肾上腺能受体激动剂山东大学药理学英文课件

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1、Chapter 8 Adrenoceptor agonists(adrenomimetic drugs,Sympathomimetic amines),-R agonists-R agonists,-R agonists Section 1 Structure-activity relationship and classification structure-activity relationship(1)Catecholamine(CA,(CA,儿茶酚胺儿茶酚胺)(2)-C：block MAO(3)N-：or selective classifications,-R agonists:AD

2、,ephedrine麻黄碱麻黄碱-R agonists 1、2-R agonists：NA 1-R agonists:phenylephrine(去氧肾上腺素去氧肾上腺素)2-R agonists：oxymetazoline(羟甲唑啉羟甲唑啉apraclonidine(阿可乐定阿可乐定)-R agonists,1、2-R agonists:Isoprenaline 1-R agonists：dobutamine(多巴酚丁胺多巴酚丁胺)2-R agonists:salbutamol沙丁胺醇沙丁胺醇section 2 、-R agonistsAdrenaline(AD,肾上腺素肾上腺素)Ephed

3、rine麻黄碱麻黄碱Dopamine(DA，多巴胺，多巴胺)Adrenaline(epinephrine,AD,肾上腺素肾上腺素)Source and Chemistry1.adrenal medulla:pheochromocyte(嗜铬细胞嗜铬细胞)2.PNMT(苯乙胺苯乙胺-N-甲基转移酶甲基转移酶)n TH DDC DH PNMTnTyrdopaDANAAD ADCHOHOHOHCH2NHCH3Pharmacokinetics1.Absorption2.Termination n Uptaken metabolism:MAO/COMT3.Excretion:VMA(3甲氧甲氧4羟扁桃酸

4、羟扁桃酸)Pheochromocytoma:10-250mg/24h 嗜铬细胞瘤嗜铬细胞瘤pharmacological actions:activate,-R1.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

5、nAdvantage and disadvantage:(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 actions3.BP:small dose:SBP,DBP large dose:SBP,DBP Do

6、uble phased response pharmacological actions4.smooth muscle:bronchial smooth muscle:2,1Gastrointestinal tract:(negative feedback)Uterus,bladder:2Pupillary dilator muscle:1 pharmacological actions5.metabolism:20%-30%(1)Carbohydrate:blood Glu ,2:glycogenolysis(糖原分解糖原分解 glyconeogenesis(糖原异生糖原异生)2:insul

7、in :glucagon(2)Lipolysis:blood fatty acid 3:triglyceride lipase(三酰甘油酶三酰甘油酶)n6.skeletal musclen7.CNSclinical uses 1.cardiac arrest2.allergic shock:first choice cautions3.bronchial asthmarolongation of local anesthetic duration5.topical hemorrhage:0.1%6.glaucoma adverse reactionsArhythmiaHypertensionC

8、NS reactionscontraindicationsEphedrine(麻黄碱麻黄碱)n陈克恢陈克恢n 药理学家。长期致力于中药理学家。长期致力于中药药理研究，是世纪国际药药药理研究，是世纪国际药理学的一代宗师，也是现代中药理学的一代宗师，也是现代中药药理学研究的创始人。他的突出药理学研究的创始人。他的突出奉献是，首先发现麻黄素的药理奉献是，首先发现麻黄素的药理作用，为推动交感胺类化合物的作用，为推动交感胺类化合物的化学合成奠定了根底，并为从天化学合成奠定了根底，并为从天然产物中寻找开发新药起了典范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作用。他还发现解救急性氰化合物中毒

9、的方法，并被沿用至今。物中毒的方法，并被沿用至今。EphedrinenMechanisms:1.direct actions：1,1,2,2-R 2.indirect actions nCharacteristics:1.stable,orally.2.action:slower,weaker and longer VS AD 3.central excitation 4.tachyphylaxisnActions:1.CNS effects 2.CVS 3.Smooth muscle 4.Increase skeletal muscle tension ephedrinenclinical

10、uses1.bronchial asthma2.nasal congestion3.hypotensive states4.Allergy(urticaria,angioneuroedema)adverse reactionsnCardiac and CNS excitation dopamine(DA,多巴胺多巴胺)qPharmacokinetics:ivd,short t1/2,not across BBBq pharmacological actions activate,1,DA-R,NA releasepharmacological actions1.Cardiovascular s

11、ystem:vessel:dilation(D1A-R),contraction(-R)nSmall dose:DBP(D1A-R)SBP nMidddle dose:SBP(1-R)DBPnLarge dose:DBP(-R)SBP2.renal vessels:small dose dilation(D1A-R)large dose contraction(-R)clinical uses1.shock2.chronic heart failure(CHF)3.acute renal failure(ARF)Mephentermine(美芬丁胺,wyamine,恢压敏)nSimilar t

12、o ephedrine(direct,indirect)ncentral excitationnUsed to prevent hypotension statenUsed to treat nasal congestionsection 3 -R agonistsv-R agonistsv 1、2-R agonistsv 1-R agonistsv 2-R agonists 1,2 Agonists noradrenaline(去甲肾上腺素，去甲肾上腺素，norepinephrine，NA，NE)source and chemistry CHOHOHOHCH2NH2NApharmacokin

13、eticspharmacological actionsstrongly activate 1,2-Rslightly activate 1-R.pharmacological actions1.vessels:contraction(-R)q coronary vessels:dilation(similar to AD)q presynaptic adrenergic terminals(2-R):NE negative feedback2.heart:excitation(1-R)3.BP:small dose:SBP DBP large dose:SBP DBP4.others:wea

14、ker than ADclinical uses n1.shock：early n2.hypotension caused by drugs intoxication n3.upper digestive tract hemorrhageadverse reactionsn1.local ischemia and necrosisn2.acute renal failure metaraminol(间羟胺间羟胺,aramine,阿拉明阿拉明)Mechanisms1.direct actions 2.indirect actionsCharacteristics1.weaker and long

15、er than NA2.little adverse reactions:renal failure,arrhythmiasUses substitute for NA in treatment of shock 1-R AgonistsnPhenylephrine(去氧肾上腺素去氧肾上腺素)nMethoxamine(甲氧明甲氧明)Phenylephrine and methoxamine 1.selective 1-R agonists:shock,hypotension2.renal vasoconstriction:significant 3.paroxysmal supraventri

16、cular tachycardia4.phenylephrinemydriasis(rapid,weak,short)2-R AgonistsnPeripheral 2-R Agonists:n oxymetazoline(羟甲唑啉羟甲唑啉)：nasal congestionn apraclonidine(阿可乐定阿可乐定):GlaucomanCentral 2-R Agonists：HBPn clonidine(可乐定可乐定)，n methyldopa 甲基多巴甲基多巴Section4-R agonists1、2-R agonist1-R agonists 2-R agonists1、2-R

17、 agonistIsoprenaline(Isop,异丙肾上腺素异丙肾上腺素)npharmacological actions:strongly activate 1、2-Rpharmacological actions1.heart:excitation(1-R)positive inotropic effect positive chronotropic effect positive dromotropic effect pharmacological actions2.vessels:Skeletal Muscle blood vessel(2-R)Coronary:direct ef

18、fect:2-R indirect effect:3.BP:SBP DBPpharmacological actionsv4.smooth muscle:relaxation especially bronchial smooth muscleclinical uses n1.cardiac arrestn2.atrial ventricular block(AVB)n3.bronchial asthma1-R agonists:dobutamine(多巴酚丁胺多巴酚丁胺)Characteristics1.selective 1-R agonist2.inotropic effectchronotropic effect in therapeutic dose3.Used in CHF caused by AMI4.tachyphylaxis2-R agonistsnSalbutamal(沙丁胺醇，舒喘灵沙丁胺醇，舒喘灵)nTerbutaline(特布他林，间羟舒喘灵特布他林，间羟舒喘灵)nClinical use:bronchial asthma