肾上腺能受体激动剂山东大学药理学英文课件

Chapter 8 Adrenoceptor agonists (adrenomimetic drugs, Sympathomimetic amines), -R agonists -R agonists, -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, -R agonists: AD,ephedrine（麻黄碱） -R agonists 1、2-R agonists ：NA 1-R agonists: phenylephrine(去氧肾上腺素) 2-R agonists：oxymetazoline(羟甲唑啉）apraclonidine(阿可乐定) -R agonists, 1、 2-R agonists : Isoprenaline 1-R agonists ：dobutamine(多巴酚丁胺) 2-R agonists: salbutamol（沙丁胺醇）,section 2 、 -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 DH PNMT TyrdopaDANAAD,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 , -R,1.heart: strongly excited (1-R) positive inotropic effect positive chronotropic effect positive dromotropic effect Coronary: dilation (1)Agonist 2-R (2)Prolong diastolic phase (3)Increase myocardial oxygen consumption adenosine,Advantage and disadvantage,2.vessels: (1) contraction(-R ) Skin, mucosa: strong Kidney: strong juxtaglomerular cells(1-R): Renin release Cerebral : (2) dilation: Skeletal Muscle (2-R) Coronary: direct effect: 2-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 feedback) Uterus, bladder: 2 Pupillary dilator muscle: 1,pharmacological actions,5. metabolism: 20%-30% (1)Carbohydrate: blood Glu , 2: glycogenolysis(糖原分解） glyconeogenesis(糖原异生) 2: insulin : glucagon (2) Lipolysis : blood fatty acid 3 : triglyceride lipase(三酰甘油酶) ,6. skeletal muscle 7. CNS,clinical uses,1.cardiac arrest 2.allergic shock: first choice cautions 3.bronchial asthma 4.prolongation of local anesthetic duration 5.topical hemorrhage: 0.1% 6. glaucoma,adverse reactions,Arhythmia Hypertension CNS reactions contraindications,Ephedrine(麻黄碱),陈克恢（） 药理学家。长期致力于中药药理研究，是世纪国际药理学的一代宗师，也是现代中药药理学研究的创始人。他的突出贡献是，首先发现麻黄素的药理作用，为推动交感胺类化合物的化学合成奠定了基础，并为从天然产物中寻找开发新药起了典范作用。他还发现解救急性氰化合物中毒的方法，并被沿用至今。,Ephedrine,Mechanisms: 1. direct actions：1 , 1,2 , 2-R 2. indirect actions Characteristics: 1. stable, orally. 2. action: slower,weaker and longer VS AD 3. central excitation 4. tachyphylaxis,Actions: 1. CNS effects 2. CVS 3. Smooth muscle 4. Increase skeletal muscle tension,ephedrine,clinical uses 1.bronchial asthma 2.nasal congestion 3.hypotensive states 4. Allergy (urticaria, angioneuroedema),adverse reactions,Cardiac and CNS excitation,dopamine (DA,多巴胺),Pharmacokinetics: ivd, short t1/2, not across BBB pharmacological actions activate, 1 , DA -R, NA release,pharmacological actions,1.Cardiovascular system: vessel: dilation (D1A-R), contraction (-R) Small dose: DBP (D1A-R) SBP Midddle dose: SBP (1 -R) DBP Large dose: DBP (-R) SBP 2. renal vessels : small dose dilation (D1A-R) large dose contraction (-R),clinical uses,1.shock 2.chronic heart failure(CHF) 3.acute renal failure (ARF),Mephentermine (美芬丁胺,wyamine,恢压敏),Similar to ephedrine (direct, indirect) central excitation Used to prevent hypotension state Used to treat nasal congestion,section 3 -R agonists,-R agonists 1、2-R agonists 1-R agonists 2-R agonists,1, 2 Agonists,noradrenaline(去甲肾上腺素，norepinephrine，NA，NE) source and chemistry,NA,pharmacokinetics,pharmacological actions,strongly activate 1, 2 -R slightly activate 1-R.,pharmacological actions,1.vessels: contraction(-R) coronary vessels :dilation (similar to AD) presynaptic adrenergic terminals (2-R):NE negative feedback 2.heart: excitation(1-R) 3.BP: small dose: SBP DBP large dose: SBP DBP 4.others: weaker than AD,clinical uses,1.shock：early 2.hypotension caused by drugs intoxication 3.upper digestive tract hemorrhage,adverse reactions,1.local ischemia and necrosis 2.acute renal failure,metaraminol (间羟胺, aramine, 阿拉明),Mechanisms1.direct actions 2.indirect actions Characteristics 1. weaker and longer than NA 2.little adverse reactions: renal failure, arrhythmias 3.tachyphylaxis Uses substitute for NA in treatment of shock,1-R Agonists,Phenylephrine(去氧肾上腺素) Methoxamine(甲氧明),Phenylephrine and methoxamine,1.selective 1-R agonists: shock, hypotension 2. renal vasoconstriction: significant 3. paroxysmal supraventricular tachycardia 4.phenylephrinemydriasis(rapid, weak, short),2-R Agonists,Peripheral 2-R Agonists: oxymetazoline(羟甲唑啉)： nasal congestion apraclonidine(阿可乐定): Glaucoma Central 2-R Agonists：HBP clonidine(可乐定)， methyldopa （甲基多巴）,Section4 -R agonists,1、 2-R agonist 1-R agonists 2-R agonists,1、 2-R agonist,Isoprenaline (Isop,异丙肾上腺素) pharmacological actions: strongly activate 1、 2-R,pharmacological actions,1.heart: excitation (1-R) positive inotropic effect positive chronotropic effect positive dromotropic effect,pharmacological actions,2.vessels: Skeletal Muscle blood vessel (2-R) Coronary: direct effect: 2-R indirect effect: 3.BP: SBP DBP,pharmacological actions,4. smooth muscle: relaxation especially bronchial smooth muscle,clinical uses,1. cardiac arrest 2. atrial ventricular block(AVB) 3. bronchia