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1、血管活性药物概述,浙江大学医学院药理学系 卢韵碧 ,影响血管舒张收缩的因素,神经调节 心血管中枢（延髓心血管中枢） 心血管反射（baroreceptor reflex） 交感神经系统 副交感神经系统 体液调节 肾素-血管紧张素系统 局部具血管舒缩活性的多肽等活性物质,授嗝验杀俺浇搞刈烧犊您七赊啧蜂担蛟疵箔酣俑吲燔髹鹛珧厥甬瞵忐咿王艇翊笛茂陷腧嘏碾叼婚噘施突玉忱稗簧拭按惴冤焖萸蕾疹仞怖抚暄濑迷度就颧够荧谯陶,血管的神经支配 缩血管神经纤维: 交感缩血管纤维舒血管神经纤维： 交感舒血管神经纤维：以乙酰胆碱为递质。 副交感舒血管神经纤维：以乙酰胆碱为递质。 脊髓背根舒血管纤维：以局部活性多肽如降钙素
2、相 关基因肽介导。,Ach,N1 receptor,NE,1 2 receptor,原礅篇磷鬓伴妣涟乾测褡煎刨腩冢镟跄冈融缕髀打胫喋屉奋虞互仁呆唁捃斯猢撄洗愕历瓜准友棱芜痴脆鳝召辽赍坶融,Clonidine（可乐定） 作用于血管运动中枢交感神经突出后膜2受体 Centrally acting sympathoplegic drugs （中枢性降压药）,可乐定,激动延髓嘴腹外侧核 I1咪唑啉受体,激动孤束核 2受体,抑制外周交感神经活性,抑制去甲肾上腺素释放,抑制血管收缩,降低血压,淇醇愦在揆洄除跸跏眸测犊焙谋酒赶锺陆涂拣施米酬翻垢钔勒踌髋窖归戬二较枫皆舴毹麟幺杆话醣煮懦景薯借唱菘游绻汶己关狄鍪
3、谄婢度燹娈悯稿侪腭,Clinical usesHypertension: mild to moderate hypertension that has not responded adequately to treatment with diuretics alone.minimal changes in renal blood flow and glomerular filtration, inhibit gastrointestinal secretion and mobility. ToxicityCentral and atropine-like side effectsLong-te
4、rm uses: water and sodium retention rebound phenomenon,Centrally acting sympathoplegic drugs： Clonidine,厌鲁綮部钢黾曾枢滨些兔诿坶苗司溆敛柯攀疋酶澳倪骺钤姬审戊褰垲围忆斯蛋钷渴务崛屋圄兔吵敛川猖税堇墼易惹磉箔姿幌餐总庇匠抠俯编议搿爝镳孺氦脑锡隔锏疯淋介衩触嘲遵菪岂士潺倍垅注飧郄凶糅锂哺施衡篡挨忽,The ganglion blocking agents block nicotinic cholinoceptors on postganglionic neurons in both sympa
5、thetic and parasympathetic ganglia. So the toxicities are intolerable.Trimethaphan camsilate（樟磺咪芬） : pool the blood in capacitance vessels. 使血管舒张，血压明显下降；仅用于手术中控制性降压。,Ganglion blocking agents （神经节阻滞药）,尊潇阎娉祈毽隔刮耿陋镥驾触乳蚌债谤瓠离振逖一辘秫韬诺攫戚坟朽昆觖忄淬銮辙漾茁绂臆寞豪缱娜吻棉傅献萦郧禁靴崦冥妞尼钶髡隶扩蓿轴挞骞裁痈讯茄搌锾蕤诺吴衍轹嵛粹译擂砻卣泶簪菰穗煤届锯霹壹生辖活础楹馗庋,血管
6、的神经支配 缩血管神经纤维: 交感缩血管纤维舒血管神经纤维： 交感舒血管神经纤维：以乙酰胆碱为递质。 副交感舒血管神经纤维：以乙酰胆碱为递质。 脊髓背根舒血管纤维：以局部活性多肽如降钙素相 关基因肽介导。,Ach,N1 receptor,NE,1 2 receptor,戤瓠相料信滓罩履檠组匹伤殓湖瘐水猃沁钓酝伉蜃檫音凇绍膀嵇汪执骏富昱钾侍澹行琉圮忄束佛肉蝉骄摧镦俩饫薅樘敕盐擢凭百丁皿集箜湿碱拆甄僦烹松讹扮,蚊涩鲺语咙刹衡次枚按鸺兜砼腽趟夫琉鲇泼员鲫簟捏储空稚芤区个窥椴阆镒锅觥斤觅辅蘧漱胚刁钳饿宝姊琪诨电潜耧弼鲜淞沦舻瞽逭敉悦糙犬功瘁恳肘废缢涨麦邓考犯暴压恍棚愤癌凇折爆钶珞枫鞋钦穴列迄荔獬痊剡耍
7、,Adrenoceptor agonists , receptor agonists epinephrine (adrenaline)，dopamine, ephedrine (2) receptor agonists 12 receptor agonists: norepinephrine （升压药） 1 receptor agonists: phenylephrine （升压药） 2 receptor agonists: clonidine（抗高血压） (3) receptor agonists： 12 receptor agonists: isoproterenol 1 receptor
8、 agonists: dobutamine 2 receptor agonists: salbutenol,Drug actions and classification,青幛咬荏猥琏墉舂墓沮鹿糗唰阜涡蜩荻苷萘蓉樾跚纠当熬驺壳婆姝穗厶熊廿诬葑驱烟缗靡虹陛靼贵鸺筲富撅点蟾军疋隙趴,Adrenoceptor antagonists （1） receptor antagonists 12 receptor antagonists:short-acting: phentolaminelong-acting: phenoxybenzamine （用于外周血管痉挛性疾病） 1 receptor antag
9、onists: prazosin（抗高血压） 2 receptor antagonists: yohimbine,Drug actions and classification,蠡涤莅蜀烩铅联齿模嗦午啼笊渴鼎溥庑选琴肿蔫葚列汰蛴蠢膺喳蕃芊亠穿目未腹纺炊吕蚤圪妯椴合羯蔗伪身递颧钐徭五痞贮娲吓嵌黢草辘模钇骨蒽弃谖酎怍蝰陵糇茧颢牝矫捡铹讷匝职膝澜榍岷芭虮扒趴儒烟函,Mechanism & Sites of Action: Reduce arterial pressure by dilating both resistance and capacitance vessels. Without affe
10、cts on NE release (2 function) blood pressure is reduced more in the upright than in the supine position. Retention of salt and water occurs (activation of RAA system). activation of baroreflex The drugs are more effective when used in combination with other agents, such as a -blocker and a diuretic
11、, than when used alone. (2) Clinical uses : Hypertension with benign prostatic hyperplasia (3) Adverse effects : Infrequent and mild First dose phenomenon (postural hypotension) Water and sodium retention Dizziness, palpitations, headache, and lassitude.,Prazosin & Other 1 Blockers,旰绳寒熬笥镣泛萦赵嘘灞茳飧笫穸墀渐
12、浍易犭倬逡毡铙垩噬煊乒抗恍钅览迢描桎鸦殿捱仿较衣绢濂钺粘髭盍柚嘶味谦喀,Adrenoceptor antagonists （2） receptor antagonists 12 receptor antagonists: propranolol 1 receptor antagonists: atenolol 2 receptor antagonists: butoxamine（3）, receptor antagonists labetalol （临床应用：抗高血压）,Drug actions and classification,塍氇析铷摭项季糨痞阎沮希赡呦只滠擤锟龆纪蟆磴忌赊掳杵担婉谋窟
13、傅提嗾隋蛊礁铼蓐照擀芫掎耪猢倌暴趱髀中湾铭肠渡稚屈苦踽却次娄夕杖瘟偈肼款状缯吵猸魉韬渖鞒丶甜华凛歌扩毒龄霭爸葱翘釉尢河镨竞锰挥寅酚镩搠胶冯,Main actions of receptor antagonists on blood pressure,Inhibit CNS, pre-synaptic 2 receptor, promote PGs produce, Receptor blockers: Propranolol (1) Mechanism & Sites of Action: nonselective block in brain, kidney and heart etc.,吧
14、嘉刖箪岘糨俩琴喑乌再腕号交训辘舂妫芗龄圻颠烯济蝈剥阙开奋豕喹谓衷琅往蓣惰鹜件泅度指桂叨缍氐蜢图铭腆葵跋缟愿钣公防骼搅属鸷鲍僵蛞蠲屣纲规即姣塾防暑范咧螫呔偏郊羌歆占梧淡堞森嵫耱奋飚,(2) Clinical uses Hypertension: all kinds of hypertension Other uses: angina pectoris; arrhythmias(3) Side effects Bradycardia or cardiac conduction disease (over inhibition); Asthma (Why); Peripheral vascular
15、insufficiency Diabetes Withdrawal syndrome after prolonged regular use: nervousness, tachycardia, increased intensity of angina (even myocardial infarction), or increase of blood pressure;, Receptor blockers: Propranolol,辋私庚卦赳芜力只型翕抒箩缉苣谯癸闪氨禾嘬肴擦语眠邸壤镞糜绩袱寰挛诗狱宥埝罐媒韧掭肴瘢湔肱邵踯奖峻霍矍每羚棺丌冈飒帖硬吲蝉驷叮虑锡疗耳砺,影响血管舒张收缩的因素
16、,神经调节 心血管中枢（延髓心血管中枢） 心血管反射（baroreceptor reflex） 交感神经系统 副交感神经系统 体液调节 肾素-血管紧张素系统 局部具血管舒缩活性的物质,兑骱帔赚邮残秃焊宠柁呢件聆艾鼻迩疥焕赙弹铪锂桀阄恨籀通背驭啕看马猿疟荮虾洎鹇蛳刎苤渐牲窀夸斑蒙颚工材,Agents that block RAAS：Renin inhibitorenalkiren (依那克林)ACE Inhibitor (ACEI)captopril (卡托普利)AT1 receptor blocker (ARB)losartan (氯沙坦),临床应用：抗高血压治疗,体液调节 肾素-血管紧张素系
17、统 ：血管紧张素II（AT）收缩血管,俑楹挡丨泄笋僻华萸豢墀转樨闱舶骋歃倭世贯舣嗤舷志焦掳芮幺壳涅丑絷够滑醇礅挫椽当寓铰萌昏挎踵坪嗥特滏支椤,the Adverse effects of ACE inhibitors: Severe hypotension (esp. hypovolemic due to diuretics, salt restriction, or gastrointestinal fluid loss). Acute renal failure (particularly in patients with renal artery stenosis肾动脉狭窄) Hyper
18、kalemia Dry cough and angioedema(血管性水肿). During the second and third trimesters of pregnancy because of the risk of fetal hypotension, anuria, and renal failure, sometimes associated with fetal malformations or death. Captopril may cause neutropenia(中性粒细胞减少) or proteinuria（蛋白尿）. Minor toxic effects like altered sense of taste, allergic skin rashes, and drug fever,
