第21章-抗心绞痛与抗动脉粥样硬化药课件.ppt

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1、 Antianginal Drugs Zhu Yi Zhun,Dept.of Pharmacology,SPFDUEmail:HypertensionTherefore,it is important to treat hypertension and reduce mortality and morbidity of these conditions End organ damageis associated with increased risk from ischemic heart disease,cerebrovascular accidents,heart and renal fa

2、ilure.Complications of untreated hypertensionHypertensive cardiovascular diseaseHypertensive cerebrovascular disease and dementiaHypertensive renal diseaseAortic dissectionAtherosclerotic complicationLEADING CAUSES OF MORTALITY IN WHO REPORTLEADING CAUSES OF MORTALITY IN WHO REPORTThe mortality of i

3、schaemic heart disease is ranked first among other diseases in the WHO statisticsMYOCARDIAL INFARCTIONMYOCARDIAL INFARCTIONMyocardial Infarction generally occurs with the abrupt decrease in coronary blood flow that follows a thrombotic occlusion of a coronary artery leads to irreversible myocardial

4、cells damage and necrosis.Angina pectorisIs the most common condition involving in tissue ischemiaVasodilator drugs are commonly used(e.g.nitroglycerin,calcium channel blocker)-blockers are also useful VasodilatorsCalcium channels blockers:arteriodilator(e.g.Nifedipine硝苯地平,verapamil异搏定,diltiazem硫氮卓酮

5、)Nitrites(increase NO):venodilator(+),Arterioles(+),ischemic zone(+).ACE inhibitors(e.g.Captopril开普通)and angiotensin II receptor antagonists(Losartan氯沙坦):mixed Nitrates&Nitrites(硝酸盐硝酸盐&亚硝酸盐亚硝酸盐)Mechanisms of action in Angina:*Endothelial-derived relaxation factor(EDRF内皮内皮衍生的松弛因子衍生的松弛因子)nitric oxide(

6、NO):induces coronary vasodilation*Nitrates dilate coronary arteries to:1)redistribute blood flow from epicardial to endocardial regions.2)relieve coronary spasm and dynamic stenosis*Reduce oxygen demandNitrates/Nitrites NO Relaxation Drugs used to treat AnginaNitrites:Amyl Nitrite(戊基亚硝酸盐戊基亚硝酸盐)Side-

7、effects of NitratesHeadache-most common side-effectwith long-acting preparations:the development of tolerance,worsening of the underlying diseases process.Failure of nitrate therapywith short-acting preparations:noncompliance(headache),loss of potency of the tablets,and incorrect timingHypotension-m

8、ost serious side-effectOther drugs used to treat anginaCalcium channel blockers-blockersIndications:chronic stable angina,unstable anginaHypertensionSuperaventricular ArrhythmiasOthers:hypertrophic cardiomyopathy,migraine and atherosclerosis.Side-effectsHeadache,facial flushing,dizziness,and constip

9、ation(but Nifedipine not)Calcium channel blocking drugsIndications:Ischemic heart diseaseHypertension Cardiac arrhythmiasOthers cardiovascular disorders:increasing stroke volume(in patients with obstructive cardiomyopathy),congestive heart failure(in certain carefully selected patients)Glaucoma,Hype

10、rthroidism,Neurologic diseases.Side-effectsWorsening of preexisting asthma and other forms of airway obstruction(nonselective agents due to 2 blockade);Rash,fever,sedation,sleep disturbance,and even depression-adrenoceptor blocking drugs Drugs for Atherosclerosis Zhu Yi Zhun,Dept.of Pharmacology,SPF

11、DUEmail:Cholesterol levelmg/dL(mmol/L)Metabolism of cholesterol 3-hydroxy-3-methyl-glutaryl-coenzyme A3-羟-3-甲戊二酰辅酶-statinLovasatinAtorvastatinFluvastatinPravastatinSimvastatinRosuvastatinLDLOxidative stressVasodilatorsCalcium channels blockers:arteriodilator(e.g.Nifedipine硝苯地平,verapamil异搏定,diltiazem

12、硫氮卓酮)Nitrites(increase NO):venodilator(+),Arterioles(+),ischemic zone(+).ACE inhibitors(e.g.Captopril开普通)and angiotensin II receptor antagonists(Losartan氯沙坦):mixed Nitrates&Nitrites(硝酸盐硝酸盐&亚硝酸盐亚硝酸盐)Mechanisms of action in Angina:*Endothelial-derived relaxation factor(EDRF内皮内皮衍生的松弛因子衍生的松弛因子)nitric ox

13、ide(NO):induces coronary vasodilation*Nitrates dilate coronary arteries to:1)redistribute blood flow from epicardial to endocardial regions.2)relieve coronary spasm and dynamic stenosis*Reduce oxygen demandNitrates/Nitrites NO Relaxation IndicationsShort-acting nitrates for acute effort angina:subli

14、ngual nitroglycerin(0.3 to 0.6 mg)every 5 minutes until pain goes or a max.of 4 to 5 tablets to be taken.Nitroglycerin spray is an alternative mode of oral administration.Long acting nitrates for angina prophylaxis:Oral preparation of nitrate is frequently given for the prophylaxis of angina.Long-ac

15、ting nitrates are not continuously effective if regularly taken over a prolonged period,unless allowance is made for a nitrate-free or-low interval.Metabolism of cholesterol 3-hydroxy-3-methyl-glutaryl-coenzyme A3-羟-3-甲戊二酰辅酶-statinLovasatinAtorvastatinFluvastatinPravastatinSimvastatinRosuvastatinLDLOxidative stressEND!