyte( 嗜铬细胞) 2. PNMT(苯乙胺-N-甲基转移酶) TH DDC DβH PNMT Tyr→→→dopa→→→→DA→→→→NA→→→→→AD AD Pharmacokinetics 1. Absorption 2. Termination Uptake metabolism: MAO/COMT 3.Excretion:VMA (3甲氧4羟扁桃酸) Normal: 2-6.8mg/24h Pheochromocytoma:10-250mg /24h （嗜铬细胞瘤） pharmacological actions: activate α, β-R 1.heart: strongly excited (β1-R) positive inotropic effect positive chronotropic effect positive dromotropic effect Coronary: dilation (1)Agonist β2-R (2)Prolong diastolic phase (3)Increase myocardial oxygen consumption ?adenosine↑ Advantage and disadvantage 2.vessels: (1) contraction(α-R ) Skin, mucosa: strong Kidney: strong juxtaglomerular cells(β1-R): Renin release↑ Cerebral : (2) dilation: Skeletal Muscle (β2-R) Coronary: direct effect: β2-R indirect effect: time of perfusion ↑ adenosine↑ pharmacological actions 3.BP: small dose: SBP↑, DBP ↓ large dose: SBP↑, DBP↑ Double phased response pharmacological actions 4. smooth muscle: bronchial smooth muscle: ?2, ?1 Gastrointestinal tract: (negative