part 6 antianginal drugs 抗心绞痛药 organic nitrates organic nitrates receptor blockers ...

Part 6Part 6 Antianginal DrugsAntianginal Drugs抗心绞痛药抗心绞痛药

• Organic nitratesOrganic nitrates• receptor blockersreceptor blockers• Calcium channel blockersCalcium channel blockers

Coronary vessels:Coronary vessels: blood supply for the blood supply for the heartheart

1. OVERVIEW1. OVERVIEW

Coronary atherosclerosis:Coronary atherosclerosis:

cause of cardiac ischemiacause of cardiac ischemia

Distribution of coronary arteries in the heartDistribution of coronary arteries in the heart

Ischemia (Ischemia (angina pectorisangina pectoris ): ): 心绞痛：心肌心绞痛：心肌氧供需不平衡氧供需不平衡

imbalance between oxygen demand and supplyimbalance between oxygen demand and supply

Classification of angina pectoris Classification of angina pectoris 心绞痛类型心绞痛类型 ::

Exertional angina (Exertional angina ( 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 )) Initial onset angina (Initial onset angina ( 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 ))

Spontaneous angina (Spontaneous angina ( 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 )) Variant [or vasospastic] anginaVariant [or vasospastic] angina ( ( 变异性变异性 [[ 痉挛性痉挛性 ]] 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 )) Postinfarction angina (Postinfarction angina ( 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 ))

Unstable anginaUnstable angina (( 不稳定性心绞痛不稳定性心绞痛 ): ): link of stable anginlink of stable angina and myocardial infarctiona and myocardial infarction


不同类型心绞痛的发生不同类型心绞痛的发生

Myocardial Myocardial oxygen demandoxygen demand is chiefly deter is chiefly determined by:mined by:

•心肌耗氧量因素：心肌耗氧量因素： •Contractility Contractility 收缩力收缩力• Heart rate Heart rate 心率心率• Wall tension Wall tension 室壁张力室壁张力• Preload (venous return )Preload (venous return )• 前负荷（静脉回流量）前负荷（静脉回流量）• Afterload (arteriolar resistance)Afterload (arteriolar resistance) • 后负荷（动脉阻力）后负荷（动脉阻力）


preloadpreloadafterloadafterload

Myocardial Myocardial oxygen demandoxygen demand is di is diminishedminished by:by: 降低心肌耗氧量：降低心肌耗氧量：• Reducing contractility Reducing contractility 收缩力收缩力

• Reducing heart rate Reducing heart rate 心率心率

• Reducing the preload Reducing the preload 前负荷前负荷

• Reducing the afterload Reducing the afterload 后负荷后负荷


Wall tension Wall tension 室壁张力室壁张力


•Myocardial Myocardial oxygen suppoxygen supplyly is chiefly determined b is chiefly determined by:y:•心肌供氧量：心肌供氧量：• AV oxygen difference AV oxygen difference 氧分压氧分压• Regional myocardial Regional myocardial distribution distribution 局部血流分布局部血流分布• coronary blood flow: coronary blood flow:

• vascular resistance, artery pressure • 血管阻力，动脉压血管阻力，动脉压

Effects of antianginal drugs Effects of antianginal drugs 抗心绞痛药作用抗心绞痛药作用 ::

Reducing oxygen demands Reducing oxygen demands 降低心肌耗氧量降低心肌耗氧量

Reducing heart rate and contractilityReducing heart rate and contractility

Dilating systemic arteries and veins ( Dilating systemic arteries and veins ( wall tension by lowe wall tension by lowering heart loads)ring heart loads)

Increasing oxygen supply Increasing oxygen supply 增加供血供氧增加供血供氧

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 其他其他 ::

Anti-platelet coagulation and thrombus formationAnti-platelet coagulation and thrombus formation


2.1 Nitrates2.1 Nitrates

NitroglycerinNitroglycerin (( 硝酸甘油硝酸甘油 ))

A. Pharmacological actions A. Pharmacological actions 药理作用药理作用

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 drugs2. Antianginal drugs

Influence of organic nitrates and dipyridamole Influence of organic nitrates and dipyridamole on the blood supply of ischemic areaon the blood supply of ischemic area


Mechanism of the effect of nitroglycerin and other nitratesMechanism of the effect of nitroglycerin and other nitrates

B. Clinical uses B. Clinical uses 临床应用临床应用• 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 vasodilation

C. Adverse reactions C. Adverse reactions 不良反应不良反应• Increase in heart rate and contractility Increase in heart rate and contractility 心率、收缩力心率、收缩力

• Symptoms due to vasodilationSymptoms due to vasodilation 血管扩张引起血管扩张引起 :: headache, flasheadache, flash, postural hypotension, collapse, h, postural hypotension, collapse, ectect..• Others:Others: methaemoglobinaemia methaemoglobinaemia （高铁血红蛋白）（高铁血红蛋白）

• Tolerance 耐受性耐受性 : avoiding steady-state plasma concentratioavoiding steady-state plasma concentration; n; • supplement of agents containing –SH supplement of agents containing –SH (captopril)(captopril)


2.1 Other nitrates 其他硝酸酯类其他硝酸酯类 Isosorbide dinitrate (( 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 )) Compared with nitroglycerin Compared with nitroglycerin 与硝酸甘油比较的特点与硝酸甘油比较的特点 ::• Orally active 口服有效• Similar but weaker effect 作用相似但较弱• Acting slowly but lasting longer 作用缓慢、持久• Larger individual variation and more adverse effects• 个体差异大，不良反应多见


2.2 2.2 receptor blockers receptor blockers 受体阻断药受体阻断药

A. Pharmacological action A. Pharmacological action 药理作用药理作用• 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 metabolismImproving myocardial metabolism• Inhibiting coagulation of plateletsInhibiting coagulation of platelets


B. Clinical uses B. Clinical uses 临床应用临床应用 stablestable and and unstableunstable pectorispectoris, , especially associated with hypespecially associated with hyp

ertension or arrhythmias, even with myocardial infarctionertension or arrhythmias, even with myocardial infarction; ; but not usbut not used fored for variant angina pectorisvariant angina pectoris

C. Notes C. Notes 注意点注意点• 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 nitroglycerin but without verapabut without verapamilmil• Contraindicated in heart depression, asthma, and sContraindicated in heart depression, asthma, and so ono on


2.3 Calcium channel blockers 2.3 Calcium channel blockers 钙拮抗剂钙拮抗剂


2.3 Calcium channel blockers2.3 Calcium channel blockers

A. Pharmacological actions A. Pharmacological actions 药理作用药理作用

• Reducing myocardial oxygen remand:Reducing myocardial oxygen remand:• heart loads heart loads : : nifedipinenifedipine

• heart rate and contractilityheart 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 plateletsInhibiting coagulation of platelets


Actions of calcium channel blockersActions of calcium channel blockers

• Selective calcium channel blockersSelective calcium channel blockers

• Dihydropyridines Dihydropyridines (( 二氢吡啶类二氢吡啶类 ):): • nifedipine nifedipine 硝苯地平硝苯地平 rapid, hypotension, reflex tachycardiarapid, hypotension, reflex tachycardia

• amlodipine amlodipine 氨氯地平氨氯地平 high bioavailability, thigh bioavailability, t1/21/2 40-50 h, long-actin 40-50 h, long-actin

g, less influences on heart rate and blood pressureg, less influences on heart rate and blood pressure

• Phenylalkylamines Phenylalkylamines (( 苯烷胺类苯烷胺类 ):): • verapamil verapamil 维拉帕米维拉帕米 reducing oxygen demands, antiarrhythmiareducing oxygen demands, antiarrhythmia

• Benzothiazepines Benzothiazepines (( 苯硫卓类苯硫卓类 ):): • diltiazem diltiazem 地尔硫卓地尔硫卓 weaker for heart depression and vasodilatioweaker for heart depression and vasodilatio

n;n; suitable for variant angina pectorissuitable for variant angina pectoris

艹

艹

B. Clinical uses B. Clinical uses 临床应用临床应用

stable and variant type:stable and variant type:

nifedipine, verapamil, diltiazemnifedipine, verapamil, diltiazem

unstable type:unstable type:

verapamil, diltiazemverapamil, diltiazem


Actions of DHP (like nifedipine) are similar to those of nitroglycerinActions of DHP (like nifedipine) are similar to those of nitroglycerin

Actions of verapamil are similar to those of Actions of verapamil are similar to those of blockers blockers

Actions of Actions of diltiazemdiltiazem are intermedial in both above drugsare intermedial in both above 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 decrea: markedly decrease; se; : variable according to the dose and effect of each drug ; : variable according to the dose and effect of each drug ; * * bl bl

ockersockers combined with nitroglycerin or Cacombined with nitroglycerin or Ca2+2+ antagonists ( antagonists (nifedipine; combinifedipine; combination with verapamil/diltiazem not be recommendatednation with verapamil/diltiazem not be recommendated))

Caution:Caution: Combination may potentiate the antianginal effects,Combination may potentiate the antianginal effects, but may induce severe hypotension but may induce severe hypotension

3. Summary of antianginal drugs3. Summary of antianginal drugs

2.4 Other drugs 2.4 Other drugs 其他药物其他药物

ACEIs ACEIs （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 cardiac remodeling Inhibiting cardiac remodeling

Nicorandil Nicorandil （尼可地尔）（尼可地尔）

• Opening ATP-sensitive KOpening ATP-sensitive K++ channel (K channel (KATPATP) ) • Lowering intracellular CaLowering intracellular Ca2+2+

• Providing NO (like nitroglycerin)Providing NO (like nitroglycerin)•Inducing ischemic preconditioning Inducing ischemic preconditioning


Molsidomine Molsidomine （吗多明）（吗多明）•Promoting collateral circulation Promoting collateral circulation •Similar to nitroglycerinSimilar to nitroglycerin•Used in stable anginaUsed in stable angina

Dipyridamole Dipyridamole （双嘧达莫，潘生丁）（双嘧达莫，潘生丁）

• Inhibiting adenosine uptake and cAMP degradationInhibiting adenosine uptake and cAMP degradation•Inhibiting pletelet aggregationInhibiting pletelet aggregation•Small doses, long-term oral administrationSmall doses, long-term oral administration


SummarySummary

Cardiovascular Cardiovascular pharmacologypharmacology

Overview of Cardiovascular DiseasesOverview 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 diseases

Overview of Cardiovascular Drugs Overview 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, arterioscVasodilatation, vasoconstriction, arteriosc

lerosislerosis

• Classification based on the mechanismsClassification based on the mechanisms• Ion channelsIon channels ：： CaCa2+2+, Na, Na++, K, K+ + channelschannels

• ReceptorsReceptors ：： Adrenoceptors, ATAdrenoceptors, AT11 receptors, receptors, etc.etc.

• EnzymesEnzymes ：： ACEI, NaACEI, Na++-K-K++-ATPase, HMG-CoA reductas-ATPase, HMG-CoA reductasee

• OthersOthers ：： DiureticsDiuretics

Cardiovascular Drugs Cardiovascular Drugs

• Antiarrhthemic drugsAntiarrhthemic drugs• Classification; Typical drugs and their propertiesClassification; Typical drugs and their properties

• Antihypertensive drugsAntihypertensive drugs• Classification; Properties of 6 main drug classesClassification; Properties of 6 main drug classes

• Drugs for treating heart failureDrugs for treating heart failure• Classification; ACEIs, Classification; ACEIs, blockers, cardiac glycoide blockers, cardiac glycoide

• Antiatheroscleotic drugsAntiatheroscleotic drugs• HMG CoA reductase inhibitors (statins)HMG CoA reductase inhibitors (statins)

• Antianginal drugsAntianginal drugs• Nitroglycerin; Nitroglycerin; blockers; Ca blockers; Ca2+2+ antagonists antagonists

part 6 antianginal drugs 抗心绞痛药 organic nitrates organic nitrates receptor blockers ...

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