antianginaldrugs抗心絞痛藥-課件-

Part6

AntianginalDrugsOrganicnitrates

receptorblockersCalciumchannelblockersPart6AntianginalDrugsO1Coronaryvessels:

bloodsupplyfortheheart1.OVERVIEWCoronaryvessels:bloodsupply2Coronaryatherosclerosis:

causeofcardiacischemiaCoronaryatherosclerosis:3DistributionofcoronaryarteriesintheheartDistributionofcoronaryarter4Ischemia(anginapectoris

):imbalancebetweenoxygendemandandsupplyIschemia(anginapectoris):5Classificationofanginapectoris:Exertionalangina(勞累性心絞痛)

Stableangina(穩(wěn)定性心絞痛)Initialonsetangina(初發(fā)型心絞痛)Acceleratedangina(惡化性心絞痛)Spontaneousangina(自發(fā)性心絞痛)Anginadecubitus(臥位型心絞痛)

Variantorvasospasticangina(變異性[痙攣性]心絞痛)Acutecoronaryinsufficiency(急性冠脈功能不全)Postinfarctionangina(梗死后心絞痛)Mixedangina(混合性心絞痛)

Unstableangina

(不穩(wěn)定性心絞痛)1.OVERVIEWClassificationofanginapecto6Myocardialoxygendemandischieflydeterminedby:Contractility

Heartrate

WalltensionPreload(venousreturn)Afterload(arteriolarresistance)

1.OVERVIEWpreloadafterloadMyocardialoxygendemandisch7Myocardialoxygendemandisdiminished

by:ReducingcontractilityReducingheartrateReducingthepreloadReducingtheafterload1.OVERVIEWWalltensionMyocardialoxygendemandisdi81.OVERVIEWMyocardialoxygensupplyischieflydeterminedby:AVoxygendifference

Regionalmyocardialdistribution

coronarybloodflow:

vascularresistance,arterypressure

1.OVERVIEWMyocardialoxygens9Effectsofantianginaldrugs:ReducingoxygendemandsReducingheartrateandcontractilityDilatingsystemicarteriesandveins(walltensionbyloweringheartloads)IncreasingoxygensupplyDilatingconductcoronaryarteries(coronarybloodflow)Promotingregionaldistribution(inischemicregions)Others:

Anti-plateletcoagulationandthrombusformation

1.OVERVIEWEffectsofantianginaldrugs:1102.1NitratesNitroglycerin

(硝酸甘油)A.Pharmacologicalactions

Dilatingvesselsandreducingheartloadswalltension;reflextachycardia

Redistributionofcoronarycirculation

dilatingconductartery:

collateralcirculationreducingwalltension:

bloodflowinischemicsubendocardialarea2.Antianginaldrugs2.1Nitrates2.Antianginaldr11Influenceoforganicnitratesanddipyridamoleonthebloodsupplyofischemicarea2.AntianginaldrugsInfluenceoforganicnitrates12Mechanismoftheeffectofnitroglycerinandothernitrates2.AntianginaldrugsMechanismoftheeffectofnit13MechanismoftheeffectofnitroglycerinandothernitratesMechanismoftheeffectofnit14B.ClinicalusesAnginapectoris:allkinds,especiallystabletype

Heartfailure：reducingheartloadsduetovasodilationC.Adversereactions

IncreaseinheartrateandcontractilitySymptomsduetovasodilation:

headache,flash,posturalhypotension,collapse,ect.

Others:methaemoglobinaemia（高鐵血紅蛋白）

Tolerance:avoidingsteady-stateplasmaconcentration;supplementofagentscontaining–SH(captopril)

2.AntianginaldrugsB.Clinicaluses2.Antiangina152.1Othernitrates

Isosorbidedinitrate(硝酸異山梨酯)Isosorbide-5-mononirate(5-硝酸異山梨酯)

Comparedwithnitroglycerin:SimilarbutweakereffectActingslowlybutlastinglongerLargerindividualvariationandmoreadverseeffects2.Antianginaldrugs2.1Othernitrates2.Antiangi16antianginaldrugs抗心絞痛藥-課件-172.2receptorblockersA.Pharmacologicalaction

Reducingoxygendemand:heartrateandcontractility

Increasingoxygensupply:diastolicperiod:perfusiontimevasculartoneinnormalregions:bloodflowinischemicregions

Others:ImprovingmyocardialmetabolismInhibitingcoagulationofplatelets2.Antianginaldrugs2.2receptorblockers2.Ant18B.Clinicaluses

stableandunstable

pectoris,especiallyassociatedwithhypertensionorarrhythmias,evenwithmyocardialinfarction;butnotusedfor

variantanginapectorisC.NotesDoseindividualization:startingfromsmalldose

Withdrawgraduallyandslowly:symptom

reboundCombinationwithnitroglycerin2.AntianginaldrugsB.Clinicaluses2.Antianginal192.3Calciumchannelblockers2.Antianginaldrugs2.3Calciumchannelblockers2202.3CalciumchannelblockersA.PharmacologicalactionsReducingmyocardialoxygenremand:heartloads:nifedipineheartrateandcontractility

:

verapamilanddiltiazem

Increasingmyocardialbloodsupply

ProtectingischemicmyocardialcellsInhibitingcoagulationofplatelets2.Antianginaldrugs2.3Calciumchannelblockers221ActionsofcalciumchannelblockersActionsofcalciumchannelblo22B.Clinicalusesstableandvarianttype:

nifedipine,verapamil,diltiazemunstabletype:

verapamil,diltiazem2.AntianginaldrugsActionsofDHP(likenifedipine)aresimilartothoseofnitroglycerinActionsofverapamilanddiltiazemaresimilartothoseofblockersB.Clinicaluses2.Antiangina232.4OtherdrugsACEIs（血管緊張素轉(zhuǎn)化酶抑制藥）TreatinghypertensionandpreventingischemicheartdiseaseReducingheartloadsInhibitingcardialremodelingNicorandil（尼可地爾）

OpeningATP-sensitiveK+channel(KATP)LoweringintracellularCa2+ProvidingNO(likenitroglycerin)Inducingischemicpreconditioning2.Antianginaldrugs2.4Otherdrugs2.Antianginal24Molsidomine（嗎多明）InhibitingadenosineuptakeandcAMPdegradationInhibitingpleteletaggregationPromotingcollateralcirculationafterlong-termuseDipyridamole（雙嘧達(dá)莫，潘生?。?/p>

InhibitingadenosineuptakeandcAMPdegradationInhibitingpleteletaggregationPromotingcollateralcirculationafterlong-termuse2.Antianginaldrugs2.Antianginaldrugs25

nitroglycerin

blockers

Ca2+antagonists

combination*Heartrate

Contractility

/Walltension

//Oxygendemand

Bloodpressure

:increase,:markedlyincrease;:decrease,:markedlydecrease;:variableaccordingtothedoseandeffectofeachdrug;*blockers

combinedwithnitroglycerinorCa2+antagonists(nifedipine;combinationwithverapamil/diltiazemnotberecommendated)Caution:

Combinationmaypotentiatetheantianginaleffects,butmayinduceseverehypotension3.Summaryofantianginaldrugsnitroglycerin26SammaryCardiovascularpharmacologySammaryCardiovascularpharmaco27OverviewofCardiovascularDiseasesCommonCardiacDiseasesAbnormalcontractility：HeartfailuresAbnormalrhythms：ArrhythmiasAbnormalbloodsupply：IschemicheartdiseasesMyocardialdisordersCommonvasculardiseasesAbnormalsystematicresistance：HypertensionDysfunctionofcoronaryvessels：CoronaryvasculardiseasesDysfunctionofcerebralvessels：Cerebralischemia,hemorrhageDysfunctionofpulmonaryvessels：PulmonaryhypertensionDysfunctionofperipheralvessels:PeripheralvasculardisorderArteriosclerosis:basisofmostCVSdiseasesOverviewofCardiovascularDis28OverviewofCardiovascularDrugsClassificationbasedontargetorgans/tissuesHeart：Heartfailures,arrhythmias,cardiacischemiaVessels：Vasodilatation,vasoconstriction,arteriosclerosisClassificationbasedonthemechanismsIonchannels：Ca2+,Na+,K+channelsReceptors：Adrenoceptors,AT1receptors,etc.Enzymes：ACEI,Na+-K+-ATPase,HMG-CoAreductaseOthers：DiureticsOverviewofCardiovascularDru29CardiovascularDrugsAntiarrhthemicdrugsClassification;TypicaldrugsandtheirpropertiesAntihypertensivedrugsClassification;Propertiesof6maindrugclassesDrugsfortreatingheartfailureClassification;ACEIs,blockers,cardiacglycoideAntiatheroscleoticdrugsHMGCoAreductaseinhibitors(statins)AntianginaldrugsNitroglycerin;blockers;Ca2+antagonistsCardiovascularDrugsAntiarrht30Part6

AntianginalDrugsOrganicnitrates

receptorblockersCalciumchannelblockersPart6AntianginalDrugsO31Coronaryvessels:

bloodsupplyfortheheart1.OVERVIEWCoronaryvessels:bloodsupply32Coronaryatherosclerosis:

causeofcardiacischemiaCoronaryatherosclerosis:33DistributionofcoronaryarteriesintheheartDistributionofcoronaryarter34Ischemia(anginapectoris

):imbalancebetweenoxygendemandandsupplyIschemia(anginapectoris):35Classificationofanginapectoris:Exertionalangina(勞累性心絞痛)

Stableangina(穩(wěn)定性心絞痛)Initialonsetangina(初發(fā)型心絞痛)Acceleratedangina(惡化性心絞痛)Spontaneousangina(自發(fā)性心絞痛)Anginadecubitus(臥位型心絞痛)

Variantorvasospasticangina(變異性[痙攣性]心絞痛)Acutecoronaryinsufficiency(急性冠脈功能不全)Postinfarctionangina(梗死后心絞痛)Mixedangina(混合性心絞痛)

Unstableangina

(不穩(wěn)定性心絞痛)1.OVERVIEWClassificationofanginapecto36Myocardialoxygendemandischieflydeterminedby:Contractility

Heartrate

WalltensionPreload(venousreturn)Afterload(arteriolarresistance)

1.OVERVIEWpreloadafterloadMyocardialoxygendemandisch37Myocardialoxygendemandisdiminished

by:ReducingcontractilityReducingheartrateReducingthepreloadReducingtheafterload1.OVERVIEWWalltensionMyocardialoxygendemandisdi381.OVERVIEWMyocardialoxygensupplyischieflydeterminedby:AVoxygendifference

Regionalmyocardialdistribution

coronarybloodflow:

vascularresistance,arterypressure

1.OVERVIEWMyocardialoxygens39Effectsofantianginaldrugs:ReducingoxygendemandsReducingheartrateandcontractilityDilatingsystemicarteriesandveins(walltensionbyloweringheartloads)IncreasingoxygensupplyDilatingconductcoronaryarteries(coronarybloodflow)Promotingregionaldistribution(inischemicregions)Others:

Anti-plateletcoagulationandthrombusformation

1.OVERVIEWEffectsofantianginaldrugs:1402.1NitratesNitroglycerin

(硝酸甘油)A.Pharmacologicalactions

Dilatingvesselsandreducingheartloadswalltension;reflextachycardia

Redistributionofcoronarycirculation

dilatingconductartery:

collateralcirculationreducingwalltension:

bloodflowinischemicsubendocardialarea2.Antianginaldrugs2.1Nitrates2.Antianginaldr41Influenceoforganicnitratesanddipyridamoleonthebloodsupplyofischemicarea2.AntianginaldrugsInfluenceoforganicnitrates42Mechanismoftheeffectofnitroglycerinandothernitrates2.AntianginaldrugsMechanismoftheeffectofnit43MechanismoftheeffectofnitroglycerinandothernitratesMechanismoftheeffectofnit44B.ClinicalusesAnginapectoris:allkinds,especiallystabletype

Heartfailure：reducingheartloadsduetovasodilationC.Adversereactions

IncreaseinheartrateandcontractilitySymptomsduetovasodilation:

headache,flash,posturalhypotension,collapse,ect.

Others:methaemoglobinaemia（高鐵血紅蛋白）

Tolerance:avoidingsteady-stateplasmaconcentration;supplementofagentscontaining–SH(captopril)

2.AntianginaldrugsB.Clinicaluses2.Antiangina452.1Othernitrates

Isosorbidedinitrate(硝酸異山梨酯)Isosorbide-5-mononirate(5-硝酸異山梨酯)

Comparedwithnitroglycerin:SimilarbutweakereffectActingslowlybutlastinglongerLargerindividualvariationandmoreadverseeffects2.Antianginaldrugs2.1Othernitrates2.Antiangi46antianginaldrugs抗心絞痛藥-課件-472.2receptorblockersA.Pharmacologicalaction

Reducingoxygendemand:heartrateandcontractility

Increasingoxygensupply:diastolicperiod:perfusiontimevasculartoneinnormalregions:bloodflowinischemicregions

Others:ImprovingmyocardialmetabolismInhibitingcoagulationofplatelets2.Antianginaldrugs2.2receptorblockers2.Ant48B.Clinicaluses

stableandunstable

pectoris,especiallyassociatedwithhypertensionorarrhythmias,evenwithmyocardialinfarction;butnotusedfor

variantanginapectorisC.NotesDoseindividualization:startingfromsmalldose

Withdrawgraduallyandslowly:symptom

reboundCombinationwithnitroglycerin2.AntianginaldrugsB.Clinicaluses2.Antianginal492.3Calciumchannelblockers2.Antianginaldrugs2.3Calciumchannelblockers2502.3CalciumchannelblockersA.PharmacologicalactionsReducingmyocardialoxygenremand:heartloads:nifedipineheartrateandcontractility

:

verapamilanddiltiazem

Increasingmyocardialbloodsupply

ProtectingischemicmyocardialcellsInhibitingcoagulationofplatelets2.Antianginaldrugs2.3Calciumchannelblockers251ActionsofcalciumchannelblockersActionsofcalciumchannelblo52B.Clinicalusesstableandvarianttype:

nifedipine,verapamil,diltiazemunstabletype:

verapamil,diltiazem2.AntianginaldrugsActionsofDHP(likenifedipine)aresimilartothoseofnitroglycerinActionsofverapamilanddiltiazemaresimilartothoseofblockersB.Clinicaluses2.Antiangina532.4OtherdrugsACEIs（血管緊張素轉(zhuǎn)化酶抑制藥）TreatinghypertensionandpreventingischemicheartdiseaseReducingheartloadsInhibitingcardialremodelingNicorandil（尼可地爾）

OpeningATP-sensitiveK+channel(KATP)LoweringintracellularCa2+ProvidingNO(likenitroglycerin)Inducingischemicpreconditioning2.Antianginaldrugs2.4Otherdrugs2.Antianginal54Molsidomine（嗎多明）InhibitingadenosineuptakeandcAMPdegradationInhibitingpleteletaggregationPromotingcollateralcirculationafterlong-termuseDipyridamole（雙嘧達(dá)莫，潘生丁）

InhibitingadenosineuptakeandcAMPdegradationInhibitingpleteletaggregationPromotingcollateralcirculationafterlong-termuse2.Antianginaldrugs2.Antianginaldrugs55

nitroglycerin

blockers

Ca2+antagonists

combination*Heartrate

Contractility

/Walltension

//Oxygendemand

Bloodpressure

:increase,:markedlyincrease;:decrease,:markedlydecrease;:variableaccordingtothedoseandeffectofeachdrug;*blockers

combinedwithnitroglycerinorCa2+antagonists(nifedipine