1、22章 Antihypertensive drugs Objectiven掌握掌握 氢氯噻嗪、普萘洛尔、硝苯地平、氢氯噻嗪、普萘洛尔、硝苯地平、卡托普利、硝普钠的降压作用、机制、卡托普利、硝普钠的降压作用、机制、临床应用。临床应用。n熟悉熟悉 抗高血压药的分类，其它常用药抗高血压药的分类，其它常用药的作用特点，抗高血压药的应用原则。的作用特点，抗高血压药的应用原则。n了解了解 其它药物的降压作用特点。其它药物的降压作用特点。途 经体 循 环肺 循 环心 脏功 能结 构血 管动 脉静 脉毛 细 血 管人 体 循 环 系 统血 液组 成分 类功 能外 在 表 现组 成血 液 循 环其 他 内 容包
2、括包括的的包括包括包括的的的的的包括包括包括血液血细胞血浆红细胞白细胞血小板组成分类静脉血动脉血氧气及少量二氧化碳营养和代谢物包括包括包括包括包括的的含氧少、暗红的含氧多、鲜红的转化运输溶解并运输主 动 脉(B)上、下 腔静 脉(F)肺 静 脉(K)肺 动 脉(I)血 管动 脉静 脉毛 细 血 管各 级 动 脉(C)各 级 静 脉(E)肺 部 毛 细 血 管(J)身 体 其 他 毛 细 血 管(D)图 12包 括包 括包 括例 如例 如例 如例 如例 如例 如例 如例 如心 脏功 能血 液动 力 器 官结 构右 心 室(H)左 心 室(A)右 心 房(G)左 心 房(L)图 13的是流 动 的
3、的包 括包 括包 括包 括血 流 向血 流 向途 经体 循 环肺 循 环血 液 循 环包 括包 括的1 introduction1.Hypertension nThe condition can be fatal if untreated,as it greatly increases the risk of thrombosis（血栓症血栓症）,stroke（卒中卒中）and renal failure.1 introductionnClassification of hypertension1 introductionnpathophysiology(病生理病生理)of hypertens
4、ion 1).sympathetic nervous system dysfunction (交感神经系统功能紊乱交感神经系统功能紊乱)SympatheticNS（）（）artery constriction peripheral resistance heart（）（）HR,CO-R(+)renin excreteBp2).RAAS 3).Others1 introductionnAntihypertensive drugs【definition】The agents can lower blood pressure,clinical used to treat hypertension a
5、nd to prevent damages in kidney,heart and brain.【significance】morbidity and mortality (发病率发病率）（死亡率死亡率）1 introductionnClassification of antihypertensive drugs 1.:DCT氢氯噻嗪氢氯噻嗪,furosemide呋塞米 2.RAAS inhibitors captopril,enalapril AT1 blockers losartan氯沙坦,valsartan缬沙坦 Renin inhibitors enalkiren依那吉仑,remiki
6、ren雷米克林1 introduction3.Adrenergic receptor blockers:1)1-R blockers:prazosin terazosin 2):propranolol 3)、-R blockers:labetalol4.:nifedipine,amlodipine1 introduction 5.Sympathetic nervous inhibitors:clonidine,methyldopa,reserpine.6.Vasodilators:hydralazine,sodium nitroprusside minoxidil,diazoxide.7.ot
7、hers2 usual drugs-Diuretic agents I.Diuretic agents【antihypertensive mechanism】early hypotensive effect diuretic effect blood volume long-term effect PVR（外周血管阻力外周血管阻力）Bp 2 usual drugs-Diuretic agents Excretion of sodium intracellular Na+intracellular Ca2+；the sensitivity of blood vessel responses to
8、 NA;produce the vasodilators (BK,PGE2).2 usual drugs-Diuretic agents【clinical uses】噻嗪类噻嗪类 thiazides basic antihypertensive agents mild hypertension used alone(25mg);moderate and severe hypertension used in combination with other antihypertensive agents.（-R blockers or ACEI)2 usual drugs-Diuretic age
9、nts 吲达帕胺吲达帕胺 indapamide diuretic effect,direct vasodilation血管舒张Bp adverse reactions small;for patient with hyperlipidemia高脂血症:replace DCT2 usual drugs-Diuretic agents呋塞米呋塞米 furosemide high efficacy diuretic,it can cause severe electrolyte imbalance（电解质失衡电解质失衡）severe hypertension,especially with chro
10、nic renal insufficiency or cardiac failure.2 usual drugs-calcium antagonistsII、Calcium antagonists blocking calcium channel vasodilationBp nifedipine(硝苯地平硝苯地平)nitrendipine(尼群地平尼群地平)lacidipine(拉西地平拉西地平)amlodipine(氨氯地平氨氯地平)2 usual drugs-calcium antagonists硝苯地平硝苯地平 nifedipine【characteristics of action】
11、1.po absorption is complete;2.It has more selectivity,used for mild or moderate hypertension.3.used alone or in combination with diuretics and -R blockers.2 usual drugs-calcium antagonists4.Reflex sympathetic activation slight tachycardia or CO;sustained-release preparations(缓释制剂缓释制剂)5.Side reaction
12、:hypotension,rash（皮疹皮疹）,tachycardia,peripheral edema（水肿水肿）,flushing面红and dizziness（眩晕眩晕）.2 usual drugs-calcium antagonists:hypertension with angina心绞痛 -nifedipine硝苯地平;with cerebral vascular disease脑血管疾病 -nimoldipine尼莫地平;with tachycardia心动过速-verapamil维拉帕米 (alone or with diuretics、-R drugs)2 usual dru
13、gs-R blocking agents III.-R blocking agents 普萘洛尔普萘洛尔 propranolol【antihypertensive mechanism】1.blocks 1 R CO;2.blocking 1-R located in the kidney renin secretion,3.the activity of RAAS 2 usual drugs-R blocking agents3.blocking-R located in the CNSperipheral sympathetic activity;（外周交感外周交感N N活性活性）4.blo
14、cking presynaptic(突触前膜突触前膜)-R2 inhibit the positive feedback（正反馈）正反馈）,NA release;5.PGI2 synthesis 血管扩张血管扩张2 usual drugs-R blocking agentspropranolol2 usual drugs-R blocking agents【antihypertensive characteristics】1.mildness,slowness,2.long duration;2.Individual variation（个体差异个体差异）of doses;2 usual dr
15、ugs-R blocking agents3.,most useful in antihypertensive therapy;especially with high plasma renin activity（高肾素活性高肾素活性）；）；or with angina（心绞痛）；or with tachycardia（心动过速）.2 usual drugs-R blocking agentsOther -R blocking agents 阿替洛尔阿替洛尔 atenolol 拉贝洛尔拉贝洛尔 labetalol、卡维洛尔卡维洛尔 carvedilol2 usual drugs-ACEIIV.
16、Renin-angiotensin system inhibitors ACEIcaptopril卡托普利 enalapril依那普利ramipril雷米普利 benazapril贝那普利cilazapril西拉普利 fosinopril福森普利2 usual drugs-ACEI 1.AngII的生成及作用的生成及作用;2.保存保存BK的活性的活性;3.保护血管内皮细胞及抗动脉粥样硬化保护血管内皮细胞及抗动脉粥样硬化;4.抗心肌缺血与心肌保护作用抗心肌缺血与心肌保护作用;5.对胰岛素的敏感性对胰岛素的敏感性;6.阻止心血管病理性重构阻止心血管病理性重构.【antihypertensive m
17、echanism】AngIAngIIBlood vessel（+）NA releaseAldosteroneVSM hyperplasiaACE（kininase II）BKloss aliveplatelet congregate聚集聚集Vasodilator血管扩张血管扩张ACEI2 usual drugs-ACEI卡托普利卡托普利 captopril【antihypertensive characteristics】1.po absorption is well，F 70%;2.Vasodilatation血管扩张血管扩张 PVR外周阻力外周阻力,but CO and HR are no
18、t significantly changed;2 usual drugs-ACEI3.cardiac protection prevention and reversion of blood vessel wall incrassation（增厚）增厚）and myocardial hypertrophy（心肌肥厚）.4.Used for all types of hypertension and severe CHF.2 usual drugs-ACEI【adverse reactions】1)hypotension(3.3%);2)characteristic cough(5%20%);
19、3)hyperkalaemia（高血钾高血钾）;4)renal function*;5)dizziness,skin rashes and alteration in taste.2 usual drugs-ACEI【contraindications】pregnancy（妊娠妊娠）;renovascular（肾血管肾血管）disease or to those with double aortic stenosis（双侧肾动脉狭窄双侧肾动脉狭窄）.(二二）AT1 blockersLosartan氯沙坦氯沙坦Valsartan缬沙坦缬沙坦Candesartan坎坎地沙坦地沙坦2 usual d
20、rugs-AT1 blockers Angiotensin II receptor（AT1）blockers 氯沙坦氯沙坦 losartan competitive block AT1 PVR blood capacities Used for hypertension.side effects similar to captopril,but cough is less common.3 other classical antihypertensive drugs .Acting on CNS 可乐定可乐定 clonidine 甲基多巴甲基多巴 methyldopa 莫索尼定莫索尼定 mox
21、onidine3 other classical antihypertensive drugs可乐定可乐定 clonidine 【characteristics of action】1.po absorption is well,F 71-82%；2.the mechanism is complex:central 2-R&I1 imidazoline-R（咪唑啉受体）（咪唑啉受体）(+)sympathetic activity PVR ;(+)presynaptic 2-R NA release 3 other classical antihypertensive drugs3.Dont r
22、enal blood flow and GFR frequently use for hypertension with renal insufficiency（肾功能不全肾功能不全）.gastric acid secretion proper for hypertension with peptic ulcer（胃潰疡）胃潰疡）.3 other classical antihypertensive drugs4.used for moderate to severe hypertension；5.untoward effects:sedation,dry mouth,orthostatic
23、hypotension（体位性低血压体位性低血压）,rebound withdrawal（停药反跳停药反跳），），sodium and water retention.Moxonidine莫索尼定 3 other classical antihypertensive drugs.Vasodilators 肼屈嗪肼屈嗪 hydralazine the effect on arterioles veins;HR,CO,renin secretion;alone used rarely3 other classical antihypertensive drugshydralazinesodium
24、nitroprusside3 other classical antihypertensive drugs硝普钠硝普钠 sodium nitroprusside【characteristics 】1.iv.gtt the effects are strong、rapid and unabiding(短暂的短暂的)；2.direct vasodilation on arterial and venous;3 other classical antihypertensive drugs3.used for （高血压危象高血压危象）;（难治性心衰难治性心衰）;.（控制性降压控制性降压）3 other
25、 classical antihypertensive drugs Ganglionic Blockers神经节阻断药神经节阻断药 美卡拉明美卡拉明 mecamylamine 樟磺咪芬樟磺咪芬 trimetaphan camsilate hypertensive crisis（高血压危象高血压危象）and to induce controlled hypotension（控制性降压控制性降压）for neurosurgery.3 other classical antihypertensive drugs 1-R blockers prazosin(哌唑嗪哌唑嗪)terazosin(特拉唑嗪特
26、拉唑嗪)doxazosin(多沙唑嗪多沙唑嗪)3 other classical antihypertensive drugs哌唑嗪哌唑嗪 prazosin 【characteristics 】1.selectively block 1-R Bp;less reflex tachycardia;prazosin3 other classical antihypertensive drugs2.coronary artery disease冠状动脉疾病,冠心病 n LDLn VLDLn triglyceride（甘油三酯甘油三酯）;n HDL;3 other classical antihype
27、rtensive drugs3.Clinical uses:i.mild to moderate hypertension;combination with other agents (diuretics and propranolol)effects;ii.acute CHF;4.untoward effects:Dizziness,headache,drowsiness.3 other classical antihypertensive drugsn First dose phenomenon(首剂现象首剂现象）the first dose 1 mg,postural hypotensi
28、on（体位性低血压体位性低血压）and syncope（晕厥晕厥）may occur,so,the first dose should be small and should be administered at bedtime.3 other classical antihypertensive drugs Adrenergic neuron blocking agents 利血平利血平 reserpine 胍乙啶胍乙啶 guanethidine cause depletion（耗竭耗竭）of NA peripheral sympathetic activity New concept of antihypertensive therapy effectively therapy and lifetime therapy（有效治疗与终生治疗）（有效治疗与终生治疗）；protect target organs （保护靶器官）（保护靶器官）reposefully hypotension （平稳降压）（平稳降压）questionsn1.抗高血压药物的分类？n2.利尿药的降压机制及其应用
