pharmacology chapter 26颜光美药理学 抗心绞痛药

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1、第26章抗心绞痛药大连医科大学李淑媛Chapter26AntianginaldrugsKeyconceptsAnginapectorisischaracterizedbychestpaincausedbyinsufficientcoronarybloodflowtomeettheoxygendemandsofthemyocardium.Thehallmarksymptomofanginaisasudden,severelypressingsubsternalpainradiatingtotheleftarm.Theimb

2、alancebetweentheoxygendemandandoxygenutilizationmayresultfromtheobstructionofbloodvesselscausedbyatheroscleroticlesionsorfromaspasmofthevascularsmoothmuscle.AlltheantianginaldrugsexerttheireffectsbydecreasingthedemandofO2ofthemyocardiumand/orincreasingthesupplyof

3、O2totheischemicregionofmyocardiumthroughdifferentmechanisms.Intreatingpatientswithstableangina,threeclassesofdrugs(nitrates,β-receptorblockers,andcalciumchannelblockers)areequallyeffectiveforreliefofanginalsymptoms.Variantangina(alsocalledPrinzmetal'sangina)cause

4、dbyspontaneouscoronaryspasmratherthanbyincreasesinmyocardialO2requirements,isabletobecontrolledbyorganicnitratesorcalciumchannelblockers,butβ-receptorblockersarecontraindicated.Nitratesdecreasecoronaryvasoconstrictionorspasmandincreaseperfusionofthemyocardiumbyre

5、laxingcoronaryarteries.β-receptorblockersdecreasetheO2demandsoftheheart.Calciumchannelblockersreducecardiaccontractilityandcausevasodilatation.Nitratesareoftenusedincombinationwithβ-receptorblockersinordertodecreaseadversereactionsandincreasetreatmentefficacy.Key

6、concepts心绞痛类型1．稳定性心绞痛2．不稳定性心绞痛3．变异性心绞痛药物治疗心绞痛的目的1．控制症状，↓心肌损害2．预防发作决定心肌供O2与需的因素O2心舒张期长短供O2需O2冠状动脉灌注压*心力冠状动脉口径心率心室内压心室壁张力心室容积侧支循环每分钟射血时间血管外压力缺血性心脏病供O2↓+需O2↑，O2的供需失却平衡→心绞痛或心肌梗死供O2↓需O2↑1．冠状动脉粥样硬化,95%心力↑2．冠状动脉痉挛心率↑3．冠状动脉血栓形成运动、情绪改变）心绞痛（1）舒张冠状动脉（2）解除冠状动脉痉挛（3）↓心前后负荷→↓心室

7、舒张末期压力→心内膜下区血流↑（4）↓心率→↑冠状动脉血流灌注时间（5）抑制或消除血栓的生成抗心肌缺血药的抗心绞痛机制：↑心肌供O2抗心绞痛药物1.硝酸酯及亚硝酸酯类：如硝酸甘油等。2.β受体阻断药：如普萘洛尔等。3.钙转运阻断药：如硝苯吡啶、硫氮草酮、心可定等。一、硝酸酯和亚硝酸类硝酸甘油(Nitroglycerin)药理作用：基本作用：直接松弛各种平滑肌。松弛血管平滑肌最显著，所松弛的节段与剂量有关剂量（μg/kg.min-1）舒张0.5V与大的冠状动脉5.0外周血管20.0心肌阻力血管低剂量则显著抑制血小板的聚集松

8、弛血管机制：Nitroglycerin↓SHNO或SNO（亚硝巯基）↓+鸟苷酸环化酶↓+抑血小板Ca2+内流↓Ca2+外流↑激活蛋白激酶血管平滑肌胞内Ca2+↓血管舒张CGMP↑心室容积↓壁张1．↓心肌耗O2心室射血时间↓力↓舒张阻力血管→外周总阻力↓→BP↓（较大剂量）舒张V→回心血量↓→心室舒张末期压力↓心室抗心