生命科学与技术学院
教 案 首 页
教研室：药理学 教师姓名：欧和生
| 课 程名 称 | 药理学 | 授课专业及班次 | 临床医学专业 |
| 授课内 容 | 肾素-血管紧张素系统药理 | 授课方式 授课时数 | 理论讲授 2学时 |
| 目 的 要 求 | 1． 熟悉肾素-血管紧张素系统对心血管系统的生理机制。 | ||
| 重 点 与 难 点 | 重点 1. ACEI和血管紧张素II受体I型阻滞剂的药理作用及其机制。 2. 托普利和氯沙坦等药物的药理作用、临床应用。 难点 肾素-血管紧张素系统对心血管系统调节的生理机制及药物作用机制。 | ||
| 授课内容及时间分配 | 1． Renin-Aangiotensin-System （20 分钟) 2． Angiotensin converting enzyme inhibitors (ACEI) （45分钟) 3． The blockade of angiotension II receptor (20 分钟) 4． 小结、布置思考题、安排下次课内容 （5分钟) | ||
| 教具教材 | 多媒体加版书 教材：杨宝峰 主编：药理学 人民卫生出版社，北京，2003年 | ||
| 参 考 书 及 网 站 | 1. 周宏灏主编：药理学 科学出版社，北京，2003年 2. Pharmacology : 天津医科大学药理教研室主编，1999年 3. H.P. Rang, M.M Dale, J.M. Ritter P.K. Moore. Pharmacology ( the fifth edition). 2003. |
Part 1 Renin-Aangiotensin-System
Introduction
1.Element of RAS (renin, angiotensinogen,angiotensin, ACE, ATR)
Renin is an enzyme that acts on angiotensinogen to catalyze the formation of the decapeptide angiotensin I.
Angiotensin I is then cleaved by ACE to yield the octapeptide angiotensin II.
ATR: AT1R, AT2R
2.The regulation effect of RAS on blood pressure
The renin-angiotensinsystem is an important participant in both the short-and long-term regulationof arterial blood pressure.
Angiotensin II acts in several ways to increase totalperipheral resistance and thereby contributes to the short-term regulation ofarterial blood pressure. Perhaps the more important is the ability of angiotensin II to inhibit excretion of Na+ and water by thekidneys.
Angiotensin II – induced changes in renal functionplay an important role in long-term stabilization of arterial blood pressure.
Part 2 Angiotensinconverting enzyme inhibitors (ACEI)
1.Pharmacological effects
(1) Inhibit the formation of Ang II.
(2) Maintain the activity of brandykinin (BK).
(3) Protection of endothelium andanti-atherosclerosis
(4) Anti-iscamiaand protection of myocardial cell
(5) Increase the sensitivity of insulin
(6) Inhibit the pathological cardiovascular remodeling
2. Clinical uses
(1) Hypertension
(2) CHF and myocardial infarction
(3) DMEM and nephropathy
3. Untoward effects
(1) Hypotension: occurring in the first use.
(2) Cough: of 6 ~ 12%
(3) Hyperkalemia
(4) Low blood sugar
(5) Renal function trauma
(6) Affection of the development of fetus and newborn.
(7) Neuro Oedema.
(8) Malfunction of taste, tetter (thedrugs with –SH).
4.The drugs of ACEI.
. Captopril
Pharmacological Action :
i Directly inhibited ACE. (IC50:23 ~ 35 nmol /L), The depressor effect associated with the activitystate of RAS.
ii The protection of heart is relatedto abolishing of ROS, such as iscamia.
Pharmacokinetics
o Absorption : Po, F=75%. Taction :30 min. Tmax=1h.
o Distribution: extensivelydistributed in body , Pb=30%.
o Metabolism: oxygen in –SH.
o Excretion: from kidney: 40-50%in parent drug and the others in metabolites.
o Hypertension: single or combination.
o CHF
o Cardiac infarct.
o DMEM-nephropathy (only captopril).
Untoward effects
Apart fromthe common side effect, cough is usually complaint.
Enalapril
o Action : the action of inhibition of ACE is 10 times stronger than captopril.
o The absorption is not affectedby food. Po. TP=4-6h. Tmaintain=24h,q.d.
o Metabolism: enalaprilat(MK22)
o Distribution extensively inbody. T1/2: 11h.
o Excretion from kidney.
o Uses: hypertensionwww.lindalemus.com/sanji/ and CHF.
o Aside effect: cough ,hypotension, hyperkalemiaetc.
Fosinopril
o Prodrug (poo-): fosinoprilacid is the activity chemical.
o Tp=3-6 h
o Pb=95%
o&www.lindalemus.com/kuaiji/nbsp; T1/2=12h
o Distribution : heart and brain(much)
o Excretion: from liver and kidney, no toxicityaccumulation for light malfunction of kidney.
o No use：lactation
Lisinopril
benazepril
Part 3 The blockade of angiotension II receptor
losartan、valsartan、erbesartan、candesartan、tasosartan、eprosartan、telmisartan
1. Pharmacological effects and mechanism
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(1) Block the AT1R vasodilatation
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Aldostrone Hypotension
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(2) Block theAT1R Renin AngII AT2RBK-NO
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Vasodilatation, regression of remodeling Hypotension.
Losartan
（1)AT1R: Losartan block AT1R>AT2R (2-3万倍). EXP3174 >losartanin blocking AT1R (10- 40 times)
（2)Vasodilate renalartery, decrease reabsorption of water and Na+in renal tube.
（3)Protect kidney：Hypertension，DM and failure of kidney.
（4)Inhibit vascular remodeling.
(1) Hypertension
(2)CHF
Part 4 Howabout combination of AT1Ranta and ACEI
1. Increase effects(cure in hypertension, CHF), decrease disadvantage of the two class drugs.
2. Have not found anyadverse effects
Questions:
1. Describe the advantages anddisadvantages of AT1R and ACEI in therapeutics of hypertension.
2. what is thecommon side effect of Captopril?
