RAAS抑制剂在心血管系统应用课件

单击以编辑母版标题样式,单击以编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击以编辑母版标题样式,单击以编辑母版文本样式,第二级,第三级,第四级,第五级,单击以编辑母版标题样式,单击以编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,RAAS抑制剂在心血管系统的应用,2014年4月,2014年4月,1,hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathy,Pathophysiology,R,enin-,A,ngiotensin-,A,ldosterone,S,ystem,RAAS,hypertension, congestive heart,2,Index,药理机制概述,ACEI ARB MRA,心血管指南更新,Q & A,Index药理机制概述,药理机制概述,药理机制概述,4,口渴,Converting,enzyme,血压,交感兴奋,抗利尿激素分泌,Converting enzyme,Antagonist,ACEI,Ang II receptor,Antagonist,ARB,醛固酮分泌,Aldosterone receptor,Antagonist,MRA,Renin,Renin inhibitor,remikiren,aliskiren,口渴 Converting,5,ACE,血管紧张素原,肾素,血管紧张素,I,Ang II,AT,1,受体,AT,2,受体,AT,3,受体,AT,4,受体,血管舒张,抗增殖,凋亡,血管完整性,PAI-1,？,血管舒张,一氧化氮,前列腺素,EDHF,无活性肽,激肽原,缓激肽,激肽释放酶,BK B,2,受体,ACE-I,抑,制,抑,制,乳糜酶旁路,ACEI,药理作用,ACE血管紧张素原肾素血管紧张素 IAng IIAT1受体A,6,(,四,),抗氧化作用,保护内皮，抗动粥，保护缺血心肌,ACEI,药理作用,(,一,),减少,Ang II,的生成,因,Ang II,量减少，削弱,Ang II,对心血管的直接和间接作用。,(,二,),减少,BK,的代谢,BK,量增加，通过激活,PLC,和,PLA2,，使,NO,和,PGI2,增加舒张血管、抗血小板聚集、抗心血管细胞肥大增生。,(,三,),抑制交感神经递质的释放,(,五）增加胰岛素敏感性,（六）肾脏保护作用,(四)抗氧化作用 保护内皮，抗动粥，保护缺血心肌ACEI药理,7,口渴,Converting,enzyme,血压,交感兴奋,抗利尿激素分泌,Converting enzyme,Antagonist,ACEI,Ang II receptor,Antagonist,ARB,醛固酮分泌,Aldosterone receptor,Antagonist,MRA,Renin,Renin inhibitor,remikiren,aliskiren,口渴 Converting,8,Angiotensin Receptors,(AT),AT,1,AT,2,359 amino acids,363 amino acids,high affinity for losartan,low affinity for losartan,low affinity for PD 123177,high affinity for PD 123177,most of the known biological effects of angiotensin II,？,Antiproliferative,抗增生,Proapoptotic,促凋亡,Vasodilatory,扩血管,Antihypertensive,抗高血压,Angiotensin Receptors (AT)AT1A,9,ARB,药理作用,ARBs,ACE inhibitors,activation of AT,1,biosynthesis of Ang II,the levels of Ang II,the levels of of Ang II,renin release,renin release,activation of AT,2,angiotensin(1-7) levels,the levels of ACE substrate,(bradykinin and Ang I,),Cough, Angioedema,Teratogenic potential,Fetopathic potential,ARB药理作用ARBsACE inhibitorsacti,10,口渴,Converting,enzyme,血压,交感兴奋,抗利尿激素分泌,Converting enzyme,Antagonist,ACEI,Ang II receptor,Antagonist,ARB,醛固酮分泌,Aldosterone receptor,Antagonist,MRA,Renin,Renin inhibitor,remikiren,aliskiren,口渴 Converting,11,醛固酮的生理、病理作用,醛固酮与心肌细胞、血管平滑肌细胞、内皮细胞、心血管的成纤维细胞、肾小管上皮细胞等细胞胞浆盐皮质激素受体（,MR,）结合，形成激素,-,受体复合物；后者通过核膜，与核中脱氧核糖核酸醛固酮反应基因结合，调节特异性,mRNA,转录，最后合成多种醛固酮诱导蛋白，从而影响心血管系统、泌尿系统和植物神经系统等，并参与组织修复，调节水、电解质和血容量。,心衰时,Ang,活性增高，醛固酮活性增高,35,倍,，血浆和组织中醛固酮水平的升高对心血管系统造成损害，引起心肌、血管平滑肌、细胞内皮细胞发生一系列变化。,醛固酮的生理、病理作用醛固酮与心肌细胞、血管平滑肌细胞、内皮,12,醛固酮致心肌纤维化的作用,醛固酮通过与,成纤维细胞,中,MR,结合,刺激,型和,型,胶原纤维,的合成,诱发纤维化。,醛固酮依赖的,Na+ -K+ -ATP,酶的转录调节可促进成纤维细胞的增生和,胶原的合成,。,醛固酮可以剂量依赖性诱导,内皮素,-1,（,ET-1,）的的合成和分泌以及,CFs ppET-1mRNA,的表达，,ET-1,可促进,CTs,增殖、胶原合成及细胞外基质的沉积，在心肌纤维化中起着重要作用。,醛固酮可激活巨噬细胞使其产生转化生长因子,(,TGF-1,),增多,TGF-1,可刺激,CTs,合成胶原, TGF-1,还可诱导,CTs,分化为心肌,CTs,而后者有更强的合成胶原的能力。,醛固酮致心肌纤维化的作用 醛固酮通过与成纤维细胞中MR结合,13,醛固酮与心律失常的关系,醛固酮储钠排钾，合并使用利尿剂时，心衰更易低钾、低镁，使心肌细胞电活动不稳定，易发生室性心律失常和猝死。,醛固酮可阻滞心肌细胞对儿茶酚胺的摄取，从而使细胞外儿茶酚胺增多，有致心律失常和促心肌缺血作用。,醛固酮影响压力感受器介导的心率调节过程，使压力反射性心动过速的反应减弱，心率变异性降低，因而推测醛固酮有降低副交感神经的作用。,醛固酮水平长期增高可诱发心肌细胞坏死和极微小的疤痕形成，其可使心肌室性心律失常的阈值降低，易发生室性心律失常和室颤。,醛固酮与心律失常的关系 醛固酮储钠排钾，合并使用利尿剂时，心,14,醛固酮逃逸现象,醛固酮逃逸：长期应用,ACEI,后，循环和组织中的醛固酮经历一段时间短暂降低后，继而又恢复甚至或超过原来水平。,研究发尽管联合应用了,ACEI,或,ARB,也不能完全长期抑制醛固酮的产生，且醛固酮逃逸现象比较普遍。,Ang,的产生还有其他旁路，包括组织蛋白,G,、组织纤溶酶原激活剂、弹性蛋白酶、糜酶。此途径不被,ACEI,抑制，不降解缓激肽。病理状态或是长期应用,ACEI,时，糜酶途径可能增强。,ARB,也不能阻断醛固酮的合成，研究表明，,Ang,可转变为,Ang2,8,（,），循此途径醛固酮仍产生。,低钠和高钾也是主要刺激醛固酮分泌的原因，另外促肾上腺皮质激素、糖皮质激素、抗利尿激素、心钠素、儿茶酚胺、血浆,HDL,也能促使醛固酮分泌。,各心衰指南对 MRA的重视增加,醛固酮逃逸现象醛固酮逃逸：长期应用ACEI后，循环和组织中的,15,本院品种,ACEI,ARB,依那普利,10 mg,缬沙坦,80 mg,培哚普利,4 mg,奥美沙坦,20 mg,福辛普利,10 mg,厄贝沙坦,150 mg,贝那普利,10 mg,氯沙坦,50 mg100 mg,赖诺普利,10 mg,坎地沙坦,4 mg,雷米普利,5 mg,替米沙坦,80 mg,卡托普利,12.5 mg,醛固酮拮抗剂,螺内酯,20 mg,本院品种ACEIARB依那普利10 mg缬沙坦80 mg培哚,16,心血管指南更新,高血压,心衰,心肌梗死,其它,心血管指南更新高血压,17,2013 ESC,高血压指南,2013 ESC 高血压指南,18,高血压,JNC8 2014,Thiazide,ACEI,ARB,or CCB,ESH/ESC 2013,BB, diuretic, CCB,ACEI, or ARB,CHEP 2013,Thiazide, BB( 60y),ACEI orARB,NICE 2011,ACEI or ARB (55y),中国,2013,Diuretics,、,BB,、,CCB,、,ACEI,和,ARB,及低剂量复方制剂。,起始治疗药物（一般人群）,高血压JNC8 2014Thiazide, ACEI, AR,19,高血压,JNC8 2014,Thiazide,ACEI, ARB, or CCB,ESH/ESC 2013,ACEI, or ARB,CHEP 2013,ACEI or ARB,（,CVD risk,）,ACEI, ARB, thiazide, or DHPCCB,ADA2013,ACEI or ARB,中国,2013,ACE or ARB,起始治疗药物（糖尿病）,高血压JNC8 2014Thiazide, ACEI, AR,20,高血压,JNC8 2014,ACEI, ARB,ESH/ESC 2013,ACEI, or ARB,CHEP 2013,ACEI or ARB,KDIGO2012,ACEI or ARB,中国,2013,ACEI orARB,，（,Cr2 mg/dl,绊利尿药,),起始治疗药物（CKD）,高血压JNC8 2014ACEI, ARB ESH/ESC,21,高血压,-,药物联用,ESH/ESC 2013,ACEI/ARB+CCB,ACEI/ARB+,Diuretics,CCB+Diuretics,BB+Diuretics (CV stroke risk?),ACEI/ARB+RASI (ESRD,高钾,),JNC 8,不将,BB,做为一线用药,NICE 2011,药物联用均包含,ACEI/ARB,高血压-药物联用ESH/ESC 2013,22,ONTARGET,：雷米普利、替米沙坦或二者联合治疗比较,结果显示：对心血管事件的影响,ARB,并不优于,ACEI,安全性方面,ARB,并不优于,ACEI,HYVET,：入选,3845,例患者，平均年龄,83.5,岁，培哚普利,结果显示：,ACEI,利尿剂使高龄高血压人群显著获益,ACCOMPLISH,：比较贝那普利,+,氨氯地平和贝那普利,+,氢氯噻嗪,结果显示：,ACEI,为核心药物的初始联合治疗显著提高血压达标率,Clinical Trials,ONTARGET：雷米普利、替米沙坦或二者联合治疗比较Cli,23,慢性心力衰竭的药物治疗,时代,药物,降低死亡率,洋地黄,？,利尿剂,？,硝酸酯,？,1980s,ACEI,24%,1990s,-,阻滞剂,36%,2000s,ARB,=ACEI?,2000s,依伐布雷定,死亡,+,住院,18%,2000s,醛固酮拮抗剂,NYHA34,30%,慢性心力衰竭的药物治疗时代药物降低死亡率洋地黄？利尿剂？硝酸,24,心力衰竭,2014,中国心力衰竭诊断和治疗指南,HF-REF,收缩性心力衰竭,HF-PEF,舒张性心力衰竭,心力衰竭2014中国心力衰竭诊断和治疗指南,25,慢性心力衰竭（,2014,中国）,慢性心力衰竭（2014中国）,26,慢性,HF-REF,ACEI,ACCF/AHA 2013,Stage B: Prevent 1)a,recent or remote history of,MI or ACS and reduced EF,(IA) 2)all reduced EF even without MI (IA) stage C:3)HF-REF,current or prior symptoms unless contraindicated (I A),ESH/ESC 2012,in addition to,a beta-blocker, for all patients,with an EF 40%(IA),中国,2014,所有,LVEF,下降,的,心衰患者，必须,且终身,使用,ACEI,（,IA),，阶段,A,人群可考虑用,ACEI,来预防心衰,（,IIA,）,。,慢性HF-REFACEIACCF/AHA 2013Stage,27,慢性,HF-REF,ARB,ACCF/AHA 2013,1)ACEI intolerant(IA),2)alternatives to ACEI as first-line(IIa A),3) symptomatic patients treated with ACEI and BB but aldosterone antagonist is not indicated or tolerated(IIb A)4) Harm :combined use of ACEI,ARB MRA harmful (IIIC),ESH/ESC 2012,1)EF 40% and unable to tolerate an ACE,(patients should also receive a beta-blocker and an MRA).(IA),2)EF 40%,and persisting symptoms (NYHAclass IIIV) despite treatment with an ACEIand a BB who are unable to tolerate an MRA.(IA),3,）,Harm :,combined use of ACEI,ARB MRA harmful,(IIIC),中国,2014,同,ACEI,，不能耐受,ACEI,（,I,A),，,经,D,ACEI,BB,改善不满意，不能耐受,MRA,（,IIb A,）,。,慢性HF-REFARBACCF/AHA 20131)ACEI,28,慢性,HF-REF,MRA,ACCF/AHA2013,1)LVEF 35%,、,NYHA II-IV(II,CV hosiptalization,BNP) GFR30 and K5mM,（,I A);,2)AMI,后、,LVEF 40%,有心衰症状或既往有糖尿病史者（,IB),；,3)Harm:GFR5mM(IIIB),ESH/ESC 2012,1)alternative to an ACEI or ARB, if neither is tolerated, EF 45% and dilated LV (or EF 35%). Patients should,also receive a BB and an MRA.(,IIb B) 2),EF 45% and dilated LV (or EF 35%) and persisting symptoms (NYHA class IIIV) treatment with BB, ACEI (or ARB), and an MRA (or ARB).(IIb B),),中国,2014,所有,LVEF 35%NYHAII-IV,的,心衰患者，,已使用,ACEI(ARB),或,BB,仍有持续症状,的患者（,IA);AMI,后、,LVEF=40%,有心衰症状或既往有糖尿病史者（,IB),慢性HF-REFMRAACCF/AHA20131)LVEF,29,慢性,HF-PEF,ACEI ARB,ACCF/AHA 2013,1),The use of beta-blocking agents, ACE inhibitors, and ARBs in patients with hypertension is,reasonable to control blood pressure in patients with HFpEF. (,IIa,C),2) The use of ARBs might be considered to decrease hospitalizations for patients with HFpEF(IIb B),ESH/ESC 2012,-,中国,2014,伴左心室肥厚者,为逆转左心室肥厚和改善左心室舒张功能，可用,ACEI,、,ARB,、,BB(IIb,C),慢性HF-PEFACEI ARBACCF/AHA 20131,30,急性心衰,ACEI ARB MRA,ACCF/AHA 2013,严重,肾功能不全 停用或减量,ACE,I, ARBs, and/or,MRA,JCS 2013,1),stabilized,acute heart failure, start ACE inhibitors and ARBs from a small dose, and,increase the dose,gradually (I,A)2) In the acute phase, use ACE inhibitors and ARBs appropriately according to the type and severity of heart failure (IIa, B)3)severely unstable hemodynamics, avoid ACE inhibitors and ARBs (IIb, C),ESH/ESC 2012,After stabilization,start ACEI(ARB) and MRA as soon as possible. Make a plan,to up-titrated,中国,2014,争议：,1,）,急性心衰的急性期、病情尚末稳定的患者不宜应用（,IIb,，,C,）。,2）,AMI,的急性心衰可以试用（,IIa,，,C,），但须起始剂量宜小。,3）,在急性期,病情稳定,48h,后逐渐,加量,（,I,，,A,）,不能耐受,ACEI,者可以应用,ARB,。,急性心衰ACEI ARB MRAACCF/AHA 2013严,31,急性心衰,ACEI ARB,（,2013 JCS),In the treatment of chronic heart failure, ACE inhibitors havebeen established as a first-line therapy for patients ranging from a symptomatic heart failure to symptomatic, severe heart failure. Because patients with acute heart failure may often have,an increase in circulating blood,volume, but not all patients have excessive fluid retention as is often observed in patients with chronic heart failure, physicians should carefully,observe for hypotension,due to adverse drug reactions to these drugs when they are given to patients with acute heart failure (,Class IIa,Level of Evidence: C,),急性心衰ACEI ARB（2013 JCS),32,心肌梗死,STEMI,UA/NSTEMI,心肌梗死STEMI,33,STEMI,ACEI,ACCF/AHA 2013,An angiotensin-converting enzyme (ACE) inhibitor should be administered,within the first 24 hours,to all patients with STEMI,with anterior location, HF, or ejection fraction (EF,) less than or equal to 0.40, unless contraindicated .(I,A,) ACE inhibitors are reasonable for all patients with STEMI and no contraindications to their use (II a,A,),ESH/ESC 2012,ACE inhibitors are indicated starting,within the first 24 h,of STEMI in patients with evidence,of heart failure, LV systolic dysfunction, diabetes or an anterior infarct,.,（,IA) ACE inhibitors should be considered in all patients in the absence of contraindications (IIa A),中国,2010,对于,合并,LVEF,0.4,或肺淤血，以及高血压、糖尿病和慢性肾病的,STEMI,患者,，只要无使用此药禁忌证，应该尽早应用,(l,，,A),。,2,）发病,24h,后，如无禁忌证，所有,STEMI,患者均应给予,ACEI,长期治疗,(l,，,A),。,STEMI,最初,24h,内，对,前壁心肌梗死,，如无低血压,(,收缩压,100mmHg),或明确使用此类药物的禁忌证，应尽早口服,ACEI,，对非前壁心肌梗死、低危患者,(LVEF,正常，心血管危险因索控制良好，已经接受血运重建治疗,),、无低血压,(,收缩压,100mmHg),和使用此药禁忌证者，应用,ACEI,也可能获益,(IIa,，,B),STEMIACEIACCF/AHA 2013An angio,34,STEMI,ARB,ACCF/AHA 2013,An angiotensin receptor blocker (ARB) should be given to patients with STEMI who have indications for but are intolerant of ACE inhibitors. (I,:B,),ESH/ESC 2012,An ARB,preferably valsartan, is an alternative to ACE inhibitors in patients with heart failure or LV systolic dysfunction,particularly those who are intolerant to ACE inhibitors.(IB),中国,2010,如果患者不能耐受,ACEI,，但存在,心力衰竭,表现，或者,LVEF,小于等于,0.40,，可考虑给予,ARB(I,，,A),。,4,）如果患者不能耐受,ACEI,，但存在,高血压,可考虑给予,ARB(I,，,B),STEMIARBACCF/AHA 2013An angiot,35,STEMI,MRA,ACCF/AHA 2013,. An aldosterone antagonist should be given to patients with STEMI and no contraindications who are already receiving,an ACE inhibitor and beta blocker,and who have an EF less than or equal to 0.40 and either symptomatic HF or diabetes mellitus (I,: B,),ESH/ESC 2012,Aldosterone antagonists, e.g. eplerenone, are indicated in patients with an,ejection fraction 40%,and heart failure or diabetes,provided no renal failure or hyperkalaemia(IB,),中国,2010,醛固酮受体拮抗剂,;,通常在,ACEI,治疗,的基础上使用。对,STEMI,后,LVEF,小于等于,0.4,、有心功能不全或糖尿病，无明显肾功能不全（血,肌酐男性小于等于,221umol/L,（,2.5mg/dl,），女性小于等于,177umol/L,（,2.0mg/dl,）、血钾小于等于,5mmol/L,的患者，应给予醛固酮受体拮抗剂,(I,，,A),。,ACEI,和螺内酯联合应用较,ACEI,和,ARB,联合应用有更好的价效比，一般不建议三者联合应用,。,STEMIMRAACCF/AHA 2013. An aldo,36,UA/NSTEMI,ACEI,用于,NSTEMI,患者的建议,类适应证,（,1,）伴有左室收缩功能异常或慢性心力衰竭、使用硝酸甘油和,BB,后仍有,高血压,的,NSTEMI,患者（证据水平,B,）,（,2,）伴有,糖尿病,的,NSTEMI,患者（证据水平,B,）,（,3,）伴心力衰竭、左室收缩功能异常、高血压或糖尿病的,NSTEMI,患者出院时带药及出院后长期使用（证据水平,A,）,a,类适应证,（,1,）所有,NSTEMI,患者（证据水平,B,）,（,2,）所有,NSTEMI,患者出院时带药及出院后长期使用（证据水平,B,）,UA/NSTEMIACEI用于NSTEMI患者的建议,37,UA/NSTEMI,1. ACEI should be given and continued indefinitely for patients recovering from UA/NSTEMI with HF, LV dysfunction (LVEF less than 0.40),hypertension, or diabetes mellitus, unless,contraindicated.,(I: A),2. An ARB should be prescribed at discharge to those UA/NSTEMI patients who are intolerant of an ACEI and who have either clinical or radiological signs of,HF and LVEF,less than,0.40.,(IA),3. Long-term aldosterone receptor blockade should be prescribed for UA/NSTEMI patients without significant renal dysfunction or hyperkalemia who are already receiving therapeutic doses of an,ACEI,have,an LVEF,less than or equal to 0.40, and have either symptomatic,HF,or diabetes,mellitus.,(IA),UA/NSTEMI1. ACEI should be giv,38,UA/NSTEMI,1. Angiotensin-converting enzyme inhibitors are reasonable for patients recovering from UA/NSTEMI in the absence of LV dysfunction, hypertension, or diabetes mellitus unless contraindicated.,(IIa A),2. Angiotensin-converting enzyme inhibitors are reasonable for patients with HF and LVEF greater than 0.40.,(IIaA),3. In UA/NSTEMI patients who do not tolerate ACE inhibitors, an angiotensin receptor blocker can be useful as an alternative to ACE inhibitors in long-term management provided there are either clinical orradiological signs of HF and LVEF less than 0.40.,(IIa B),1. The combination of,an ACE inhibitor and an angiotensinmreceptor,blocker may be considered in the longterm management of patients recovering from UA/ NSTEMI with persistent symptomatic HF and LVEF less than 0.40 despite conventional therapy including an ACE inhibitor or an angiotensin receptor blocker alone.,(IIb B),UA/NSTEMI1. Angiotensin-conver,39,临床试验 病例数,ACEI,病例选择 观察月 结果,SAVE 2231,卡托普利 心衰,I-II,级,24-60,降死亡率,18%,12.5-150 mg/d,AIRE 1986,雷米普利 心梗后,6-15,降死亡率,22%,2.5-5 mg/d,SMILE 1556,左分普利 心梗后心衰,1.5,降死亡率,25%,7.25-30mg,，,bid,重心衰减,41%,GISSI-3 19394,赖诺普利 心梗后心衰,1.5,降死亡率,11%,2.5-5 mg,，,bid,ISIS-4 58050,卡托普利 心梗后,1.0,降死亡率,6%,6.25-50 mg,，,bid,TRACE 1749,群多普利 心梗后心衰,24-50,降死亡率,25%,1 mg/d,Clinical Trials,临床试验 病例数 ACEI 病例选,40,临床试验 病例数,ACEI,病例选择 观察月 结果,CONSENUS II 253,依那普利,IV 6-12,降死亡率,6,月,40%,，,12.5-40 mg/d,1,年,31%,SOLVD-Treat 2569,依那普利,I-III 22-55,降死亡率,21%,2.5-20 mg/d,减轻心衰,SOLVD-Prevt 4228,依那普利,I-II 15-62,减心衰危险性,37%,2.5-20 mg/d,无症状心衰,VHeFTI 804,依那普利,III 6-68,降猝死率,36%,20 mg/d,Clinical Trials,Clinical Trials,41,房颤（,2014 ESC),ACEIs and ARBs,抗房颤抗心房纤维化 抑制血管紧张素,II,致心律失常的作用。包括刺激心房纤维化、肥大、解偶缝隙连接，钙处理受损、离子通道改变，激活氧化应激，促进炎症,醛固酮受体拮抗剂,房颤（2014 ESC)ACEIs and ARBs抗房颤抗,42,RAAS抑制剂在心血管系统应用课件,43,左心室肥厚（,2013 ESC),左心室肥厚（2013 ESC),44,稳定性缺血性心脏病,（,2012,美国）,稳定性缺血性心脏病（2012美国）,45,Q1 RAASI,的药物选择,which one is the best?,Q1 RAASI的药物选择which one is t,46,药物,半衰期（,h,）,IC 50,剂量及给药方法,组织亲和,肾衰调量,赖诺普利,12,1.7,5 40 mg, qd,50%,贝那普利,11,2,5 40 mg, qd,*,50%,培哚普利,3 10,2.4,4 8 mg, qd,*,25%,依那普利,11,1-5.2,5 40 mg, qd,*,50%,雷米普利,13 17,1.5-4.2,2.5 10 mg, qd,*,50%,福辛普利,12,11,10 40 mg, qd,*,100%,卡托普利,2,23-35,12.5 100 mg, tid,*,15%,迅速起效,HF,证据最多,肾脏保护,亲水性,咳嗽少,药物半衰期（h）IC 50剂量及给药方法组织亲和肾衰调量赖诺,47,药物,半衰期（,h,）,起效,max,剂量及给药方法,特殊人群,缬沙坦,6-8,2-4w,80-160 mg, qd,奥美沙坦,13,20-40 mg, qd,重度肝肾不全调量,厄贝沙坦,11-15,4-6w,150-300 mg, qd,氯沙坦,7.6,3-6w,50 100 mg, qd,坎地沙坦,11,4-12 mg, qd,严重肝肾调量,替米沙坦,18-24,20 80 mg, qd,严重肝禁用，不能透析清除,螺内酯,13-24,20-60 mg,GFR30,禁用,作用最强,降尿酸,HF,推荐,药物半衰期（h）起效max剂量及给药方法特殊人群缬沙坦6-8,48,Q2 RAASI,在肾功能不全患者的应用,which one is the best?,Q2 RAASI在肾功能不全患者的应用which on,49,2007,中国专家共识,-,肝肾双排,？,糖尿病肾病和蛋白尿是,ACEI,和,ARB,共同的适应症,非糖尿病肾病是,ACEI,独有的适应症,贝那普利对肾脏的保护作用最强,对肾功能不全的患者可以调量使用,经济性,慢性肾功能不全,ACEI,的适应症而非禁忌症,2007中国专家共识-肝肾双排？糖尿病肾病和蛋白尿是 ACE,50,血管神经性水肿 并非在用药初期出现,急性肾功能衰竭 心衰患者血容量不足,低血压,100 mmHg-,慎重用药,可在充分补液后使用,肌酐升高,30%,以上 需停药或换药,大于,264 umol/L g,恶化肾功,血管神经性水肿 并非在用药初期出现,51,螺内酯,GFR5 mM,禁用,ACEI/ARB,和螺内酯 高血钾强度相似,应配合呋塞米和氢氯噻嗪等。防止高钾 心脏停搏,肾功能不全尤为注意,螺内酯,52,Q3 ACEI,和,ARB,联用,Q3 ACEI和ARB联用,53,欧洲药物管理局（,EMA,）：避免联用两种在肾素,-,血管紧张素,-,醛固酮系统有独立作用的药物。根据欧洲药物的调整，,ACEI,、,ARB,和直接肾素抑制剂都没有联用的循证依据，特别是,糖尿病肾病的病人,严禁联用,ACEI,和,ARBs,。,联用,RAS,系统抑制药的重要危险包括了高钾血症，低血压和肾功能的进一步恶化,高血压指南：不推荐联用,心衰指南：可以联用（,IIb B),欧洲药物管理局（EMA）：避免联用两种在肾素-血管紧张素-醛,54,谢谢 ！,谢谢 ！,55,