antianginaldrugs抗心绞痛药.ppt

Part 6 Antianginal Drugs Organic nitrates receptor blockers Calcium channel blockersCoronary vessels:Coronary vessels:blood supply for the heartblood supply for the heart1.OVERVIEWCoronary atherosclerosis:Coronary atherosclerosis:cause of cardiac ischemiacause of cardiac ischemiaDistribution of coronary arteries in the heartDistribution of coronary arteries in the heartIschemia(Ischemia(angina pectorisangina pectoris):):imbalance between oxygen demand and supply imbalance between oxygen demand and supplyClassification of angina pectoris:Exertional angina(Exertional angina(劳累性心绞痛劳累性心绞痛劳累性心绞痛劳累性心绞痛)Stable anginaStable angina(稳定性心绞痛稳定性心绞痛稳定性心绞痛稳定性心绞痛)Initial onset angina(Initial onset angina(初发型心绞痛初发型心绞痛初发型心绞痛初发型心绞痛)Accelerated angina(Accelerated angina(恶化性心绞痛恶化性心绞痛恶化性心绞痛恶化性心绞痛)Spontaneous angina(Spontaneous angina(自发性心绞痛自发性心绞痛自发性心绞痛自发性心绞痛)Angina decubitus(Angina decubitus(卧位型心绞痛卧位型心绞痛卧位型心绞痛卧位型心绞痛)Variant or vasospastic anginaVariant or vasospastic angina(变异性变异性变异性变异性 痉挛性痉挛性痉挛性痉挛性 心绞痛心绞痛心绞痛心绞痛)Acute coronary insufficiency(Acute coronary insufficiency(急性冠脉功能不全急性冠脉功能不全急性冠脉功能不全急性冠脉功能不全)Postinfarction angina(Postinfarction angina(梗死后心绞痛梗死后心绞痛梗死后心绞痛梗死后心绞痛)Mixed angina(Mixed angina(混合性心绞痛混合性心绞痛混合性心绞痛混合性心绞痛)Unstable anginaUnstable angina (不稳定性心绞痛不稳定性心绞痛不稳定性心绞痛不稳定性心绞痛)1.OVERVIEWMyocardial oxygen demand is chiefly determined by:Contractility Contractility Heart rateHeart rate Wall tension Wall tension Preload(venous return Preload(venous return)Afterload(arteriolar resistance)Afterload(arteriolar resistance)1.OVERVIEWpreloadpreloadafterloadafterloadMyocardial oxygen demand is diminished by:Reducing contractility Reducing contractility Reducing heart rate Reducing heart rate Reducing the preload Reducing the preload Reducing the afterload Reducing the afterload1.OVERVIEWWall tension Wall tension 1.OVERVIEWMyocardial oxygen supply is chiefly determined by:AV oxygen difference AV oxygen difference Regional myocardial Regional myocardial distribution distribution coronary blood flow:coronary blood flow:vascular resistance,artery pressure Effects of antianginal drugs:Reducing oxygen demandsReducing oxygen demands Reducing heart rate and contractility Reducing heart rate and contractility Dilating systemic arteries and veins(Dilating systemic arteries and veins(wall tension by wall tension by lowering lowering heart loads)heart loads)Increasing oxygen supplyIncreasing oxygen supply Dilating conduct coronary arteries(Dilating conduct coronary arteries(coronary blood flow)coronary blood flow)Promoting regional distribution(Promoting regional distribution(in ischemic regions)in ischemic regions)Others:Others:Anti-platelet coagulation and thrombus formation Anti-platelet coagulation and thrombus formation 1.OVERVIEW2.1 NitratesNitroglycerin(硝酸甘油硝酸甘油硝酸甘油硝酸甘油)A.Pharmacological actions Dilating vessels and reducing heart loadsDilating vessels and reducing heart loads wall tension wall tension ;reflex tachycardiareflex tachycardia Redistribution of coronary circulationRedistribution of coronary circulation dilating conduct artery:dilating conduct artery:collateral circulation collateral circulation reducing wall tension:reducing wall tension:blood flow in ischemic subendocardial area blood flow in ischemic subendocardial area 2.Antianginal drugsInfluence of organic nitrates and dipyridamole Influence of organic nitrates and dipyridamole on the blood supply of ischemic areaon the blood supply of ischemic area2.Antianginal drugsMechanism of the effect of Mechanism of the effect of nitroglycerin and other nitroglycerin and other nitratesnitrates2.Antianginal drugsMechanism of the effect of Mechanism of the effect of nitroglycerin and other nitroglycerin and other nitratesnitratesB.Clinical uses Angina pectoris:Angina pectoris:all kinds,especially stable typeall kinds,especially stable type Heart failureHeart failure：reducing heart loads due to vasodilationreducing heart loads due to vasodilationC.Adverse reactions Increase in heart rate and contractilityIncrease in heart rate and contractility Symptoms due to vasodilation:Symptoms due to vasodilation:headache,flash,postural headache,flash,postural hypotension,collapse,hypotension,collapse,ectect.Others:Others:methaemoglobinaemia methaemoglobinaemia（高铁血红蛋白）（高铁血红蛋白）（高铁血红蛋白）（高铁血红蛋白）Tolerance:avoiding steady-state plasma concentration;avoiding steady-state plasma concentration;supplement of agents containing supplement of agents containing SH SH(captopril)(captopril)2.Antianginal drugs2.1 Other nitrates Isosorbide dinitrate(硝酸异山梨酯硝酸异山梨酯硝酸异山梨酯硝酸异山梨酯)Isosorbide-5-mononirate(5-(5-硝酸异山梨酯硝酸异山梨酯硝酸异山梨酯硝酸异山梨酯)Compared with nitroglycerin:Compared with nitroglycerin:Similar but weaker effect Acting slowly but lasting longer Larger individual variation and more adverse effects2.Antianginal drugs2.2 receptor blockersA.Pharmacological actionA.Pharmacological action Reducing oxygen demand:Reducing oxygen demand:heart rate and contractility heart rate and contractility Increasing oxygen supply:Increasing oxygen supply:diastolic period diastolic period :perfusion time perfusion time vascular tone in normal regions vascular tone in normal regions :blood flow in ischemic regions blood flow in ischemic regions Others:Others:Improving myocardial metabolism Improving myocardial metabolism Inhibiting coagulation of platelets Inhibiting coagulation of platelets2.Antianginal drugsB.Clinical uses stablestable and and unstableunstable pectorispectoris,especially associated with especially associated with hypertension or arrhythmias,even with myocardial infarctionhypertension or arrhythmias,even with myocardial infarction;but not but not used forused for variant angina pectorisvariant angina pectorisC.Notes Dose individualization:Dose individualization:starting from small dosestarting from small dose Withdraw gradually and slowly:Withdraw gradually and slowly:symptomsymptom reboundrebound Combination with nitroglycerin Combination with nitroglycerin2.Antianginal drugs2.3 Calcium channel blockers2.Antianginal drugs2.3 Calcium channel blockersA.Pharmacological actions Reducing myocardial oxygen remand:Reducing myocardial oxygen remand:heart loads heart loads :nifedipinenifedipine heart rate and contractility heart rate and contractility :verapamil and diltiazemverapamil and diltiazem Increasing myocardial blood supplyIncreasing myocardial blood supply Protecting ischemic myocardial cellsProtecting ischemic myocardial cells Inhibiting coagulation of platelets Inhibiting coagulation of platelets2.Antianginal drugsActions of calcium channel blockersActions of calcium channel blockersB.Clinical uses stable and variant type:stable and variant type:nifedipine,verapamil,diltiazemnifedipine,verapamil,diltiazem unstable type:unstable type:verapamil,diltiazemverapamil,diltiazem2.Antianginal drugsActions of DHP(like nifedipine)are similar to those of nitroglycerinActions of DHP(like nifedipine)are similar to those of nitroglycerinActions of verapamil and diltiazem are similar to those of Actions of verapamil and diltiazem are similar to those of blockers blockers2.4 Other drugs2.4 Other drugsACEIs ACEIs（血管紧张素转化酶抑制药）（血管紧张素转化酶抑制药）（血管紧张素转化酶抑制药）（血管紧张素转化酶抑制药）Treating hypertension and preventing ischemic heart Treating hypertension and preventing ischemic heart disease disease Reducing heart loadsReducing heart loads Inhibiting cardial remodeling Inhibiting cardial remodeling Nicorandil Nicorandil（尼可地尔）（尼可地尔）（尼可地尔）（尼可地尔）Opening ATP-sensitive KOpening ATP-sensitive K+channel(K channel(KATPATP)Lowering intracellular Ca Lowering intracellular Ca2+2+Providing NO(like nitroglycerin)Providing NO(like nitroglycerin)Inducing ischemic preconditioning Inducing ischemic preconditioning 2.Antianginal drugsMolsidomine Molsidomine（吗多明）（吗多明）（吗多明）（吗多明）Inhibiting adenosine uptake and cAMP degradation Inhibiting adenosine uptake and cAMP degradation Inhibiting pletelet aggregationInhibiting pletelet aggregation Promoting collateral circulation after long-term usePromoting collateral circulation after long-term useDipyridamole Dipyridamole（双嘧达莫，潘生丁）（双嘧达莫，潘生丁）（双嘧达莫，潘生丁）（双嘧达莫，潘生丁）Inhibiting adenosine uptake and cAMP degradation Inhibiting adenosine uptake and cAMP degradation Inhibiting pletelet aggregationInhibiting pletelet aggregation Promoting collateral circulation after long-term usePromoting collateral circulation after long-term use2.Antianginal drugs nitroglycerinnitroglycerin blockers blockers CaCa2+2+antagonists antagonists combination*combination*Heart rateHeart rate Contractility Contractility /Wall tensionWall tension /Oxygen demandOxygen demand Blood pressureBlood pressure :increase,:increase,:markedly increase;:markedly increase;:decrease,:decrease,:markedly:markedly decrease;decrease;:variable according to the dose and effect of each drug;:variable according to the dose and effect of each drug;*blockers blockers c combined with nitroglycerin or Caombined with nitroglycerin or Ca2+2+antagonists(antagonists(nifedipine;nifedipine;combination with verapamil/diltiazem not be recommendatedcombination with verapamil/diltiazem not be recommendated)Caution:Caution:Combination may potentiate the antianginal Combination may potentiate the antianginal effects,but may induce severe hypotensioneffects,but may induce severe hypotension3.Summary of antianginal drugsSammaryCardiovascular pharmacologyOverview of Cardiovascular Diseases Common Cardiac DiseasesCommon Cardiac Diseases Abnormal contractilityAbnormal contractility：Heart failuresHeart failures Abnormal rhythmsAbnormal rhythms：ArrhythmiasArrhythmias Abnormal blood supplyAbnormal blood supply：Ischemic heart diseases Ischemic heart diseases Myocardial disordersMyocardial disorders Common vascular diseasesCommon vascular diseases Abnormal systematic resistanceAbnormal systematic resistance：HypertensionHypertension Dysfunction of coronary vesselsDysfunction of coronary vessels：Coronary vascular diseasesCoronary vascular diseases Dysfunction of cerebral vesselsDysfunction of cerebral vessels：Cerebral ischemia,hemorrhageCerebral ischemia,hemorrhage Dysfunction of pulmonary vesselsDysfunction of pulmonary vessels：Pulmonary hypertensionPulmonary hypertension Dysfunction of peripheral vessels:Dysfunction of peripheral vessels:Peripheral vascular disorderPeripheral vascular disorder Arteriosclerosis:Arteriosclerosis:basis of most CVS diseasesbasis of most CVS diseasesOverview of Cardiovascular Drugs Classification based on target organs/tissuesClassification based on target organs/tissues HeartHeart：Heart failures,arrhythmias,cardiac ischemiaHeart failures,arrhythmias,cardiac ischemia VesselsVessels：Vasodilatation,vasoconstriction,Vasodilatation,vasoconstriction,arteriosclerosisarteriosclerosisClassification based on the mechanismsClassification based on the mechanisms Ion channelsIon channels：CaCa2+2+,Na,Na+,K,K+channelschannels ReceptorsReceptors：Adrenoceptors,ATAdrenoceptors,AT1 1 receptors,receptors,etc.etc.EnzymesEnzymes：ACEI,NaACEI,Na+-K-K+-ATPase,HMG-CoA-ATPase,HMG-CoA reductasereductase OthersOthers：DiureticsDiureticsCardiovascular Drugs Antiarrhthemic drugsAntiarrhthemic drugs Classification;Typical drugs and their propertiesClassification;Typical drugs and their propertiesAntihypertensive drugsAntihypertensive drugs Classification;Properties of 6 main drug classesClassification;Properties of 6 main drug classesDrugs for treating heart failureDrugs for treating heart failure Classification;ACEIs,Classification;ACEIs,blockers,cardiac glycoideblockers,cardiac glycoideAntiatheroscleotic drugsAntiatheroscleotic drugs HMG CoA reductase inhibitors(statins)HMG CoA reductase inhibitors(statins)Antianginal drugsAntianginal drugs NitroglycerinNitroglycerin;blockers;blockers;CaCa2 2+antagonists+antagonists