Pharmacology Chapter 26颜光美药理学 抗心绞痛药VIP免费

第第2626章抗心绞痛药章抗心绞痛药大连医科大学李淑媛Chapter26AntianginaldrugsKeyconceptsKeyconceptsAnginapectorisischaracterizedbychestpaincausedbyinsufficientcoronarybloodflowtomeettheoxygendemandsofthemyocardium.Thehallmarksymptomofanginaisasudden,severelypressingsubsternalpainradiatingtotheleftarm.Theimbalancebetweentheoxygendemandandoxygenutilizationmayresultfromtheobstructionofbloodvesselscausedbyatheroscleroticlesionsorfromaspasmofthevascularsmoothmuscle.AlltheantianginaldrugsexerttheireffectsbydecreasingthedemandofO2ofthemyocardiumand/orincreasingthesupplyofO2totheischemicregionofmyocardiumthroughdifferentmechanisms.Intreatingpatientswithstableangina,threeclassesofdrugs(nitrates,β-receptorblockers,andcalciumchannelblockers)areequallyeffectiveforreliefofanginalsymptoms.Variantangina(alsocalledPrinzmetal'sangina)causedbyspontaneouscoronaryspasmratherthanbyincreasesinmyocardialO2requirements,isabletobecontrolledbyorganicnitratesorcalciumchannelblockers,butβ-receptorblockersarecontraindicated.Nitratesdecreasecoronaryvasoconstrictionorspasmandincreaseperfusionofthemyocardiumbyrelaxingcoronaryarteries.β-receptorblockersdecreasetheO2demandsoftheheart.Calciumchannelblockersreducecardiaccontractilityandcausevasodilatation.Nitratesareoftenusedincombinationwithβ-receptorblockersinordertodecreaseadversereactionsandincreasetreatmentefficacy.Keyconcepts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↓心室抗心绞痛机制：2．舒张冠状动脉,↑心肌供血供O2（1）选择性舒张冠状动脉输送血管，并舒张狭窄血管，利于血液流入狭窄远心端舒张非缺血区输送血管→利于血径侧支分流向缺血区（2）↓心前负荷→↓心室舒张末期压力→利于血从心外膜下区流向心内膜下区（3）剌激侧支血管的生成，舒张侧支血管（4）心肌耗O2↓继发非缺血区血管阻力↑，迫使血流从非缺血区流到缺血区（5）预防/逆转冠状动脉收缩和痉挛注意：血管舒张→BP↓→反射性兴奋心脏→心力↑、心率↑→耗O2↑→部份抵消其有益作用体内过程：见附表，口服生物利用度仅8%∴不宜口服给药应用1．各型心绞痛速效、高效、方便、经济、能迅速控制发作，↑运动耐量，改善缺血心电图，↓运动时心律失常的发生一般舌下含0.3～0.6mg或喷雾剂每次0.4mg，必要时５min再给一次预防贴膜片剂或其他长效硝酸酯类２↓心...